US008802713B2

(12) United States Patent (10) Patent No.: US 8,802,713 B2 Ohata et al. (45) Date of Patent: Aug. 12, 2014

(54) 3-ALKOXY-1-PHENYLPYRAZOLE FOREIGN PATENT DOCUMENTS DERVATIVES AND PESTICIDES JP 482.541 1, 1973 JP 5262741 10, 1993 (75) Inventors: Satoru Ohata, Iwata (JP); Katsuya JP 2000 198768 T 2000 Kato, Iwata (JP); Keiji Toriyabe, Iwata JP 2OOO 2196.79 8, 2000 (JP); Yoshihiro Ito, Tokyo (JP); Ryuji JP 2007-284356 11, 2007 Hamaguchi, Tokyo (JP); Yuki Nakano, JP 2007-284386 11, 2007 Tokyo (JP) JP 2007-2843.87 11, 2007 WO 2004 O13106 2, 2004 WO 2006 O21462 3, 2006 (73) Assignees: Kumiai Chemical Industry Co., Ltd., WO 2006 O27 198 3, 2006 Tokyo (JP); Ihara Chemical Industry WO 2007 O81019 7/2007 Co., Ltd., Tokyo (JP) (*) Notice: Subject to any disclaimer, the term of this OTHER PUBLICATIONS patent is extended or adjusted under 35 Mueller, Hans-Georg et al., Synthese Und Eigenschaften Von U.S.C. 154(b) by 467 days. Thioncyanessigestern, Arch.Pharm., vol. 321, pp. 879-884 (1988). Hartke, Klaus et al., “Zur Reaktion Von Dithionmalonsaeureestern (21) Appl. No.: 12/682,059 MitNucleophilen Stickstorffbasen'', Arch.Pharm., vol.321, pp. 863 871 (1988). (22) PCT Filed: Oct. 17, 2008 Gotthardt, Hans et al., “Reaktionen Von 4.5-Diphenyl-1,3,4- Oxadiazolylium-2.Dicyan-methanid Mit Methanol und Singulett (86). PCT No.: PCT/UP2008/068902 Sauerstoe”, Chem. Ber, vol. 118, pp. 403-408 (1985). S371 (c)(1), Extended European Search Report issued Dec. 23, 2011, in European (2), (4) Date: Apr. 8, 2010 Patent Application No. 08838803.8. (87) PCT Pub. No.: WO2009/051245 Primary Examiner — Samantha Shterengarts PCT Pub. Date: Apr. 23, 2009 (74) Attorney, Agent, or Firm — Oblon, Spivak, (65) Prior Publication Data McClelland, Maier & Neustadt, L.L.P. US 2010/0210704 A1 Aug. 19, 2010 (57) ABSTRACT (30) Foreign Application Priority Data To provide pesticides such as insecticides, miticides and nem Oct. 18, 2007 (JP) ...... 2007-271857 aticides, which are excellent in the safety, pesticidal effects, Oct. 18, 2007 (JP) ...... 2007-271858 residual effectiveness, etc., which further have infiltration, and which can be applied by soil treatment. (51) Int. Cl. A pesticide comprising a 3-alkoxy-1-phenyl-pyrazole deriva A6 IK3 L/45 (2006.01) CO7D 23L/TO (2006.01) tive represented by the formula I oran agriculturally accept CO7D 23L/22 (2006.01) able salt thereof as an active ingredient: AOIN 43/56 (2006.01) C07D 231/52 (2006.01) (52) U.S. Cl. Rs R4 CPC ...... A0IN 43/56 (2013.01); C07D 231/22 O-R (2013.01); C07D 231/52 (2013.01) MN R6 N USPC ...... 514/.407: 548/367.1: 548/367.4: le 548/369.4: 548/370.1; 548/368.4: 548/366.1 R (58) Field of Classification Search R7 Rs R3 CPC ...... A61K31/415; C07D 231/10 USPC ...... 514/.407: 548/366.1, 367.1, 367.4, 548/368.4, 369.4, 370.1 wherein, for example, R is a C-Co alkyl group or the like, See application file for complete search history. R is a hydrogenatom or the like, R is a hydrogenatom or the like, and each of R. Rs. R and Rs which are independent of (56) References Cited one another, is a hydrogenatom or the like, and R, is a C-C, U.S. PATENT DOCUMENTS haloalkylthio group or the like. 2003, OO69242 A1 4/2003 Toriyabe et al. 2005/0215797 A1 9, 2005 Nakatani et al. 23 Claims, No Drawings US 8,802,713 B2 1. 2 3-ALKOXY-1-PHENYLPYRAZOLE insecticides, miticides and nematicides, which are excellent DERVATIVES AND PESTICDES in the safety, pesticidal effects, residual effectiveness, etc., which have infiltration, and which can be applied by soil TECHNICAL FIELD treatment. The present invention relates to novel 3-alkoxy-1-phenyl Means to Accomplish the Object pyrazole derivatives and their salts, their production interme diates, and pesticides containing the derivatives or their salts To develop pesticides having the above-described pre as an active ingredient. ferred characteristics, the present inventors have prepared 10 various 3-alkoxy-1-phenyl-pyrazole derivatives, and con BACKGROUND ART ducted extensive studies on their physiological activities. As a result, they have found that 3-alkoxy-1-phenyl-pyrazole Heretofore, pyrazole derivatives analogous to those of the derivatives (hereinafter sometimes referred to as the com present invention, for example, Non-Patent Documents 1 to 3 pounds of the present invention) represented by the following and Patent Documents 1 to 6 are known. Among them, Non 15 formula I have effects against various pests in agricultural Patent Documents 1 to 3 and Patent Documents 1, 3 and 4 and horticultural fields, and pests which have acquired resis disclose 3-alkoxy-1-phenyl-pyrazole derivatives but failed to tance. They have found that the compounds exhibit very high disclose agricultural chemicals. effects especially against mites represented by two-spotted Patent Document 2 discloses 3-alkoxy-1-phenyl-pyrazole spider mite, Kanzawa spider mite and citrus red mite, pest derivatives, but failed to disclose a 3-alkoxy-1-phenyl-pyra hemipterans represented by brown rice planthopper, green Zole derivative wherein the 3-position of the phenyl group is rice leafhopper and cotton aphid, pest coleoptera represented substituted by a haloalkylthio group or a haloalkyl sulfinyl by rice water weevil, rice leaf beetle and chafers, nematodes group, according to the present invention. represented by Southern root-knot nematode, and pest lepi Further, Patent Document 5 discloses 4-alkoxypyrazole dopterans represented by diamondbackmoth, beat armyworm derivatives, but failed to disclose 3-alkoxy-1-phenyl-pyra 25 and cotton bollworm, have high activity even by soil treat Zole derivatives according to the present invention. ment with which safe and labor-saving application becomes Patent Document 6 discloses 3-, 4- or 5-phenylpyrazole possible, and exhibit fungicidal effects against rice blast dis derivatives wherein a carbon atom of pyrazole and a phenyl ease. The present invention has been accomplished on the group are bonded, but failed to disclose 3-alkoxy-1-phenyl basis of these discoveries. pyrazole derivatives according to the present invention. 30 The present invention provides the following (1) to (10). Non-Patent Document 1: Arch. Pharm., 321,879 (1988) (1) A 3-alkoxy-1-phenyl-pyrazole derivative represented Non-Patent Document 2: Arch. Pharm., 321,863 (1988) by the formula II or an agriculturally acceptable salt thereof: Non-Patent Document 3: Chem. Ber, 118, 403 (1985) Patent Document 1: JP-B-48-2541 Patent Document 2: JP-A-5-262741 35 I Patent Document 3: WO2006/027198 Rs R4 Patent Document 4: WO2006/021462 O-R Patent Document 5: JP-A-2000-198768 MN R6 N Patent Document 6: WO2007/081019 e 40 R DISCLOSURE OF THE INVENTION R7 Rs R3 Object to be Accomplished by the Invention wherein R is a C-Co alkyl group (which may be mono In recent years, in agricultural and horticultural fields, due 45 Substituted or poly-substituted preferably by a cyano group or to use of pesticides such as insecticides, miticides and nem a hydroxy group), a C-Co haloalkyl group, a Cs-Co aticides for many years, pests have acquired resistance and cycloalkyl group (which may be mono-Substituted or poly are hardly controlled. Further, use of highly noxious pesti Substituted preferably by a halogen atom, a cyano group, a cides has been a problem. methyl group, a methoxy group or a trifluoromethyl group), a With respect to application of a pesticide, in a case where a 50 CCs cycloalkyl C-Cs alkyl group (which may be mono pesticide is directly sprayed to a plant for example, no suffi substituted or poly-substituted preferably by a halogen atom, cient pesticidal effect is obtained in Some cases due to non a cyano group, a methyl group, a methoxy group or a trifluo uniform spraying, transpiration, decomposition by light, out romethyl group), a C-Cs alkoxy C-C alkyl group (which flow of chemicals by rain, etc. On the other hand, when a may be mono-substituted or poly-substituted preferably by a pesticide is applied to the soil and is absorbed from e.g. the 55 halogen atom or a cyano group), a C-Cs alkoxy C-C alk root of a plant, the chemical will spread all over the plant enyl group (which may be mono-Substituted or poly-substi body, and a stable effect will be obtained. Further, pesticides tuted preferably by a halogenatom or a cyanogroup), a C-Cs applicable to Soil treatment are advantageous to those who are alkoxy C-C alkoxy C-C alkyl group (which may be mono engaged in agriculture from Such a viewpoint that exposure to substituted or poly-substituted preferably by a halogen atom the chemical by spraying is Small, and the method for apply 60 or a cyano group), a C-Coalkenyl group (which may be ing the chemical is simple, thus leading to power saving. mono-substituted or poly-substituted preferably by a halogen However, at present, very few pesticides Such as insecti atom or a cyano group), a C-Co alkynyl group (which may cides, miticides and nematicides, which can be utilized for be mono-substituted or poly-substituted preferably by a halo soil treatment and which are practical, have been known. gen atom or a cyano group), a C-Coalkynyloxy C1-C alkyl It is an object of the present invention to solve the above 65 group (which may be mono-Substituted or poly-substituted problems of conventional pesticides Such as insecticides, preferably by a halogen atom or a cyano group), a C-Cs miticides and nematicides, and to provide pesticides such as alkylthio C-C alkyl group (which may be mono-Substituted US 8,802,713 B2 3 4 or poly-substituted preferably by a halogen atom or a cyano R is a hydrogenatom, a hydroxy group, a halogenatom, a group), a C-C alkylsulfinyl C-C alkyl group (which may cyano group, a carboxy group, a HC(X) group, an R(R) be mono-substituted or poly-substituted preferably by a halo N(C=X) group, an azide group, a nitro group, a C-C alkyl gen atom or a cyano group), a C-C alkylsulfonyl C-Cs group (which may be mono-Substituted or poly-substituted alkyl group (which may be mono-Substituted or poly-substi preferably by a halogen atom, a cyano group, a hydroxy tuted preferably by a halogen atom or a cyano group), a group, a H2NC(=X) group, a carboxy group, a C-C alkyl C-C alkylsulfonyl group (which may be mono-substituted (1H-1,2,4-triazol)-1-yl group, a C-C alkoxy C(=X) group or poly-substituted preferably by a halogen atom or a cyano or 1,2,4-triazole), a C-C alkenyl group (which may be group), a benzenesulfonyl group (which may be mono-Sub mono-substituted or poly-substituted preferably by a halogen stituted or poly-substituted preferably by a halogen atom, a 10 atom or a cyano group), a C-C alkynyl group (which may be cyano group, a C-Cs alkyl group, a C-Cs alkoxy group, a mono-substituted or poly-substituted preferably by a halogen trifluoromethyl group, a difluoromethoxy group, a trifluo atom or a cyano group), a C-C cycloalkyl group (which may romethoxy group or a trifluoromethylthio group), a C-Co be mono-substituted or poly-substituted preferably by a halo thiocyanatoalkyl group (which may be mono-Substituted or gen atom, a cyano group or a methyl group), a C-Cs poly-substituted preferably by a halogen atom or a cyano 15 cycloalkyl C-C alkyl group (which may be mono-Substi group), an aryl-C(=X) group which may be mono-Substi tuted or poly-substituted preferably by a halogen atom, a tuted or poly-substituted by a Substituent group C, a C-Co cyano group or a methyl group), a C-C alkyl C(=X) group alkyl-C(=X) group (which may be mono-substituted or (which may be mono-substituted or poly-substituted prefer poly-substituted preferably by a halogen atom, a cyano ably by a halogen atom or a cyano group), a C-Cs alkenyl group, a C-C alkoxy group or a C-C alkylthio group), a C(=X) group (which may be mono-Substituted or poly-Sub C-C alkyl C(=X)C-C alkyl group (which may be mono stituted preferably by a halogen atom or a cyano group), a substituted or poly-substituted preferably by a halogen atom C-Cs cycloalkyl C(=X) group (which may be mono-Substi or a cyano group), a C-C alkoxy C(=X)C-C alkyl group tuted or poly-substituted preferably by a halogen atom, a (which may be mono-substituted or poly-substituted prefer cyano group or a C-C alkyl group), a C-C alkoxy group ably by a halogen atom or a cyano group), a pentafluorothio 25 (which may be mono-substituted or poly-substituted prefer C-C alkyl group, a tri(C-C)alkylsilyl C-C alkyl group ably by a halogenatom or a cyano group), a C-C cycloalky (which may be mono-substituted or poly-substituted prefer loxy group (which may be mono-Substituted or poly-substi ably by a halogen atom or a cyano group), a C-C trialkyl tuted preferably by a halogenatom or a cyano group), a C-C, silyl group (which may be mono-Substituted or poly-substi alkoxy C-C alkyl group (which may be mono-Substituted or tuted preferably by a cyano group or a halogenatom), an aryl 30 poly-substituted preferably by a halogen atom or a cyano group which may be mono-Substituted or poly-substituted by group), a C-C alkoxy C(=X) group (which may be mono a substituent group C, an aryl C-C alkyl group which may be substituted or poly-substituted preferably by a halogen atom mono-Substituted or poly-substituted by a Substituent group or a cyano group), a mercapto group, a thiocyanato group, a C., an aryloxy C-C alkyl group which may be mono-Substi C-C alkylthio group (which may be mono-Substituted or tuted or poly-substituted by a Substituent group C, an arylthio 35 poly-substituted preferably by a halogen atom or a cyano C-Cs alkyl group which may be mono-Substituted or poly group), a C-C alkylsulfinyl group (which may be mono Substituted by a Substituent group C, a heteroaryl group which substituted or poly-substituted preferably by a halogen atom may be mono-substituted or poly-substituted by a substituent ora cyano group), a C-C alkylsulfonyl group (which may be group C, a heteroaryl C-C alkyl group which may be mono mono-substituted or poly-substituted preferably by a halogen Substituted or poly-substituted by a Substituent group C, a 40 atom or a cyano group), a C-C cycloalkylthio group (which heteroaryloxy C-Cs alkyl group which may be mono-Substi may be mono-substituted or poly-substituted preferably by a tuted or poly-substituted by a Substituent group C, a het halogen atom or a cyano group), a C-C cycloalkylsulfinyl eroarylthio C-C alkyl group which may be mono-Substi group (which may be mono-Substituted or poly-substituted tuted or poly-substituted by a substituent group C., a preferably by a halogen atom or a cyano group), a C-Cs tetrahydrofurfuryl group, a tetrahydrofurfuryl C-C alkyl 45 cycloalkylsulfonyl group (which may be mono-Substituted or group which may be mono-Substituted or poly-substituted by poly-substituted preferably by a halogen atom or a cyano a substituent group C, an R(R)NC(=X) group or an R. group), a C-Calkylsulfonyloxy group (which may be mono (R)NC(=X)C-C alkyl group; substituted or poly-substituted preferably by a halogen atom R is a hydrogen atom, a hydroxy group, a halogenatom, a or a cyano group), an Rs (Rs.)N group, an Rs (Rs.)C=N cyano group, a H2NC(=X) group, a carboxy group, a C-C, 50 group or an RON=C(R) group; alkoxy C(=X) group, a HC(=X) group, a nitro group, an each of Ra Rs. Re and Rs which are independent of one amino group, an azide group, a C-C alkyl group (which may another, is a hydrogen atom, an amino group, an azide group. be mono-substituted or poly-substituted preferably by a halo a nitro group, a hydroxy group, a halogen atom, a carbamoyl gen atom or a cyano group), a C-C alkoxy group (which group, a cyano group, a carboxy group, a HC(X) group, a may be mono-substituted or poly-substituted preferably by a 55 C-C alkyl group (which may be mono-Substituted or poly halogen atom or a cyano group), a C-C alkoxy C-C alkyl Substituted preferably by a halogen atom), a C-C alkoxy group (which may be mono-Substituted or poly-substituted group (which may be mono-Substituted or poly-substituted preferably by a halogen atom or a cyano group), a C-C, preferably by a halogenatom), a formylamino group, a C-C, alkenyl group (which may be mono-Substituted or poly-Sub alkyl C(=X) group, an amino group (which may be mono stituted preferably by a halogen atom or a cyano group), a 60 substituted or poly-substituted preferably by a halogen atom C-C alkynyl group (which may be mono-substituted or or a cyano group), a C-C alkylthiocarbonylamino group poly-substituted preferably by a halogen atom or a cyano (which may be mono-substituted or poly-substituted prefer group), a C-C cycloalkyl group (which may be mono-Sub ably by a halogen atom or a cyano group), a C-C alkenyl stituted or poly-substituted preferably by a halogen atom, a group (which may be mono-Substituted or poly-substituted cyano group or a methyl group), or a C-C alkyl C(=X) 65 preferably by a halogen atom or a cyano group), a C-C, group (which may be mono-Substituted or poly-substituted alkynyl group (which may be mono-Substituted or poly-Sub preferably by a halogen atom or a cyano group); stituted preferably by a halogen atom or a cyano group), or a US 8,802,713 B2 5 6 C-C cycloalkyl group (which may be mono-Substituted or mono-substituted or poly-substituted preferably by a halogen poly-substituted preferably by a halogenatom, a cyano group atom or a cyano group), a benzenesulfonyl group which may or a methyl group); be mono-substituted or poly-substituted by a substituent R is a Chaloalkylthio group, a C-C haloalkylsulfinyl group C, a C-C alkyl C(=X) group (which may be mono group, a C-Chaloalkenylthio group, a C-C haloalkenyl substituted or poly-substituted preferably by a halogen atom, Sulfinyl group, a cyclopropylmethylthio group (which may be a cyano group, a hydroxy group, an acetyl group, a C1-C4 mono-substituted or poly-substituted preferably by a halogen alkoxy group, a C-C alkylthio group, a C-C alkylsulfinyl atom), or a cyclopropylmethylsulfinyl group (which may be group, a C-C alkylsulfonyl group, a C-C alkoxy C(=X) mono-substituted or poly-substituted preferably by a halogen group or a dimethylamino group), a C-Cs alkyl C(=X)C atom); 10 X is an oxygen atom or a Sulfur atom; (=X) group (which may be mono-Substituted or poly-Sub each of RandR, which are independent of each other, is stituted preferably by a halogen atom, a cyano group, a a hydrogen atom, a C-C alkyl group (which may be mono hydroxy group, an acetyl group, a C-C alkoxy group, a substituted or poly-substituted preferably by a halogen atom C-C alkylthio group, a C-C alkylsulfinyl group, a C-C, or a cyano group), a C-C cycloalkyl group (which may be 15 alkylsulfonyl group, a C-C alkoxycarbonyl group or a dim mono-substituted or poly-substituted preferably by a halogen ethylamino group), a C-C alkoxy C(=X) group (which atom, a C-C alkyl group, a C-C alkoxy group or a cyano may be mono-substituted or poly-substituted preferably by a group), or a C-C alkoxy group (which may be mono-Sub halogen atom, a cyano group, a hydroxy group, an acetyl stituted or poly-substituted preferably by a halogenatom or a group, a C-C alkoxy group, a C-C alkylthio group, a cyano group), C-C alkylsulfinyl group, a C-C alkylsulfonyl group, a R, and R, may form a 3- to 6-membered ring together C-C alkoxy C(=X) group or a dimethylamino group), a with the nitrogenatom to which they are bonded, and in Such C-Cs alkoxy C(=X)C(=X) group (which may be mono a case, in this ring, at least one structure selected from the substituted or poly-substituted preferably by a halogen atom, group consisting of an oxygenatom, a Sulfur atom, a carbonyl a cyano group, a hydroxy group, an acetyl group, a C1-C4 group and an N-methylamino group may be present in addi 25 alkoxy group, a C-C alkylthio group, a C-C alkylsulfinyl tion to the nitrogen atom to which R, and R, are bonded; group, a C-C alkylsulfonyl group, a C-C alkoxycarbonyl each of RandR, which are independent of each other, is group or a dimethylamino group), a C-C alkenyl C(=X) a hydrogen atom, a cyano group, an amino group, a hydroxy group (which may be mono-Substituted or poly-substituted group, a formyl group, a C-C alkyl group (which may be preferably by a halogen atom, a cyano group or a hydroxy mono-substituted or poly-substituted preferably by a halogen 30 group), a C-C alkynyl C(=X) group (which may be mono atom, a cyano group, a hydroxy group, a carboxy group, a substituted or poly-substituted preferably by a halogen atom, C-C alkoxy C(=X) group or a trimethylsilyl group), a a cyano group or a hydroxy group), a C-Cs cycloalkyl C-C alkenyl group (which may be mono-substituted or C(=X) group (which may be mono-Substituted or poly-Sub poly-substituted preferably by a halogen atom or a cyano stituted preferably by a halogen atom, a cyano group or a group), a C-C alkynyl group (which may be mono-substi 35 hydroxy group), a C-C alkyl C(=X)C-C alkyl group tuted or poly-substituted preferably by a halogen atom or a (which may be mono-substituted or poly-substituted prefer cyano group), a C-C alkoxy group (which may be mono ably by a halogenatom, a cyano group or a hydroxy group), an substituted or poly-substituted preferably by a halogen atom R(R)N group, an R(R)NC(=X) group, or a C-Cs or a cyano group), a C-C cycloalkyl group (which may be alkylthio C(=X) group (which may be mono-substituted or mono-substituted or poly-substituted preferably by a halogen 40 poly-substituted preferably by a halogen atom, a cyano atom, a cyano group or a methyl group), a C-C cycloalkyl group, a C-C alkyl group, a C-C alkoxy group, a trifluo C-C alkyl group (which may be mono-substituted or poly romethyl group or a hydroxy group); Substituted preferably by a halogen atom, a cyano group or a each of RandR which are independent of each other, is methyl group), a C-C alkoxy C-C alkyl group (which may a hydrogen atom, a C-C alkyl group (which may be mono be mono-substituted or poly-substituted preferably by a halo 45 substituted or poly-substituted preferably by a halogen atom gen atom, a cyano group or a trimethylsilyl group), a C-Cs or a cyano group), a C-C alkoxy group (which may be alkylthio C-C alkyl group (which may be mono-substituted mono-substituted or poly-substituted preferably by a halogen or poly-substituted preferably by a halogen atom or a cyano atom or a cyano group), or a C-C cycloalkyl group (which group), a C-C alkylsulfinyl C-C alkyl group (which may may be mono-substituted or poly-substituted preferably by a be mono-substituted or poly-substituted preferably by a halo 50 halogen atom, a C-C alkyl group, a C-C alkoxy group or gen atom or a cyano group), a C-C alkylsulfonyl C-C, a cyano group); alkyl group (which may be mono-Substituted or poly-substi R and R may form a 3- to 6-membered ring together tuted preferably by a halogenatom or a cyano group), a C-Cs with the nitrogenatom to which they are bonded, and in Such alkylsulfonyl group (which may be mono-Substituted or poly a case, in this ring, at least one structure selected from the Substituted preferably by a halogenatom or a cyano group), a 55 group consisting of an oxygenatom, a Sulfur atom, a carbonyl C-C alkylsulfinyl group (which may be mono-substituted or group and an N-methylamino group may be present in addi poly-substituted preferably by a halogen atom or a cyano tion to the nitrogen atom to which R and Rs are bonded; group), a C-C alkylthio group (which may be mono-Substi each of RandR which are independent of each other, is tuted or poly-substituted preferably by a halogen atom or a a hydrogenatom, a halogenatom, a C-C alkyl group (which cyano group), a C-Cs alkenylsulfonyl group (which may be 60 may be mono-substituted or poly-substituted preferably by a mono-substituted or poly-substituted preferably by a halogen halogenatom or a cyano group), a C-C alkoxy group (which atom or a cyano group), a C-Cs alkoxy C-C alkylsulfonyl may be mono-substituted or poly-substituted preferably by a group (which may be mono-Substituted or poly-substituted halogen atom or a cyano group), a C-Cs cycloalkyl group preferably by a halogen atom or a cyano group), a C-Cs (which may be mono-substituted or poly-substituted prefer cycloalkylsulfonyl group (which may be mono-Substituted or 65 ably by a halogenatom or a cyano group), an amino group, a poly-substituted preferably by a halogen atom or a cyano dimethylamino group, a C-C alkylthio group, an imidazolyl group), a di(C-Calkyl)aminosulfonyl group (which may be group, an aryl group which may be mono-Substituted or poly US 8,802,713 B2 7 8 Substituted by a Substituent group C, or a heteroaryl group tuted preferably by a halogen atom or a cyano group), a which may be mono-substituted or poly-substituted by a sub C-C alkylsulfonyl group (which may be mono-Substituted stituent group C.; or poly-substituted preferably by a halogen atom or a cyano Rs, and Rs may form a 3- to 6-membered ring together group), a benzenesulfonyl group (which may be mono-Sub with the nitrogenatom to which they are bonded, and in Such stituted or poly-substituted preferably by a halogen atom, a a case, in this ring, at least one structure selected from the cyano group, a C-Cs alkyl group, a C-Cs alkoxy group, a group consisting of an oxygenatom, a Sulfur atom, a carbonyl trifluoromethyl group, a difluoromethoxy group, a trifluo group and an N-methylamino group may be present in addi romethoxy group or a trifluoromethylthio group), a C-Co tion to the nitrogenatom to which Rand Rare bonded; and thiocyanatoalkyl group (which may be mono-Substituted or each of R, and R, which are independent of each other, is 10 poly-substituted preferably by a halogen atom or a cyano hydrogen atom, a C-C alkyl group (which may be mono group), an aryl-C(=X) group which may be mono-Substi substituted or poly-substituted preferably by a halogen atom tuted or poly-substituted by a Substituent group C, a C-Co or a cyano group), a C-C alkenyl group (which may be alkyl-C(=X) group (which may be mono-substituted or mono-substituted or poly-substituted preferably by a halogen poly-substituted preferably by a halogen atom, a cyano atom or a cyano group), or a C-C alkynyl group (which may 15 group, a C-C alkoxy group or a C-C alkylthio group), a be mono-substituted or poly-substituted preferably by a halo C-C alkyl C(=X)C-C alkyl group (which may be mono gen atom or a cyano group); Substituent group C.: substituted or poly-substituted preferably by a halogen atom a halogen atom, a cyano group, a hydroxy group, a nitro or a cyano group), a C-C alkoxy C(=X)C-Cs alkyl group group, an amino group, a carboxy group, a formyl group, a (which may be mono-substituted or poly-substituted prefer C-C alkyl group (which may be mono-Substituted or poly ably by a halogen atom or a cyano group), a pentafluorothio Substituted preferably by a halogen atom, a cyano group or a C-C alkyl group, a tri(C-C)alkylsilyl C-C alkyl group methoxy group), a C-C alkoxy group (which may be mono (which may be mono-substituted or poly-substituted prefer substituted or poly-substituted preferably by a halogen atom ably by a halogen atom or a cyano group), a C-C trialkyl or a cyano group), a C-C alkoxycarbonyl group, a C-Cs silyl group (which may be mono-Substituted or poly-substi cycloalkyl group, a C-C alkylthio group (which may be 25 tuted preferably by a cyano group or a halogenatom), an aryl mono-substituted or poly-substituted preferably by a halogen group which may be mono-Substituted or poly-substituted by atom, a cyano group or a methoxy group), a C-C alkylsulfi a Substituent group C, an aryl C-C alkyl group which may be nyl group (which may be mono-Substituted or poly-substi mono-Substituted or poly-substituted by a Substituent group tuted preferably by a halogen atom, a cyano group or a meth C., an aryloxy C-C alkyl group which may be mono-Substi oxy group), a C-Calkylsulfonyl group (which may be 30 tuted or poly-substituted by a Substituent group C, an arylthio mono-substituted or poly-substituted preferably by a halogen C-Cs alkyl group which may be mono-Substituted or poly atom, a cyano group or a methoxy group), or a C-C alkyl substituted by a substituent group C, a heteroaryl group which Sulfonyloxy group (which may be mono-Substituted or poly may be mono-substituted or poly-substituted by a substituent Substituted preferably by a halogen atom, a cyano group or a group C, a heteroaryl C-C alkyl group which may be mono methoxy group). 35 Substituted or poly-substituted by a Substituent group C, a (2) The 3-alkoxy-1-phenyl-pyrazole derivative or an agri heteroaryloxy C-Cs alkyl group which may be mono-Substi culturally acceptable salt thereof according to the above (1), tuted or poly-substituted by a Substituent group C, a het wherein in the above formula I, eroarylthio C-C alkyl group which may be mono-Substi R is a C-C alkyl group (which may be mono-Substituted tuted or poly-substituted by a Substituent group C, a or poly-substituted preferably by a cyano group or a hydroxy 40 tetrahydrofurfuryl group, a tetrahydrofurfuryl C-C alkyl group), a C-Cohaloalkyl group, a Cs-Co cycloalkyl group group which may be mono-Substituted or poly-substituted by (which may be mono-substituted or poly-substituted prefer a substituent group C, an R(R)NC(=X) group or an R. ably by a halogen atom, a cyano group, a methyl group, a (R)NC(=X)C-C alkyl group; methoxy group or a trifluoromethyl group), a CCs R is a hydrogenatom, a hydroxy group, a halogenatom, a cycloalkyl C-C alkyl group (which may be mono-Substi 45 cyano group, a H2NC(=X) group, a carboxy group, a tuted or poly-substituted preferably by a halogen atom, a HC(=X) group, a nitro group, an amino group, an azide cyano group, a methyl group, a methoxy group or a trifluo group, a C-C alkyl group (which may be mono-Substituted romethyl group), a C-Cs alkoxy C-C alkyl group (which or poly-substituted preferably by a halogen atom or a cyano may be mono-substituted or poly-substituted preferably by a group), a C-C alkoxy group (which may be mono-substi halogen atom or a cyano group), a C-C alkoxy C-Cs alk 50 tuted or poly-substituted preferably by a halogen atom or a enyl group (which may be mono-Substituted or poly-substi cyano group), a C-C alkoxy C-C alkyl group (which may tuted preferably by a halogenatom or a cyano group), a C-Cs be mono-substituted or poly-substituted preferably by a halo alkoxy C-C alkoxy C-C alkyl group (which may be mono gen atom or a cyano group), a C-C alkenyl group (which substituted or poly-substituted preferably by a halogen atom may be mono-substituted or poly-substituted preferably by a or a cyano group), a C-Coalkenyl group (which may be 55 halogen atom or a cyano group), a C-C alkynyl group mono-substituted or poly-substituted preferably by a halogen (which may be mono-substituted or poly-substituted prefer atom or a cyano group), a C-Co alkynyl group (which may ably by a halogenatom or a cyano group), a C-Cs cycloalkyl be mono-substituted or poly-substituted preferably by a halo group (which may be mono-Substituted or poly-substituted gen atom or a cyano group), a C-Clo alkynyloxy C1-C alkyl preferably by a halogen atom, a cyano group or a methyl group (which may be mono-Substituted or poly-substituted 60 group), or a C-C alkyl C(=X) group (which may be mono preferably by a halogen atom or a cyano group), a C-Cs substituted or poly-substituted preferably by a halogen atom alkylthio C-C alkyl group (which may be mono-Substituted or a cyano group); or poly-substituted preferably by a halogen atom or a cyano R is a hydrogenatom, a hydroxy group, a halogen atom, a group), a C-C alkylsulfinyl C-C alkyl group (which may cyano group, a carboxy group, a HC(X) group, an Rs (Rs.) be mono-substituted or poly-substituted preferably by a halo 65 N(C=X) group, an azide group, a nitro group, a C-C alkyl gen atom or a cyano group), a C-C alkylsulfonyl C-Cs group (which may be mono-Substituted or poly-substituted alkyl group (which may be mono-Substituted or poly-substi preferably by a halogen atom, a cyano group, a hydroxy US 8,802,713 B2 9 10 group, a H2NC(=X) group, a carboxy group, a C-C alkoxy may be mono-substituted or poly-substituted preferably by a C(=X) group or 1,2,4-triazole), a C-C alkenyl group halogen atom), or a cyclopropylmethylsulfinyl group (which (which may be mono-substituted or poly-substituted prefer may be mono-substituted or poly-substituted preferably by a ably by a halogen atom or a cyano group), a C-C alkynyl halogen atom); group (which may be mono-Substituted or poly-substituted X is an oxygen atom or a Sulfur atom; preferably by a halogen atom or a cyano group), a C-Cs each of RandR, which are independent of each other, is cycloalkyl group (which may be mono-Substituted or poly a hydrogen atom, a C-C alkyl group (which may be mono Substituted preferably by a halogen atom, a cyano group or a substituted or poly-substituted preferably by a halogen atom methyl group), a C-C cycloalkyl C-C alkyl group (which or a cyano group), a C-C cycloalkyl group (which may be may be mono-substituted or poly-substituted preferably by a 10 mono-substituted or poly-substituted preferably by a halogen halogen atom, a cyano group or a methyl group), a C-C, atom, a C-C alkyl group, a C-C alkoxy group or a cyano alkyl C(=X) group (which may be mono-substituted or poly group), or a C-C alkoxy group (which may be mono-Sub Substituted preferably by a halogenatom or a cyano group), a stituted or poly-substituted preferably by a halogenatom or a C-C alkenyl C(=X) group (which may be mono-substi cyano group), tuted or poly-substituted preferably by a halogen atom or a 15 R, and R, may form a 3- to 6-membered ring together cyano group), a C-C cycloalkyl C(=X) group (which may with the nitrogenatom to which they are bonded, and in Such be mono-substituted or poly-substituted preferably by a halo a case, in this ring, at least one structure selected from the gen atom, a cyano group or a C-C alkyl group), a C-C, group consisting of an oxygenatom, a Sulfur atom, a carbonyl alkoxy group (which may be mono-Substituted or poly-Sub group and an N-methylamino group may be present in addi stituted preferably by a halogen atom or a cyano group), a tion to the nitrogen atom to which R, and R, are bonded; C-C cycloalkyloxy group (which may be mono-substituted each of RandR, which are independent of each other, is or poly-substituted preferably by a halogen atom or a cyano a hydrogen atom, a cyano group, an amino group, a hydroxy group), a C-C alkoxy C-C alkyl group (which may be group, a C-C alkyl group (which may be mono-Substituted mono-substituted or poly-substituted preferably by a halogen or poly-substituted preferably by a halogen atom, a cyano atom or a cyano group), a C-C alkoxy C(=X) group (which 25 group, a hydroxy group, a carboxy group, a C-C alkoxy may be mono-substituted or poly-substituted preferably by a C(=X) group or a trimethylsilyl group), a C-C alkenyl halogen atom or a cyano group), a mercapto group, a thiocy group (which may be mono-Substituted or poly-substituted anato group, a C-Calkylthio group (which may be mono preferably by a halogen atom or a cyano group), a C-Cs substituted or poly-substituted preferably by a halogen atom alkynyl group (which may be mono-Substituted or poly-Sub or a cyano group), a C-C alkylsulfinyl group (which may be 30 stituted preferably by a halogen atom or a cyano group), a mono-substituted or poly-substituted preferably by a halogen C-C alkoxy group (which may be mono-Substituted or poly atom or a cyano group), a C-C alkylsulfonyl group (which substituted preferably by a halogenatom or a cyano group), a may be mono-substituted or poly-substituted preferably by a C-C cycloalkyl group (which may be mono-Substituted or halogenatom or a cyanogroup), a C-C cycloalkylthiogroup poly-substituted preferably by a halogenatom, a cyano group (which may be mono-substituted or poly-substituted prefer 35 or a methyl group), a C-C cycloalkyl C-C alkyl group ably by a halogenatom or a cyano group), a C-C cycloalkyl (which may be mono-substituted or poly-substituted prefer Sulfinyl group (which may be mono-Substituted or poly-Sub ably by a halogen atom, a cyano group or a methyl group), a stituted preferably by a halogen atom or a cyano group), a C-Cs alkoxy C-C alkyl group (which may be mono-Sub C-Cs cycloalkylsulfonyl group (which may be mono-Substi stituted or poly-substituted preferably by a halogen atom, a tuted or poly-substituted preferably by a halogen atom or a 40 cyano group or a trimethylsilyl group), a C-Calkylthio cyano group), a C-C alkylsulfonyloxy group (which may be C-C alkyl group (which may be mono-Substituted or poly mono-substituted or poly-substituted preferably by a halogen Substituted preferably by a halogenatom or a cyano group), a atom or a cyano group), an Rs.(Rs.)N group, an RARs) C-Cs alkylsulfinyl C-C alkyl group (which may be mono C=N group or an RON=C(R) group; substituted or poly-substituted preferably by a halogen atom each of Ra Rs. Re and Rs which are independent of one 45 or a cyano group), a C-C alkylsulfonyl C-C alkyl group another, is a hydrogen atom, an amino group, an azide group. (which may be mono-substituted or poly-substituted prefer a nitro group, a hydroxy group, a halogen atom, a carbamoyl ably by a halogen atom or a cyano group), a C-C alkylsul group, a cyano group, a carboxy group, a HC(X) group, a fonyl group (which may be mono-Substituted or poly-substi C-C alkyl group (which may be mono-substituted or poly tuted preferably by a halogenatom or a cyano group), a C-Cs Substituted preferably by a halogen atom), a C-C alkoxy 50 alkylsulfinyl group (which may be mono-Substituted or poly group (which may be mono-Substituted or poly-substituted Substituted preferably by a halogenatom or a cyano group), a preferably by a halogen atom), a formylamino group, a C-Cs alkylthio group (which may be mono-Substituted or C-Calkylcarbonylamino group (which may be mono-Sub poly-substituted preferably by a halogen atom or a cyano stituted or poly-substituted preferably by a halogenatom or a group), a C-C alkenylsulfonyl group (which may be mono cyano group), a C-C alkylthiocarbonylamino group (which 55 substituted or poly-substituted preferably by a halogen atom may be mono-substituted or poly-substituted preferably by a or a cyano group), a C-C alkoxy C-C alkylsulfonyl group halogen atom or a cyano group), a C-C alkenyl group (which may be mono-substituted or poly-substituted prefer (which may be mono-substituted or poly-substituted prefer ably by a halogenatom or a cyano group), a C-C cycloalkyl ably by a halogen atom or a cyano group), a C-C alkynyl Sulfonyl group (which may be mono-Substituted or poly group (which may be mono-Substituted or poly-substituted 60 Substituted preferably by a halogenatom or a cyano group), a preferably by a halogen atom or a cyano group), or a C-C, di(C-C alkyl)aminosulfonyl group (which may be mono cycloalkyl group (which may be mono-Substituted or poly substituted or poly-substituted preferably by a halogen atom Substituted preferably by a halogen atom, a cyano group or a or a cyano group), a benzenesulfonyl group which may be methyl group); mono-Substituted or poly-substituted by a Substituent group R is a C-C haloalkylthio group, a C-C haloalkylsulfi 65 C., a C-Cs alkyl C(=X) group (which may be mono-Substi nyl group, a C-Chaloalkenylthio group, a C-C haloalk tuted or poly-substituted preferably by a halogen atom, a enylsulfinyl group, a cyclopropylmethylthio group (which cyano group, a hydroxy group, an acetyl group, a C-C, US 8,802,713 B2 11 12 alkoxy group, a C-C alkylthio group, a C-C alkylsulfinyl each of R, and R, which are independent of each other, is group, a C-C alkylsulfonyl group, a C-C alkoxy C(=X) hydrogen atom, a C-C alkyl group (which may be mono group or a dimethylamino group), a C-Cs alkyl C(=X)C substituted or poly-substituted preferably by a halogen atom (=X) group (which may be mono-Substituted or poly-Sub or a cyano group), a C-C alkenyl group (which may be stituted preferably by a halogen atom, a cyano group, a mono-substituted or poly-substituted preferably by a halogen hydroxy group, an acetyl group, a C-C alkoxy group, a atom or a cyano group), or a C-C alkynyl group (which may C-C alkylthio group, a C-C alkylsulfinyl group, a be mono-substituted or poly-substituted preferably by a halo C-C alkylsulfonyl group, a C-C alkoxycarbonyl group or a gen atom or a cyano group); Substituent group C. dimethylamino group), a C-Calkoxy C(=X) group (which a halogen atom, a cyano group, a hydroxy group, a nitro may be mono-substituted or poly-substituted preferably by a 10 group, an amino group, a carboxy group, a formyl group, a halogen atom, a cyano group, a hydroxy group, an acetyl C-C alkyl group, a C-C alkoxy group, a C-C alkoxycar group, a C-C alkoxy group, a C-C alkylthio group, a bonyl group, a difluoromethoxy group, a trifluoromethoxy C-C alkylsulfinyl group, a C-C alkylsulfonyl group, a group, a C-Cs cycloalkyl group, a trifluoromethyl group, a C-C alkoxy C(=X) group or a dimethylamino group), a 15 trifluoromethylthio group, a C-Calkylthio group, a C-C, C-Cs alkoxy C(=X)C(=X) group (which may be mono alkylsulfinyl group, a C-C alkylsulfonyl group or a substituted or poly-substituted preferably by a halogen atom, C-C alkylsulfonyloxy group. a cyano group, a hydroxy group, an acetyl group, a C-C, (3) A 3-alkoxy-1-phenyl-pyrazole derivative represented alkoxy group, a C-C alkylthio group, a C-C alkylsulfinyl by the formula II" or an agriculturally acceptable salt thereof: group, a C-C alkylsulfonyl group, a C-C alkoxycarbonyl group or a dimethylamino group), a C-C alkenyl C(=X) group (which may be mono-Substituted or poly-substituted preferably by a halogen atom, a cyano group or a hydroxy R15 R14 group), a C-C alkynyl C(=X) group (which may be mono N O-R substituted or poly-substituted preferably by a halogen atom, 25 R16 N a cyano group or a hydroxy group), a C-Cs cycloalkyl le C(=X) group (which may be mono-Substituted or poly-Sub R12 stituted preferably by a halogen atom, a cyano group or a R17 R18 R13 hydroxy group), a C-C alkyl C(=X)C-C alkyl group (which may be mono-substituted or poly-substituted prefer 30 ably by a halogenatom, a cyano group or a hydroxy group), an wherein R is a C-C alkyl group (which may be mono R(R)N group, an R(R)NC(=X) group, or a C-Cs Substituted or poly-substituted preferably by a cyano group or alkylthio C(=X) group (which may be mono-substituted or a hydroxy group), or a C-C haloalkyl group, poly-substituted preferably by a halogen atom, a cyano R2 is a hydrogen atom, a hydroxy group, a halogen atom, group, a C-C alkyl group, a C-C alkoxy group, a trifluo 35 a cyano group, a nitro group, an amino group or a C-C alkyl romethyl group or a hydroxy group); group (which may be mono-Substituted or poly-substituted each of RandR which are independent of each other, is preferably by a halogen atom or a cyano group), a hydrogen atom, a C-C alkyl group (which may be mono R1 is a hydrogen atom, a hydroxy group, a halogen atom, substituted or poly-substituted preferably by a halogen atom a cyano group, a carboxy group, a HC(X) group, an Rs. or a cyano group), a C-C alkoxy group (which may be 40 (R)N(C=X) group, a C-C alkyl group (which may be mono-substituted or poly-substituted preferably by a halogen mono-substituted or poly-substituted preferably by a halogen atom or a cyano group), or a C-C cycloalkyl group (which atom, a cyano group, a hydroxy group, a H2NC(=X) group, may be mono-substituted or poly-substituted preferably by a a carboxy group or a C-C alkoxy C(=X) group), a C-C, halogen atom, a C-C alkyl group, a C-C alkoxy group or alkenyl group (which may be mono-Substituted or poly-Sub a cyano group); 45 stituted preferably by a halogen atom or a cyano group), a Rs, and R may form a 3- to 6-membered ring together C-C alkynyl group (which may be mono-Substituted or with the nitrogenatom to which they are bonded, and in Such poly-substituted preferably by a halogen atom or a cyano a case, in this ring, at least one structure selected from the group), a C-C cycloalkyl group (which may be mono-Sub group consisting of an oxygenatom, a Sulfur atom, a carbonyl stituted or poly-substituted preferably by a halogen atom, a group and an N-methylamino group may be present in addi 50 cyano group or a methyl group), a C-C alkyl C(=X) group tion to the nitrogen atom to which R and Rs are bonded; (which may be mono-substituted or poly-substituted prefer each of RandR which are independent of each other, is ably by a halogen atom or a cyano group), a C-C alkenyl a hydrogenatom, a halogenatom, a C-C alkyl group (which C(=X) group (which may be mono-Substituted or poly-Sub may be mono-substituted or poly-substituted preferably by a stituted preferably by a halogen atom or a cyano group), a halogenatom or a cyano group), a C-C alkoxy group (which 55 C-Cs cycloalkyl C(=X) group (which may be mono-Substi may be mono-substituted or poly-substituted preferably by a tuted or poly-substituted preferably by a halogen atom, a halogen atom or a cyano group), a C-Cs cycloalkyl group cyano group or a C-C alkyl group), a C-C alkoxy group (which may be mono-substituted or poly-substituted prefer (which may be mono-substituted or poly-substituted prefer ably by a halogenatom or a cyano group), an amino group, a ably by a halogenatom or a cyano group), a C-C cycloalky dimethylamino group, a C-C alkylthio group, or an imida 60 loxy group (which may be mono-Substituted or poly-substi Zolyl group; tuted preferably by a halogenatom or a cyano group), a C-C, Rs, and Rs may form a 3- to 6-membered ring together alkoxy C-C alkyl group (which may be mono-Substituted or with the nitrogenatom to which they are bonded, and in Such poly-substituted preferably by a halogen atom or a cyano a case, in this ring, at least one structure selected from the group), a C-C alkoxy C(=X) group (which may be mono group consisting of an oxygenatom, a Sulfur atom, a carbonyl 65 substituted or poly-substituted preferably by a halogen atom group and an N-methylamino group may be present in addi or a cyano group), an Rs (Rs.)N group or an Rs (Rs.) tion to the nitrogenatom to which RandRs are bonded; and C=N group, US 8,802,713 B2 13 14 each of Ra Rs. Re and Rs which are independent of one substituted or poly-substituted preferably by a halogen atom, another, is a hydrogen atom, a hydroxy group, a halogen a cyano group, a methyl group, a methoxy group or a trifluo atom, a cyano group, a C-C alkyl group (which may be romethyl group), a C-Cs alkoxy C-C alkyl group (which mono-substituted or poly-substituted preferably by a halogen may be mono-substituted or poly-substituted preferably by a atom), or a C-C alkoxy group (which may be mono-substi halogen atom or a cyano group), a C-Cs alkoxy C-C alk tuted or poly-substituted preferably by a halogen atom), enyl group (which may be mono-Substituted or poly-substi R7 is a C-C haloalkylthio group or a C-C haloalkyl tuted preferably by a halogenatom or a cyano group), a C-Cs Sulfinyl group, alkoxy C-C alkoxy C-C alkyl group (which may be mono X is an oxygen atom or a Sulfur atom, substituted or poly-substituted preferably by a halogen atom each of RandR, which are independent of each other, 10 or a cyano group), a C-Coalkenyl group (which may be is a hydrogen atom, a cyano group, a C-C alkyl group mono-substituted or poly-substituted preferably by a halogen (which may be mono-substituted or poly-substituted prefer atom or a cyano group), a C-Co alkynyl group (which may ably by a halogen atom, a cyano group, a hydroxy group, a be mono-substituted or poly-substituted preferably by a halo carboxy group, a C-C alkoxy C(=X) group or a trimethyl gen atom or a cyano group), a C-Co alkynyloxy C-C alkyl silyl group), a C-C alkenyl group (which may be mono 15 group (which may be mono-Substituted or poly-substituted substituted or poly-substituted preferably by a halogen atom preferably by a halogen atom or a cyano group), a C-Cs or a cyano group), a C-C alkynyl group (which may be alkylthio C-C alkyl group (which may be mono-Substituted mono-substituted or poly-substituted preferably by a halogen or poly-substituted preferably by a halogen atom or a cyano atom or a cyano group), a C-C alkoxy group (which may be group), a C-C alkylsulfinyl C-C alkyl group (which may mono-substituted or poly-substituted preferably by a halogen be mono-substituted or poly-substituted preferably by a halo atom or a cyano group), a C-C alkoxy C-C alkyl group gen atom or a cyano group), a C-C alkylsulfonyl C-Cs (which may be mono-substituted or poly-substituted prefer alkyl group (which may be mono-Substituted or poly-substi ably by a halogen atom, a cyano group or a trimethylsilyl tuted preferably by a halogen atom or a cyano group), a group), a C-C alkyl C(=X) group (which may be mono C-Co alkylsulfonyl group (which may be mono-Substituted substituted or poly-substituted preferably by a halogen atom, 25 or poly-substituted preferably by a halogen atom or a cyano a cyano group, a hydroxy group, an acetyl group, a C-C, group), a benzenesulfonyl group (which may be mono-Sub alkoxy group, a C-C alkylthio group, a C-C alkylsulfinyl stituted or poly-substituted preferably by a halogen atom, a group, a C-C alkylsulfonyl group, a C-C alkoxy C(=X) cyano group, a C-Cs alkyl group, a C-Cs alkoxy group, a group or a dimethylamino group), a C-Calkoxy C(=X) trifluoromethyl group, a difluoromethoxy group, a trifluo group (which may be mono-Substituted or poly-substituted 30 romethoxy group or a trifluoromethylthio group), a C-Co preferably by a halogen atom, a cyano group, a hydroxy thiocyanatoalkyl group (which may be mono-Substituted or group, an acetyl group, a C-C alkoxy group, a C-C alky poly-substituted preferably by a halogen atom or a cyano lthio group, a C-C alkylsulfinyl group, a C-C alkylsulfo group), an aryl-C(=X) group which may be mono-Substi nyl group or a C-C alkoxy C(=X) group), a C-C alkenyl tuted or poly-substituted by a Substituent group C', a C-Co C(=X) group (which may be mono-Substituted or poly-Sub 35 alkyl-C(=X) group (which may be mono-substituted or stituted preferably by a halogen atom, a cyano group or a poly-substituted preferably by a halogen atom, a cyano hydroxy group), a C-C cycloalkyl C(=X) group (which group, a C-C alkoxy group or a C-C alkylthio group), a may be mono-substituted or poly-substituted preferably by a C-Cs alkyl C(=X)C-C alkyl group (which may be mono halogen atom, a cyano group or a hydroxy group), or an substituted or poly-substituted preferably by a halogen atom R(R)NC(=X) group, and 40 or a cyano group), a C-C alkoxy C(=X)C-C alkyl group each of RandR which are independent of each other, (which may be mono-substituted or poly-substituted prefer is a hydrogen atom, a C-C alkyl group (which may be ably by a halogen atom or a cyano group), a pentafluorothio mono-substituted or poly-substituted preferably by a halogen C-Co alkyl group, a tri(C-C)alkylsilyl C-C alkyl group atom or a cyano group), or a C-C alkoxy group (which may (which may be mono-substituted or poly-substituted prefer be mono-substituted or poly-substituted preferably by halo 45 ably by a halogen atom or a cyano group), a C-C trialkyl gen or a cyano group). silyl group (which may be mono-Substituted or poly-substi (4) A 3-alkoxy-1-phenyl-pyrazole derivative represented tuted by a cyano group or a halogen atom), an aryl group by the formula I" or an agriculturally acceptable salt which may be mono-substituted or poly-substituted by a sub thereof: stituent group C', an aryl C-C alkyl group which may be 50 mono-Substituted or poly-substituted by a Substituent group C.', an aryloxy C-C alkyl group which may be mono-Substi tuted or poly-substituted by a substituent group C', an arylthio R25 R24 C-Cs alkyl group which may be mono-Substituted or poly O-R Substituted by a Substituent group C', a heteroaryl group MNN 55 which may be mono-substituted or poly-substituted by a sub le stituent group C', a heteroaryl C-C alkyl group which may R22 be mono-substituted or poly-substituted by a substituent group C', a heteroaryloxy C-C alkyl group which may be R27 R28 R23 mono-Substituted or poly-substituted by a Substituent group 60 C.', a heteroarylthio C-C alkyl group which may be mono wherein R is a C-C alkyl group (which may be mono Substituted or poly-substituted by a substituent group C', a Substituted or poly-substituted preferably by a cyano group or tetrahydrofurfuryl group, a tetrahydrofurfuryl C-C alkyl a hydroxy group), a C-Co haloalkyl group, a C-Co group which may be mono-Substituted or poly-substituted by cycloalkyl group (which may be mono-Substituted or poly a Substituent group C', an R(R)NC(=X) group or an Substituted preferably by a halogen atom, a cyano group, a 65 R(R)NC(=X)C-C alkyl group; methyl group, a methoxy group or a trifluoromethyl group), a R22 is a hydrogen atom, a hydroxy group, a halogen atom, CCs cycloalkyl C-Cs alkyl group (which may be mono a cyano group, a H2NC(=X) group, a carboxy group, a US 8,802,713 B2 15 16 HC(=X) group, a nitro group, an amino group, an azide each of R, R2s, Re and Rs which are independent of one group, a C-C alkyl group (which may be mono-substituted another, is a hydrogen atom, an amino group, an azide group. or poly-substituted preferably by a halogen atom or a cyano a nitro group, a hydroxy group, a halogen atom, a carbamoyl group), a C-C alkoxy group (which may be mono-Substi group, a cyano group, a carboxy group, a HC(X) group, a tuted or poly-substituted preferably by a halogen atom or a C-C alkyl group (which may be mono-Substituted or poly cyano group), a C-C alkoxy C-C alkyl group (which may Substituted preferably by a halogen atom), a C-C alkoxy be mono-substituted or poly-substituted preferably by a halo group (which may be mono-Substituted or poly-substituted gen atom or a cyano group), a C-C alkenyl group (which preferably by a halogen atom), a formylamino group, a may be mono-substituted or poly-substituted preferably by a C-Calkylcarbonylamino group (which may be mono-Sub 10 stituted or poly-substituted preferably by a halogenatom or a halogen atom or a cyano group), a C-C alkynyl group cyano group), a C-C alkylthiocarbonylamino group (which (which may be mono-substituted or poly-substituted prefer may be mono-substituted or poly-substituted preferably by a ably by a halogenatom or a cyano group), a C-Cs cycloalkyl halogen atom or a cyano group), a C-C alkenyl group group (which may be mono-Substituted or poly-substituted (which may be mono-substituted or poly-substituted prefer preferably by a halogen atom, a cyano group or a methyl 15 ably by a halogen atom or a cyano group), a C-C alkynyl group), or a C-C alkyl C(=X) group (which may be mono group (which may be mono-Substituted or poly-substituted substituted or poly-substituted preferably by a halogen atom preferably by a halogen atom or a cyano group), or a C-C, or a cyano group); cycloalkyl group (which may be mono-Substituted or poly R2 is a hydrogen atom, a hydroxy group, a halogenatom, Substituted preferably by a halogen atom, a cyano group or a a cyano group, a carboxy group, a HC(X) group, an R2, methyl group); (R)N(C=X) group, an azide group, a nitro group, a C-C, R, is a C-Chaloalkylthio group, a C-Chaloalkylsulfi alkyl group (which may be mono-Substituted or poly-substi nyl group, a C-Chaloalkenylthio group, a C-C haloalk tuted preferably by a halogenatom, a cyano group, a hydroxy enylsulfinyl group, a cyclopropylmethylthio group (which group, a H2NC(=X) group, a carboxy group, a C-C alkoxy may be mono-substituted or poly-substituted preferably by a C(=X) group or 1,2,4-triazole), a C-C alkenyl group 25 halogen atom), or a cyclopropylmethylsulfinyl group (which (which may be mono-substituted or poly-substituted prefer may be mono-substituted or poly-substituted preferably by a ably by a halogen atom or a cyano group), a C-C alkynyl halogen atom); group (which may be mono-Substituted or poly-substituted X is an oxygen atom or a Sulfur atom; preferably by a halogen atom or a cyano group), a C-Cs each of RandR, which are independent of each other, cycloalkyl group (which may be mono-Substituted or poly 30 is a hydrogen atom, a C-C alkyl group (which may be Substituted preferably by a halogen atom, a cyano group or a mono-substituted or poly-substituted preferably by a halogen methyl group), a C-C cycloalkyl C-C alkyl group (which atom or a cyano group), a C-Cs cycloalkyl group (which may may be mono-substituted or poly-substituted preferably by a be mono-substituted or poly-substituted preferably by a halo halogen atom, a cyano group or a methyl group), a C-C, gen atom, a C-C alkyl group, a C-C alkoxy group or a alkyl C(=X) group (which may be mono-substituted or poly 35 cyano group), or a C-C alkoxy group (which may be mono Substituted preferably by a halogenatom or a cyano group), a substituted or poly-substituted preferably by a halogen atom C-Cs alkenyl C(=X) group (which may be mono-Substi or a cyano group), tuted or poly-substituted preferably by a halogen atom or a R, and R, may form a 3- to 6-membered ring together cyano group), a C-Cs cycloalkyl C(=X) group (which may with the nitrogenatom to which they are bonded, and in Such be mono-substituted or poly-substituted preferably by a halo 40 a case, in this ring, at least one structure selected from the gen atom, a cyano group or a C-C alkyl group), a C-C, group consisting of an oxygenatom, a Sulfur atom, a carbonyl alkoxy group (which may be mono-Substituted or poly-Sub group and an N-methylamino group may be present in addi stituted preferably by a halogen atom or a cyano group), a tion to the nitrogenatom to which R, and R2, are bonded; C-Cs cycloalkoxy group (which may be mono-Substituted or each of R2, and R2, which are independent of each other, poly-substituted preferably by a halogen atom or a cyano 45 is a hydrogenatom, a cyano group, an amino group, a hydroxy group), a C-C alkoxy C-C alkyl group (which may be group, a C-C alkyl group (which may be mono-Substituted mono-substituted or poly-substituted preferably by a halogen or poly-substituted preferably by a halogen atom, a cyano atom or a cyano group), a C-C alkoxy C(=X) group (which group, a hydroxy group, a carboxy group, a C-C alkoxycar may be mono-substituted or poly-substituted preferably by a bonyl group or a trimethylsilyl group), a C-C alkenyl group halogen atom or a cyano group), a mercapto group, a thiocy 50 (which may be mono-substituted or poly-substituted prefer anato group, a C-Calkylthio group (which may be mono ably by a halogen atom or a cyano group), a C-C alkynyl substituted or poly-substituted preferably by a halogen atom group (which may be mono-Substituted or poly-substituted or a cyano group), a C-C alkylsulfinyl group (which may be preferably by a halogen atom or a cyano group), a C-C, mono-substituted or poly-substituted preferably by a halogen alkoxy group (which may be mono-Substituted or poly-Sub atom or a cyano group), a C-C alkylsulfonyl group (which 55 stituted preferably by a halogen atom or a cyano group), a may be mono-substituted or poly-substituted preferably by a C-C cycloalkyl group (which may be mono-Substituted or halogenatom or a cyanogroup), a C-C cycloalkylthiogroup poly-substituted preferably by a halogenatom, a cyano group (which may be mono-substituted or poly-substituted prefer or a methyl group), a C-C cycloalkyl C-C alkyl group ably by a halogenatom or a cyano group), a C-C cycloalkyl (which may be mono-substituted or poly-substituted prefer Sulfinyl group (which may be mono-Substituted or poly-Sub 60 ably by a halogen atom, a cyano group or a methyl group), a stituted preferably by a halogen atom or a cyano group), a C-C alkoxy C-C alkyl group (which may be mono-Sub C-Cs cycloalkylsulfonyl group (which may be mono-Substi stituted or poly-substituted preferably by a halogen atom, a tuted or poly-substituted preferably by a halogen atom or a cyano group or a trimethylsilyl group), a C-C alkylthio cyano group), a C-C alkylsulfonyloxy group (which may be C-C alkyl group (which may be mono-Substituted or poly mono-substituted or poly-substituted preferably by a halogen 65 Substituted preferably by a halogenatom or a cyano group), a atom or a cyano group), an R2s.(R2s.)N group, an R2s (R2s) C-Cs alkylsulfinyl C-C alkyl group (which may be mono C=N group or an RON=C(R) group; substituted or poly-substituted preferably by a halogen atom US 8,802,713 B2 17 18 or a cyano group), a C-C alkylsulfonyl C-C alkyl group R and R may form a 3- to 6-membered ring together (which may be mono-substituted or poly-substituted prefer with the nitrogenatom to which they are bonded, and in Such ably by a halogen atom or a cyano group), a C-C alkylsul a case, in this ring, at least one structure selected from the fonyl group (which may be mono-Substituted or poly-substi group consisting of an oxygenatom, a Sulfur atom, a carbonyl tuted preferably by a halogenatom or a cyano group), a C-Cs group and an N-methylamino group may be present in addi alkylsulfinyl group (which may be mono-Substituted or poly tion to the nitrogenatom to which R- and R2 are bonded; Substituted preferably by a halogenatom or a cyano group), a each of RandR which are independent of each other, C-Cs alkylthio group (which may be mono-Substituted or is a hydrogen atom, a halogen atom, a C-C alkyl group poly-substituted preferably by a halogen atom or a cyano (which may be mono-substituted or poly-substituted by halo group), a C-C alkenylsulfonyl group (which may be mono 10 gen or a cyano group), a C-C alkoxy group (which may be substituted or poly-substituted preferably by a halogen atom mono-substituted or poly-substituted preferably by halogen or a cyano group), a C-C alkoxy C-C alkylsulfonyl group or a cyano group), a C-C cycloalkyl group (which may be (which may be mono-substituted or poly-substituted prefer mono-substituted or poly-substituted preferably by a halogen ably by a halogenatom or a cyano group), a C-C cycloalkyl atom or a cyano group), an amino group, a dimethylamino Sulfonyl group (which may be mono-Substituted or poly 15 group, a C-C alkylthio group, or an imidazolyl group; Substituted preferably by a halogenatom or a cyano group), a R2s, and Ras may form a 3- to 6-membered ring together di (C-Calkyl)aminosulfonyl group (which may be mono with the nitrogenatom to which they are bonded, and in Such substituted or poly-substituted preferably by a halogen atom a case, in this ring, at least one structure selected from the or a cyano group), a benzenesulfonyl group which may be group consisting of an oxygenatom, a Sulfur atom, a carbonyl mono-Substituted or poly-substituted by a Substituent group group and an N-methylamino group may be present in addi O', a C-C alkyl C(=X) group (which may be mono-substi tion to the nitrogen atom to which Ras, and Rs are bonded; tuted or poly-substituted preferably by a halogen atom, a and cyano group, a hydroxy group, an acetyl group, a C-C, each of R2, and R2, which are independent of each other, alkoxy group, a C-C alkylthio group, a C-C alkylsulfinyl is hydrogen atom, a C-C alkyl group (which may be mono group, a C-C alkylsulfonyl group, a C-C alkoxycarbonyl 25 substituted or poly-substituted preferably by a halogen atom group or a dimethylamino group), a C-Cs alkyl C(=X)C or a cyano group), a C-C alkenyl group (which may be (=X) group (which may be mono-Substituted or poly-Sub mono-substituted or poly-substituted preferably by a halogen stituted preferably by a halogen atom, a cyano group, a atom or a cyano group), or a C-C alkynyl group (which may hydroxy group, an acetyl group, a C-C alkoxy group, a be mono-substituted or poly-substituted preferably by a halo C-C alkylthio group, a C-C alkylsulfinyl group, a C-C, 30 gen atom or a cyano group); alkylsulfonyl group, a C-Calkoxycarbonyl group or a dim Substituent group C': ethylamino group), a C-C alkoxy C(=X) group (which a halogen atom, a cyano group, a hydroxy group, a nitro may be mono-substituted or poly-substituted preferably by a group, an amino group, a carboxy group, a formyl group, a halogen atom, a cyano group, a hydroxy group, an acetyl C-C alkyl group, a C-C alkoxy group, a C-C alkoxycar group, a C-C alkoxy group, a C-C alkylthio group, a 35 bonyl group, a difluoromethoxy group, a trifluoromethoxy C-C alkylsulfinyl group, a C-C alkylsulfonyl group, a group, a C-Cs cycloalkyl group, a trifluoromethyl group, a C-C alkoxycarbonyl group or a dimethylamino group), a trifluoromethylthio group, a C-C alkylthio group, a C-C, C-Cs alkoxy C(=X)C(=X) group (which may be mono alkylsulfinyl group, a C-C alkylsulfonyl group, or a substituted or poly-substituted preferably by a halogen atom, C-C alkylsulfonyloxy group. a cyano group, a hydroxy group, an acetyl group, a C-C, 40 (5) A pesticide comprising the 3-alkoxy-1-phenyl-pyra alkoxy group, a C-C alkylthio group, a C-C alkylsulfinyl Zole derivative or an agriculturally acceptable salt thereof as group, a C-C alkylsulfonyl group, a C-Calkoxycarbonyl defined in the above (1), (2), (3) or (4) as an active ingredient. group or a dimethylamino group), a C-C alkenyl C(=X) (6) An agricultural or horticultural insecticide comprising group (which may be mono-Substituted or poly-substituted the 3-alkoxy-1-phenylpyrazole derivative oran agriculturally preferably by a halogen atom, a cyano group or a hydroxy 45 acceptable salt thereofas defined in the above (1), (2), (3) or group), a C-C alkynyl C(=X) group (which may be mono (4) as an active ingredient. substituted or poly-substituted preferably by a halogen atom, (7) A miticide comprising the 3-alkoxy-1-phenylpyrazole a cyano group or a hydroxy group), a C-Cs cycloalkyl derivative or an agriculturally acceptable salt thereof as C(=X) group (which may be mono-Substituted or poly-Sub defined in the above (1), (2), (3) or (4) as an active ingredient. stituted preferably by a halogen atom, a cyano group or a 50 (8) A nematicide comprising the 3-alkoxy-1-phenylpyra hydroxy group), a C-C alkyl C(=X)C-C alkyl group Zole derivative or an agriculturally acceptable salt thereof as (which may be mono-substituted or poly-substituted prefer defined in the above (1), (2), (3) or (4) as an active ingredient. ably by a halogenatom, a cyano group or a hydroxy group), an (9) A method for controlling a pest, which comprises R(R)N group, an R(R)NC(X) group, or a C-Cs applying an effective amount of the 3-alkoxy-1-phenylpyra alkylthio C(=X) group (which may be mono-substituted or 55 Zole derivative or an agriculturally acceptable salt thereof as poly-substituted preferably by halogen, a cyano group, a defined in the above (1), (2), (3) or (4). C-C alkyl group, a C-C alkoxy group, a trifluoromethyl (10) The 1-phenyl-pyrazole derivative or a salt thereof group or a hydroxy group); according to the above (1), wherein in the formula I., R is a each of RandR which are independent of each other, hydrogen atom. is a hydrogen atom, a C-C alkyl group (which may be 60 mono-substituted or poly-substituted preferably by halogen Effects of the Invention or a cyano group), a C-C alkoxy group (which may be mono-substituted or poly-substituted preferably by halogen The compounds of the present invention exhibit excellent or a cyano group), or a C-C scycloalkyl group (which may be pesticidal effects against a wide range of pests in agricultural mono-substituted or poly-substituted preferably by a halogen 65 and horticultural fields, and can control pests which have atom, a C-C alkyl group, a C-C alkoxy group or a cyano acquired resistance. Especially, they exhibit outstanding group); effects against mites represented by two-spotted spider mite, US 8,802,713 B2 19 20 Kanzawa spider mite and citrus red mite, pest hemipterans decyl group, a 1-methylnonyl group, a 2-methylnonyl group, represented by brown rice planthopper, green rice leafhopper a 6-methylnonyl group, a 7-methylnonyl group, a 8-methyl and cotton aphid, pest coleoptera represented by rice water nonyl group, a 1-ethyloctyl group or a 1-propylheptyl group. weevil, rice leaf beetle and chafers, nematodes represented by The C-Co alkyl group means, unless otherwise specified, Southern root-knot nematode, and pest lepidopterans repre a linear or branched alkyl group having from 3 to 10 carbon sented by diamondbackmoth, rice stem borer and cotton boll atoms, such as a group having at least 3carbon atoms exem worm. Further, since they are excellent in infiltration, safe and plified for the above C-C alkyl group. labor-saving application by soil treatment is possible. The C-C alkyl C(=X) group means a (C-C alkyl)-C (—X) group wherein the alkyl moiety is as defined above, BEST MODE FOR CARRYING OUT THE 10 Such as a methylcarbonyl group, a methylthiocarbonyl group, INVENTION an ethylthiocarbonyl group, an ethylcarbonyl group, a propy lcarbonyl group or abutylcarbonyl group. Symbols and terms used in this specification will be The C-C alkyl C(=X) group means a (C-C alkyl)-C described below. (—X) group wherein the alkyl moiety is as defined above, In the present invention, a pesticide means an insecticide, a 15 Such as a methylcarbonyl group, a methylthiocarbonyl group, miticide, a nematicide, etc. for agricultural and horticultural an ethylcarbonyl group, an ethylthiocarbonyl group, a propy fields, for animals such as domestic animals and pets, for lcarbonyl group, a butylcarbonyl group, a pentylcarbonyl household use and for epidemic prevention. group or a hexylcarbonyl group. The halogen atom represents a fluorine atom, a chlorine The C-C alkyl C(=X) group means a (C-C alkyl)-C atom, a bromine atom or an iodine atom. (—X) group wherein the alkyl moiety is as defined above, An expression by a symbol of element and a Subscript such Such as the above-exemplified group, or a heptylcarbonyl as C-C means that the number of elements in the Subsequent group or an octylcarbonyl group. group is within the range of the number represented by the The C-C alkyl C(=X) group means a (C-C alkyl)-C Subscript. For example, in this case, the above expression (=X)—group wherein the alkyl moiety is as defined above, means a number of carbon atoms of from 1 to 3, and an 25 Such as the above-exemplified group, or a nonylcarbonyl expression of C-C means a number of carbonatoms of from group or a decylcarbonyl group. 1 to 6, and an expression of C-C means a number of carbon The C-Cs alkyl C(=X)C-C alkyl group means a (C-Cs atoms of from 1 to 12. alkyl)-C(=X)—(C-C alkyl) group wherein the alkyl moi The C-C alkyl group means, unless otherwise specified, ety is as defined above. Such as a methylcarbonylmethyl a linear or branched alkyl group having from 1 to 4 carbon 30 group, a methylthiocarbonylmethyl group, an ethylcarbonyl atoms, such as a methyl group, an ethyl group, a n-propyl methyl group, a propylcarbonylmethyl group, a butylcarbo group, an isopropyl group, a n-butyl group, a S-butyl group, an nylmethyl group, a pentylcarbonylmethyl group, a hexylcar isobutyl group or a tert-butyl group. The same applies here bonylmethyl group, a heptylcarbonylmethyl group or an inafter. octylcarbonylmethyl group. The C-C alkyl group means, unless otherwise specified, 35 The C-C alkylcarbonylamino group means a (C-Cs a linear or branched alkyl group having from 1 to 6 carbon alkyl)carbonylamino group wherein the alkyl moiety is as atoms, such as the above-exemplified group or a n-pentyl defined above, such as a methylcarbonylamino group, an group, a 1-methylbutyl group, a 2-methylbutyl group, a 3-me ethylcarbonylamino group, a propylcarbonylamino group, a thylbutyl group, a 1-ethylpropyl group, a 1,1-dimethylpropyl hexylcarbonylamino group, a heptylcarbonylamino group or group, a 1,2-dimethylpropyl group, a neopentyl group, a 40 an octylcarbonylamino group. n-hexyl group, a 1-methylpentyl group, a 2-methylpentyl The C-Cs alkylthiocarbonylamino group means a (C-Cs group, a 3-methylpentyl group, a 4-methylpentyl group, a alkyl)-C(=S)NH group wherein the alkyl moiety is as 1-ethylbutyl group, a 2-ethylbutyl group, a 1,1-dimethylbutyl defined above, Such as a methylthiocarbonylamino group, an group, a 1,2-dimethylbutyl group, a 1,3-dimethylbutyl group, ethylthiocarbonylamino group, a propylthiocarbonylamino a 2.2-dimethylbutyl group, a 2,3-dimethylbutyl group, a 3.3- 45 group, a hexylthiocarbonylamino group, a heptylthiocarbo dimethylbutyl group, a 1.1.2-trimethylpropyl group, a 1.2.2- nylamino group or an octylthiocarbonylamino group. trimethylpropyl group or a 1-ethyl-1-methylpropyl group. The pentafluorothio C-C alkyl group means a FS The C-Cs alkyl group means, unless otherwise specified, (C-Co alkyl) group wherein the alkyl moiety is as defined a linear or branched alkyl group having from 1 to 8 carbon above, Such as a pentafluorothiomethyl group, a pentafluo atoms, such as the above-exemplified group or a n-heptyl 50 rothioethyl group, a pentafluorothiopropyl group, a pen group, a 1-methylhexyl group, a 5-methylhexyl group, a 1.1- tafluorothiobutyl group, a pentafluorothiopentyl group, a dimethylpentyl group, a 2.2-dimethylpentyl group, a 4.4- pentafluorothiohexyl group or a pentafluorothiodecyl group. dimethylpentyl group, a 1-ethylpentyl group, a 2-ethylpentyl The C-Cs haloalkyl group means, unless otherwise speci group, a 1,1,3-trimethylbutyl group, a 1.2.2-trimethylbutyl fied, a linear or branched alkyl group having from 1 to 8 group, a 1,3,3-trimethylbutyl group, a 2.2,3-trimethylbutyl 55 carbonatoms substituted by from 1 to 17identical or different group, a 2,3,3-trimethylbutyl group, a 1-propylbutyl group, a halogenatoms, such as a fluoromethyl group, a chloromethyl 1.1.2.2-tetramethylpropyl group, an octyl group, a 1-methyl group, a bromomethyl group, a difluoromethyl group, a heptyl group, a 3-methylheptyl group, a 6-methylheptyl dichloromethyl group, a trifluoromethyl group, a trichlorom group, a 2-ethylhexyl group, a 5.5-dimethylhexyl group, a ethyl group, a chlorodifluoromethyl group, a bromodifluo 2,4,4-trimethylpentyl group or a 1-ethyl-1-methylpentyl 60 romethyl group, a 2-fluoroethyl group, a 1-chloroethyl group, group. a 2-chloroethyl group, a 1-bromoethyl group, a 2-bromoethyl The C-Co alkyl group means, unless otherwise specified, group, a 2.2-difluoroethyl group, a 1,2-dichloroethyl group, a a linear or branched alkyl group having from 1 to 10 carbon 2,2-dichloroethyl group, a 2.2.2-trifluoroethyl group, 2.2.2- atoms, such as the above-exemplified group or anonyl group, trichloroethyl, 1,1,2,2-tetrafluoroethyl, a pentafluoroethyl a 1-methyloctyl group, a 2-methyloctyl group, a 3-methyloc 65 group, a 2-bromo-2-chloroethyl group, a 2-chloro-1.1.2.2- tyl group, a 7-methyloctyl group, a 1-ethylheptyl group, a tetrafluoroethyl group, a 1-chloro-1,2,2,2-tetrafluoroethyl 6,6-dimethylheptyl group, a 3.5.5-trimethylhexyl group, a group, a 1-chloropropyl group, a 2-chloropropyl group, a US 8,802,713 B2 21 22 3-chloropropyl group, a 2-bromopropyl group, a 3-bro Such as a cyclopropyl group, a cyclobutyl group, a cyclopen mopropyl group, a 2-bromo-1-methylethyl group, a 3-io tyl group or a cyclohexyl group. dopropyl group, a 2,3-dichloropropyl group, a 2,3-dibro The C-Cs cycloalkyl group means, unless otherwise mopropyl group, a 3,3,3-trifluoropropyl group, a 3.3.3- specified, a cycloalkyl group having from 3 to 8 carbonatoms, trifluoro-2-propyl group, a 3,3,3-trichloropropyl group, a 5 Such as the above-exemplified group, or a cycloheptyl group 3-bromo-3,3-difluoropropyl group, a 2,2-difluoropropyl or a cyclooctyl group. group, a 3.3-dichloro-3-fluoropropyl group, a 2.2.3,3-tet The C-C cycloalkyl group means, unless otherwise rafluoropropyl group, a 1-bromo-3,3,3-trifluoropropyl group, specified, a cycloalkyl group having from 3 to 10 carbon a 2.2.3.3.3-pentafluoropropyl group, a 2.2.2-trifluoro-1-trif atoms, such as the above-exemplified group, or a cyclononyl luoromethylethyl group, a heptafluoropropyl group, a 1.2.2, 10 group or a cyclodecyl group. The C-C cycloalkyl C-C alkyl group means, unless 2-tetrafluoro-1-trifluoromethylethyl group, a 1,1,2,3,3,3- otherwise specified, a (C-C cycloalkyl)-(C-C alkyl)group hexafluoropropyl group, a 2-chlorobutyl group, a wherein the cycloalkyl moiety and the alkyl moiety are as 3-chlorobutyl group, a 4-chlorobutyl group, a 2-chloro-1,1- defined above. Such as a cyclopropylmethyl group, a cyclobu dimethylethyl group, a 4-bromobutyl group, a 3-bromo-2- 15 tylmethyl group, a cyclopentylmethyl group or a cyclohexy methylpropyl group, a 2-bromo-1,1-dimethylethyl group, a lmethyl group. 2,2-dichloro-1,1-dimethylethyl group, a 2-chloro-1-chlo The C-C cycloalkyl C-C alkyl group means, unless romethyl-2-methylethyl group, a 4.4.4-trifluorobutyl group, a otherwise specified, a (C-C cycloalkyl)-(C-C alkyl)group 3,3,3-trifluoro-1-methylpropyl group, a 3,3,3-trifluoro-2- wherein the cycloalkyl moiety and the alkyl moiety are as methylpropyl group, a 2,3,4-trichlorobutyl group, a 2.2.2- defined above, Such as the above-exemplified group, or a trichloro-1,1-dimethylethyl group, a 4-chloro-4,4-difluo cyclopropylpentyl group, a cyclopropyloctyl group, a robutyl group, a 4.4-dichloro-4-fluorobutyl group, a cyclobutylhexyl group, a cyclopentylheptyl group or a cyclo 4-bromo-4,4-difluorobutyl group, a 2,4-dibromo-4,4-difluo hexyloctyl group. robutyl group, a 3,4-dichloro-3,4,4-trifluorobutyl group, 3.3- The C-Cs cycloalkyl C(=X) group means a (C-Cs dichloro-4,4,4-trifluorobutyl, a 4-bromo-3,3,4,4-tetrafluo 25 cycloalkyl)-C(=X)—group wherein the cycloalkyl moiety robutyl group, a 4-bromo-3-chloro-3,4,4-trifluorobutyl is as defined above. Such as a cyclopropylcarbonyl group, a group, a 2.2.3,3,4,4-hexafluorobutyl group, a 2.2.3.4.4.4- cyclopropylthiocarbonyl group, a cyclobutylcarbonyl group, hexafluorobutyl group, a 2.2.2-trifluoro-1-methyl-1-trifluo a cyclopentylcarbonyl group or a cyclohexylcarbonyl group. romethylethyl group, a 3,3,3-trifluoro-2-trifluoromethylpro The C-C cycloalkyloxy group means a (C-Cs pyl group, a 2.2.3.3.4.4.4-heptafluorobutyl group, a 3.3.4.4. 30 cycloalkyl)-O-group wherein the cycloalkyl moiety is as 4-pentafluoro-2-butyl group, a 2,3,3,3-tetrafluoro-2- defined above, Such as a cyclopropyloxy group, a cyclobuty trifluoromethylpropyl group, al 1.1.2.2.3.3.4.4- loxy group, a cyclopentyloxy group, a cyclohexyloxy group, octafluorobutyl group, a nonafluorobutyl group, perfluoro a cycloheptyloxy group or a cyclooctyloxy group. tert-butyl, a 4-chloro-1,1,2,2,3,3,4,4-octafluorobutyl group, a The C-C cyclo alkylthio group means a (C-Cs 5.5,5-trifluoropentyl group, a 4.4.5.5.5-pentafluoropentyl 35 cycloalkyl)-S-group wherein the cycloalkyl moiety is as group, a 3.3.4.4.5.5.5-heptafluoropentyl group, a 3.3.4.4.5.5, defined above, such as a cyclopropylthio group, a cyclobu 5-heptafluoro-2-pentyl group, a 2.2.3.3.4.4.5.5.5-nonafluo tylthio group, a cyclopentylthio group, a cyclohexylthio ropentyl group, a 2.2.3.3.4.4.5.5-octafluoropentyl group, a group, a cycloheptylthio group or a cyclooctylthio group. perfluoropentyl group, a 4.4.5.5.5-pentafluoro-2-butyl group, The C-C cycloalkylsulfinyl group means a (C-Cs a 2.2-bis(trifluoromethyl)propyl group, a 2.2.3.3.4.4.5.5.6.6. 40 cycloalkyl)-SO-group wherein the cycloalkyl moiety is as 6-undecafluorohexyl group, a 3.3.4.4.5.5.6.6.6-nonafluoro defined above, Such as a cyclopropylsulfinyl group, a hexyl group, a 4.4.5.5.6.6.6-heptafluorohexyl group, a 2.2.3, cyclobutylsulfinyl group, a cyclopentylsulfinyl group, a 3.4.4.5,5,6,6-decafluorohexyl group, a 4.4,4-trifluoro-3,3-bis cyclohexylsulfinyl group, a cycloheptylsulfinyl group or a (trifluoromethyl)butyl group, a perfluorohexyl group, a cyclooctylsulfinyl group. 1H, 1 H-perfluoroheptyl group, a 1H, 1H,2H2H-perfluoro 45 The C-C cycloalkylsulfonyl group means a (C-Cs heptyl group, a 1H, 1H,2H2H.3H.3H-perfluoroheptyl group, cycloalkyl)-SO-group wherein the cycloalkyl moiety is as a 1H, 1 H.7H-perfluoroheptyl group, a perfluoroheptyl group, defined above, Such as a cyclopropylsulfonyl group, a a 2-(perfluoro-3-methylbutyl)ethyl group, a 1H, 1H-perfluo cyclobutylsulfonyl group, a cyclopentylsulfonyl group, a rooctyl group, a 1H, 1 H.2H2H-perfluorooctyl group, a cyclohexylsulfonyl group, a cycloheptylsulfonyl group or a 1H, 1H,2H2H.3H.3H-perfluorooctyl group, a 6-(perfluoro 50 cyclooctylsulfonyl group. hexyl)ethyl group, a 1H, 1 H.8H-perfluorooctyl group or a The C-C cycloalkylsulfonyloxy group means a (C-Cs perfluorooctyl group. cycloalkyl)-SO-O-group wherein the cycloalkyl moiety The C-Co haloalkyl group means, unless otherwise is as defined above, such as a cyclopropylsulfonyloxy group, specified, a linear or branched alkyl group having from 3 to 10 a cyclobutylsulfonyloxy group, a cyclopentylsulfonyloxy carbonatoms substituted by from 1 to 21 identical or different 55 group, a cyclohexylsulfonyloxy group, a cycloheptylsulfony halogenatoms, such as a group having at least 3 carbonatoms loxy group or a cyclooctylsulfonyloxy group. exemplified for the above C-Chaloalkyl group, or a 1H, 1H The C-C alkenyl group means, unless otherwise speci perfluorononyl group, a 1H, 1 H.2H2H-perfluorononyl fied, a linear or branched alkenyl group having from 2 to 4 group, a 1H, 1H,2H2H.3H.3H-perfluorononyl group, a carbon atoms, such as a vinyl group, a 1-propenyl group, an 6-(perfluoro-1-methylethyl)hexyl group, a 1H, 1H,9H-per 60 isopropenyl group, a 2-propenyl group, a 1-butenyl group, a fluorononyl group, a perfluorononyl group, a 1H, 1H-perfluo 1-methyl-1-propenyl group, a 2-butenyl group, a 1-methyl rodecyl group, a 1H, 1 H.2H2H-perfluorodecyl group, a 2-propenyl group, a 3-butenyl group, a 2-methyl-1-propenyl 1H, 1H,2H2H.3H.3H-perfluorodecyl group, a 6-(perfluo group, a 2-methyl-2-propenyl group or a 1,3-butadienyl robutyl)hexyl group, a 1H, 1H.9H-perfluorodecyl group or a group. perfluorodecyl group. 65 The C-C alkenyl group means, unless otherwise speci The C-C cycloalkyl group means, unless otherwise fied, a linear or branched alkenyl group having from 2 to 6 specified, a cycloalkyl group having from 3 to 6 carbonatoms, carbonatoms, such as the above-exemplified group, or 1-pen US 8,802,713 B2 23 24 tenyl, a 1-ethyl-2-propenyl group, a 2-pentenyl group, a 1-butynyloxypropyl group, a 1-pentynyloxybutyl group, a 1-methyl-1-butenyl group, a 3-pentenyl group, a 1-methyl-2- 1-hexynyloxypentyl group or a 1-heptynyloxyhexyl group. butenyl group, a 4-pentenyl group, a 1-methyl-3-butenyl The C-C alkynyl C(=X) group means a (C-C alkynyl)- group, a 3-methyl-1-butenyl group, a 1,2-dimethyl-2-prope C(=X)— group wherein the alkynyl moiety is as defined nyl group, a 1,1-dimethyl-2-propenyl group, a 2-methyl-2- above, such as an ethinylcarbonyl group, an ethinylthiocar butenyl group, a 3-methyl-2-butenyl group, a 1,2-dimethyl bonyl group, a 1-propynylcarbonyl group, a 1-propynylthio 1-propenyl group, a 2-methyl-3-butenyl group, a 3-methyl carbonyl group, a 2-propynylcarbonyl group, a 1-butynylcar 3-butenyl group, a 1,3-pentadienyl group, a 1-vinyl-2- bonyl group, a 1-methyl-2-propynylcarbonyl group, a propenyl group, a 1-hexenyl group, a 1-propyl-2-propenyl 2-butynylcarbonyl group, a 3-butynylcarbonyl group, a group, a 2-hexenyl group, a 1-methyl-1-pentenyl group, a 10 1-pentynylcarbonyl group, a 1-ethyl-2-propynylcarbonyl 1-ethyl-2-butenyl group, a 3-hexenyl group, a 4-hexenyl group, a 2-pentynylcarbonyl group, a 3-pentynylcarbonyl group, a 5-hexenyl group, a 1-methyl-4-pentenyl group, a group, a 1-methyl-2-butynylcarbonyl group, a 4-pentynylcar 1-ethyl-3-butenyl group, a 1-(isobutyl) vinyl group, a 1-ethyl bonyl group, a 1-methyl-3-butynylcarbonyl group, a 2-me 1-methyl-2-propenyl group, a 1-ethyl-2-methyl-2-propenyl thyl-3-butynylcarbonyl group, a 1-hexynylcarbonyl group, a group, a 1-(isopropyl)-2-propenyl group, a 2-methyl-2-pen 15 1-(n-propyl)-2-propynylcarbonyl group, a 2-hexynylcarbo tenyl group, a 3-methyl-3-pentenyl group, a 4-methyl-3-pen nyl group, a 1-ethyl-2-butynylcarbonyl group, a 3-hexynyl tenyl group, a 1,3-dimethyl-2-butenyl group, a 1,1-dimethyl carbonyl group, a 1-methyl-2-pentynylcarbonyl group, a 3-butenyl group, a 3-methyl-4-pentenyl group, a 4-methyl-4- 1-methyl-3-pentynylcarbonyl group, a 4-methyl-1-pentynyl pentenyl group, a 1,2-dimethyl-3-butenyl group, a 1.3- carbonyl group, a 3-methyl-1-pentynylcarbonyl group, a dimethyl-3-butenyl group, a 1.1.2-trimethyl-2-propenyl 5-hexynylcarbonyl group, a 1-ethyl-3-butynylcarbonyl group, a 1.5-hexadienyl group, a 1-vinyl-3-butenyl group or a group, a 1-ethyl-1-methyl-2-propynylcarbonyl group, a 2.4-hexadienyl group. 1-(isopropyl)-2-propynylcarbonyl group, a 1,1-dimethyl-2- The C-C alkenyl group means, unless otherwise speci butynylcarbonyl group, a 2.2-dimethyl-3-butynylcarbonyl fied, a linear or branched alkenyl group having from 2 to 8 group or a 2-octynylcarbonyl group. carbon atoms, such as the above-exemplified group, or a 25 The C-C alkoxy group means a (C-C alkyl)-O-group 1-octenyl group or a 2-octenyl group. wherein the alkyl moiety is as defined above, Such as a meth The C-Coalkenyl group means, unless otherwise speci oxy group, an ethoxy group, a n-propoxy group, an isopro fied, a linear or branched alkenyl group having from 2 to 10 poxy group, a n-butoxy group, an isobutoxy group or a tert carbon atoms, such as the above-exemplified group, or a butoxy group. 1-nonenyl group, 1-decenyl group or a 2-decenyl group. 30 The C-C alkoxy group means an (alkyl)-O— group hav The C-C alkenyl C(=X) group means a (C-C alkenyl)- ing from 1 to 6 carbon atoms wherein the alkyl moiety is as C(=X)— group wherein the alkenyl moiety is as defined defined above, such as a methoxy group, an ethoxy group, a above, such as an ethenylcarbonyl group, an ethenylthiocar n-propoxy group, an isopropoxy group, a n-butoxy group, an bonyl group, a 2-propenylcarbonyl group, a 2-butenylcarbo isobutoxy group, a tert-butoxy group, a pentyloxy group, an nyl group, a 3-pentenylcarbonyl group or a 3-hexenylcarbo 35 isopentyloxy group, a hexyloxy group or an isohexyloxy nyl group. group. The C-C alkynyl group means, unless otherwise speci The C-Cs alkoxy group means a (C-C alkyl)-O-group fied, a linear or branched alkynyl group having from 2 to 4 wherein the alkyl moiety is as defined above, such as the carbon atoms, such as an ethinyl group, a 1-propynyl group, above-exemplified group, or a heptyloxy group or an octy a 2-propynyl group, a 1-butynyl group, a 1-methyl-2-propy 40 loxy group. nyl group, a 2-butynyl group or a 3-butynyl group. The C-C alkoxy(C=X) group means a (C-C alkoxy)C The C-C alkynyl group means, unless otherwise speci (=X)— group wherein the alkoxy moiety is as defined fied, a linear or branched alkynyl group having from 2 to 6 above, such as a group of e.g. methoxycarbonyl, methox carbon atoms, such as the above-exemplified group, or a ythiocarbonyl, ethoxycarbonyl, ethoxythiocarbonyl, n-pro 1-pentynyl group, a 1-ethyl-2-propynyl group, a 2-pentynyl 45 poxycarbonyl, isopropoxycarbonyl. n-butoxycarbonyl, group, a 3-pentynyl group, a 1-methyl-2-butynyl group, a isobutoxycarbonyl or tert-butoxycarbonyl. 4-pentynyl group, a 1-methyl-3-butynyl group, a 2-methyl The C-C alkoxy C-C alkyl group means a (C-C, 3-butynyl group, a 1-hexynyl group, a 1-(n-propyl)-2-propy alkoxy)-(C-C alkyl)group wherein the alkyl moiety and the nyl group, a 2-hexynyl group, a 1-ethyl-2-butynyl group, a alkoxy moiety areas defined above, such as a methoxymethyl 3-hexynyl group, a 1-methyl-2-pentynyl group, a 1-methyl 50 group, a methoxypropyl group, a methoxybutyl group, an 3-pentynyl group, a 4-methyl-1-pentynyl group, a 3-methyl ethoxymethyl group, an ethoxypropyl group, an ethoxybutyl 1-pentynyl group, a 5-hexynyl group, a 1-ethyl-3-butynyl group, an isopropoxymethyl group, a n-butoxymethyl group, group, a 1-ethyl-1-methyl-2-propynyl group, a 1-(isopropyl)- an isobutoxymethyl group, a 2-methoxyethyl group, a 2-propynyl group, a 1,1-dimethyl-2-butynyl group or a 2.2- 2-ethoxyethyl group, a 2-propoxyethyl group, a 2-isopro dimethyl-3-butynyl group. 55 poxyethyl group, a 2-(n-butoxy)ethyl group, a 2-isobutoxy The C-C alkynyl group means, unless otherwise speci ethyl group, a 3-methoxypropyl group, a 3-ethoxypropyl fied, a linear or branched alkynyl group having from 2 to 8 group or a 4-methoxybutyl group. carbon atoms, such as the above-exemplified group, or a The C-C alkoxy C-C alkyl group means a (C-Cs 2-octynyl group. alkoxy)-(C-C alkyl)group wherein the alkyl moiety and the The C-Co alkynyl group means, unless otherwise speci 60 alkoxy moiety are as defined above, such as the above-exem fied, a linear or branched alkynyl group having from 2 to 10 plified group, or a pentyloxymethyl group, a heptyloxym carbon atoms, such as the above-exemplified group, or a ethyl group or an octyloxymethyl group. 2-nonynyl group or a 2-decynyl group. The C-C alkoxy C-C alkyl group means a (C-Cs The C-Coalkynyloxy C-C alkyl group means a (C-Co alkoxy)-(C-C alkyl)group wherein the alkyl moiety and the alkynyl)-O-(C-Calkyl) group wherein the alkyl moiety 65 alkoxy moiety areas defined above, such as a methoxymethyl and the alkynyl moiety are as defined above. Such as an group, an ethoxymethyl group, an isopropoxymethyl group, a ethinyloxymethyl group, a 1-propynyloxyethyl group, a n-butoxymethyl group, an isobutoxymethyl group, a penty US 8,802,713 B2 25 26 loxymethyl group, a 2-methoxyethyl group, a 2-ethoxyethyl ioethyl group, a methylthiopropyl group, a methylthiobutyl group, a 2-propoxyethyl group, a 2-isopropoxyethyl group, a group, an ethylthiomethyl group, a propylthiomethyl group, a 2-(n-butoxy)ethyl group, a2-isobutoxyethyl group, a 3-meth butylthiomethyl group, a pentylthiomethyl group, a hexylthi oxypropyl group, a 3-ethoxypropyl group, a 4-methoxybutyl omethyl group or an octylthiomethyl group. group, a 5-methoxypentyl group or a 6-methoxyhexyl group. The C-C alkylthio C-C alkyl group means a (C-Cs The C-C alkoxy C-C alkoxy C-C alkyl group means alkyl)-S—(C-C alkyl)- group wherein the alkyl moieties a (C-C alkoxy)-(C-C alkoxy)-(C-C alkyl) group are as defined above, such as the above-exemplified group, or wherein the alkyl moiety and the alkoxy moieties are as a propylthiopentyl group, abutylthiohexyl group, a pentylth defined above, such as a 2-methoxyethoxymethyl group, a iooctyl group or a hexylthiooctyl group. 2-(2-methoxyethoxy)ethyl group, a 2-2-trifluoromethoxy 10 The C-C alkylsulfinyl group means a (C-C alkyl)-SO 1.1.2.2-tetrafluoroethoxy)-2,2-difluoroethyl group or a group wherein the alkyl moiety is as defined above, such as a 2-(2-perfluoropropoxy(perfluoropropoxy)-1,1,2-trifluoro methylsulfinyl group, an ethylsulfinyl group, a n-propylsulfi ethyl group. nyl group, an isopropylsulfinyl group, a butylsulfinyl group, The C-C alkoxy C-C alkoxy C-C alkyl group (which an isobutylsulfinyl group or a tert-butylsulfinyl group. may be mono-Substituted or poly-substituted by a halogen 15 The C-C alkylsulfinyl group means a (C-C alkyl)-SO atom or a cyano group) means a (C-Calkoxy)-(C-Cs group wherein the alkyl moiety is as defined above, such as alkoxy)-(C-C alkyl)group wherein the alkyl moiety and the the above-exemplified group, or an octylsulfinyl group. alkoxy moieties are as defined above, and these moieties may The C-Cs alkylsulfinyl C-C alkyl group means a (C-Cs be mono-Substituted or poly-substituted by a halogenatom or alkyl)-SO (C-C alkyl) group wherein the alkyl moieties a cyano group, such as a 2-methoxyethoxymethyl group, a are as defined above, such as a methylsulfinylmethyl group, 2-(2-methoxyethoxy)ethyl group, a 2-2-trifluoromethoxy an ethylsulfinylmethyl group, a n-propylsulfinylmethyl 1.1.2.2-tetrafluoroethoxy)-2,2-difluoroethyl group or a group, an isopropylsulfinylmethyl group, a butylsulfinylm 2-(2-perfluoropropoxy(perfluoropropoxy)-1,1,2-trifluoro ethyl group, an isobutylsulfinylmethyl group, a tert-butyl ethyl group. Sulfinylmethyl group, a pentylsulfinylmethyl group or a hexy The C-C alkoxy C(=X) group means a (C-C alkyl)- 25 lsulfinylmethyl group. O—C(=X)—group wherein the alkyl moiety is as defined The C-Cs alkylsulfinyl C-C alkyl group means a (C-Cs above, Such as a methoxycarbonyl group, a methoxythiocar alkyl)-SO-(C-Calkyl) group wherein the alkyl moiety is bonyl group, an ethoxycarbonyl group, an ethoxythiocarbo as defined above, Such as the above-exemplified group, or a nyl group, a n-propoxycarbonyl group, an isopropoxycarbo pentylsulfinylpentyl group or a hexylsulfinyloctyl group. nyl group or abutoxycarbonyl group. 30 The C-C alkylsulfonyl group means a (C-C alkyl)- The C-C alkoxy(C=X) group means a (C-C alkyl)- SO - group wherein the alkyl moiety is as defined above, O C(=X)—group wherein the alkyl moiety is as defined such as a methylsulfonyl group, an ethylsulfonyl group, a above, Such as the above-exemplified group, or a pentyloxy n-propylsulfonyl group or an isopropylsulfonyl group. carbonyl group, a hexyloxycarbonyl group, a heptyloxycar The C-C alkylsulfonyl group means a (C-C alkyl)- bonyl group or an octyloxycarbonyl group. 35 SO - group wherein the alkyl moiety is as defined above, The C-C alkoxy C(=X)C-Cs alkyl group means a (C- Such as the above-exemplified group, or a pentylsulfonyl Cs alkyl)-O-C(=X)—(C-C alkyl)- group wherein the group, a hexylsulfonyl group, a heptylsulfonyl group or an alkyl moieties are as defined above. Such as a methoxycarbo octylsulfonyl group. nylmethyl group, an ethoxycarbonylmethyl group, a pro The C-Co alkylsulfonyl group means a (C-Co alkyl)- poxycarbonylmethyl group, abutoxycarbonylmethyl group, 40 SO - group wherein the alkyl moiety is as defined above, a pentyloxycarbonylmethyl group, a hexyloxycarbonylm Such as the above-exemplified group, or a nonylsulfonyl ethyl group, a heptyloxycarbonylmethyl group or an octy group or a decylsulfonyl group. loxycarbonylmethyl group. The C-C alkylsulfonyl C-C alkyl group means a (C-Cs The C-C alkoxy C-C alkenyl group means a (C-Cs alkyl)-SO (C-C alkyl) group wherein the alkyl moieties alkoxy)-(C-Calkenyl) group wherein the alkyl moiety and 45 are as defined above, such as a methylsulfonylmethyl group, the alkoxy moiety are as defined above, Such as a methoxy an ethylsulfonylethyl group, a n-propylsulfonylpropyl group ethenyl group, a methoxypropenyl group, a methoxybutenyl or an isopropylsulfonylpropyl group. group, a methoxymenthenyl group, a methoxyhexyl group, a The C-C alkylsulfonyl C-C alkyl group means a (C-Cs methoxyheptenyl group or a methoxyoctenyl group. alkyl)-SO (C-Calkyl) group wherein the alkyl moieties The C-Cs alkoxy C-C alkylsulfonyl group means a (C- 50 are as defined above, such as the above-exemplified group, or Cs alkoxy)-(C-C alkyl)-SO - group wherein the alkyl a methylsulfonylpentyl group, an ethylsulfonylhexyl group, a moiety and the alkoxy moiety are as defined above, Such as a n-propylsulfonylhexyl group or an isopropylsulfonyloctyl methoxymethylsulfonyl group, an ethoxymethylsulfonyl group. group, abutoxymethylsulfonyl group or an octyloxymethyl The C-C alkylsulfonyloxy group means a (C-C alkyl)- Sulfonyl group. 55 SO. O— group wherein the alkyl moiety is as defined The C-C alkylthio group means a (C-C alkyl)-S— above, Such as a methylsulfonyloxy group, an ethylsulfony group wherein the alkyl moiety is as defined above, such as a loxy group, a n-propylsulfonyloxy group or an isopropylsul methylthio group, an ethylthio group, a n-propylthio group, fonyloxy group. an isopropylthio group, a butylthio group, an isobutylthio The C-C alkenylsulfonyl group means a (C-C alkenyl)- group or a tert-butylthio group. 60 SO - group wherein the alkenyl group is as defined above, The C-C alkylthio group means a (C-C alkyl)-S— Such as a vinylsulfonyl group, a 1-propenylsulfonyl group, an group wherein the alkyl moiety is as defined above, such as isopropenylsulfonyl group, a 2-propenylsulfonyl group, a the above-exemplified group, or a pentylthio group, a hexy 1-butenylsulfonyl group, a 1-methyl-1-propenylsulfonyl lthio group, a heptylthio group or an octylthio group. group, a 2-butenylsulfonyl group, a 1-methyl-2-propenylsul The C-C alkylthio C-C alkyl group means a (C-Cs 65 fonyl group, a 3-butenylsulfonyl group, a 2-methyl-1-prope alkyl)-S—(C-C alkyl)- group wherein the alkyl moiety is as nylsulfonyl group, a 2-methyl-2-propenylsulfonyl group or a defined above. Such as a methylthiomethyl group, a methylth 1,3-butadienylsulfonyl group. US 8,802,713 B2 27 28 The C-Cs thiocyanatoalkyl group means a NCS (C-Cs The heteroaryl group means an aromatic heterocyclic alkyl) group wherein the alkyl moiety is as defined above, group or a condensed heterocyclic group, Such as a pyrrolyl Such as a thiocyanatoethyl group, a thiocyanatopropyl group, group, a furanyl group, a thienyl group, an oxazolyl group, an a thiocyanatobutyl group, a thiocyanatopentyl group or a isoxazolyl group, an imidazolyl group, a 1,2,4-oxadiazolyl thiocyanatohexyl group. group, a 1.2.3-oxadiazolyl group, a 1.3,4-oxadiazolyl group, The C-Co thiocyanatoalkyl group means a NCS (C- a 1,2,4-triazolyl group, a 1,2,3-triazolyl group, a thiazolyl Coalkyl)group wherein the alkyl moiety is as defined above, group, an isothiazolyl group, a 1,2,4-thiadiazolyl group, a Such as a thiocyanatomethyl group, a thiocyanatoethyl group, 1,2,3-thiadiazolyl group, a 1.3,4-thiadiazolyl group, apyridyl a thiocyanatopropyl group, a thiocyanatobutyl group, a thio group, a pyrimidinyl group, a pyrazinyl group, a pyridazinyl cyanatopentyl group, a thiocyanatohexyl group or a thiocy 10 group, a 1,3,5-triazinyl group, a 1,2,4-triazinyl group, a ben anatodecyl group. ZOxazolyl group, a benzimidazolyl group, a benzotriazolyl The C-Cs haloalkylcarbonyl group means a (C-Cs group, a benzothiazolyl group, a quinolinyl group, a haloalkyl)-C(=O)—group wherein the haloalkyl moiety is quinazolinyl group, a quinoxalinyl group, a phthalazinyl as defined above, Such as a chloroacetyl group, a chlorodif group or a naphthylidinyl group. luoroacetyl group, a difluoroacetyl group, a trifluoroacetyl 15 The heteroaryl C-C alkyl group means a (heteroaryl)- group, a dichloroacetyl group, a trichloroacetyl group or a (C-C alkyl) group wherein the heteroaryl and the alkyl pentafluoropropionyl group. moiety areas defined above. Such as a thienylmethyl group or The C-C alkyl C(=X)C(=X) group means a (C-C a pyridylmethyl group. alkyl)-C(=X)—C(=X) group wherein the alkyl moiety is as The heteroaryl C-C alkyl group means a (heteroaryl)- defined above, such as a methylcarbonylcarbonyl group, a (C-Cs alkyl) group wherein the heteroaryl and the alkyl methylthiocarbonylcarbonyl group, an ethylcarbonylthiocar moiety are as defined above. Such as a 2-thienylmethyl group, bonyl group, an ethylthiocarbonylcarbonyl group, a propyl a 3-thienylmethyl group, a 2-pyridylmethyl group or a 3-py carbonylcarbonyl group, abutylthiocarbonylcarbonyl group, ridylmethyl group. a pentylcarbonylthiocarbonyl group or a hexylcarbonylcar The heteroaryl C-C alkyl C(=X) group means a (het bonyl group. 25 eroaryl)-(C-C alkyl)-C(=X)— group wherein the het The C-C alkoxy C(=X)C(=X) group means a (C-Cs eroaryland the alkyl moiety are as defined above, such as a alkyl)-O C(=X)—C(=X) group wherein the alkyl moiety 2-thienylmethylcarbonyl group, a 3-thienylmethylcarbonyl is as defined above. Such as an ethoxycarbonylcarbonyl group, a 2-pyridylmethylcarbonyl group or a 3-pyridylmeth group, a methoxythiocarbonylcarbonyl group, an ethoxycar ylcarbonyl group. bonylcarbonyl group, an ethoxycarbonylthiocarbonyl group, 30 The heteroaryloxy C-C alkyl group means a (heteroaryl)- a n-propoxycarbonylcarbonyl group, an isopropoxycarbon O—(C-C alkyl) group wherein the heteroaryland the alkyl ylcarbonyl group, a butoxythiocarbonylcarbonyl group, a moiety are as defined above, such as a 2-pyridyloxymethyl pentyloxythiocarbonylcarbonyl group, a hexyloxycarbon group or a 3-pyridyloxyethyl group. ylthiocarbonyl group, a heptyloxycarbonylthiocarbonyl The heteroarylthio C-C alkyl group means a (heteroaryl)- group or an octyloxythiocarbonylcarbonyl group. 35 S—(C-C alkyl) group wherein the heteroaryland the alkyl The aryl group means an aromatic hydrocarbon group, moiety are as defined above, such as a 2-pyridylthiomethyl Such as phenyl or naphthyl. group or a 3-pyridylthioethyl group. The aryl (C-C) alkyl group means an (aryl)-(C-C alkyl) The tetrahydrofurfuryl C-C alkyl group means a (tetrahy group wherein the aryl and the alkyl moiety are as defined drofurfuryl)-(C-Calkyl) group wherein the alkyl moiety is above, such as a benzyl group, a phenethyl group, a 3-phe 40 as defined above. Such as a 2-tetrahydrofurfurylmethyl group, nylpropyl group or a naphthylmethyl group. a 3-tetrahydrofurfurylmethyl group, a 2-(2-tetrahydrofurfu The aryl C-C alkyl group means an (aryl)-(C-C alkyl) ryl)ethyl group or a 2-(3-tetrahydrofurfuryl)ethyl group. group wherein the aryl and the alkyl moiety are as defined The tri(C-C)alkylsilyl C-C alkyl group may, for above, Such as the above-exemplified group, or a 5-phenyl example, be a trimethylsilylmethyl group, a 2-trimethylsilyl pentyl group, a 6-phenylhexyl group or a 7-phenylheptyl 45 ethyl group, a 3-trimethylsilylpropyl group or a 4-trimethyl group. silylbutyl group. The aryloxy C-C alkyl group means an (aryl)-O-(C-Cs The C-C trialkylsilyl group may, for example, be a tri alkyl) group wherein the aryl and the alkyl moiety are as methylsilyl group, a triethylsilyl group or a tripropylsilyl defined above. Such as a phenoxymethyl group, a 2-phenoxy group. ethyl group, a 3-phenoxypropyl group, a 1-naphthyloxym 50 The C-C haloalkylthio group may, for example, be a ethyl group, a 2-naphthyloxymethyl group or a 2-(1-naphthy 1-chloroethylthio group, a 2-fluoroethylthio group, a 2.2- loxy)ethyl group. difluoroethylthio group, a 2.2.2-trifluoroethylthio group, a The arylthio C-Cs alkyl group means an (aryl)-S—(C-Cs 1.2.2.2-tetrafluoroethylthio group, a 1.1.2.2.2-pentafluoroet alkyl) group wherein the aryl and the alkyl moiety are as hylthio group, a 2-chloro-2,2-difluoroethylthio group, a defined above, Such as a phenylthiomethyl group, a phe 55 1-chloro-2,2-difluoroethylthio group, 1-chloropropylthio, a nylthiomethyl group, a naphthylthiomethyl group or a naph 2-chloropropylthio group, a 3-chloropropylthio group, a 2.2, thylthioethyl group. 3,3-tetrafluoropropylthio group, a 3,3,3-trifluoropropylthio The aryl C(=X) group may, for example, be a phenylcar group, a 2.2.3.3.3-pentafluoropropylthio group or a 2.2.3.3. bonyl group, a phenylthiocarbonyl group or a naphthylcarbo 3.4.4.4-octafluorobutylthio group. nylethyl group. 60 The C-C haloalkylsulfinyl group may, for example, be a The aryl C(=X)C-C alkyl group may, for example, be a 1-chloroethylsulfinyl group, a 2-fluoroethylsulfinyl group, phenylcarbonylmethyl group or a phenylcarbonylethyl 2,2-difluoroethylsulfinyl, a 2.2.2-trifluoroethylsulfinyl group. group, a 1.2.2.2-tetrafluoroethylsulfinyl group, a 1.1.2.2.2- The aryloxy C-C alkyl group may, for example, be a pentafluoroethylsulfinyl group, a 1-chloro-2,2-difluoroethyl phenoxymethyl group or a phenoxyethyl group. 65 Sulfinyl group, a 1-chloropropylsulfinyl group, 2-chloropro The arylthio C-C alkyl group may, for example, be a pylsulfinyl, a 3-chloropropylsulfinyl group, a 2.2.3,3- phenylthiomethyl group or a phenylthioethyl group. tetrafluoropropylsulfinyl grOup, a 3,3,3-

US 8,802,713 B2 33 34 TABLE 2-continued Comp. No. R2 R Rs 1-102 CH CH 1-103 CH CH SCHCF 1-104 CH CH 1-105 CFCHFOCF, CH CH SCHCF, 1-106 CFCHFOCF, CH CH

TABLE 3

Comp. No. R R2 R R4 R 6

-109 -110 -111 -112 -113 -114 r -115 -116 -117 -118 -119 -120 -121 -122 -123 -124 -125 -126 -127 -128 -129 -130 -131 -132 -133 -134 -13S S C -136 -137 -138 -139 -140 -141 -142 -143

-145 -146 -147 -148 -149 -1SO 2 C H F C F3 -151 -152 12121212121212121212121212121212121212 -153 333 -154 2222 3333 -155 i: -156 -157 7 -158 -159 -160 C -161 222 333 t -162 333

TABLE 4 Comp. No. R Rs. Rs Rs 1-163 H NHCHC=CH F H CH SCHCFC H 1-164 H NHCHC=CH F H CH S(O)CHCFC H

US 8,802,713 B2 39 40 TABLE 6-continued Comp. No. R -279 -280 -281 -282 -283 -284 -285 -286 -287 -288 -289 -290 -291 -292 -293 -294 -295 HCHOCH2CHOCH -296 HCHOCH2CHOCH -297 -298 -299 -300 -301 SSSSSSSSSS -302 12121212121212121212 -303 -304 -30S -306 -307 -3O8 -309 -310 -311 -312 -313 -314 -315 -316 -317 -318 -319 -320 -321 -322 -323 -324 S (O) C 12 -32S -326 FCHFOCF, SSSSSSSSSSSSS (O) C 12121212121212121212121212

TABLE 7 Comp. No. R R5 R6 Rs 1-327 CH F H CH, SCHCF H

1-328 CH F H CH, H

US 8,802,713 B2 93 94 TABLE 38 Comp. No. R2 R R6 1-2045 H H CH SCHCF. H

1-2046 H H CH S(O)CHCF. H.

-2047 OH SCHCF. H -2048 OH -2049 C(O)OH SCHCF. H -2OSO C(O)OH -2051 C(O)H -2052 C(O)H -2053 NO, -2054 NO, -2055 CH SCHCF. H -2O56 CH -2057 OCH SCHCF. H -2O58 OCH, 2 -2059 CHOCH SCHCF. H -2060 CHOCH -2061 CH=CH, -2062 CH=CH, -2063 C=CCH -2O64 C=CCH -206S C(O)CH SCHCF. H -2066 C(O)CH, 2 -2067 OH SCHCF. H -2O68 OH -2069 CH=CH, -2070 2 C 2 CH=CH, -2O71 C=CCH -2O72 C=CCH -2O73 CHPr-C SCHCF. H -2074 CHPr-C 2 -2O75 C(O)CH SCHCF. H -2O76 C(O)CH -2O77 CHOCH SCHCF. H -2O78 CHOCH -2O79 NHCN -2O8O NHCN -2081 NHCHPr-c SCHCF. H -2O82 NHCH-Pr-c -2083 NHC HOCH SCHCF. H -2084 NHC HOCH -2O85 NHC(O)C(O)CH, SCHCF. H -2O86 NHC(O)C(O)CH -2087 NHC(O)C(O)OCH, -2088 NHC(O)C(O)OCH, -2089 NCH(O)CHC=CH -2090 NCH(O)CHC=CH -2091 NHC(O)NH, SCHCF. H -2092 NHC(O)NH, -2093 CH SCHCF. H -2094 CH -2095 CH SCHCF. H -2096 CH

55 The compounds of the present invention represented by the following formula I can be produced in accordance with the following production processes. However, their production is not limited to these processes. Hereinafter, for example, a compound represented by the 60 OH R1-L formula I-II and “a compound I-II' are the same. II)

A compound of the present invention of the formula I can 65 be produced by a process exemplified by the following scheme: US 8,802,713 B2 96 -continued The reaction time varies depending upon the reaction tem Rs R4 perature, the reaction Substrate, the reaction amount, etc., and O-R it is usually from 10 minutes to 20 hours. MN In a case where a compound II wherein L is a hydroxy R6 N le group is used, the compound I can be produced also by R using an azodicarboxylic acid ester in a solvent in the pres R Rs R3 ence of triphenylphosphine. The aZodicarboxylic acid ester may, for example, be diethylazodicarboxylate or dibenzyl azodicarboxylate. 10 The amount of use of triphenylphosphine is from 1 to 3 wherein R. R. R. R. R. R. R., and Rs are as defined mols, preferably 1.1 mols per 1 mol of the compound I-1. above, and L is a halogen atom, a C-C alkylsulfonyloxy The amount of use of azodicarboxylic acid ester is from 1 group (which may be mono-Substituted or poly-substituted to 3 mols, preferably 1.1 mols per 1 mol of the compound by halogen atom), a benzenesulfonyloxy group (which may 15 I-1. be mono-Substituted or poly-substituted by a halogenatom, a The solvent to be preferably used may, for example, bean lower alkyl group or a nitro group), a hydroxy group or a ether such as diethyl ether, tetrahydrofuran or dioxane. dihydroxyboryl group (B(OH)). As the compound III, for Further, in a case where a perfluoro C-C alkylolefin or a example, an iodonium compound, a perfluoro C-Co alky perfluoro C-C alkoxytrifluoroethylene or the like is used as lolefin, a perfluoro C-Calkoxytrifluoroethylene, diaz the compound II, the solvent may, for example, be prefer omethane or trimethylsilyldiazomethane may also be used. ably an ether such as diethyl ether, tetrahydrofuran or diox The compound of the present invention represented by the ane; an aromatic hydrocarbon Such as benzene, toluene, formula I can be produced by reacting the compound I-1 Xylene or chlorobenzene; or an aprotic polar solvent such as with the compound II in a solvent in the presence or absence acetonitrile, N,N-dimethylformamide, N,N-dimethylaceta of a base. Further, in a case where L is a dihydroxyboryl 25 mide, N-methyl-2-pyrrolidone, dimethylsulfoxide or sul group (B(OH)), it can be produced by reaction in the pres folane. ence of a catalyst. The base to be used in this reaction may, for example, be Further, in a case where R and R are a hydroxy group, preferably an organic base such as triethylamine, N,N-dim production is possible in the same manner as above. ethylaniline, pyridine, 4-N,N-dimethylaminopyridine or 1.8- The amount of use of the compound III may be properly 30 diazabicyclo5.4.0-7-undecene, and two types of bases may selected from a range of from 1 to 100 mols per 1 mol of the be used simultaneously. compound I-1, and is preferably from 1.1 to 3.3mols. The amount of use of the base is from 0.01 to 1,000 mols, The solvent to be used in this reaction may, for example, be preferably from 0.1 to 50 mols per 1 mol of the compound III, an ether Such as diethyl ether, tetrahydrofuran or dioxane; an and this amount of use is the same as the amount of use of the aromatic hydrocarbon Such as benzene, toluene, Xylene or 35 catalyst and the amount of use of a solvent. chlorobenzene, a halogenated hydrocarbon Such as dichlo The reaction temperature may be optionally selected from romethane, chloroform or dichloroethane; an aprotic polar a range of from -30° C. to the reflux temperature of the solvent such as N,N-dimethylformamide, N,N-dimethylac reaction system, and it is preferably within a range of from 0° etamide, N-methyl-2-pyrrolidone, dimethylsulfoxide or sul C. to 50° C. The reaction time varies depending upon the folane; an alcohol Such as methanol, ethanol or isopropyl 40 reaction temperature, the reaction Substrate, the reaction alcohol; a nitrile Such as acetonitrile or propionitrile; an ester amount, etc., and it is usually from 1 to 20 hours. Such as ethyl acetate, ethyl propionate; an aliphatic hydrocar The perfluoro C-C alkylolefin may, for example, be bon Such as pentane, hexane, cyclohexane or heptane; a pyri hexafluoropropene, and the perfluoro C-C alkoxytrifluoro dine Such as pyridine or picoline; or water, or a solvent ethylene may, for example, be trifluoromethoxytrifluoroeth mixture thereof. 45 ylene, pentafluoroethoxytrifluoroethylene or heptafluoropro The amount of the above solvent is from 0.5 to 100 L per 1 poxytrifluoroethylene. mol of the compound I-1, preferably from 1.0 to 10 L. Further, in a case where an iodonium compound is used as The base to be used in this reaction may, for example, bean the compound III, the amount of use is from 1 to 10 mols, inorganic base Such as a hydroxide of an alkali metal Such as preferably from 1 to 3 mols per 1 mol of the compound III. Sodium hydroxide or potassium hydroxide, a hydroxide of an 50 The solvent to be used may, for example, be preferably a alkaline earth metal Such as calcium hydroxide or magnesium halogenated hydrocarbon Such as dichloromethane or dichlo hydroxide, a carbonate of an alkali metal Such as sodium roethane, and the base to be used may, for example, be pref carbonate or potassium carbonate, or an alkali metal bicar erably a pyridine Such as pyridine. bonate Such as Sodium hydrogen carbonate or potassium The reaction temperature may be optionally selected from hydrogen carbonate; a metal hydride Such as sodium hydride 55 a range of from -30° C. to the reflux temperature of the or potassium hydride; a metal salt of an alcohol Such as reaction system, and it is preferably within a range of from 0° Sodium methoxide, Sodium ethoxide or potassium tert-butox C. to 50° C. The reaction time varies depending upon the ide; or an organic base Such as triethylamine, N,N-dimethy reaction temperature, the reaction Substrate, the reaction laniline, pyridine, 4-N,N-dimethylaminopyridine or 1,8-di amount, etc., and it is usually from 5 minutes to 20 hours. azabicyclo5.4.0-7-undecene. 60 The iodonium compound may, for example, be perfluoro The amount of use of the base may be properly selected propyl phenyliodonium trifluoromethanesulfonate, perfluor from a range of from 0 to 5 mols per 1 mol of the compound oisopropyl phenyliodonium trifluoromethanesulfonate, per I-1, and is preferably from 0 to 1.2 mols. fluorobutyl phenyliodonium trifluoromethanesulfonate, The reaction temperature may be optionally selected from perfluoropentyl phenyliodonium trifluoromethanesulfonate, a range of from -30° C. to the reflux temperature of the 65 perfluorohexyl phenyliodonium trifluoromethanesulfonate reaction system, and it is preferably within a range of from 0° or perfluorooctyl phenyliodonium trifluoromethane C. to 150° C. Sulfonate. US 8,802,713 B2 97 98 In a case where L is a dihydroxyboryl group (B(OH)), the aromatic hydrocarbon Such as benzene, toluene, Xylene or Solvent to be used in this reaction may, for example, be chlorobenzene, a halogenated hydrocarbon Such as dichlo preferably a halogenated hydrocarbon Such as dichlo romethane, chloroform or dichloroethane; an aprotic polar romethane or dichloroethane, and the base to be used may, for solvent such as N,N-dimethylformamide, N,N-dimethylac example, be preferably an organic base Such as triethylamine, etamide, N-methyl-2-pyrrolidone, dimethylsulfoxide or sul N,N-dimethylaniline, pyridine, 4-N,N-dimethylaminopyri folane; an alcohol Such as methanol, ethanol or isopropyl dine or 1,8-diazabicyclo[5.4.0-7-undecene, and two types of alcohol; a nitrile Such as acetonitrile or propionitrile; an ester bases may be used simultaneously. Such as ethyl acetate or ethyl propionate; an aliphatic hydro The amount of use of a compound wherein L is a dihy carbon Such as pentane, hexane, cyclohexane or heptane; a droxyboryl group (B(OH)) is from 1 to 10 mols, preferably 10 pyridine Such as pyridine or picoline; or water, or a solvent from 1 to 3 mols per 1 mol of the compound II. mixture thereof. In this reaction, as the catalyst, copper acetate may be used, The amount of the solvent is from 0.5 to 100 L, preferably and its amount of use is from 0.1 to 10 mols, preferably from from 1 to 10 L per 1 mol of the compound I-2. 1 to 3 mols per 1 mol of the compound II. Further, in such a 15 The base to be used in this reaction may, for example, bean case, powdery molecular sieves 4A may be used as an addi inorganic base Such as a hydroxide of an alkali metal Such as tive, and the amount of use is from 1 to 100 g, preferably from Sodium hydroxide or potassium hydroxide, a hydroxide of an 10 to 20 g per 1 g of the compound II. alkaline earth metal such as calcium hydroxide or magnesium The reaction temperature may be optionally selected from hydroxide, a carbonate of an alkali metal Such as sodium a range of from -30° C. to the reflux temperature of the carbonate or potassium carbonate, or an alkali metal bicar reaction system, and it is preferably within a range of room bonate Such as Sodium hydrogen carbonate or potassium temperature. hydrogen carbonate; a metal hydride Such as Sodium hydride The reaction time varies depending upon the reaction tem or potassium hydride; a metal salt of an alcohol Such as perature, the reaction Substrate, the reaction amount, etc., and Sodium methoxide, Sodium ethoxide or potassium tert-butox it is usually from 1 to 48 hours. 25 ide; or an organic base such as triethylamine, N,N-dimethy laniline, pyridine, 4-N,N-dimethylaminopyridine or 1,8-di A compound of the present invention represented by the aZabicyclo5.4.0-7-undecene; or ammonia. formula I-a can be produced also by a process exemplified The amount of use of the base may be properly selected by the following scheme: from a range of from 0 to 5 mols per 1 mol of the compound 30 I-2, and is preferably from 0 to 2.2 mols. The reaction temperature may be optionally selected from R5 R4 O-R a range of from -30° C. to the reflux temperature of the NS R3b-L2 reaction system, and it is preferably within a range of from 0° C. to 150° C. R6 ---III 2 R 35 The reaction time varies depending upon the reaction tem perature, the reaction Substrate, the reaction amount, etc., and R R NH it is usually from 10 minutes to 20 hours. 7 8 Ra1

R 6 2 R Rs R4 O-R 45 N R7a-L3 R R N R I-3r 7 Ra1 YRib 6 2 R -- I-a H-S Rs R3 50 wherein R. R. R. R. R. R. Rs. RandR, areas defined I-3 above, and L is a halogen atom, a C-C alkylsulfonyloxy Rs R4 O-R group (which may be mono-Substituted or poly-substituted by a halogenatom), a benzenesulfonyloxy group (which may N be mono-Substituted or poly-substituted by a halogenatom, a 55 R 6 lower alkyl group or a nitro group), a C-C alkylcarbonyloxy 21 R2 group (which may be mono-Substituted or poly-substituted by a halogen atom), or a hydroxy group. Ra-S Rs R3 That is, the compound of the present invention of the for I-b mula I can be produced by reacting the compound I-2 with 60 the compound III in a solvent in the presence or absence of a base. wherein R. R. R. R. Rs. R and Rs are as defined above, The amount of use of the compound III may be properly R is a C-Chaloalkyl group, a C-Chaloalkenyl group or selected from a range of from 1 to 100 mols per 1 mol of the a cyclopropylmethyl group (which may be mono-Substituted compound I-2, and is preferably from 1.1 to 2.2mols. 65 or poly-substituted by a halogen atom), and L is a halogen The solvent to be used in this reaction may, for example, be atom, a C-C alkylsulfonyloxy group (which may be mono an ether Such as diethyl ether, tetrahydrofuran or dioxane; an Substituted or poly-substituted by a halogen atom), or a ben US 8,802,713 B2 99 Zenesulfonyloxy group (which may be mono-Substituted or -continued poly-substituted by a halogen atom, a lower alkyl group or a Rs R4 nitro group). SN O-R That is, the compound of the present invention of the for R6 N mula II-b can be produced by reacting the compound I-3 le with the compound I-3r in a solvent in the presence or R2 absence of a base or a radical initiator. Further, a disulfide R Rs N compound which is an oxidative dimer of the compound I-3 R9 NH may be used instead of the compound I-3. 10 I-2 The amount of use of the compound I-3r may be properly selected from a range of from 1 to 5 mols per 1 mol of the wherein R. R. R. R. R. R. Rs and Rs are as defined compound I-3, and is preferably from 1 to 1.5 mols. above, and R is an acetyl group. The solvent to be used in this reaction may, for example, be 15 That is, the compound of the present invention represented an ether Such as diethyl ether, tetrahydrofuran or dioxane; an by the formula I-2 can be produced by reacting the com aromatic hydrocarbon Such as benzene, toluene, Xylene or pound I-4 in a solvent in the presence or absence of a base or chlorobenzene: an aprotic polar solvent such as N,N-dimeth an acid. ylformamide, N,N-dimethylacetamide, N-methyl-2-pyrroli The solvent to be used in this reaction may, for example, be done, dimethylsulfoxide or Sulfolane; an alcohol Such as an ether Such as diethyl ether, tetrahydrofuran or dioxane; an methanol, ethanol or methyl celloSolve; an aliphatic hydro aromatic hydrocarbon Such as benzene, toluene, Xylene or carbon Such as pentane, hexane, cyclohexane or heptane; a chlorobenzene: an aprotic polar solvent such as N,N-dimeth pyridine Such as pyridine or picoline; or water, or a solvent ylformamide, N,N-dimethylacetamide, N-methyl-1-2-pyr mixture thereof. rolidone, dimethylsulfoxide or sulfolane; an alcohol such as The amount of the solvent is from 0.5 to 100 L, preferably 25 methanol, ethanol or methyl celloSolve; an aliphatic hydro carbon Such as pentane, hexane, cyclohexane or heptane; a from 1 to 10 L per 1 mol of the compound I-3. pyridine such as pyridine orpicoline; water, a carboxylic acid The base to be used in this reaction may be the same one as Such as acetic acid; or a solvent mixture thereof. defined for the above Production Process 2. The amount of use of the solvent is from 0.5 to 100 L, The amount of the base may be properly selected from a 30 preferably from 1 to 10 L per 1 mol of the compound I-4. range of from 0 to 5mols per 1 mol of the compound I-3, and The base to be used in this reaction may be the same one as is preferably from 0 to 1.5 mols. defined for the above Production Process 2. The amount of The radical initiator to be used in this reaction may, for use of the base may be properly selected from a range of from example be sulfurous acid, a sulfite salt or a sulfite adduct 0 to 10 mols per 1 mol of the compound I-4, and is prefer Such as Rongalit (sodium formaldehyde Sulfoxylate). 35 ably from 0 to 2 mols. In a case where the radical initiator is used, its amount of The acid to be used in this reaction may, for example, be a use may be properly selected from a range of from 0.01 to 5 Sulfonic acid such as methanesulfonic acid or p-toluene mols per 1 mol of the compound I-3, and is preferably from Sulfonic acid; an inorganic acid Such as hydrochloric acid, 0.05 to 1.2 mols. 40 hydrobromic acid or Sulfuric acid, or a carboxylic acid Such as acetic acid or trifluoroacetic acid. The reaction temperature may be optionally selected from a range of from 0°C. to the reflux temperature of the reaction The amount of use of the acid may be properly selected system, and it is preferably within a range of from 20° C. to from a range of from Oto 100 mols per 1 mol of the compound 60° C. I-4, and is preferably from 0 to 10 mols. 45 The reaction temperature may be optionally selected from The reaction time varies depending upon the reaction tem a range of from 0°C. to the reflux temperature of the reaction perature, the reaction Substrate, the reaction amount, etc., and system, and it is preferably within a range of from 20° C. to it is usually from 30 minutes to 20 hours. 120° C. The reaction time varies depending upon the reaction tem 50 perature, the reaction Substrate, the reaction amount, etc., and formula I-2 can be produced by a process exemplified by the A compound of the present invention represented by the following scheme: formula II can be produced also by a process exemplified by 55 the following scheme: Rs R4 Rs R4 O-R 60 N R6 He R 6 21 H HsHalogenating agent, nitrating agent, R7 Rs formylating agent, R R7 Rs R3 acylating agent 65 I-4) US 8,802,713 B2 101 102 -continued Rs R4 O-R Rs R4 O R1

/N N= Oxidizing agent R6 N2 5 R6 N2 R He R" 2 R7 Rs R3 v Rs R3 R7a 10 I-b wherein R. R. R. Rs. R. R., and Rs are as defined above, Rs R4 O R1 and R2 is a halogen atom, a nitro group, a formyl group or a N= trifluoroacetyl group. R That is, the compound of the present invention represented 15 6 2 R2 by the formula I-c can be produced by reacting the com pound I-5 with a halogenating agent, a nitrating agent, a O-HS Rs R3 formylating agent or an acylating agent in a solvent. The halogenating agent may, for example, be fluorine, R7a chlorine, bromine, iodine, N-chlorosuccinimide, N-bromo I-d Succinimide, N-iodosuccinimide, Sulfuryl chloride, iodine monochloride, tert-butyl hypochlorite, N-fluoro-N'-(chlo romethyl)-triethylenediaminebis(tetrafluoroborate) O wherein R. R. R. R. R. R. Rs and R-7, are as defined 1-fluoro-2,6-dichloropyridinium tetrafluoroborate. above. 25 The compound I-d of the present invention can be pro The nitrating agent may, for example, be nitric acid, potas duced by reacting the compound I-b with an oxidizing agent sium nitrate, fuming nitric acid or nitronium tetrafluorobo in a solvent in the presence or absence of a catalyst. rate. The oxidizing agent to be used in this reaction may, for The formylating agent may, for example, be a Vilsmeier example, be hydrogen peroxide, m-chloroperbenzoic acid, reagent. 30 perbenzoic acid, sodium periodate, OXONE (tradename, The acylating agent may, for example, be trifluoroacetic manufactured by E.I. DuPont, containing potassium hydro anhydride. genperoxosulfate), N-chlorosuccinimide, N-bromosuccin As a Lewis acid catalyst, aluminum chloride, titanium imide, tert-butyl hypochlorite or sodium hypochlorite. tetrachloride, iron or ferric chloride may, for example, be The amount of use of the oxidizing agent may be properly used. The amount of use of the Lewis acid catalyst may be 35 selected from a range of from 1 to 6 mols per 1 mol of the properly selected from a range of from 1 to 5 mols per 1 mol compound I-b, and is preferably from 1 to 1.2 mols. of the compound I-5), and is preferably from 1 to 2 mols. The catalyst to be used in this reaction may, for example, be The amount of use of the halogenating agent, the nitrating Sodium tungstate. agent, the formylating agent or the acylating agent may be The amount of use of the catalyst may be properly selected properly selected from a range of from 1 to 5 mols per 1 mol 40 from a range of from 0 to 1 mol per 1 mol of the compound of the compound I-5), and is preferably from 1 to 2 mols. I-b, and is preferably from 0.001 to 0.1 mol. The solvent to be used in this reaction may, for example, be The solvent to be used in this reaction may, for example, be sulfuric acid; an ether such as diethyl ether, tetrahydrofuran or an ether Such as diethyl ether, tetrahydrofuran or dioxane; an dioxane; an aromatic hydrocarbon Such as benzene, toluene, aromatic hydrocarbon Such as benzene, toluene, Xylene or 45 chlorobenzene, an aprotic polar solvent such as acetonitrile, Xylene or chlorobenzene: a halogenated hydrocarbon Such as N,N-dimethylformamide, N,N-dimethylacetamide, N-me dichloromethane, chloroform or dichloroethane; an aprotic thyl-2-pyrrolidone, dimethylsulfoxide or sulfolane; an alco polar solvent such as N,N-dimethylformamide, N,N-dim hol Such as methanol, ethanol or isopropyl alcohol; a haloge ethylacetamide, N-methyl-2-pyrrolidone, dimethylsulfoxide nated hydrocarbon Such as dichloromethane, chloroform or or Sulfolane; an alcohol Such as methanol, ethanol or isopro 50 dichloroethane; an aliphatic hydrocarbon Such as pentane, pyl alcohol; a nitrile Such as acetonitrile or propionitrile; hexane, cyclohexane or heptane; a ketone Such as acetone, water, a carboxylic acid Such as acetic acid; an acid anhydride methyl ethyl ketone or cyclohexanone; a carboxylic acid Such Such as acetic anhydride; pyridine; carbon disulfide; or a as acetic acid; water, or a solvent mixture thereof. solvent mixture thereof. The amount of use of the solvent is from 0.5 to 100 L, The amount of use of the solvent is from 0.5 to 100 L, 55 preferably from 1 to 10 L per 1 mol of the compound I-b. preferably from 1 to 10 L per 1 mol of the compound I-5. The reaction temperature may be optionally selected from The reaction temperature may be optionally selected from a range of from -60° C. to the reflux temperature of the a range of from -60° C. to the reflux temperature of the reaction system, and it is preferably within a range of from 0° reaction system, and it is preferably within a range of from C. to 50° C. -20° C. to 100° C. 60 The reaction time varies depending upon the reaction tem The reaction time varies depending upon the reaction tem perature, the reaction Substrate, the reaction amount, etc., and perature, the reaction Substrate, the reaction amount, etc., and it is usually from 10 minutes to 20 hours. it is usually from 10 minutes to 20 hours.

Rs R4 O Rs R4 O NS --- / R6 NHNH, Cl R6 NS2

R7 Rs R Rs NH2 A-1 -N-O O Rs R4 OH Rs R4 O N N f f R6 Na R6 N

R7 Rs O I-1b) I-1c)

25 wherein R. R. R. R., and Rs are as defined above. The reaction time varies depending upon the reaction tem The compound I-1a can be produced by reacting the perature, the reaction Substrate, the reaction amount, etc., and compound A-1 with cyanoacetylchloride in the presence or it is usually from 10 minutes to 20 hours. absence of an acid or a base. The compound I-1 b can be produced by reacting the 30 compound A-1 with malonyl chloride in the presence or In both the reactions, the reaction temperature may be 45 optionally selected from a range of from 0°C. to the reflux The compound I-3 which is a starting material in Produc temperature of the reaction system, and it is preferably within tion Process 3, can be produced by a process exemplified by a range of from 0° C. to 50° C. The reaction time varies the following scheme: depending upon the reaction temperature, the reaction Sub strate, the reaction amount, etc., and it is usually from 10 50 minutes to 10 hours. Rs R4

HC-S Rs 65 A-1 I-3b) US 8,802,713 B2 108 -continued The solvent to be used in this step 6 may, for example, bean Rs R4 aromatic hydrocarbon Such as benzene, toluene, Xylene or chlorobenzene, a halogenated hydrocarbon Such as dichlo Cyclization romethane; or a solvent mixture thereof. R6 NH-NH --Step 3 The amount of use of the solvent is from 0.5 to 100 L, preferably from 0 to 10 L per 1 mol of the compound I-3f. HC-S Rs The base to be used in this step 6 may be the same base as defined for the production process 2. The amount of use of the I-3c) base may be properly selected from a range of from 3 to 10 Rs R4 10 mols per 1 mol of the compound I-3f, and is preferably from N OH 3to 5 mols. R6 N^ s Alkylation The reaction temperature may be optionally selected from le Step 4 a range of from -30° C. to the reflux temperature of the R 15 reaction system, and it is preferably within a range of from 0° HC-S Rs R3 C. to 150° C. The reaction time varies depending upon the reaction tem I-3d perature, the reaction Substrate, the reaction amount, etc., and Rs R4 it is usually from 10 minutes to 20 hours. N O-R R6 N^ s Oxidation -e- The compound of the present invention represented by the le Step 5 formula I-6a can be produced also by a process exemplified R by the following scheme: HC-S R8 R3 25 I-3e Rs R4 O-R Rs R4 (CFCO)2O N N O-R 3. 2 R H R6 N^ s (CH3CO)2O Her -- 6 2 Br le Step 6 30 R R R8 R3 HC-SV Rs. Rs O I-6 Rs R4 O-R 35 NS Rs R4 MN O-R R 6 2 H R6 N le 40 R Rs R3 R2 HS Rs. Rs I-6a

I-3 wherein R. R. R. R. R. R., and Rs are as defined above. 45 That is, the compound of the present invention represented wherein R. R. R. R. Rs. R and Rs are as defined above. by the formula I-6a can be produced by reacting the com The compound I-3a is methylated to obtain the com pound I-6 with hydrogen in the presence of a metal catalyst pound I-3b (step 1), which is diazotized and reduced to in the presence or absence of a base in a solvent. produce the compound I-3c (step 2). This production pro The amount of use of hydrogen may be properly selected cess is disclosed in WO2006/043635. 50 from a range of from 1 to 1.3 mols per 1 mol of the compound The compound I-3d can be produced in the same manner I-6), and is preferably from 1 to 1.1 mols. as in the above Production Process 7 or 8 (step 3). As the metal catalyst, for example, a palladium catalyst Further, the compound I-3e can be produced in the same Such as palladium-carbon may be used, and the amount of use manner as in the above Production Process 1 (step 4), and the 55 of the catalyst may be properly selected from a range of from compound I-3f can be produced in the same manner as in the 0.1 to 1 part by mass per 1 part by mass of the compound of above production process 6 (step 5). the formula I-6, and is preferably from 0.2 to 0.5 part by The compound I-3 can be produced by reacting the com a SS. pound I-3f with trifluoroacetic anhydride or acetic anhy The base to be used in this step may be the same base as dride in the presence of a base in or without a solvent (step 6). 60 defined for the above Production Process 2. The amount of use of trifluoroacetic anhydride may be The amount of use of the base may be properly selected properly selected from a range of from 1 to 100 mols per 1 mol from a range of from 0 to 5 mols per 1 mol of the compound of the compound I-3f, and is preferably from 1.1 to 1.2 mol. I-6), and is preferably from 0 to 1.1 mols. In a case where acetic anhydride is used, its amount may be The solvent to be used in this reaction may, for example, be properly selected from a range of from 1 to 100 mols per 1 mol 65 an alcohol Such as methanol, ethanol or isopropyl alcohol; a of the compound I-3f, and is preferably the same amount as carboxylic acid such as acetic acid; water, or a solvent mix the reaction solvent. ture thereof. US 8,802,713 B2 109 110 The amount of use of the solvent is from 0.5 to 100 L, pound I-7 with a nitrite ester in the presence or absence of preferably from 1 to 10 L per 1 mol of the compound I-6). copper(II) chloride or copper(II) bromide in a solvent. The reaction temperature may be optionally selected from The amount of use of copper(II) chloride or copper(II) a range of from -60° C. to the reflux temperature of the bromide may be properly selected from a range of from 0 to reaction system, and it is preferably within a range of from 5 20 mols per 1 mol of the compound I-7, and is preferably -20° C. to 100° C. from 0.0 to 5 mols. The reaction time varies depending upon the reaction tem The nitrite ester may, for example, be tert-butyl nitrite or perature, the reaction Substrate, the reaction amount, etc., and amyl nitrite. The amount of use of the nitrite ester may be it is usually from 0.5 to 240 hours. properly selected from a range of from 1 to 5mols per 1 mol 10 of the compound I-7, and is preferably from 1 to 2 mols. The compound of the present invention represented by the The solvent to be used in this reaction may, for example, be formula I-7a can be produced also by a process exemplified an ether Such as diethyl ether, tetrahydrofuran or dioxane; an by the following scheme: aromatic hydrocarbon Such as benzene, toluene, Xylene or chlorobenzene, an aprotic polar solvent such as acetonitrile, 15 N,N-dimethylformamide, N,N-dimethylacetamide, N-me Rs R4 O-R thyl-2-pyrrolidone, dimethylsulfoxide or sulfolane; a haloge nated hydrocarbon Such as dichloromethane, chloroform or 7 Nitrite ester Ho dichloroethane; an aliphatic hydrocarbon Such as pentane, CuCl2 or CuBr2 hexane, cyclohexane or heptane; a ketone Such as acetone, methyl ethyl ketone or cyclohexanone; a carboxylic acid Such as acetic acid; or a solvent mixture thereof. The amount of use of the solvent is from 0.5 to 100 L, preferably from 1 to 10 L per 1 mol of the compound I-7 in both the cases. In both the reactions, the reaction temperature may be optionally selected from a range of from -20°C. to the reflux temperature of the reaction system, and it is preferably within a range of from 0° C. to 100° C. The reaction time varies 30 depending upon the reaction temperature, the reaction Sub strate, the reaction amount, etc., and it is usually from 10 minutes to 24 hours. A compound represented by the formula I-8a to a com wherein R. R. R. R. R., and Rs are as defined above, and 35 pound of the present invention represented by the formula each of R" and R." which are independent of each other, is a I-8h can be produced also by a common process exemplified hydrogen atom, a chlorine atom or a bromine atom. by the following scheme. The compound I-8 can be pro That is, the compound of the present invention represented duced by a process disclosed in .

Reduction R7 Rs. COOEt

Rs COOH Oxidation I-8b) Amidation Acid chloridation Florio Reduction US 8,802,713 B2

-continued Rs R4 Oxidation Rs R4 Rs R4 O-R N O-R N O-R R6 N R6 N R6 N le le le R2 R2 R2 R Rs. CHF2 R Rs. CONH2 R Rs. CH2OH I-8c) I-8d I-8e Florio

Rs R4 Rs R4 N O-R N O-R R6 N Dehydration R6 N le le R2 R2 R Rs \ R Rs. CHF NOH I-8g. I-8f Dehydration Y Rs R4 N O-R R6 N le R R7 Rs. CN I-8h wherein R. R. R. R. R. R., and Rs are as defined above. The solvent to be used in this reaction may, for example, be That is, the compound I-8a can be produced by reacting dichloromethane, dichloroethane or chlorobenzene. the compound I-8 with a reducing agent in the presence of a The compound I-8d can be produced by reacting the Solvent at low temperature. 40 compound I-8b) with e.g. oxalyldichloride, thionyl chloride The reducing agent to be used in this reaction may be an or N,N'-carbonyldiimidazole, followed by reaction with organic aluminum compound Such as diisobutylaluminum ammonia. hydride. The compound I-8e can be produced by reacting the The amount of use of the reducing agent is within a range compound I-8b) with e.g. oxalyl dichloride or thionyl chlo of from 1 to 2 mols, preferably from 1 to 1.3 mols per 1 mol 45 ride to obtain an acid chloride, which is then reduced by a of the compound I-8. reducing agent Such as sodium borohydride. The compound I-8b) can be produced by hydrolyzing the The compound I-8f can be produced by reacting the compound I-8 by using a base or an acid. compound I-8a with hydroxyammonium chloride. The base to be used in this reaction may, for example, be a The amount of use of hydroxyammonium chloride is hydroxide of an alkali metal Such as sodium hydroxide or 50 within a range of from 1 to 5 mols, preferably from 1 to 2 mols potassium hydroxide. per 1 mol of the compound I-8a. The amount of use of the base is within a range of from 1 to The compound I-8h can be produced by reacting the 5 mols, preferably from 1 to 2 mols per 1 mol of the com compound I-8d or 1-8f with e.g. oxalyldichloride, thionyl pound I-8. chloride, acetic anhydride or trifluoroacetic anhydride. In a The acid to be used in this reaction may, for example, be 55 hydrochloric acid, hydrobromic acid or sulfuric acid. case where R is an ethoxycarbonyl group, in the same man The amount of use of the acid is within a range of from 1 ner as above, R can be cyanated. mol to the amount of the solvent, preferably from 1 to 100 The compound I-8a can be produced also by reacting the mols per 1 mol of the compound I-8. compound I-8e with an oxidizing agent such as manganese The compound I-8c can be produced by reacting the 60 dioxide in a solvent. The amount of use of the oxidizing agent compound I-8a with a fluorinating agent such as diethy is within a range of from 2 to 500 mols, preferably from 8 lamino sulfur trifluoride. The compound I-8g can also be mols to 50 mols per 1 mol of the compound I-8a. produced by reacting the compound I-8e with a fluorinating The solvent to be used in this reaction may, for example, be agent such as diethylamino Sulfate trifluoride. a halogenated hydrocarbon Such as dichloromethane, chloro The amount of use of the fluorinating agent is within a 65 form or dichloroethane; an aliphatic hydrocarbon Such as range of from 1 to 2 mols, preferably from 1 to 1.2 mols per pentane, hexane, cyclohexane or heptane; an alcohol Such as 1 mol of the compound I-8a or the compound I-8g. methanol or ethanol; or a solvent mixture thereof. US 8,802,713 B2 113 Further, the Production Process 13 is a process of convert ing the Substituent at the 5-position of the pyrazole ring, and Rs R4 with respect to the 4-position of the pyrazole ring also, pro N O-CH duction is possible in the same manner as in this Production / N Deamination Process. R6 N -- le O-CH A compound of the present invention represented by the R Rs NH2 O formula I-9 can be produced by a process exemplified by the following scheme from a compound represented by the for 1-9 mula A-1: 10 Rs R4 MN O-CH O R6 N le O-CH CH-O O-CHs 15 R Rs R" O R 5 R4 CH-O CN 1-9a 1-9r R6 NHNH - I - R Rs 76i A-1 Rs R4 25 MN O-CH R6 N le CN

Rs R4 30 R Rs R" O-CHs N 1-9b) R6 N le O-CHs

35 wherein R3", R. R. R. R., and Rs are as defined above. R Rs NH2 O 1-9 The compound of the present invention represented by the formula I-1 can be produced also by a process exemplified by the following scheme from a compound represented by the wherein R. R. R. R., and Rs are as defined above. 40 formula I-d: It can be produced by reacting the compound represented by the formula A-1 with the compound represented by the formula I-9r in the presence of a solvent. Rs R4 N OR' HCl, HBr, BBr, or The amount of use of the compound I-9r is within a range 45 / N ammonia of from 1 to 2 mols, preferably from 1 to 1.2 mols per 1 mol R6 N -- of the compound A-1. le The solvent to be used in the present reaction may, for R example, bean alcohol Such as methanol, ethanol or isopropyl R Rs. R3 alcohol; water, a carboxylic acid Such as acetic acid; or a 50 I-d solvent mixture thereof. Rs R4 The reaction temperature may be optionally selected from OH a range of from -20° C. to the reflux temperature of the N reaction system, and it is preferably within a range of from 0° R6 N 55 le C. to 100° C. R The reaction time varies depending upon the reaction tem R7 R8 R3 perature, the reaction Substrate, the reaction amount, etc., and it is usually from 0.5 to 24 hours. I-1 Further, by a production process exemplified by the fol 60 lowing scheme, production of the compound I-9aby deami nation of the pyrazole 5-position, can be carried out in the wherein R1' is a methyl group, an acetyl group or a benzyl same manner as in the above Production Process 12, and group, and R. R. R. R. R. R., and Rs areas defined above. production of the compound I-9b) which is a cyanated prod The formula I-1 can be produced by reacting the formula uct of the ethoxycarbonyl group at the pyrazole 4-position, 65 I-d with hydrogen chloride (hydrochloric acid), a hydrogen can be carried out in the same manner as in the above Pro bromide solution, borontribromide or ammonia in the pres duction Process 13. ence of a solvent. US 8,802,713 B2 115 116 The amount of use of hydrogen chloride, the hydrogen carbonate of an alkali metal Such as Sodium carbonate or bromide solution or boron tribromide is within a range of potassium carbonate; or a bicarbonate of an alkali metal Such from 1 to 1,000 mols, preferably from 1.0 to 100mols per 1 as Sodium hydrogen carbonate or potassium hydrogen car mol of the compound I-d. bonate; a metal hydride Such as Sodium hydride or potassium The solvent to be used in this reaction may, for example, be hydride; or an organic base such as triethylamine, N,N-dim an alcohol Such as methanol, ethanol or isopropyl alcohol; ethylaniline, pyridine, 4-N,N-dimethylaminopyridine or 1.8- water, a carboxylic acid such as acetic acid; or a solvent diazabicyclo5.4.0-7-undecene. mixture thereof, or dichloromethane, dichloroethane, chlo The amount of use of the base may be properly selected robenzene, etc. from a range of from 0 to 5 mols per 1 mol of the compound The reaction temperature may be optionally selected from 10 A-3, and is preferably from 0 to 1.2 mols. a range of from -68° C. to the reflux temperature of the The solvent to be used in this reaction may, for example, be reaction system, and it is preferably within a range of from 0° an ether Such as diethyl ether, tetrahydrofuran or dioxane; an C. to 100° C. aromatic hydrocarbon Such as benzene, toluene, Xylene or The reaction time varies depending upon the reaction tem chlorobenzene, an aprotic polar solvent such as acetonitrile, perature, the reaction Substrate, the reaction amount, etc., and 15 N,N-dimethylformamide, N,N-dimethylacetamide, N-me it is usually from 0.5 to 24 hours. thyl-2-pyrrolidone, dimethylsulfoxide or sulfolane; a haloge nated hydrocarbon Such as dichloromethane, chloroform or The compound represented by the formula I-10 can be dichloroethane, an aliphatic hydrocarbon Such as pentane, produced from a compound represented by the formula A-3 hexane, cyclohexane or heptane; a ketone Such as acetone, by means of the compounds represented by the formulae methyl ethyl ketone or cyclohexanone; a carboxylic acid Such I-10a and I-10b. as acetic acid; or a solvent mixture thereof.

O CH Rs R4 O O rt , Sr N O 9 ulus M R6 NHNH-4 C Y O-C N CH R7 Rs R7 Rs O A-3 I-10a |imelillonelius O CH3 Rs R4 H N O rt , SrN O Hvorovsis M R6 N Hydrolysis N le le

R Rs OCH R Rs OCH I-10 I-10b)

Rs R4 N OH R6 N le

R Rs OCH I-10c

The compound I-10a can be produced by reacting the The amount of the above solvent is from 0.5 to 100 L, compound A-3 with malonyl chloride in the presence or to preferably from 1.0 to 10L per 1 mol of the compound (A-3). absence of a base in a solvent. The amount of use of malonyl chloride is from 1 to 3 mols, The reaction temperature may be optionally selected from preferably 1.0 mol per 1 mol of A-3. a range of from -68° C. to the reflux temperature of the The base to be used may, for example, bean inorganic base reaction system, and it is preferably within a range of from 0° Such as a hydroxide of an alkali metal such as sodium hydrox 65 C. to 100° C. The reaction time varies depending upon the ide or potassium hydroxide; a hydroxide of an alkaline earth reaction temperature, the reaction Substrate, the reaction metal Such as calcium hydroxide or magnesium hydroxide; a amount, etc., and it is usually from 0.5 to 24 hours. US 8,802,713 B2 117 118 The compound I-10b) can be produced by reacting the ketones Such as cyclohexanone, methyl ethyl ketone and iso compound I-10a) with trimethylsilyldiazomethane in the phorone; ethers such as dioxane and tetrahydrofuran, ali presence or absence of a base in a solvent. phatic hydrocarbons such as kerosene and light oil; aromatic The amount of use of trimethylsilyldiazomethane is from 1 hydrocarbons such as Xylene, trimethylbenzene, tetramethyl to 3 mols, preferably 1.0 mol per 1 mol of 1-10a). benzen, methylnaphthalene and solvent naphtha, haloge The base to be used may, for example, bean inorganic base nated hydrocarbons such as chlorobenzene; acid amides Such Such as a hydroxide of an alkali metal such as sodium hydrox as dimethylacetamide; esters such as glycerin esters of fatty ide or potassium hydroxide; a hydroxide of an alkaline earth acids; nitriles Such as acetonitrile; and Sulfur-containing com metal Such as calcium hydroxide or magnesium hydroxide; a pounds such as dimethyl sulfoxide. carbonate of an alkali metal Such as Sodium carbonate or 10 The Surfactants include, for example, metal salts of alkyl potassium carbonate; or a bicarbonate of an alkali metal Such benzenesulfonic acids, metal salts of dinaphthylmethanedis as Sodium hydrogen carbonate or potassium hydrogen car ulfonic acids, salts of alcohol Sulfates, alkylarylsulfonates, bonate; a metal hydride Such as Sodium hydride or potassium lignin Sulfonates, polyoxyethylene glycol ethers, polyoxy hydride; or an organic base such as triethylamine, N,N-dim ethylene alkyl aryl ethers, polyoxyethylene sorbitan ethylaniline, pyridine, 4-N,N-dimethylaminopyridine or 1.8- 15 monoalkylates and salts of a formalin condensate of naphtha diazabicyclo5.4.0-7-undecene. lenesulfonate. The amount of use of the base may be properly selected The other adjuvants include, for example, adhesive agents from a range of from 0 to 5 mols per 1 mol of the compound and thickeners such as carboxymethylcellulose, gum arabic, I-10a, preferably from 0 to 1.2 mols. Sodium arginate, guar gum, tragacanth gum, and polyvinyl The solvent to be used in this reaction may, for example, be alcohol; antifoaming agents such as metal soap; physical an ether Such as diethyl ether, tetrahydrofuran or dioxane; an property improvers such as fatty acids, alkyl phosphate salts, aromatic hydrocarbon Such as benzene, toluene, Xylene or silicone and paraffin, and coloring agents. chlorobenzene, an aprotic polar solvent such as acetonitrile, When these formulations are practically used, they may be N,N-dimethylformamide, N,N-dimethylacetamide, N-me used directly or after diluted with a diluent such as water to a thyl-2-pyrrolidone, dimethylsulfoxide or sulfolane; a haloge 25 predetermined concentration. nated hydrocarbon Such as dichloromethane, chloroform or Various formulations containing the compounds of the dichloroethane; an aliphatic hydrocarbon Such as pentane, present invention, whether diluted or not, may be applied by hexane, cyclohexane or heptane; a ketone Such as acetone, conventional methods, i.e., application methods (such as methyl ethyl ketone or cyclohexanone; a carboxylic acid Such spraying, misting, atomizing, dusting, granule application, as acetic acid; an alcoholic solvent Such as methanol or etha 30 paddy water application and seeding box application), Soil nol; or a solvent mixture thereof. treatment (Such as mixing or drenching), Surface application The amount of the above solvent is from 0.5 to 100 L, (such as painting, dressing and covering), dipping, poison preferably from 1.0 to 10L per 1 mol of the compound I-10a). bait or Smoking. The reaction temperature may be optionally selected from Further, the above active ingredients may be incorporated a range of from -68° C. to the reflux temperature of the 35 into livestock feeds so as to prevent infestation or growth of reaction system, and it is preferably within a range of from 0° pest, especially pest insects after they are voided in excre C. to 100° C. The reaction time varies depending upon the ment. reaction temperature, the reaction Substrate, the reaction Otherwise, they can also be applied by a so-called ultra-low amount, etc., and it is usually from 0.5 to 24 hours. Volume, high concentration application method. The propor The compound I-10 can be produced in the same manner 40 tion of the active ingredient in a pesticide in the case of the as in the process of hydrolysis disclosed in Production Pro ultra-low Volume, high concentration application method, is cess 13 from the compound I-10b). The compound I-10 suitably selected as required, and it is from 0.1 to 20 mass %, and the compound I-10care in a chemical equilibrium state. preferably from 0.5 to 10mass % in the case of a dust or a When a compound of the present invention is used as the granule, and from 1 to 80% mass %, preferably from 10 to 50 active ingredient of a pesticide, it may be used by itself. 45 mass % in the case of an emulsifiable concentrate or a wet However, it can be formulated into various formulations such table powder. as an emulsifiable concentrate, a Suspension, a dust, a gran The pesticides of the present invention are applied, when ule, a tablet, a wettable powder, a water-soluble concentrate, they are diluted with a diluent, usually at an active ingredient a liquid formulation, a flowable, a water dispersible granule, concentration of from 0.1 to 5,000 ppm. When they are used an aerosol, a paste, an oil miscible solution, an emulsion and 50 directly, the dose per unit area is from 0.1 to 5,000 g, prefer a Smoking agent in combination with various carriers, Surfac ably from 5 to 2,000 g per 1 ha in terms of the compound that tants and other adjuvants which are commonly used for for serves as the active ingredient. However, the dose is not mulation as agricultural adjuvants. They are blended usually limited to Such specific range. in Such proportions that the active ingredient is from 0.1 to The compounds of the present invention are sufficiently 90mass %, preferably from 1 to 70 mass % and the agricul 55 effective when used alone. However, they may be used, if tural adjuvants are from 10 to 99.9 mass %, preferably from necessary, in combination or in admixture with fertilizers or 20 to 90 mass % based on the entire amount (100mass %) of other agrochemicals such as insecticides, miticides, nemati the pesticide. cides, fungicides, antivirus agents, attractants, herbicides and The carriers to be used for such formulation may be clas plant growth modulating agents, and Such combined or sified into solid carriers and liquid carriers. The solid carriers 60 admixed use can sometimes produce improved effects. include, for example, animal and plant powders such as Examples of other insecticidal compounds which may be starch, activated carbon, soybean powder, wheat flour, wood used in combination or in admixture, will be given below. flour, fish flour and powdered milk, and mineral powders such Acetamiprid, clothianidin, dinotefuran, imidacloprid, as talc, kaolin, bentonite, calcium carbonate, Zeolite, diato nitenpyram, thiacloprid, thiamethoxam, ethiprole, fipronil. maceous earth, white carbon, clay, alumina, ammonium Sul 65 acetoprol, chromafenozide, halofenozide, methoxyfenozide, fate and urea. The liquid carriers include, for example, water, tebufenozide, acrinathrin, allethrin, alpha-cypermethrin, alcohols such as isopropyl alcohol and ethylene glycol, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, US 8,802,713 B2 119 120 bioresmethrin, cycloprothrin, cyfluthrin, cyhalothrin, cyper Examples of other herbicidal compounds and plant growth methrin, cyphenothrin, deltamethrin, empenthrin, esfenvaler modulating compounds which may be used in combination or ate, fenpropathrin, fenvalerate, flucythrinate, flumethrin, in admixture, will be given below. gamma-cyhalothrin, imiprothrin, lambda-cyhalothrin, Diphenamid, naproanilide, napropamide, pentanochlor, methothrin, permethrin, phenothrin, prallethrin, resmethrin, propanil, flamprop-M, MCPA-thioethyl, clodinafop-propar Kadethrin, tau-fluvalinate, tefluthrin, tetramethrin, Zeta gyl, cyhalofop-butyl, diclofop-methyl, fenoxaprop-P-ethyl, cypermethrin, tralomethrin, transfluthrin, etofenproX, halfen fenoxaprop-ethyl, fluazifop-butyl, fluazifop-P-butyl, haloxy proX, Silafluofen, benSultap, cartap, thiocyclam, thiosultap fop, haloxyfop-P, haloxyfop-P-methyl, metamifop, pro Sodium, acephate, azamethiphos, azinphos-ethyl, azinphos paquizafop, quizalofop-ethyl, quizalofop-P, quizalofop-P- methyl, cadusafos, chlorethoxyfos, chlorfenvinphos, 10 ethyl, quizalofop-P-tefuryl, isoxaben, propyZamide, chlormephos, chlorpyrifos, chlorpyrifos-methyl, couma chlorthal-dimethyl, benfuresate, ethofumesate, 2.3.6-TBA, dicamba, dichlobenil, bentaZone, benazolin, diguat dibro phos, cyanophos, demeton-S-methyl, diazinon, dichlorvos, mide, paraquat dichloride, asulam, carbetamide, chlor dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, propham, propham, acetochlor, alachlor, butachlor, dimeth ethion, ethoprophos, famphur, fenamiphos, fenitrothion, 15 achlor, dimethenamid, metaZachlor, metolachlor, fenthion, fosthiazate, heptenophos, isocarbophos, isox pethoxamid, pretilachlor, propachlor, propisochlor, S-meto athion, malathion, mecarbam, methamidophos, methi lachlor, thenylchlor, alloxydim, butroxydim, clethodim, dathion, mevinphos, monocrotophos, naled, omethoate, oxy cycloxydim, profoxydim, Sethoxydim, tepraloxydim, demeton-methyl, parathion, parathion-methyl, phenthoate, tralkoxydim, benfluralin, butralin, dinitramine, ethal fluralin, phorate, phosalone, phosmet, phosphamidon, phoxim, pir oryzalin, pendimethalin, trifluralin, dinoterb, DNOC, acif imiphos-methyl, profenofos, propetamphos, prothiofos, luorfen, bifenox, fluoroglycofen-ethyl, fomesafen, HC-252, pyraclofos, pyridaphenthion, quinalphos, Sulfotep, tebupir lactofen, oxyfluorfen, aclonifen, glyphosate, glyphosate-tri imfos, temephos, terbufos, tetrachlorvinphos, thiometon, mesium (sulfosate), bromoxynil, ioxynil, imazamethabenz triaZophos, trichlorfon, vamidothion, imicyafos, flupyrazo methyl, imaZamox, imazamethapyr(imazapic), imazapyr, fos, aldicarb, bendiocarb, benfuracarb, carbaryl, carbofuran, 25 imaZaquin, imazethapyr, isoxaflutole, clomaZone, cinidon carbosulfan, ethiofencarb, fenobucarb, formetanate, furathio ethyl, flumiclorac-pentyl, flumioxazin, oxadiargyi, oxadia carb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl. Zon, pentoxazone, flufenacet, mefenacet, 2,4-D, 2.4-DB, pirimicarb, propoXur, trimethacarb. XMC, Xylylcarb, alany clomeprop, dichlorprop, dichlorprop-P, MCPA, MCPB, carb, butocarboxim, butoxycarboxim, thiodicarb, thiofanox, mecoprop, mecoprop-P potassium, desmedipham, phenme bistrifluoron, chlorfluaZuron, diflubenZuron, flucycloxuron, 30 dipham, pyraflufen-ethyl, pyridate, forchlorfenuron, thidi flufenoXuron, hexaflumuron, lufenuron, novaluron, noviflu aZuron, bilanafos, glufosinate-ammonium, glufosinate-so muron, teflubenZuron, triflumuron, abamectin, emamectin, dium, butamifos, bensulide, naptalam, benzofenap, chlorfenapyr, fenoxycarb, hydroprene, kinoprene, methop pyrazolynate, pyrazoxyfen, pyrasulfotole, maleic hydrazide, rene, pyriproxyfen, dienochlor, cyenopyrafen, cyflumetofen, norflurazon, chloridazon, dithiopyr, thiazopyr, diflufenican, spiromesifen, Spirodiclofen, Spirotetramat, Flubendiamide, 35 picolinafen, clopyralid, fluoroxypyr, picloram, triclopyr, flurimfen, flonicamid, metaflumizon, rynaxypyr, lepmectin, diflumetorim, butafenacil, fenclorim, ancymidol, flurprimi pyridalyl, fluacrypyrim, indoxacarb, bromopropylate, triaz dol, bispyribac-Sodium, pyribenZoxim, pyriftalid, pyrimino amate, fenazaquin, fenpyroximate, pyridaben, tebufenpyrad, bac-methyl, pyrithiobac-Sodium, chlormeduat chloride, clofentezine, etoxazole, hexythiazox, pymetrozine, bupro mepiduat chloride, quinoxyfen, quinclorac, quinmerac, fezin, 1.3-dichloropropene (1.3-D), isocarbophos, ammo 40 diflufenZopyr, flucarbazone-sodium, propoxycarbazone-so nium N-methyldithiocarbamate (NCS), azocyclotin, dium, propoxycarbazone, amidosulfuron, azim Sulfuron, ben endosulfan, chlordane, chloropicrin, cyhexatin, spinosad, Sulfuron-methyl, chlorimuron-ethyl, chlorSulfuron, cinosul sodium dimethyldithiocarbamate, fenbutatin oxide, flusulfa furon, cyclosulfamuron, ethametsulfuron-methyl, mide, methyl isothiocyanate (MITC), rotenone, CL900167, ethoxysulfuron, flazasulfuron, flupyrsulfuron-methyl-so sodium aluminium fluoride, pyrifluguinazon, RU-15525, 45 dium, foramsulfuron, halosulfuron-methyl, imaZosulfuron, XDE-175 and ZXI-8901. iodosulfulon-methyl-Sodium, mesosulfuron-methyl, metSul Examples of other fungicidal compounds which may be furon-methyl, nicosulfuron, oxasulfuron, primisulfuron-me used in combination or in admixture, will be given below. thyl, prosulfuron, pyrazosulfuron-ethyl, rimsulfuron, Sulfo Amisulbrom, benomyl, benthiavalicarb-isopropyl, benthi meturon-methyl, sulfosulfuron, thifensulfuron-methyl, opyrade, ethaboxam, bitertanol, blasticidin-S, boscalid, cap 50 triasulfuron, tribenuron-methyl, trifloxysulfuron-sodium, tri tan, carbendaZol, carpropamid, chlorothalonil, cyaZofamid, flusulfuron-methyl, tritosulfuron, flucetosulfuron, fentraza cyflufenamid, cymoxanil, diclomeZine, dimoxystrobin, mide, fluthiacet-methyl, butylate, cycloate, dimepiperate, dithianon, edifenphos, fenamidone, fenarimol, fenbucona EPTC, esprocarb, molinate, orbencarb, pebulate, prosulfo Zole, fluazinam, fluopicolide, fluoxastrobin, flutolanil, folpet, carb, thiobencarb, tiocarbazil, tri-allate, pyributicarb, fosetyl. fthalide, guaZatine, hexaconazole, hydroxyisoxazole, 55 ametryn, atrazine, cyanazine, dimethametryn, prometon, hymexaZol, iprobenfos, iprodione, iprovalicarb, isoprothi prometryn, propazine, simazine, simetryn, terbumeton, ter olane, isotianil, kasugamycin, mandipropamid, maneb, buthylazine, terbutryn, trietazine, hexaZinone, metamitron, mepanipyrim, mepronil, metalaxyl, metrafenone, myclobu metribuzin, amitrole, flupoxame, amicarbazone, carfentra tanyl, orysastrobin, oxadixyl, oxolinic acid, pefurazoate, pen Zone-ethyl, SulfentraZone, cloranSulam-methyl, dicloSulam, cycuron, phenazine oxide, picoxystrobin, polycarbamate, 60 florasulam, flumetSulam, metoSulam, penoXSulam, mesotri polyoxin, probenazole, prochloraz, procymidone, propam one, Sulcotrione, tefuryltrion, bromacil, lenacil, terbacil, ocarb-hydrochloride, propiconazole, propineb, produinazid, chlorotoluron, dimefuron, diuron, fluometuron, isoproturon, pyraclostrobin, pyribencarb, pyroquilon, Simeconazole, isouron, karbutilate, linuron, methabenzthiaZuron, metoben Streptomycin, tecloftalam, thiabendazole, thiophanate-me Zuron, metoXuron, monolinuron, neburon, siduron, tebuthi thyl, thiuram, tiadinil, tolnifanide, triadimefon, tricyclazole, 65 uron, oxaziclomefone, anilofos, benzobicyclon, prodiamine, trifloxystrobin, triflumizole, triforine, validamycin, Vinchlo cinmethylin, pyraclonil, pyroxySulam, triaziflam, etobenza Zoline, Zineb and Ziram. nid, bromobutide, daimuron, cafenstrole, benzfendizone, US 8,802,713 B2 121 122 pinoxaden, aminopyralid, toprameZone, tembotrione, ily Aclerdidae, Aclerda takahashii, etc., family Diaspididae, indanofan, pyrimisulfan, thiencarbazone, bencarbazone and California red scale (Aonidiella aurantii), San Jose scale pyroxasulfone. (Cosmockaspis perniciosus), arrowhead scale (Unaspis The above agricultural formulations are disclosed in The vanonensis), etc., family Miridae, western tarnished plant Pesticidal Manual, 13th edition (published by British Crop 5 bug (Lygus hesperus), rice leaf bug (Trigonotylus Caelestia Protection Council, 2004), SHIBUYA INDEX 10th edition, lium), etc., family Tingitidae, AZalea lace bug (Stephanitis 11th edition and 12th edition, published by Shibuya Index pyrioides), pear lace bug (Stephanitis nashi), etc., family Research Association), or Monthly Fine Chemical 2006, Vol. Pentatomidae, whitespotted spined bug (Eysarcoris aeneus), 35, No. 7 (published by CMC Publishing Co., Ltd., 2006) or rice Stink bug (Lagynotomus elongatus), Southern green Stink known. 10 bug (Nezara viridula), brownwinged green bug (Plautia cros The compounds of the present invention exhibit excellent sota), etc., family Thyreocoridae, bean plataspid (Megacopta pesticidal effects against pests such as pest orthoptera, pest cribraria), etc., family Lygaeidae, oriental chinch bug (Cav thysanoptera, pest hemipterans, pest coleoptera, pest diptera, elerius saccharivorus), etc., family Malcidae, Malicus japoni pest lepidopterans, pest hymenoptera, pest collembola, pest cus, etc., family Pyrrhocoridae, red cotton stainer (Dysdercus thysanura, pest blattaria, pest isoptera, pest psocoptera, pest 15 cingulatus), etc., family Alylidae, paddy bug (Leptocorisa mallophaga, pest anoplura, plant-parasitic mites, plant-para acuta), rice bug (Leptocorisa Chinensis), etc., family Cor sitic nematodes, plant-parasitic molluscs, other pests, unfa eidae, coreid bug (Anacanthocoris stricornis), etc., family Vorable animals, insanitary insects, and parasites. As Rhopalidae, Rhopalus maculatus, etc., family Cimicidae, bed examples of the above pests, the following species may be bug (Cimex lectularis), etc. mentioned. Pest Coleoptera, for example, family Scarabalidae, cupre Pest orthoptera, for example, family Tettigoniidae, Ruspo ous chafer (Anomala cuprea), soybeam beetle (Anomala lia lineosa, etc., family Gryllidae, Emma field cricket (Te rufocuprea), Japanese beetle (Popillia japonica), coconut rhi leogryllus emma), etc., family Gryllotalpidae, mole cricket noceros beetle (Oryctes rhinoceros), etc., family Elateridae, (Gryllotalpa Orientalis), family Acrididae, rice grasshopper barley wireworm (Agriotes Ogurae), Sugarcane click beetle (Oxya hyla intricate), migratory locust (Locusta migratoria), 25 (Melanotus Okinawensis), Sweetpotato wireworm (Melano migratory glasshopper (Melanoplus sanquinipes), etc., fam tus fortnunifortnuni), etc., family Dermestidae, varied car ily Pyrgomorphoidae, Smaller longheaded locust (Atracto pet beetle (Anthrenus verbasci), etc., family Bostrichidae, morpha lata), family Eneopterinae. EuScyrtus japonicus, Heterobostrychus hamatipennis, etc., family Anobiidae, family Tridactylidae, Xva iaponicus, etc. drugstore beetle (Stegobium paniceum), etc., family Ptinidae, Pest thysanoptera, for example, family Thripidae, flower 30 brown spider beetle (Pinus clavipes), etc., family Trogossiti thrips (Frankliniella intonsa), western flower thrips (Fran dae, cadelle beetle (Tenebroides manritanicus), etc., family Kliniella occidentalis), yellow tea thrips (Scirtothrips dorsa Cleridae, red-legged hambeetle (Necrobia rufipes), family lis), melon thrips (Thrips palmi), onion thrips (Thrips tabaci), Nitidulidae, dried fruit beetle (Carpophilus hemipterus), etc., etc., family Phlaeothripidae, Ponticulothrips diospyrosi, rice family Silvanidae, foreign grain beetle (Ahasverus advena), aculeated thrips (Haplothrips aculeatus), etc. 35 etc., family Laemophloeidae, rusty grain beetle (Cryptolestes Pest hemipterans, for example, family Cicadidae, Mogan ferrugineus), etc., family Coccinellidae, Mexican bean beetle nia minuta, etc., family Aphrophoridae, Aphrophora interme (Epilachna varivestis), twenty-eight-spotted ladybird dia, etc., family Membracidae, Machaerotypus Sibiricus, etc., (Henosepilachna vigintioctopunctata), etc., family Tenebri family Cicadellidae, grape leafhopper (Arboridia apicalis), oridae, mealworn beetle (Tenebrio molitor), red flour beetle tea green leafhopper (Empoasca Onuki), green rice leafhop 40 (Tribolium castaneum), etc., family Meloidae, bean blister per (Nephotettix cincticeps), Zig-Zag rice leafhopper (Recilia beetle (Epicauta qorhami), etc., family Cerambycidae, Asian dorsalis), etc., family Cixiidae, Pentastiridius apicalis, etc., longhorn beetle (Anoplophora glabripennis), grape borer family Delphacidae, Small brown planthopper (Laodelphax (Xylotrechus pyrrhoderus), Japanese pine Sawyer (Monocha striatellus), brown rice planthopper (Nilaparvata lugens), mus alternatus), etc., family Bruchidae, adzuki bean weevil white-backed planthopper (Sogatella fircifera), etc., family 45 (Callosobruchus chinensis), etc., family Chrysomelidae, Meenoplidae, Nisia nervosa, etc., family Derbidae, Colorado potato beetle (Leptinotarsa decemlineata), western Kamendaka saccharivora, etc., family Achilidae, red fungus corn rootworm (Diabrotica virgifera), brassica leaf beetle bug (Achilus flammeus), etc., family Ricaniidae, Orosanga (Phaedon brassicae), flea beetle (Phyllotreta striolata), etc., japonicus, etc., family Flatidae, Mimophantia maritima, etc., family Brentidae, Sweetpotato weevil (Cylas formicarius), family Psyllidae, Cacopsylla pyrisuga, etc., family Calophy 50 etc., family Curculionidae, alfalfa weevil (Hypera postica), idae, Calophya mangiferae, etc., family Phylloxeridae, grape vegetable weevil (Listroderes costirostris), west Indian phylloxera (Daktulosphaira vitifoliae), etc., family Adel Sweetpotato weevil (Euscepes postfasciatus), etc., family gidae, larch woolyadelgid (Adelges laricis), hemlock wooly Erirhinidae, rice plant weevil (Echinocnemus bipunctatus), adelgid (Adelges tsugae), etc., family Aphdidae, pea aphid rice water weevil (Lissorhoptrus Oryzophilus), etc., family (Acyrthosiphon pisum), cotton aphid (Aphis gossypii), spi 55 Curculioridae, maize weevil (Sitophilus zeanais), hunting raea aphid (Aphis spiraecola), turrip aphid (Lipaphis ery billbug (Sphenophrus venatus), etc., family Scolytidae, com simi), green peach aphid (Myzus persicae), green bug mon pine shoot beetle (Tomicus piniperda), etc., family Platy (Schizaphis graminum), bird cherry-oat aphid (Rhopalosi podidae, ambrosia beetle (Crossotarsus niponicus), etc., fam phum padi), etc., family Aleyrodidae, orange spiny whitefly ily Bostrichidae, Lyctus brunneus, etc. (Aleurocanthus spiniferus), Sweetpotato whitefly (Bemisia 60 Pest diptera, for example, family Tipulidae, rice crane fly tabaci), silverleaf whitefly (Bemisia argentifolii), greenhouse (Tipula aino), etc., family Bibionidae, lovebug (Plecia nearc whitefly (Trialeurodes vaporariorum), etc., family Margar tica), etc., family Mycetoplilidae, Exechia Shiitakevora, etc., odidae, giant margarodid scale (Drosicha corpulenta), Icerva family Sciaridae, potato Scab-gnat (Pnyxia scabiei), etc., purchasi, etc., family Pseudococcidae, pineapple mealybug family Cecidomyiidae, soybean pod gall midge (Asphondylia (Dysmicoccus brevipes), citrus mealybug (Planococcus 65 yushimai), hessian fly (Mayetiola destructor), etc., family citri), Comstock mealybug (Pseudococcus Comstocki), etc., Culicidae, yellow fever mosquito (Aedes aegypti), common family Coccidae, Soft scale (Ceroplastes ceriferus), etc., fam house mosquito (Culex pipiens pallens), etc., family Simuli US 8,802,713 B2 123 124 idae, Simulium takahashii, etc., family Chironomidae, rice (Agrotis ipsilon), Autographa nigrisigna, cotton bollworm midge (Chironomus Oryzae), etc., family Tabanidae, deerfly (Helicoverpa armigera), corn earworm (Helicoverpa zea), (Chrysops suavis), Tabanus trigonus, etc., family Syrphidae, tabaco budworm (Heliothis virescens), beet armyworm onion bulb fly (Eumerus Strigatus), etc., family Tephritidae, (Spodoptera exigua), common cutworm (Spodoptera litura), oriental fruit fly (Bactrocera dorsalis), Japanese cherry fruit etc. fly (Euphranta japonica), Mediterranean fruit fly (Ceratitis Pest hymenoptera, for example, family Argidae, rose argid capitata), etc., family Agromyzidae, American serpentine sawfly (Arge pagana), etc., family Tenthredinidae, chestnut leafminer (Liriomyza trifolii), garden pea leafminer (Chro sawfly (Apethymus kuri), turnip sawfly (Athalia rosae rufi matomyia horticola), etc., family Chloropidae, wheat stem cornis), etc., family Cynipidae, chestnut gall wasp (Dryocos maggot (Meromyza nigriventris), etc., family Drosophilidae, 10 mus kuriphilus), etc., family Vespidae, hornet (Vespa simil cherry drosophila (Drosophila Suzukii), common fruit fly lima xanthoptera), etc., family Formicidae, red imported fire (Drosophila melanogaster), etc., family Ephydridae, rice ant (Solenopsis invicta), etc., family Megachilidae, Mega leafminer (Hydrellia griseola), etc., family Hippoboscidae, chile nipponica, etc. forest fly (Hippobosca equina), etc., family Scathophagidae, Pest collembola, for example, family Sminthuridae, garden Parallelomma Sasakawae, etc., family Anthomyiidae, onion 15 springtail (Bourletiella hortensis), etc. fly (Delia antiqua), seed-corn fly (Delia platura), etc., family Pest thysanura, for example, family Lepismatidae, silver Fanniidae, little house fly (Fannia canicularis), etc., family fish (Lepisma saccharina), Ctenolepisma villosa, etc. Muscidae, housefly (Musca domestica), stable fly (Stomoxy's Pest blattaria, for example, family Blattidae, American calcitrans), etc., family Sarcophagidae, flesh fly (Sarcophaga cockroach (Periplaneta americana), family Biattellidae, Ger peregrina), etc., family Gastrophilidae, horse bot fly (Gas man cockroach (Blattella germanica), etc. terophilus intestinalis), etc., family Hypodermatidae, com Pest isoptera, for example, family Kalotermitidae, western mon cattle grab (Hypoderma lineatum), etc., family drywood termite (Incisitermes minor), etc., family Rhinoter Oestridae, ship nasal botfly (Oestrus ovis), etc. mitidae, Formosan Subterranean termite (Coptotermes for Pest lepidopterans, for example, family Hepialidae, Swift mosanus), etc., family Termitidae, black-winged subterra moth (Endoclita excrescens), etc., family Heliozelidae, Anti 25 nean termite (Odontotermes formosanus), etc. spilla ampelopsia, etc., family Cossidae, Zeuzera leuconotum, Pest pSocoptera, for example, family Trogiidae, booklouse etc., family Tortricidae, apple tortrix (Archips fiascocuprea (Trogium pulsatorium), etc., family Liposcelididae, LipOsce nus), Summer fruit tortrix moth (Adoxophyes Orana fasciata), lis corrodens, etc. oriental fruit moth (Grapholita molesta), oriental tea tortrix Pest mallophaga, for example, family Philopteridae, poul (Homona magnanima), soybean pod borer (Leguminivora 30 try wing louse (Lipeurus caponis), etc., family Trichodec glycinivorella), codling moth (Cydia pomonella), etc., family tidae, cattlebiting louse (Damalinia bovis), etc. Tortricidae, vine moth (Eupoecilia ambiguella), etc., family Pest anoplura, for example, family Haematopinidae, pig Psychidae, Bambalina sp., tea bagworm (Euneta minuscula), louse (Haematopinus suis), etc., family Pediculidae, body etc., family Tineidae, European grain moth (Nemapogon louse (Pediculus humanus), etc., family Linognathidae, granella), casemaking clothes moth (Tinea translucens), etc., 35 dogsucking louse (Linognathus setosus), etc., family Pedicu family Bucculatricidae, pear leaf miner (Bucculatrix pyri lidae, crab louse (Pthirus pubis), etc. vOrella), etc., family Lyonetiidae, peach leafminer (Lyonetia Plant-parasitic mites, for example, family Eupodidae, blue clerkella), etc., family Gracillarridae, tea leafroller (Calop oat mite (Penthaleus major), etc., family Tarsonemidae, tilia theivora), apple leafminer (Phyllonorycter ringoniella), cyclamen mite (Phytonemus pallidus), broad mite (Polyph etc., family Phyllocnistidae, citrus leafminer (Phyllocnistis 40 agotarisonemus latus), etc., family Pyemotidae, one of pye citrella), etc., family Acrolepiidae, allium leafminer (Acrol motesmite (Siteroptes sp.), etc., family Tenuipalpidae, citrus epiopsis sapporensis), etc., family Yponomeutidae, diamond flat mite (Brevipalpus lewisi), etc., family Tuckerellidae, back moth (Plutella xylostella), Yponomeuta Orientalis, etc., tuckerellid mite (Tuckerella pavoniformis), etc., family Tet family Argyresthiidae, apple fruit moth (Argyresthia conju ranychidae, apricot spider mite (Eotetranychus boreus), cit gella), etc., family Sesiidae, Nokona regalis, etc., family 45 rus red mite (Panonychus citri), European red mite (Panony Gelechiidae, potato tuberworm (Phthorimaea operculella), chus ulmi), two-spotted spider mite (Tetranvchus urticae), Angoumois grain moth (Sitotroga cerealella), pink bollworm Kanzawa spider mite (Tetranychus kanzawaii), etc., family (Pectinophora gossypiella), etc., family Carposinidae, peach Phytoptidae, Trisetacus pini, etc., family Eriophyidae, pink fruit moth (Carposina Sasakii), etc., family Zygaenidae, Illib citrus rust mite (Aculops pelekassi), pear rust mite (Epitrim erispruni, etc., family Limacodidae, oriental moth (Monema 50 erus pyri), citrus rust mite (Phylocoptruta oleivOra), etc., flavescens), etc., family Crambidae, Ancylolonia japonica, family Diptilomiopidae, Diptacus crenatae, etc., family rice stem borer (Chilo suppressalis), rice leafroller (Cnapha Acaridae, brown legged grain mite (Aleuroglyphus ovatus), locrocis medinalis, oriental corn borer (Ostrinia firmacalis), mould mite (Trophagus putrescentiae), bulb mite (Rhizogly European corn borer (Ostrinia nubilalis), etc., family Pyral phus robini), etc. idae, tropical warehouse moth (Cadra cautella), greater wax 55 Plant-parasitic nematodes, for example, family Longi moth (Galleria mellonella), etc., family Pterophoridae, Nip doridae, California dagger nematode (Xiphinema index), etc., poptilia vitis, etc., family Papilionidae, Asian Swallowtail family Trichodoridae, Christie's stubby root nematode (Papilio xuthus), etc., family Pieridae, common cabbage (Paratrichodorus minor), etc., family Rhabditidae, Rhabdi worm (Pieris rapae), etc., family Hesperiidae, migrant skip tella sp., etc., family Tylenchidae Aglenchus sp., etc., family per (Parnara guttata guttata), etc., family Geometridae, giant 60 Tylodoridae Cephalenchus sp., etc., family Anguinidae, looper (Ascotis selenaria), etc., family Lasiocampidae, pine strawberry bud nematode (Nothotylenchus acris), potato rot moth (Dendrolimus spectabilis), tent caterpillar (Malaco nematode (Dity lenchus destructor), etc., family Hoplolaimi Soma neustrium testaceum), etc., family Sphingidae, convol dae, reniform nematode (Rotylenchulus reniformis), Stein Vulus hawk-moth (Agrius convolvuli), etc., family Lymantri er's spiral nematode (Helicotylenchus dihystera), etc., family idae, tea tussock moth (Arna pseudoconspersa), gypsy moth 65 Paratylenchidae, Paratylenchus curvitatus, etc., family (Lymantria dispar), etc., family Arctiidae, fall webworm (Hy Meloidogynidae, Southern root-knot nematode (Meloidogyne phantria cunea), etc., family Noctuidae, black cutworm moth incognita), northern root-knot nematode (Meloidogyne US 8,802,713 B2 125 126 hapla), etc., family Heteroderidae, potato cyst nematode The compounds of the present invention can be used for (Globodera rostochiensis), soybean cyst nematode (Het plants which have acquired characteristics such as resistance erodera glycines), etc., family Telotylenchi, tobacco stunt to pests, resistance to diseases or resistance to herbicides, by nematode (Tvlenchorhynchus claytoni), etc., family gene recombination, artificial hybridization, etc. Further, they Tylenchidae, Psilenchus sp., etc., family Criconematidae, have controlling effects also against pests which show resis one ofring nematode (Criconenoides sp.), etc., family Tylen tance to organophosphorus compounds, carbamate com chulidae, citrus root nematode (Tilenchulus semipenetrans), pounds, synthetic pyrethroid compounds, acylurea com etc., family Sphaeronematidae, Sphaeronema cameliae, etc., pounds or conventional insecticides. family Pratylenchidae, citrus burrowing nematode (Radop Now, production processes, formulation methods and holus citrophilus), banana root nematode (Radopholus simi 10 application of the compounds of the present invention will be lis), false root-knot nematode (Nacobbus aberrans), northern described in detail with reference to Examples, but they are by root lesion nematode (Pratylenchus penetrans), root lesion no means restricted to Such specific Examples. nematode (Pratylenchus coffeae), etc., family lotonchiidae, EXAMPLES lotonchium ungulatum, etc., family Aphlenchidae, mycopha 15 gous nematode worm (Aphelenchus avenae), etc., family In the following Examples, the Support for column chro Aphelenchoididae, rice white tip nematode (Aphelenchoides matography is a silica gel, and the compositional ratio (e.g. besseyi), strawberry foliar nematode (Aphelenchoides 1:4) of the developing solvent (e.g. ethyl acetate:hexane) is fragariae), etc., family Parasitaphelenchidae, pine wood based on the Volume in all cases. nematode (Bursaphelenchus xvilophilus), etc. Further, the concentration of an aqueous Solution of e.g. Plant-parasitic molluscs, for example, family Ampullar Sodium thiosulfate, Sodium hydrogen carbonate or potassium ridae, channeled applesnail (Pomacea canaliculata), etc., carbonate used in Examples is from a 1 mass % aqueous family Veronicellidae, garden slug (Leavicaulis alte), etc., Solution to a saturated aqueous Solution in all cases. family Achatinidae, giant African Snail (Achatina fillica), etc., family Philomycidae, Meghinatium bilineatum, etc., 25 Example 1 family Succineidae, refined amber Snail (Succinea lauta), etc., family Discidae, poor disk Snail (Discus pauper), etc., Preparation of 5-acetylamino-1-(2-fluoro-4-methyl family Zonitidae, glass snail (Zonitoides vessOensis), etc., 5-(2,2,2-trifluoroethylthio)phenyl)-3-(2,2,3,3,3-pen family Limacidae, yellow slug (Limax flavus), grey field slug tafluoropropoxy)pyrazole (compound No. 1-17 of (Deroceras reticulatum), etc., family Helicarionidae, Par 30 the present invention) akaliella harimensis, etc., family Bradybaenidae, Korean round Snail (Acusta despecta Sieboldiana), Asian trampsnail 5.0 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri (Bradybaena similaris), etc. fluoroethylthio)phenyl)-3-hydroxypyrazole was dissolved in Other pests, unfavorable animals, insanitary insects, 100 mL of dimethylsulfoxide, and 2.3 g of potassium carbon insects on domestic animals, and parasites, for example, order 35 ate was added, followed by stirring at room temperature for 5 Acarina, family Macronyssidae, temperate poultry mite (Or minutes. To this solution, 6.4 g of 2.2.3.3.3-pentafluoropropyl nithonyssus Sylviarum), etc., family Parasitidae, Varroa mite nonafluorobutanesulfonate was added, followed by stirring at (Varroa jacobsoni), etc., family Dermanyssidae, red mite room temperature for 12 hours. Extraction with ethyl acetate (Dermanyssus gallinae), etc., family Macronyssidae, temper was carried out, the organic layer was dried over anhydrous ate poultry mite (Ornithonyssus Sylviarium), etc., family IXo 40 magnesium sulfate, the solvent was distilled off under didae, cattle tick (Boophilus microplus), brown dog tick (Rhi reduced pressure, and the obtained residue was purified by picephalus sanquineus), bush tick (Haemaphysalis column chromatography (developing solvent ethyl acetate: longicornis), etc., family Sarcoptidae, Scabies mite (Sarcop hexane=1:4) to obtain 5.3 g of 5-acetylamino-1-(2-fluoro-4- tes scabiei), etc., order Isopoda, family Armadillidiidae, com methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(2,2,3,3,3- mon woodlouse (Armadillidium vulgare), etc., order Deca 45 pentafluoropropoxy)pyrazole. poda, family Cambaridae, red Swamp crawfish (Procambarus H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.08 (3H, s), clarkii), etc., order Isopoda, family Oniscidae, common pill 2.53 (3H, s), 3.40 (2H, q), 4.66 (3H, t), 6.22(1H, s), 7.03 (1H, bug (Armadillidium vulgare), etc., class Chilopoda, for brs), 7.16 (1H, d), 7.60 (1H, d) example, order Scutigeromorpha, family Scutigeridae, house centipede (Thereuonema tuberculate), family Scolopen 50 Example 2 dridae, Vietnamese centipede (Scolopendra subspinipes), etc., class Diplopoda, for example, order Polydesmida, fam Preparation of 5-acetylamino-1-(2-fluoro-4-methyl ily Paradoxosomatidae, greenhouse millipede (Oxidus graci 5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-(2,2,3,3,3- lis), etc., order Araneae, family Theridiidae, redback spider pentafluoropropoxy)pyrazole (compound No. 1-18 (Latrodectus hasseltii), etc., order Araneae, family Clubion 55 of the present invention) idae, Chiracanthium japonicum, etc., order Scorpiones, Ara bian fat-tailed Scorpion (Androctonus crassicauda), etc., 0.2 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri nemathelminthe endoparasite, roundworm (Ascaris lumbri fluoroethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy) coides), etc., pinworm (Syphacia sp.), etc., filaria (Wuchere pyrazole was dissolved in 10 mL of chloroform, and 0.1 g of ria bancrofti), etc., flatworm endoparasite, Chinese liver fluke 60 m-chloroperbenzoic acid (purity: 75%) was added under (Distomum sp.), lung fluke (Paragonimus westermanii), cooling with ice. After stirring for 30 minutes under cooling Metagonimus yokokawai, Schistosoma japonicum, pork tape with ice, the solution was washed with an aqueous Sodium worm (Taenia solium), Taeniarhynchus saginatus, Echino thiosulfate Solution and then washed with an aqueous potas coccus sp., tapeworm (Diphyllobothrium latum), etc. sium carbonate solution, and then dried over anhydrous mag The compounds of the present invention exhibit pesticidal 65 nesium sulfate. Then, the solvent was distilled off under effects also against the above-described pests which have reduced pressure, and the obtained residue was purified by acquired resistance to existing pesticides, etc. column chromatography (developing solvent ethyl acetate: US 8,802,713 B2 127 128 hexane=1:2) to obtain 0.2 g of 5-acetylamino-1-(2-fluoro-4- acetate was carried out, and the organic layer was dried over methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-(2,2,3,3,3- anhydrous magnesium Sulfate. Then, the solvent was distilled pentafluoropropoxy)pyrazole. off under reduced pressure, and the obtained residue was H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.08 (3H, s), purified by column chromatography (developing solvent 2.46 (3H, s), 3.43-3.53 (2H, m), 4.67 (2H, t), 6.19 (1H, s), 5 ethyl acetate:hexane=1:4) to obtain 0.9 g of 5-amino-4- 7.20 (1H, d), 7.22 (1H, brs), 8.08 (1H, d) chloro-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole. Example 3 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.52 (3H, s), 3.38 (2H, q), 3.88 (2H, s), 4.70 (2H, t), 7.14 (1H,d), 7.60 (1H, Preparation of 5-amino-1-(2-fluoro-4-methyl-5-(2.2, 10 d) 2-trifluoroethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluo ropropoxy)pyrazole (compound No. 1-9 of the Example 6 present invention) Preparation of 5-amino-4-bromo-1-(2-fluoro-4-me 1.2 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri- 15 thyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(2,2,3,3,3- fluoroethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluoropropoxy) pentafluoropropoxy)pyrazole (compound No. 1-45 pyrazole was dissolved in 50 mL of ethanol, and an aqueous of the present invention) Solution comprising 0.5g of concentrated Sulfuric acid in 2.0 mL of water was added, followed by reflux with heating for 6 2.0 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoro hours. After cooling to room temperature, the solvent was 20 ethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyra distilled offunder reduced pressure, and extraction with ethyl Zole was dissolved in 50 mL of acetonitrile, and 0.8g of acetate was carried out. The organic layer was dried over N-bromosuccinimide was added under cooling with ice. anhydrous magnesium sulfate, the solvent was distilled off After stirring for 10minutes under cooling with ice, the sol under reduced pressure, and the obtained residue was purified vent was distilled off under reduced pressure, extraction with by column chromatography (developing solvent ethyl 25 ethyl acetate was carried out, and the organic layer was dried acetate:hexane=1:4) to obtain 0.9 g of 5-amino-1-(2-fluoro over anhydrous magnesium sulfate. Then, the solvent was 4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(1,1,2,3,3,3- distilled off under reduced pressure, and the obtained residue hexafluoropropoxy)pyrazole. was purified by column chromatography (developing solvent 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.52 (3H, s), ethyl acetate:hexane=1:4) to obtain 2.0 g of 5-amino-4- 3.39 (2H, q), 3.83 (2H, s), 5.03-5.20 (1H, m), 5.47 (1H, s), 30 bromo 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) 7.14 (1H, d), 7.64 (1H, d) phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole. H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.52 (3H, s), Example 4 3.38 (2H, q), 3.92 (2H, s), 4.70 (2H, t), 7.14 (1H,d), 7.60 (1H, d) Preparation of 5-amino-1-(2-fluoro-4-methyl-5-(2.2, 35 2-trifluoroethylthio)phenyl-4-fluoro-3-(2,2,3,3,3- Example 7 pentafluoropropoxy)pyrazole (compound No. 1-41 of the present invention) Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo roethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropro 1.0 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoro- 40 poxy)-5-trifluoroacetylaminopyrazole (compound ethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyra No. 1-29 of the present invention) Zole was dissolved in 30 mL of acetonitrile, and 0.8g of N-fluoro-N'-(chloromethyl)-triethylenediaminebis(tet 1.2 g of 4-bromo-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoro rafluoroborate) was added, followed by stirring at room tem ethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)-5-trif. perature for 24 hours. Then, the solvent was distilled offunder 45 luoroacetylaminopyrazole was dissolved in 200 mL of etha reduced pressure, and the obtained residue was purified by nol, and 1.2 g of 10% palladium carbon was added. 430 mL of column chromatography (developing solvent ethyl acetate: hydrogen was blown over a period of 10 days at room tem hexane=1:4) to obtain 0.3 g of 5-amino-1-(2-fluoro-4-me perature under reduced pressure, the solvent was distilled off thyl-5-(2.2.2-trifluoroethylthio)phenyl-4-fluoro-3-(2,2,3,3, under reduced pressure, and the obtained residue was purified 3-pentafluoropropoxy)pyrazole. 50 by column chromatography (developing solvent ethyl H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.51 (3H, s), acetate:hexane:acetic acid=10:40: 1) to obtain 1.0 g of 1-2- 3.38 (2H, q), 3.62 (2H, s), 4.70 (2H, t), 7.12(1H,d), 7.59 (1H, fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(2.2, d) 3,3,3-pentafluoropropoxy)-5-trifluoroacetylaminopyrazole. 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.54 (3H, s), Example 5 55 3.40 (2H, q), 4.70 (2H, t), 6.30 (1H, s), 7.19 (1H,d), 7.63 (1H, d) Preparation of 5-amino-4-chloro-1-(2-fluoro-4-me thyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(2,2,3,3,3- Example 8 pentafluoropropoxy)pyrazole (compound No. 1-43 of the present invention) 60 Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo roethylthio)phenyl-5-methyl-3-(2,2,3,3,3-pentafluo 0.9 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoro ropropoxy)pyrazole (compound No. 1-91 of the ethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyra present invention) Zole was dissolved in 10 mL of acetonitrile, and 0.3g of N-chlorosuccinimide was added undercooling with ice. After 65 0.7 g of 3-hydroxy-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo stirring for 10minutes under cooling with ice, the solvent was roethylthio)phenyl-5-methylpyrazole was dissolved in 15 distilled off under reduced pressure, extraction with ethyl mL of dimethylsulfoxide, and 0.36 g of potassium carbonate US 8,802,713 B2 129 130 and 0.94 g of 2.2.3,3,3-pentafluoropropyl nonafluorobutyl H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.55 (3H, s), sulfonate were added, followed by stirring at room tempera 3.37 (2H, q), 4.71 (2H, t), 7.15(1H, d), 7.55 (1H, d) ture for 5 hours. After completion of the reaction, the reaction Solution was poured into water, extraction with ethyl acetate Example 11 was carried out, washing with a saturated salt solution was carried out, the organic layer was dried over anhydrous mag Preparation of 5-acetylamino-1-(2-fluoro-4-methyl nesium sulfate, the solvent was distilled off under reduced 5-(2.2.2-trifluoroethylthio)phenyl)-3-(1,1,2,2,3,3,3- pressure, and the obtained residue was purified by column heptafluoropropoxy)pyrazole (compound No. 1-267 chromatography (ethyl acetate:hexane=1:10) to obtain 0.90 g of the present invention) of 1-2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phe 10 nyl-5-methyl-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole. 2.1 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri fluoroethylthio)phenyl)-3-hydroxypyrazole was dissolved in 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.13 (3H, s), 60 mL of dichloromethane, and 0.51 g of pyridine was added. 2.52 (3H, s), 3.37 (2H, q), 4.65(2H, t), 5.74 (1H, s), 7.12 (1H, To the obtained solution, 3.0 g of (perfluoro-n-propyl)phe d), 7.56 (1H, d) 15 nyliodonium trifluoromethanesulfonate was slowly added, followed by stirring at room temperature for 1 hour. The Example 9 solvent was distilled off under reduced pressure, a saturated salt Solution was added, extraction with ethyl acetate was carried out, the organic layer was dried over anhydrous Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo sodium sulfate, the solvent was distilled off under reduced roethylsulfinyl)phenyl-5-methyl-3-(2,2,3,3,3-pen pressure, and the obtained residue was purified by column tafluoropropoxy)pyrazole (compound No. 1-92 of chromatography (developing solvent ethylacetate:hexane-1: the present invention) 4) to obtain 0.10 g of 5-acetylamino-1-(2-fluoro-4-methyl 5-(2,2,2-trifluoroethylthio)phenyl)-3-(1,1,2,2,3,3,3-hep 25 tafluoropropoxy)pyrazole. 0.3 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.11 (3H, s), phenyl-5-methyl-3-(2,2,3,3,3-pentafluoropropoxy)pyra 2.55 (3H, s), 3.41 (2H, q), 6.53 (1H, s), 7.10 (1H, brs), 7.19 Zole was dissolved in 10 mL of chloroform, and 0.16g of m-chloroperbenzoic acid (purity: 75%) was slowly added (1H, d), 7.63 (1H, d) under cooling with ice. After stirring for 30 minutes under 30 Example 12 cooling with ice, the Solution was washed with an aqueous sodium thiosulfate solution and then washed with an aqueous Preparation of 5-acetylamino-1-(2-fluoro-4-methyl Sodium hydrogen carbonate solution, and then dried over 5-(2,2,2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2,2,3, anhydrous magnesium Sulfate. Then, the solvent was distilled 3.3-heptafluoropropoxy)pyrazole (compound No. off under reduced pressure, and the obtained residue was 35 1-268 of the present invention) purified by column chromatography (ethylacetate:hexane-1: 2) to obtain 0.30 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 60 mg of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2- roethylsulfinyl)phenyl-5-methyl-3-(2,2,3,3,3-pentafluoro trifluoroethylthio)phenyl)-3-(1,1,2,2,3,3,3-heptafluoropro propoxy)pyrazole. poxy)pyrazole was dissolved in 10 mL of chloroform, and 30 40 mg of m-chloroperbenzoic acid (purity: 75%) was added 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.15 (3H, s), under cooling with ice. After stirring for 30 minutes under 2.46 (3H, s), 3.40-3.59 (2H, q), 4.65 (2H, t), 5.77 (1H, s), 7.17 cooling with ice, the Solution was washed with an aqueous (1H, d), 8.06 (1H, d) Sodium thiosulfate solution and then washed with an aqueous potassium carbonate Solution, and then dried over anhydrous Example 10 45 magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (developing solvent ethyl acetate: Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo hexane=1:2) to obtain 53 mg of 5-acetylamino-1-(2-fluoro roethylthio)phenyl-4,5-dichloro-3-(2,2,3,3,3-pen 4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-(1.1.2.2, tafluoropropoxy)pyrazole (compound No. 1-111 of 50 3,3,3-heptafluoropropoxy)pyrazole. the present invention) H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.10 (3H, s), 2.48 (3H, s), 3.41-3.62 (2H, m), 6.50 (1H, s), 7.22 (1H, d), 0.7 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) 7.49 (1H, brs), 8.09 (1H, d) phenyl-5-amino-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole 55 Example 13 was dissolved in 15 mL of acetonitrile, 1.04 g of copper(II) chloride was added, and tert-butyl nitrite (0.24 g) was drop Preparation of 5-acetylamino-1-(2-fluoro-4-methyl wise added under cooling with ice. After stirring at room 5-(2.2.2-trifluoroethylthio)phenyl)-3-1,1,2-trif. temperature for 12 hours, the solvent was distilled off under luoro-2-(trifluoromethoxy)ethoxypyrazole (com reduced pressure, extraction with ethyl acetate was carried 60 pound No. 1-15 of the present invention) out, and the organic layer was dried over anhydrous magne sium sulfate. Then, the solvent was distilled offunder reduced 3.0 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri pressure, and the obtained residue was purified by column fluoroethylthio)phenyl)-3-hydroxypyrazole was dissolved in chromatography (ethyl acetate:hexane=1:10) to obtain 0.3 g 40 mL of dimethylformamide, 25 g of triethylamine was of 1-2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phe 65 added, and stirring was carried out at 50° C. for 3 hours while nyl-4,5-dichloro-3-(2,2,3,3,3-pentafluoropropoxy)pyra trifluoromethyl trifluorovinyl ether was blown. To this solu Zole. tion, ethyl acetate was added, the solution was washed with a US 8,802,713 B2 131 132 saturated aqueous solution of citric acid, the organic layer was Example 16 dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue Preparation of 4-chloro-1-(2-fluoro-4-methyl-5-(2.2, was purified by column chromatography (developing solvent 2-trifluoroethylsulfinyl)phenyl-3-1,1,2-trifluoro-2- ethyl acetate:hexane=1:4) to obtain 1.71 g of 5-acetylamino 5 (trifluoromethoxy)ethoxypyrazole (compound No. 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl-3- 1-290 of the present invention) {1,1,2-trifluoro-2-(trifluoromethoxy)ethoxypyrazole. 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.45 (3H, s), 0.24 g of 4-chloro-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo 3.37-3.57 (2H, m), 3.76 (2H, s), 4.65 (2H, t), 5.25 (1H, s), roethylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) 7.17 (1H, d), 8.12 (1H, d) 10 ethoxypyrazole was dissolved in 10 mL of chloroform, and 0.11 g of m-chloroperbenzoic acid (purity: 75%) was added Example 14 under cooling with ice. After stirring for 30 minutes under cooling with ice, the Solution was washed with an aqueous Preparation of 5-acetylamino-1-(2-fluoro-4-methyl Sodium thiosulfate solution and then washed with an aqueous 5-(2,2,2-trifluoroethylsulfinyl)phenyl-3-1,1,2- 15 Sodium hydrogen carbonate solution, and then dried over trifluoro-2-(trifluoromethoxy)ethoxypyrazole (com anhydrous sodium sulfate. The solvent was distilled offunder pound No. 1-16 of the present invention) reduced pressure, and the obtained residue was purified by column chromatography (developing solvent ethyl acetate: 0.5g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri hexane=1:2) to obtain 0.21 g of 4-chloro-1-(2-fluoro-4-me fluoroethylthio)phenyl)-3-1,1,2-trifluoro-2-(trifluo thyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-1,1,2-trif romethoxy)ethoxypyrazole was dissolved in 10 mL of chlo luoro-2-(trifluoromethoxy)ethoxypyrazole. roform, and 0.22 g of m-chloroperbenzoic acid (purity: 75%) 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.45 (3H, s), was added under cooling with ice. After stirring for 30 min 3.39-3.62 (2H, m), 6.13 (1H, dt), 7.19 (1H, d), 7.97 (1H, s), utes under cooling with ice, the solution was washed with an 8.41 (1H, s) aqueous Sodium thiosulfate solution and then washed with an 25 aqueous sodium hydrogen carbonate solution, and dried over Example 17 anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure, and the obtained residue was purified Preparation of 4,5-dichloro-1-(2-fluoro-4-methyl-5- by column chromatography (developing solvent ethyl (2.2.2-trifluoroethylthio)phenyl)-3-(1,1,2-trifluoro acetate:hexane=1:1) to obtain 0.46 g of 5-acetylamino-1-(2- 30 2-(trifluoromethoxy)ethoxypyrazole (compound fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-3- No. 1-291 of the present invention) {1,1,2-trifluoro-2-(trifluoromethoxy)ethoxypyrazole. 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.07 (3H, s), 0.7 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoro 2.45 (3H, s), 3.38-3.56 (2H, m), 6.03 (1H, d), 6.44 (1H, s), ethylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) 7.20 (1H, d), 7.77 (1H, brs), 8.01 (1H, d) 35 ethoxypyrazole was dissolved in 30 mL of acetonitrile, 2.9 g, of copper(II) chloride was added, and 0.36 g of tert-butyl Example 15 nitrite was added under reflux with heating. After reflux with heating for 2 hours, the solvent was distilled off under Preparation of 4-chloro-1-(2-fluoro-4-methyl-5-(2.2, reduced pressure, a Saturated Salt solution was added, and 2-trifluoroethylthio)phenyl-3-1,1,2-trifluoro-2- 40 extraction with ethyl acetate was carried out. The organic (trifluoromethoxy)ethoxypyrazole (compound No. layer was dried over anhydrous sodium sulfate, the solvent 1-289 of the present invention) was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (developing 0.9 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoro solvent ethyl acetate:hexane=1:8) to obtain 0.59 g of 4.5- ethylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) 45 dichloro-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) ethoxypyrazole was dissolved in 30 mL of acetonitrile, and phenyl)-3-1,1,2-trifluoro-2-(trifluoromethoxy) 0.27g of N-chlorosuccinimide was added under cooling with ethoxypyrazole. ice. After stirring for 10 minutes under cooling with ice, the H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.56 (3H, s), solvent was distilled off under reduced pressure, extraction 3.38 (2H, q), 6.11 (1H, dt), 7.17 (1H, d), 7.59 (1H, d) with ethyl acetate was carried out, and the organic layer was 50 dried over anhydrous magnesium sulfate. The solvent was Example 18 distilled off under reduced pressure, and the obtained residue was purified by column chromatography (developing solvent Preparation of 4,5-dichloro-1-(2-fluoro-4-methyl-5- ethyl acetate:hexane=1:4) to obtain 5-amino-4-chloro-1-(2- (2.2.2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2-trif. fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(1,1, 55 luoro-2-(trifluoromethoxy)ethoxypyrazole (com 2-trifluoro-2-(trifluoromethoxy)ethoxypyrazole. Then, the pound No. 1-292 of the present invention) obtained pyrazole derivative was dissolved in 30 mL of tet rahydrofuran, and 0.3 mL oft-butyl nitrite was added under 0.35 g of 4.5-dichloro-1-(2-fluoro-4-methyl-5-(2.2.2-trif cooling with ice. After stirring at room temperature for 12 luoroethylthio)phenyl)-3-1,1,2-trifluoro-2-(trifluo hours, the solvent was distilled off under reduced pressure, 60 romethoxy)ethoxypyrazole was dissolved in 10 mL of chlo and the obtained residue was purified by column chromatog roform, and 0.15g of m-chloroperbenzoic acid (purity: 75%) raphy (ethyl acetate:hexane=1:10) to obtain 0.75 of 4-chloro was added under cooling with ice. After stirring for 30 min 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl-3- utes under cooling with ice, the Solution was washed with an {1,1,2-trifluoro-2-(trifluoromethoxy)ethoxypyrazole. aqueous sodium thiosulfate solution and then washed with an H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.50 (3H, s), 65 aqueous sodium hydrogen carbonate Solution, and then dried 3.40 (2H, q), 6.15 (1H, dt), 7.13 (1H, d), 7.93 (1H, s), 7.94 over anhydrous sodium sulfate. The solvent was distilled off (1H, d) under reduced pressure, and the obtained residue was purified US 8,802,713 B2 133 134 by column chromatography (developing solvent ethyl at room temperature for 30 minutes. The reaction solution acetate:hexane=1:2) to obtain 0.35 g of 4,5-dichloro-1-(2- was cooled with ice again, and 0.21 g of methyl iodide was fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-3- added, followed by stirring at room temperature for 1 hour. {1,1,2-trifluoro-2-(trifluoromethoxy)ethoxypyrazole. Then, water was injected, extraction with ethyl acetate was 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.49 (3H, s), 5 carried out, and after washing with water, the organic layer 3.41-3.59 (2H, m), 6.09 (1H, dt), 7.23 (1H, d), 8.10 (1H, d) was dried over anhydrous magnesium Sulfate. The Solvent was distilled offunder reduced pressure, the obtained residue Example 19 was dissolved in 10 mL of ethanol, and 10 mL of a 35 mass % hydrochloric acid aqueous solution was added, followed by Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 10 stirring under reflux with heating for 1 hour. The reaction roethylthio)phenyl-5-methyl-3-(3,3,3-trifluoropro mixture was poured into water, extraction with ethyl acetate poxy)pyrazole (compound No. 1-249 of the present was carried out, and after washing with water, the organic invention) layer was dried over anhydrous magnesium Sulfate. The Sol vent was distilled off under reduced pressure, and the 0.6 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) 15 obtained residue was purified by column chromatography phenyl)-3-hydroxy-5-methylpyrazole was dissolved in 4 mL (developing solvent ethyl acetate:hexane=1:4) to obtain 0.44 of tetrahydrofuran, and 0.23 g of 3,3,3-trifluoropropanol, g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phe 0.75 g of triphenylphosphine and 0.71 g of 1,1'-(aZodicarbo nyl)-3-(1,1,2,3,3,3-hexafluoropropoxy)-5-methylaminopy nyl)dipiperidine were added, followed by stirring at room razole. temperature for 12hours. After completion of the reaction, the H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.50 (3H, s), reaction solution was distilled off under reduced pressure, 2.84 (3H, d), 3.38 (2H, q), 3.64 (1H, brd), 5.01-5.25 (1H, m), and the obtained residue was purified by column chromatog 5.34 (1H, s), 7.12 (1H, d), 7.60 (1H, d) raphy (ethyl acetate:hexane=1:4) to obtain 0.61 g of 1-2- fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl-5-me Example 22 thyl-3-(3,3,3-trifluoropropoxy)pyrazole. 25 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.13 (3H, s), Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 2.52 (3H, s), 2.53-2.70 (2H, m), 3.37 (2H, q), 4.41 (2H, t), roethylsulfinyl)phenyl)-3-(1,1,2,3,3,3-hexafluoro 5.67 (1H, s), 7.10 (1H, d), 7.57 (1H, d) propoxy)-5-methylaminopyrazole (compound No. 1-187 of the present invention) Example 20 30 0.4 g of 5-methylamino-1-(2-fluoro-4-methyl-5-(2.2.2- Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo trifluoroethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluoropro roethylsulfinyl)phenyl-5-methyl-3-(3,3,3-trifluoro poxy)pyrazole was dissolved in 10 mL of chloroform, and propoxy)pyrazole (compound No. 1-250 of the 190 mg of m-chloroperbenzoic acid (purity: 75%) was added present invention) 35 under cooling with ice. After stirring for 1 hour under cooling with ice, the solution was washed with an aqueous Sodium 0.29 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth thiosulfate solution and then washed with an aqueous Sodium ylthio)phenyl-5-methyl-3-(3,3,3-trifluoropropoxy)pyrazole hydrogen carbonate solution, and then dried over anhydrous was dissolved in 10 mL of chloroform, and 0.17 g of m-chlo sodium sulfate. The solvent was distilled off under reduced roperbenzoic acid (purity: 75%) was slowly added under 40 pressure, and the obtained residue was purified by column cooling with ice. After stirring for 30 minutes under cooling chromatography (developing solvent ethylacetate:hexane-1: with ice, the solution was washed with an aqueous sodium 2) to obtain 0.4 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoro thiosulfate Solution and then washed with an aqueous sodium ethylsulfinyl)phenyl)-3-(1,1,2,3,3,3-hexafluoropropoxy)-5- hydrogen carbonate solution, and then dried over anhydrous methylaminopyrazole. magnesium sulfate. The solvent was distilled off under 45 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.45 (3H, s), reduced pressure, and the obtained residue was purified by 2.84 (3H, d), 3.35-3.58 (2H, m), 3.64 (1H, brd), 5.01-5.22 column chromatography (ethyl acetate:hexane-1:2) to obtain (1H, m), 5.36 (1H, s), 7.17 (1H, d), 8.10 (1H, d) 0.30 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfi nyl)phenyl-5-methyl-3-(3,3,3-trifluoropropoxy)pyrazole. Example 23 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.15 (3H, s), 50 2.45 (3H, s), 2.53-2.70 (2H, m), 3.39-3.59 (2H, m), 4.41 (2H, Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo t), 5.70 (1H, s), 7.15 (1H, d), 8.06 (1H, d) roethylthio)phenyl-5-methylamino-3-1,1,2-trif luoro-2-(heptafluoropropoxy)ethoxypyrazole (com Example 21 pound No. 1-347 of the present invention) 55 Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 0.5g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri roethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluoropro fluoroethylthio)phenyl)-3-1,1,2-trifluoro-2-(heptafluoro poxy)-5-methylaminopyrazole (compound No. 1-186 propoxy)ethoxypyrazole was dissolved in 5 mL of dimeth of the present invention) ylformamide, and under cooling with ice, the solution was 60 dropwise added to a Suspension having 40 mg of Sodium 0.5g of 5-acetylamino-1-(2-fluoro-4-methyl-5-2.2.2-trif hydride suspended in 10 mL of dimethylformamide, and after luoroethylthio)phenyl)-3-1,1,2-trifluoro-2-(heptafluoro completion of the dropwise addition, stirring was carried out propoxy)ethoxypyrazole was dissolved in 5 mL of dimeth at room temperature for 30 minutes. The reaction solution ylformamide, and the Solution was dropwise added to a was cooled with ice again, and 0.13 g of methyl iodide was Suspension having 55mg of Sodium hydride Suspended in 10 65 added, followed by stirring at room temperature for 1 hour. mL of dimethylformamide under cooling with ice, and after Then, the reaction mixture was poured into water, extraction completion of the dropwise addition, stirring was carried out with ethyl acetate was carried out, and after washing with US 8,802,713 B2 135 136 water, the organic layer was dried over anhydrous magnesium lowed by stirring under reflux with heating for 2 hours. The sulfate. The solvent was distilled offunder reduced pressure, reaction mixture was poured into water, extraction with ethyl the obtained residue was dissolved in 10 mL of ethanol, and acetate was carried out, and after washing with water, the 10 mL of a 35 mass % hydrochloric acid aqueous solution was organic layer was dried over anhydrous magnesium sulfate. added, followed by stirring under reflux with heating for one The solvent was distilled off under reduced pressure, and the hour. The reaction mixture was poured into water, extraction obtained residue was purified by column chromatography with ethyl acetate was carried out, and after washing with (developing solvent ethyl acetate:hexane-1:4) to obtain 1.4g water, the organic layer was dried over anhydrous magnesium of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phe sulfate. The solvent was distilled offunder reduced pressure, nyl)-3-(2,2,3,3,3-pentafluoropropoxy)-5-(2-propyny and the obtained residue was purified by column chromatog 10 lamino)pyrazole. raphy (developing solvent ethyl acetate:hexane-1:4) to H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.28 (1H, t), obtain 0.31 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth 2.51 (3H, s), 3.38 (2H, q), 3.84 (3H, brs) 4.65 (2H, t), 5.30 ylthio)phenyl-5-methylamino-3-1,1,2-trifluoro-2-(hep (1H, s), 7.12 (1H, d), 7.60 (1H, d) tafluoropropoxy)ethoxypyrazole. 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.51 (3H, s), 15 Example 26 2.84 (3H, d), 3.37 (2H, q), 3.63 (1H, s), 5.32(1H, s), 6.15-6.30 (1H, m), 7.12 (1H, d), 7.60 (1H, d) Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo roethylsulfinyl)phenyl)-3-(2,2,3,3,3-pentafluoropro Example 24 poxy)-5-(2-propynylamino)pyrazole (compound No. 1-162 of the present invention) Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo roethylsulfinyl)phenyl-5-methylamino-3-1,1,2- 0.51 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth trifluoro-2-(heptafluoropropoxy)ethoxypyrazole ylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)-5-(2-pro (compound No. 1-348 of the present invention) pynylamino)pyrazole was dissolved in 10 mL of chloroform, 25 and 240 mg of m-chloroperbenzoic acid (purity: 75%) was 0.15 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth added under cooling with ice. After stirring for 1 hour under ylthio)phenyl-5-methylamino-3-1,1,2-trifluoro-2-(hep cooling with ice, the Solution was washed with an aqueous tafluoropropoxy)ethoxypyrazole was dissolved in 10 mL of Sodium thiosulfate solution and then washed with an aqueous chloroform, and 73 mg of m-chloroperbenzoic acid (purity: Sodium hydrogen carbonate solution and then dried over 75%) was added under cooling with ice. After stirring for one 30 anhydrous sodium sulfate. The solvent was distilled offunder hour under cooling with ice, the solution was washed with an reduced pressure, and the obtained residue was purified by aqueous sodium thiosulfate solution and then washed with an column chromatography (developing solvent ethyl acetate: aqueous sodium hydrogen carbonate solution, and then dried hexane=1:2) to obtain 0.39 g of 1-2-fluoro-4-methyl-5-(2, over anhydrous sodium sulfate. The solvent was distilled off 2.2-trifluoroethylsulfinyl)phenyl)-3-(2,2,3,3,3-pentafluoro under reduced pressure, and the obtained residue was purified 35 propoxy)-5-(2-propynylamino)pyrazole. by column chromatography (developing solvent ethyl H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.29 (1H, t), acetate:hexane=1:2) to obtain 0.12 g of 1-2-fluoro-4-me 2.44 (3H, s), 3.38-3.57 (2H, m), 3.84 (3H, brs) 4.65 (2H, t), thyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-5-methy 5.33 (1H, s), 7.17 (1H, d), 8.09 (1H, d) lamino-3-1,1,2-trifluoro-2-(heptafluoropropoxy) ethoxypyrazole. 40 Example 27 H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.45 (3H, s), 2.84 (3H, d), 3.37-3.56 (2H, m), 3.62 (1H, s), 5.34 (1H, s), Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 6.14-6.27 (1H, m), 7.17 (1H, d), 8.10 (1H, d) roethylthio)phenyl-5-(2-propynylamino)-3-1,1,2- trifluoro-2-(heptafluoropropoxy)ethoxypyrazole Example 25 45 (compound No. 1-357 of the present invention) Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 0.7 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri roethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropro fluoroethylthio)phenyl)-3-1,1,2-trifluoro-2-(heptafluoro poxy)-5-(2-propynylamino)pyrazole (compound No. propoxy)ethoxypyrazole was dissolved in 5 mL of dimeth 1-161 of the present invention) 50 ylformamide, and under cooling with ice, the solution was dropwise added to a Suspension having 50 mg of Sodium 2.0 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri hydride suspended in 10 mL of dimethylformamide, and after fluoroethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy) completion of the dropwise addition, stirring was carried out pyrazole was dissolved in 15 mL of dimethylformamide, and at room temperature for 30 minutes. The reaction solution under cooling with ice, the solution was dropwise added to a 55 was cooled with ice again, and 0.15g of 1-bromo-2-propyne Suspension having 0.23g of sodium hydride Suspended in 10 was added, followed by stirring at room temperature for 1 mL of dimethylformamide, and after completion of the drop hour. Then, the reaction mixture was poured into water, wise addition, stirring was carried out at room temperature for extraction with ethyl acetate was carried out, and after wash 30minutes. The reaction solution was cooled with ice again, ing with water, the organic layer was dried over anhydrous and 0.72 g of 1-bromo-2-propyne was added, followed by 60 magnesium sulfate. The solvent was distilled off under stirring at room temperature for 1 hour. Then, the reaction reduced pressure, the obtained residue was dissolved in 20 mixture was poured into water, extraction with ethyl acetate mL of ethanol, and 20 mL of a 35mass % hydrochloric acid was carried out, and after washing with water, the organic aqueous solution was added, followed by stirring under reflux layer was dried over anhydrous magnesium Sulfate. The Sol with heating for 2 hours. The reaction mixture was poured vent was distilled off under reduced pressure, the obtained 65 into water, extraction with ethyl acetate was carried out, and residue was dissolved in 20 mL of ethanol, and 20 mL of a 35 after washing with water, the organic layer was dried over mass % hydrochloric acid aqueous solution was added, fol anhydrous magnesium sulfate. The solvent was distilled off US 8,802,713 B2 137 138 under reduced pressure, and the obtained residue was purified pyrazole was dissolved in 10 mL of chloroform, and 90mg of by column chromatography (developing solvent ethyl m-chloroperbenzoic acid (purity: 75%) was added under acetate:hexane=1:4) to obtain 0.3 g of 1-2-fluoro-4-methyl cooling with ice. After stirring for 1 hour under cooling with 5-(2,2,2-trifluoroethylthio)phenyl-5-(2-propynylamino)-3- ice, the Solution was washed with an aqueous Sodium thio {1,1,2-trifluoro-2-(heptafluoropropoxy)ethoxypyrazole. 5 Sulfate solution and then washed with an aqueous Sodium 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.30 (1H, t), hydrogen carbonate solution, and then dried over anhydrous 2.51 (3H, s), 3.68 (2H, q), 3.87 (2H, s), 3.87 (1H, s), 5.52(1H, sodium sulfate. The solvent was distilled off under reduced s), 6.13-6.33 (1H, m), 7.14 (1H, d), 7.61 (1H, d) pressure to obtain 0.16 g of 5-chloro 1-2-fluoro-4-methyl Example 28 5-(2,2,2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2,3,3,3- 10 hexafluoropropoxy)pyrazole. Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.47 (3H, s), roethylsulfinyl)phenyl-5-(2-propynylamino)-3-(1,1, 2-trifluoro-2-(heptafluoropropoxy)ethoxypyrazole 3.31-3.59 (2H, m), 5.01-5.19 (1H, m), 6.27 (1H, s), 7.21 (1H, (compound No. 1-358 of the present invention) d), 8.10 (1H, d) 15 0.17 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth Example 31 ylthio)phenyl-5-(2-propynylamino)-3-1,1,2-trifluoro-2- (heptafluoropropoxy)ethoxypyrazole was dissolved in 10 Preparation of 5-acetylamino-1-(2-fluoro-4-methyl mL of chloroform, and 80 mg of m-chloroperbenzoic acid 5-(2.2.2-trifluoroethylthio)phenyl)-3-1,1,2-trif. (purity: 75%) was added under cooling with ice. After stirring 20 luoro-2-(heptafluoropropoxy)ethoxypyrazole (com for one hour under cooling with ice, the solution was washed pound No. 1-370 of the present invention) 5.0 g of with an aqueous sodium thiosulfate Solution and then washed 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo with an aqueous sodium hydrogen carbonate solution, and roethylthio)phenyl)-3-hydroxypyrazole was dis then dried over anhydrous sodium sulfate. The solvent was solved in 40 mL of dimethylformamide, 27.8g of distilled off under reduced pressure, and the obtained residue was purified by column chromatography (developing solvent 25 triethylamine was added, and stirring was carried out ethyl acetate:hexane=1:2) to obtain 0.13 g of 1-2-fluoro-4- at 60° C. for 4 hours while heptafluoropropyl trifluo methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-5-(2-propy rovinyl ether was blown. The reaction mixture was nylamino)-3-(1,1,2-trifluoro-2-(heptafluoropropoxy) poured into water, extraction with ethyl acetate was ethoxypyrazole. carried out, and after washing with water, the organic 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.30 (1H, s), '' layer was dried over anhydrous magnesium sulfate. 2.45 (3H, s), 3.38-3.59 (2H, m), 3.87 (2H, s), 3.87 (1H, s), Then, the solvent was distilled off under reduced 6.13-6.27 (1H, m), 7.18 (1H, d), 8.11 (1H, d) pressure, and the obtained residue was purified by column chromatography (developing solvent ethyl Example 29 acetate:hexane=1:2) to obtain 1.56 g of 5-acety 35 lamino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroeth Preparation of 5-chloro-1-(2-fluoro-4-methyl-5-(2.2, ylthio)phenyl-3-1,1,2-trifluoro-2-(heptafluoropro 2-trifluoroethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluo poxy)ethoxypyrazole. ropropoxy)pyrazole (compound No. 1-253 of the present invention) H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.10 (3H, s), 40 2.54 (3H, s), 3.40 (2H, q), 6.21 (1H, dt), 6.49 (1H, s), 7.14 1.09 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo (1H, brs), 7.18 (1H, d), 7.61 (1H, d) roethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluoropropoxy) pyrazole was dissolved in 30 mL of acetonitrile, 0.31 g of Example 32 copper(II) chloride was added, and 0.4 g of tert-butyl nitrite was dropwise added at -20°C., followed by stirring at -20° 45 Preparation of 5-acetylamino-1-(2-fluoro-4-methyl C. for 2 hours. The reaction mixture was poured into water, 5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-1,1,2- extraction with ethyl acetate was carried out, and after wash trifluoro-2-(heptafluoropropoxy)ethoxypyrazole ing with water, the organic layer was dried over anhydrous (compound No. 1-371 of the present invention) magnesium sulfate. Then, the solvent was distilled off under reduced pressure, and the obtained residue was purified by 50 0.45 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2- column chromatography (developing solvent ethyl acetate: trifluoroethylthio)phenyl-3-1,1,2-trifluoro-2-(heptafluo hexane=1:40) to obtain 0.23 g of 5-chloro-1-(2-fluoro-4- ropropoxy)ethoxypyrazole was dissolved in 10 mL of chlo methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(1,1,2,3,3,3- roform, and 1.6 g of m-chloroperbenzoic acid (purity: 75%) hexafluoropropoxy)pyrazole. was added under cooling with ice. After stirring for 30 min H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.54 (3H, s), 55 utes under cooling with ice, the Solution was washed with an 3.37 (2H, q), 5.02-5.18 (1H, m), 6.24 (1H, s), 7.15 (1H, d), aqueous sodium thiosulfate solution and then washed with an 7.60 (1H, d) aqueous sodium hydrogen carbonate Solution, and then dried over anhydrous sodium sulfate. Then, the solvent was dis Example 30 tilled off under reduced pressure, and the obtained residue 60 was purified by column chromatography (developing solvent Preparation of 5-chloro 1-2-fluoro-4-methyl-5-(2.2, ethyl acetate:hexane=1:1) to obtain 0.41 g of 5-acetylamino 2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2,3,3,3- 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phe hexafluoropropoxy)pyrazole (compound No. 1-254 nyl-3-1,1,2-trifluoro-2-(heptafluoropropoxy) of the present invention) ethoxypyrazole. 65 H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.09 (3H, s), 0.15 g of 5-chloro 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 2.47 (3H, s), 3.40-3.61 (2H, m), 6.19 (1H, dt), 6.45 (1H, s), roethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluoropropoxy) 7.21 (1H, d), 7.55 (1H, brs), 8.07 (1H, d) US 8,802,713 B2 139 140 Example 33 ture for 2 hours. The formed crystals were collected by filtra tion and washed with water to obtain 10.0 g of 2-fluoro-4- Preparation of 5-acetylamino-3-2,2-difluoro-2-(2- methyl-5-methylthioaniline. trifluoromethoxy-(1,1,2,2-tetrafluoroethoxy) Then, a solution of 9.2 g of the obtained 2-fluoro-4-methyl ethoxy)-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroeth 5-methylthioaniline in 10 mL of acetic acid was dropwise ylthio)phenylpyrazole (compound No. 1-374 of the added to a mixed solution comprising 32 g of concentrated present invention) Sulfuric acid, 4.1 g of sodium nitrite and 15 mL of acetic acid at 5° C. or below over a period of 15 minutes, followed by 0.5g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri stirring at 5° C. or below for 3 hours. This reaction mixture 10 was dropwise added to a mixed solution comprising 20.2 g of fluoroethylthio)phenyl)-3-hydroxypyrazole was dissolved in tin(II) chloride dihydrate and 100 mL of a 6N hydrochloric 10 mL of dimethylsulfoxide, and 0.28g of potassium carbon acid aqueous solution at 5°C. or below, followed by stirring ate and 1.0 g of 2,2-difluoro-2-(2-trifluoromethoxy-(1,1,2,2- for 30 minutes. To this reaction mixture, 20 mL oftoluene was tetrafluoroethoxy)ethyl nonafluorobutylsulfonate were added, followed by neutralized with a 10% sodium hydroxide added, followed by stirring at room temperature for 12 hours. 15 aqueous solution. Insoluble matters were separated by filtra After completion of the reaction, the reaction solution was tion, and the organic layer was dried over anhydrous magne poured into water, extraction with ethyl acetate was carried sium sulfate and concentrated under reduced pressure to out, and after washing with a saturated Salt solution, the obtain 6.2 g of 2-fluoro-4-methyl-5-methylthiophenylhydra organic layer was dried over anhydrous magnesium Sulfate, Z10. the solvent was distilled off under reduced pressure, and the Then, the obtained hydrazine derivative was dissolved in obtained residue was purified by column chromatography 50 mL of tetrahydrofuran, and to this solution, 5.1 g of (ethyl acetate:hexane=1:4) to obtain 0.67g of 5-acetylamino cyanoacetylchloride was added, followed by stirring at room 3-2,2-difluoro-2-(2-trifluoromethoxy-(1,1,2,2-tetrafluoro temperature for 2 hours. Then, the solvent was distilled off ethoxy)}ethoxy)-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroet under reduced pressure, the residue was dissolved in 50 mL of hylthio)phenylpyrazole. 25 1-propanol, and 3.1 g of methanesulfonic acid was added, 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.08 (3H, s), followed by reflux with heating for 3 hours. After cooling to 2.53 (3H, s), 3.39 (2H, q), 4.60 (2H, t), 6.22(1H, s), 7.05 (1H, room temperature, the solvent was distilled offunder reduced brs), 7.16 (1H, d), 7.59 (1H, d) pressure, followed by neutralization with sodium hydrogen carbonate to a pH of 7, and extraction with ethyl acetate was Example 34 30 carried out. The organic layer was dried over anhydrous mag nesium sulfate, and the solvent was distilled off under Preparation of 5-acetylamino-3-2,2-difluoro-2-(2- reduced pressure to obtain 5.5 g of 5-amino-1-(2-fluoro-4- trifluoromethoxy-(1,1,2,2-tetrafluoroethoxy) methyl-5-methylthiophenyl)-3-hydroxypyrazole in the form ethoxy)-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroeth of yellow crystals (melting point: 230-232C.). ylsulfinyl)phenylpyrazole (compound No. 1-375) 35 Then, the obtained pyrazole derivative was dissolved in 50 mL of toluene, and to this solution, 6.0 g of acetyl chloride 0.42 g of 5-acetylamino-3-2,2-difluoro-2-(2-trifluo was added, followed by reflux with heating for 12 hours. After romethoxy-(1,1,2,2-tetrafluoroethoxy)-1-(2-fluoro-4-me cooling to room temperature, the solvent was distilled off thyl-5-(2.2.2-trifluoroethylthio)phenylpyrazole was dis under reduced pressure, the residue was dissolved in 30 mL of solved in 10 mL of chloroform, and 0.15 g of 40 ethanol, and 20 mL of a 25mass % ammonia water was added, m-chloroperbenzoic acid (purity: 75%) was added under followed by stirring at room temperature for 30minutes. The cooling with ice. After stirring for 30 minutes under cooling solvent was distilled off under reduced pressure, and the with ice, the solution was washed with an aqueous sodium obtained solid was washed with diisopropyl ether to obtain thiosulfate Solution and then washed with an aqueous sodium 5.2 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-methylth hydrogen carbonate solution, and then dried over anhydrous 45 iophenyl)-3-hydroxypyrazole in the form of paleyellow crys sodium sulfate. Then, the solvent was distilled off under tals (melting point: 204-205° C.). reduced pressure, and the obtained residue was purified by Then, 5.0 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-me column chromatography (developing solvent ethyl acetate: thylthiophenyl)-3-hydroxypyrazole was dissolved in 100 mL hexane=1:1) to obtain 0.43 g of 5-acetylamino-3-2,2-dif of dimethylsulfoxide, and 2.1 g of potassium carbonate was luoro-2-(2-trifluoromethoxy-(1,1,2,2-tetrafluoroethoxy) 50 added, followed by stirring at room temperature for 5 min ethoxy)-1-(2-fluoro-4-methyl-5-(2.2.2- utes. To this solution, 6.2 g of 2.2.3,3,3-pentafluoropropyl trifluoroethylsulfinyl)phenylpyrazole. nonafluorobutanesulfonate was added, followed by stirring at H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.08 (3H, s), room temperature for 12 hours. Then, extraction with ethyl 2.46 (3H, s), 3.41.-3.60 (2H, m), 4.61 (2H, t), 6.19 (1H, s), acetate was carried out, the organic layer was dried over 7.20 (1H, d), 7.30 (1H, brs), 8.07 (1H, d) 55 anhydrous magnesium Sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was purified Example 35 by silica gel column chromatography (developing solvent ethyl acetate:hexane=1:4) to obtain 5.1 g of 5-acetylamino Preparation of 5-acetylamino-1-(2-fluoro-4-methyl 1-(2-fluoro-4-methyl-5-methylthiophenyl)-3-(2,2,3,3,3- 5-(2-chloro-2,2-difluoroethylthio)phenyl)-3-(2,2,3,3, 60 pentafluoropropoxy)pyrazole ('H-NMR (CDCL/TMS 8 3-pentafluoropropoxy)pyrazole (compound No. (ppm) value) 8: 2.13 (3H, s), 2.37 (3H, s), 2.47 (3H, s), 4.67 1-177 of the present invention) (2H, t), 6.22 (1H, s), 7.07 (1H, d), 7.14 (1H, brs), 7.17 (1H, d)). 9.2 g of 2-fluoro-4-methyl-5-mercaptoaniline disclosed in Then, 5.0 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-me WO2006/043635 was dissolved in 70 mL of water, and 9.7g 65 thylthiophenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole of potassium carbonate and 8.3 g of iodomethane were added was dissolved in 150 mL of chloroform, and 3.4 g of m-chlo under cooling with ice, followed by stirring at room tempera roperbenzoic acid (purity: 75%) was added under cooling US 8,802,713 B2 141 142 with ice. After stirring for 30 minutes under cooling with ice, H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.05 (3H, d), the Solution was washed with an aqueous Sodium thiosulfate 2.43 (3H, s), 3.41-3.51 (2H, m), 4.65 (2H, t), 6.14 (1H, s), Solution and then washed with an aqueous potassium carbon 7.18 (1H, d), 7.68 (1H, brs), 8.01 (1H, d) ate Solution, and then dried over anhydrous magnesium Sul fate. Then, the solvent was distilled off under reduced pres Example 37 Sure, and the obtained residue was purified by silica gel column chromatography (developing solvent ethyl acetate: Preparation of 5-acetylamino-1-(2-fluoro-4-methyl hexane=1:2) to obtain 4.7 g of 5-acetylamino-1-(2-fluoro-4- 5-(2.2.2-trifluoroethylthio)phenyl)-3-(1,1,2,2-tet methyl-5-methylsulfinylphenyl)-3-(2,2,3,3,3-pentafluoro rafluoroethoxy)pyrazole (compound No. 1-1367 of propoxy)pyrazole (H-NMR (CDCL/TMSö (ppm) value) 8: 10 the present invention) 2.09 (3H, s), 2.43 (3H, s), 2.74 (3H, s), 4.66 (2H, t), 6.21 (1H, s), 7.15 (1H, d), 7.45 (1H, brs), 8.02 (1H, d)). 1.0 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri Then, 4.5g of 5-acetylamino-1-(2-fluoro-4-methyl-5-me fluoroethylthio)phenyl)-3-hydroxypyrazole was dissolved in thylsulfinylphenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyra 50 mL of dimethylformamide, and 0.04 g of potassium car 15 bonate was added, followed by stirring at 90° C. Further, 1.5 Zole was dissolved in 200 mL of acetic anhydride, followed g of a cadmium powder was added to 50 mL of acetonitrile, by stirring at 120° C. for 6 hours. Acetic anhydride was 4.9 g of tetrafluoro-1,2-diiodoethane was dropwise added distilled off under reduced pressure, the obtained residue was under reflux with heating to form tetrafluoroethylene, which dissolved in 150 mL of ethanol, and 4.0 g of potassium was blown at 90° C. for one hour. Then, extraction with ethyl carbonate was added, followed by stirring at room tempera acetate was carried out, the organic layer was dried over ture for 12hours. Neutralization with a 6N hydrochloric acid anhydrous magnesium Sulfate, the solvent was distilled off aqueous solution was carried out, and extraction with ethyl under reduced pressure, and the obtained residue was purified acetate was carried out. The organic layer was dried over by column chromatography (developing solvent ethyl anhydrous magnesium sulfate, the solvent was distilled off acetate:hexane=1:4) to obtain 0.4 g of 5-acetylamino-1-(2- under reduced pressure, and the obtained residue was purified 25 fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(1,1, by silica gel column chromatography (developing solvent 2.2-tetrafluoroethoxy)pyrazole. ethyl acetate:hexane=1:4) to obtain 3.8 g of 5-acetylamino H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.06 (3H, s), 1-(2-fluoro-4-methyl-5-mercaptophenyl)-3-(2,2,3,3,3-pen 2.52 (1H, s), 3.40 (2H, q), 5.85-6.12 (1H, m), 6.45 (1H, s), tafluoropropoxy)pyrazole ("H-NMR (CDCL/TMS 8 (ppm) 7.15 (1H, d), 7.45 (1H, s), 7.60 (1H, d) value) 8: 2.09 (3H, s), 2.38 (3H, s), 3.39 (1H, s), 4.66 (2H, t), 30 6.20 (1H, s), 7.09 (1H, d), 7.14 (1H, brs), 7.39 (1H, d)). Example 38 Then, 1.5g of 5-acetylamino-1-(2-fluoro-4-methyl-5-mer captophenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole was Preparation of 5-acetylamino-1-(2-fluoro-4-methyl dissolved in 20 mL of dimethylformamide, and 0.32 g of 5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2,2- sodium carbonate and 1.5 g of 2-chloro-2,2-difluoroethyl 35 tetrafluoroethoxy)pyrazole (compound No. 1-1368 nonafluorobutanesulfonate were added, followed by stirring of the present invention) at room temperature for 12hours. Then, extraction with ethyl acetate was carried out, the organic layer was dried over 0.4 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri anhydrous magnesium sulfate, the solvent was distilled off fluoroethylthio)phenyl)-3-(1,1,2,2-tetrafluoroethoxy)pyra under reduced pressure, the obtained residue was purified by 40 Zole was dissolved in 10 mL of chloroform, and 0.2 g of silica gel column chromatography (developing solvent ethyl m-chloroperbenzoic acid (purity: 75%) was added under acetate:hexane=1:4) to obtain 1.3 g of 5-acetylamino-1-(2- cooling with ice. After stirring for 30 minutes under cooling fluoro-4-methyl-5-(2-chloro-2,2-difluoroethylthio)phenyl with ice, the solution was washed with an aqueous Sodium 3-(2,2,3,3,3-pentafluoropropoxy)pyrazole. thiosulfate Solution and then washed with an aqueous potas 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.08 (3H, s), 45 sium carbonate solution, and then dried over anhydrous mag 2.53 (3H, s), 3.62 (2H, t), 4.66 (2H, t), 6.21 (1H, s), 7.07 (1H, nesium sulfate. Then, the solvent was distilled off under brs), 7.15 (1H, d), 7.60 (1H, d) reduced pressure, and the obtained residue was purified by column chromatography (developing solvent ethyl acetate: Example 36 hexane=1:2) to obtain 0.3 g of 5-acetylamino-1-(2-fluoro-4- 50 methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2,2- Preparation of 5-acetylamino-1-(2-fluoro-4-methyl tetrafluoroethoxy)pyrazole. 5-(2-chloro-2,2-difluoroethylsulfinyl)phenyl)-3-(2.2, 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.07 (3H, s), 3.3.3-pentafluoropropoxy)pyrazole (compound No. 2.45 (3H, s), 3.37-3.59 (2H, m), 5.99 (1H, t), 6.44 (1H, s), 1-178 of the present invention) 7.20 (1H, d), 7.76 (1H, brs), 8.04 (1H, d) 55 0.6 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2-chloro Example 39 2,2-difluoroethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropro poxy)pyrazole was dissolved in 20mL of chloroform, and 0.3 Preparation of 5-amino-4-chloro-1-(2-fluoro-4-me g of m-chloroperbenzoic acid (purity: 75%) was added under thyl-5-(2,2,2-trifluoroethylthio)phenyl)-3-(1,1,2,3,3, cooling with ice. After stirring for 30 minutes under cooling 60 3-hexafluoropropoxy)pyrazole (compound No. 1-263 with ice, the solution was washed with an aqueous sodium of the present invention) thiosulfate Solution and then washed with an aqueous potas sium carbonate Solution, and dried over anhydrous magne 2.9 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoro sium sulfate. Then, the solvent was distilled offunder reduced ethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluoropropoxy)pyra pressure, the obtained residue was purified by Silica gel col 65 Zole was dissolved in 30 mL of acetonitrile, and 0.9g of umn chromatography (developing solvent ethyl acetate:hex N-chlorosuccinimide was added under cooling with ice. After ane=1:2) to obtain 0.6 g of the title compound. stirring for 30minutes under cooling with ice, the solvent was US 8,802,713 B2 143 144 distilled off under reduced pressure, extraction with ethyl pressure, the obtained residue was dissolved in 10 mL of acetate was carried out, and the organic layer was dried over ethanol, and 10 mL of a 35 mass % hydrochloric acid aqueous anhydrous magnesium Sulfate. Then, the solvent was distilled solution was added, followed by stirring under reflux with off under reduced pressure, and the obtained residue was heating for one hour. The reaction mixture was poured into purified by column chromatography (developing solvent water, extraction with ethyl acetate was carried out, and after ethyl acetate:hexane=1:4) to obtain 3.12 g of 5-amino-4- washing with water, the organic layer was dried over anhy chloro-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) drous magnesium sulfate. Then, the solvent was distilled off phenyl)-3-(1,1,2,3,3,3-hexafluoropropoxy)pyrazole. under reduced pressure, and the obtained residue was purified H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.53 (3H, s), by column chromatography (developing solvent ethyl 3.39 (2H, q), 3.95 (2H, brs), 5.22 (1H, dd), 7.15 (1H, d), 7.62 10 acetate:hexane=1:4) to obtain 0.34g of 4-chloro-1-(2-fluoro (1H, d) 4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(1,1,2,3,3,3- hexafluoropropoxy)-5-methylaminopyrazole. Example 40 H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.53 (3H, s), Preparation of 5-amino-4-chloro 1-2-fluoro-4-me 15 2.91 (3H, d), 3.38 (2H, q), 3.51 (1H, brs), 5.22(1H, dd), 7.14 thyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2, (1H, d), 7.59 (1H, d) 3,3,3-hexafluoropropoxy)pyrazole (compound No. 1-264 of the present invention) Example 42 0.3 g of 4-chloro-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoro Preparation of 4-chloro-1-(2-fluoro-4-methyl-5-(2.2, ethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluoropropoxy)-5- 2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2,3,3,3- aminopyrazole was dissolved in 10 mL of chloroform, and hexafluoropropoxy)-5-methylaminopyrazole (com 140 mg of m-chloroperbenzoic acid (purity: 75%) was added pound No. 1-262 of the present invention) under cooling with ice. After stirring for one hour under cooling with ice, the Solution was washed with an aqueous 25 0.24 g of 4-chloro-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo Sodium thiosulfate Solution and then washed with an aqueous roethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluoropropoxy)-5- Sodium hydrogen carbonate solution, and then dried over methylaminopyrazole was dissolved in 10 mL of chloroform, anhydrous sodium sulfate. Then, the solvent was distilled off and 120 mg of m-chloroperbenzoic acid (purity: 75%) was under reduced pressure, and the obtained residue was purified added under cooling with ice. After stirring for one hour by column chromatography (developing solvent ethyl 30 under cooling with ice, the solution was washed with an acetate:hexane=1:2) to obtain 0.24 g of 5-amino-4-chloro aqueous sodium thiosulfate solution and then washed with an 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phe aqueous sodium hydrogen carbonate Solution, and then dried nyl)-3-(1,1,2,3,3,3-hexafluoropropoxy)pyrazole. over anhydrous sodium sulfate. Then, the solvent was dis H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.47 (3H, s), tilled off under reduced pressure, and the obtained residue 3.39-3.61 (2H, m), 3.96 (2H, brs), 5.20(1H, dd), 7.21 (1H, d), 35 was purified by column chromatography (developing solvent 8.13 (1H, d) ethyl acetate:hexane=1:2) to obtain 0.24 g of 4-chloro-1-(2- fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-3- Example 41 (1,1,2,3,3,3-hexafluoropropoxy)-5-methylaminopyrazole. Preparation of 4-chloro-1-(2-fluoro-4-methyl-5-(2.2, 40 H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.46 (3H, s), 2-trifluoroethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluo 2.90 (3H, s), 3.39-3.60 (2H, m), 5.20 (1H, dd), 7.19 (1H, d), ropropoxy)-5-methylaminopyrazole (compound No. 8.10 (1H, d) 1-261 of the present invention) Example 43 0.8g of 5-amino-4-chloro-1-(2-fluoro-4-methyl-5-(2.2.2- 45 trifluoroethylthio)phenyl)-3-(1,1,2,3,3,3-hexafluoropro Preparation of 5-acetylamino-1-(2-fluoro-4-methyl poxy)pyrazole was dissolved in 20 mL of acetic anhydride. 5-(2.2.2-trifluoroethylthio)phenyl)-3-(2.2.3.3.4.4.5, After stirring for 3 hours under reflux with heating, acetic 5.5-nonafluoropentyloxy)pyrazole (compound No. anhydride was distilled off under reduced pressure, the 1-77 of the present invention) obtained residue was dissolved in 20 mL of tetrahydrofuran, 50 and 20 mL of a 25 mass % ammonia water was added under 0.5g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri cooling with ice. After stirring for one hour under cooling fluoroethylthio)phenyl)-3-hydroxypyrazole was dissolved in with ice, the solvent was distilled off under reduced pressure, 10 mL of dimethylsulfoxide, and 0.23g of potassium carbon extraction with ethyl acetate was carried out, and the organic ate was added, followed by stirring at room temperature for 5 layer was dried over anhydrous magnesium Sulfate. Then, the 55 minutes. To this solution, 0.79 g of 2.2.3,3,3-pentafluoropro solvent was distilled off under reduced pressure, the obtained pyl nonafluorobutanesulfonate was added, followed by stir residue was dissolved in 5 mL of dimethylformamide, and the ring at room temperature for 12 hours. Then, extraction with Solution was dropwise added to a suspension having 50 mg of ethyl acetate was carried out, the organic layer was dried over sodium hydride suspended in 10 mL of dimethylformamide anhydrous magnesium Sulfate, the solvent was distilled off under cooling with ice. After completion of the dropwise 60 under reduced pressure, and the obtained residue was purified addition, stirring was carried out at room temperature for 30 by column chromatography (developing solvent ethyl minutes. The reaction Solution was cooled with ice again, and acetate:hexane=1:4) to obtain 0.55g of 5-acetylamino-1-(2- 0.18 g of methyl iodide was added, followed by stirring at fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(2.2, room temperature for one hour. Water was injected, extraction 3.3.4.4.5.5.5-nonafluoropentyloxy)pyrazole. with ethyl acetate was carried out, and after washing with 65 H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.09 (3H, s), water, the organic layer was dried over anhydrous magnesium 2.53 (3H, s), 3.40 (2H, q), 4.72 (2H, t), 6.22(1H, s), 7.03 (1H, sulfate. Then, the solvent was distilled off under reduced brs), 7.16 (1H, d), 7.60 (1H, d) US 8,802,713 B2 145 146 Example 44 under reduced pressure to obtain 0.90 g of 1-2-fluoro-4- methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(2,2,3,3,3- Preparation of 5-acetylamino-1-(2-fluoro-4-methyl pentafluoropropoxy)pyrazole-5-carboxylic acid. 5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-(2,2,3,3,4, 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.54 (3H, s), 4.5.5.5-nonafluoropentyloxy)pyrazole (compound 3.36 (2H, q), 4.70 (2H, t), 6.58 (1H, s), 7.08 (1H, d), 7.59 (1H, No. 1-78 of the present invention) d) 0.2 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri fluoroethylthio)phenyl)-3-(2.2.3.3.4.4.5.5.5-nonafluoro Example 47 pentyloxy)pyrazole was dissolved in 10 mL of chloroform, 10 and 77 mg of m-chloroperbenzoic acid (purity: 75%) was Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo added under cooling with ice. After stirring for 30 minutes roethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropro under cooling with ice, the solution was washed with an poxy)pyrazole-5-carboxyamide (compound No. aqueous Sodium thiosulfate solution and then washed with an aqueous potassium carbonate solution, and then dried over 15 1-139 of the present invention) anhydrous magnesium Sulfate. Then, the solvent was distilled off under reduced pressure, and the obtained residue was 0.84 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth purified by column chromatography (developing solvent ylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole ethyl acetate:hexane=1:2) to obtain 0.19 g of 5-acetylamino 5-carboxylic acid was dissolved in 10 mL of dichlo 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phe romethane, and 0.2 mL of oxalyl dichloride and N,N- nyl)-3-(2.2.3.3.4.4.5.5.5-nonafluoropentyloxy)pyrazole. dimethylformamide in a catalytic amount were added, 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.08 (3H, s), followed by stirring at room temperature for 1 hour. Then, the 2.46 (3H, s), 3.41-3.54 (2H, m), 4.72 (2H, t), 6.19 (1H, s), solvent was distilled off under reduced pressure, and the 7.20 (1H, d), 7.24 (1H, brs), 8.08 (1H, d) resulting product was dissolved in 10 mL of tetrahydrofuran, 25 and the Solution was dropwise added to a mixed solution Example 45 comprising 30 mL of a 25 mass % ammonia water and 40 mL of tetrahydrofuran at -30°C. Then, stirring was carried out Preparation of ethyl 1-2-fluoro-4-methyl-5-(2.2.2- for 12 hours while the temperature was slowly increased to trifluoroethylthio)phenyl)-3-(2,2,3,3,3-pentafluoro room temperature. Then, the solvent was distilled off under propoxy)pyrazole-5-carboxylate (compound No. 30 reduced pressure, extraction with ethyl acetate was carried 1-143 of the present invention) out, the organic layer was dried over anhydrous sodium Sul fate, the solvent was distilled off under reduced pressure, and 1.0 g of ethyl 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth the obtained residue was purified by column chromatography ylthio)phenyl)-3-hydroxypyrazole-5-carboxylate was dis (developing solvent ethyl acetate:hexane=1:3) to obtain 0.80 solved in 20 mL of dimethylsulfoxide, and 0.47g of potas 35 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phe sium carbonate was added, followed by stirring at room nyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole-5-carboxya temperature for 5 minutes. To this solution, 1.14 g of 2.2.3.3. mide. 3-pentafluoropropyl nonafluorobutanesulfonate was added, H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.51 (3H, s), followed by stirring at room temperature for 12hours. Extrac 3.38 (2H, q), 4.71 (2H, t), 5.57 (1H, br), 5.80 (1H, br), 6.25 tion with ethyl acetate was carried out, the organic layer was 40 (1H, s), 7.07 (1H, d), 7.63 (1H, d) dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (developing solvent Example 48 ethyl acetate:hexane=1:4) to obtain 1.1 g of ethyl 1-2- fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(2.2, 45 Preparation of 5-cyano-1-(2-fluoro-4-methyl-5-(2.2, 3,3,3-pentafluoropropoxy)pyrazole-5-carboxylate. 2-trifluoroethylthio)phenyl)-3-(2,2,3,3,3-pentafluo 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 1.25 (3H, t), ropropoxy)pyrazole (compound No. 1-133 of the 2.53 (3H, s), 3.37 (2H, q), 4.24 (2H, q), 4.70 (2H, t), 6.51 (1H, present invention) s), 7.09 (1H, d), 7.60 (1H, d) 50 0.80 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth Example 46 ylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 5-carboxyamide was dissolved in 20 mL of tetrahydrofuran, roethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropro 0.42 g of triethylamine was added, and 0.52g of trifluoroace poxy)pyrazole-5-carboxylic acid (compound No. 55 tic anhydride was slowly dropwise added under cooling with 1-145 of the present invention) ice. After stirring at room temperature for 2 hours, the solvent was distilled off under reduced pressure, and extraction with 0.95 g of ethyl 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroet ethyl acetate was carried out. The organic layer was dried over hylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole anhydrous magnesium Sulfate, the solvent was distilled off 5-carboxylate was dissolved in 20 mL of ethanol. To this 60 under reduced pressure, and the obtained residue was purified Solution, a solution having 0.42 g of potassium hydroxide by column chromatography (developing solvent ethyl dissolved in 10 mL of water was added, followed by stirring acetate:hexane=1:4) to obtain 0.60 g of 5-cyano-1-(2-fluoro at room temperature for 30 minutes. Concentrated hydrochlo 4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(2,2,3,3,3- ric acid was added to adjust the pH to 2, the solvent was pentafluoropropoxy)pyrazole. distilled off under reduced pressure, extraction with ethyl 65 H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.56 (3H, s), acetate was carried out, and the organic layer was dried over 3.40 (2H, q), 4.74 (2H, t), 6.52(1H, s), 7.21 (1H,d), 7.65 (1H, anhydrous sodium sulfate. Then, the solvent was distilled off d) US 8,802,713 B2 147 148 Example 49 followed by stirring at room temperature for 12 hours. Then, the reaction solution as subjected to filtration, the filtrate was Preparation of 5-cyano-1-(2-fluoro-4-methyl-5-(2.2, distilled under reduced pressure, and the obtained residue was 2-trifluoroethylsulfinyl)phenyl)-3-(2,2,3,3,3-pen purified by column chromatography (developing solvent tafluoropropoxy)pyrazole (compound No. 1-134 of 5 ethyl acetate:hexane=1:4) to obtain 1.02 g of 1-2-fluoro-4- the present invention) methyl-5-(2.2.2-trifluoroethylthio)phenyl-5-formyl-3-(2.2, 3.3.3-pentafluoropropoxy)pyrazole. 0.40 g of 5-cyano-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.55 (3H, s), roethylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyra 3.38 (2H, q), 4.73 (2H, t), 6.56(1H, s), 7.14 (1H,d), 7.63 (1H, Zole was dissolved in 10 mL of chloroform, and 200mg of 10 d) m-chloroperbenzoic acid (purity: 75%) was added under cooling with ice. After stirring for one hour under cooling Example 52 with ice, the solution was washed with an aqueous sodium thiosulfate Solution and then washed with an aqueous sodium Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo hydrogen carbonate solution, and then dried over anhydrous 15 roethylthio)phenyl-5-(hydroxyimino)methylene-3- magnesium sulfate. Then, the solvent was distilled off under (2.2.3,3,3-pentafluoropropoxy)pyrazole (compound reduced pressure, and the obtained residue was purified by No. 1-205 of the present invention) column chromatography (developing solvent ethyl acetate: hexane=1:2) to obtain 0.40 g of 5-cyano-1-(2-fluoro-4-me 0.3 g of 1-2-fluoro-4-methyl-5-(2,2,2-trifluoroethylsulfi thyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-(2,2,3,3,3- nyl)phenyl-5-formyl-3-(2,2,3,3,3-pentafluoropropoxy) pentafluoropropoxy)pyrazole. pyrazole was dissolved in 10 mL of methanol, and 79mg of 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.49 (3H, s), Sodium acetate and 67 mg of hydroxylammonium chloride 3.43-3.58 (2H, m), 4.74 (2H, t), 6.56 (1H, s), 7.27 (1H, d), were added, followed by stirring under reflux with heating for 8.16 (1H, d) 2 hours. Then, the solvent was distilled off under reduced 25 pressure, extraction with ethyl acetate was carried out, the Example 50 organic layer was dried over anhydrous Sodium sulfate, the solvent was distilled off under reduced pressure, and the Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo obtained residue was purified by column chromatography roethylthio)phenyl-5-hydroxymethyl-3-(2,2,3,3,3- (developing solvent ethyl acetate:hexane=1:3) to obtain 0.31 pentafluoropropoxy)pyrazole (compound No. 1-201 30 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phe of the present invention) nyl-5-(hydroxyimino)methylene-3-(2,2,3,3,3-pentafluoro propoxy)pyrazole. 3.97 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth 'H-NMR (CDCL/TMS 8 (ppm) value) 8: (majar) 2.54 ylthio)phenyl)-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole (3H, s), 3.38 (2H, q), 4.69 (2H, t), 6.25 (1H, s), 7.13 (1H, d), 5-carboxylic acid was dissolved in 60 mL of dichlo 35 7.58 (1H, s), 7.58 (1H, d), 7.80 (1H, s) romethane, and 0.93 mL of oxalyl dichloride and N,N- dimethylformamide in a catalytic amount were added, Example 53 followed by stirring at room temperature for 1 hour. Then, the solvent was distilled offunder reduced pressure, the resulting Preparation of 5-cyano-1-(2-fluoro-4-methyl-5-(2.2, product was dissolved in 50 mL of tetrahydrofuran, and 1.56 40 2-trifluoroethylthio)phenyl-3-1,1,2-trifluoro-2- g of sodium borohydride was added, followed by cooling to (trifluoromethoxy)ethoxypyrazole (compound No. -20°C. 20 mL of water was slowly dropwise added, and then, 1-668 of the present invention) stirring was carried out for 12 hours while the temperature was slowly increased to room temperature. Then, the Solvent 1.1 g of ethyl 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth was distilled offunder reduced pressure, extraction with ethyl 45 ylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) acetate was carried out, the organic layer was dried over ethoxypyrazole-5-carboxylate was dissolved in 30 mL of anhydrous sodium sulfate, the solvent was distilled off under toluene, followed by cooling to -78° C., and 2.6 mL of a reduced pressure, and the obtained residue was purified by toluene solution (1.0 mol/L) of diisobutyl aluminum hydride column chromatography (developing solvent ethyl acetate: was slowly dropwise added. After stirring for 3 hours, a hexane=1:2) to obtain 3.01 g of 1-2-fluoro-4-methyl-5-(2, 50 saturated aqueous solution of ammonium chloride was 2.2-trifluoroethylthio)phenyl-5-hydroxymethyl-3-(2,2,3,3, added, extraction with ethyl acetate was carried out, the 3-pentafluoropropoxy)pyrazole. organic layer was dried over anhydrous magnesium sulfate, H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.52 (3H, s), the solvent was distilled off under reduced pressure, and the 3.39 (2H, q), 4.49 (2H, d), 4.67 (2H, t), 6.00 (1H, s), 7.12(1H, obtained residue was purified by column chromatography 55 (developing solvent ethyl acetate:hexane=1:3) to obtain 0.95 d), 7.63 (1H, d) g of 5-formyl-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroeth Example 51 ylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) ethoxypyrazole (H-NMR (CDCL/TMS 8 (ppm) value) 8: Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 2.56 (3H, s), 3.39 (2H, q), 6.05 (1H, dt), 6.85 (1H, s), 7.17 roethylthio)phenyl-5-formyl-3-(2,2,3,3,3-pentafluo 60 (1H, d), 7.66 (1H, d), 9.72 (1H, d)). ropropoxy)pyrazole (compound No. 1-199 of the Then, 0.43 g of 5-formyl-1-(2-fluoro-4-methyl-5-(2.2.2- present invention) trifluoroethylthio)phenyl-3-1,1,2-trifluoro-2-(trifluo romethoxy)ethoxypyrazole was dissolved in 15 mL of 1.5g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfi methanol, and 110 mg of Sodium acetate and 90 mg of nyl)phenyl-5-hydroxymethyl-3-(2,2,3,3,3-pentafluoropro 65 hydroxylammonium chloride were added, followed by stir poxy)pyrazole was dissolved in 30 mL of chloroform and 10 ring under reflux with heating for 2 hours. Then, the solvent mL of methanol, and 3.0 g of manganese dioxide was added, was distilled offunder reduced pressure, extraction with ethyl US 8,802,713 B2 149 150 acetate was carried out, the organic layer was dried over ethyl acetate was carried out, the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under anhydrous magnesium Sulfate, the solvent was distilled off reduced pressure, and the obtained residue was purified by under reduced pressure, and the obtained residue was purified column chromatography (developing solvent ethyl acetate: by column chromatography (developing solvent ethyl acetate:hexane=1:4) to obtain 0.17 g of 1-2-fluoro-4-me hexane=1:3) to obtain 0.29g of 1-2-fluoro-4-methyl-5-(2.2, thyl-5-(2.2.2-trifluoroethylthio)phenyl-5-fluoromethyl-3- 2-trifluoroethylthio)phenyl-5-(hydroxyimino)methylene {1,1,2-trifluoro-2-(trifluoromethoxy)ethoxypyrazole. 3-1,1,2-trifluoro-2-(trifluoromethoxy)ethoxypyrazole 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.54 (3H, s), (H-NMR (CDCL/TMS 8 (ppm) value)6: (majar) 2.55 (3H, 3.38 (2H, q), 5.20 (2H, d), 6.05 (1H, dt), 6.39 (1H, s), 7.16 s), 3.38 (2H, q), 6.05 (1H, dt), 6.54 (1H, s), 7.15 (1H, d), 7.61 (1H, d), 7.63 (1H, d) (1H, d), 7.71 (1H, brs), 7.83 (1H, d)). 10 Then, 0.28 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroet Example 56 hylthio)phenyl-5-(hydroxyimino)methylene-3-1,1,2-trif luoro-2-(trifluoromethoxy)ethoxypyrazole was dissolved in Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 10 mL of tetrahydrofuran, 0.12g of triethylamine was added, roethylsulfinyl)phenyl-5-fluoromethyl-3-1,1,2- and 0.13 g of trifluoroacetic anhydride was slowly dropwise 15 trifluoro-2-(trifluoromethoxy)ethoxypyrazole (com added under cooling with ice. After stirring at room tempera pound No. 1-1580 of the present invention) ture for 2 hours, the solvent was distilled off under reduced pressure, and extraction with ethyl acetate was carried out. 0.17 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth The organic layer was dried over anhydrous magnesium Sul ylthio)phenyl-5-fluoromethyl-3-1,1,2-trifluoro-2-(trifluo fate, the solvent was distilled off under reduced pressure, and romethoxy)ethoxypyrazole was dissolved in 10 mL of chlo the obtained residue was purified by column chromatography roform, and 78 mg of m-chloroperbenzoic acid (purity: 75%) (developing solvent ethyl acetate:hexane=1:4) to obtain 0.28 was added under cooling with ice. After stirring for one hour g of 5-cyano-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroeth under cooling with ice, the solution was washed with an aqueous sodium thiosulfate solution and then washed with an ylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) aqueous sodium hydrogen carbonate Solution, and then dried ethoxypyrazole. 25 over anhydrous magnesium sulfate. Then, the solvent was 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.57 (3H, s), distilled off under reduced pressure, and the obtained residue 3.40 (2H, q), 6.05 (1H, dt), 6.79 (1H, s), 7.23 (1H, d), 7.68 was purified by column chromatography (developing solvent (1H, d) ethyl acetate:hexane=1:2) to obtain 0.12 g of 1-2-fluoro-4- methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-5-fluorom Example 54 30 ethyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) ethoxypyrazole. Preparation of 5-cyano-1-(2-fluoro-4-methyl-5-(2.2, H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.48 (3H, s), 2-trifluoroethylsulfinyl)phenyl-3-1,1,2-trifluoro-2- 3.40-3.58 (2H, m), 5.24 (2H, d), 6.04 (1H, dt), 6.40 (1H, s), (trifluoromethoxy)ethoxypyrazole (compound No. 7.21 (1H, d), 8.13 (1H, d) 1-669 of the present invention) 35 Example 57 0.19 g of 5-cyano-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo roethylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) Preparation of 5-difluoromethyl-1-(2-fluoro-4-me ethoxypyrazole was dissolved in 10 mL of chloroform, and thyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-1,1,2- 88 mg of m-chloroperbenzoic acid (purity: 75%) was added 40 trifluoro-2-(trifluoromethoxy)ethoxypyrazole (com under cooling with ice. After stirring for one hour under pound No. 1-1531 of the present invention) cooling with ice, the Solution was washed with an aqueous 0.50 g of 5-formyl-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo Sodium thiosulfate Solution and then washed with an aqueous roethylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) Sodium hydrogen carbonate solution, and then dried over ethoxypyrazole was dissolved in 15 mL ofdichloromethane, anhydrous magnesium Sulfate. Then, the solvent was distilled 45 and 0.65 g of diethylaminosulfur trifluoride was dropwise off under reduced pressure, and the obtained residue was added under cooling with ice, followed by stirring at room purified by column chromatography (developing solvent temperature for 12 hours. Extraction with ethyl acetate was ethyl acetate:hexane=1:1) to obtain 0.16 g of 5-cyano-1-(2- carried out, the organic layer was dried over anhydrous mag fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-3- nesium sulfate, the solvent was distilled off under reduced {1,1,2-trifluoro-2-(trifluoromethoxy)ethoxypyrazole. 50 pressure, and the obtained residue was purified by column H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.50 (3H, s), chromatography (developing solvent ethylacetate:hexane-1: 3.43-3.57 (2H, m), 6.04 (1H, dt), 6.83 (1H, s), 7.28 (1H, d), 4) to obtain 0.50 g of 5-difluoromethyl-1-(2-fluoro-4-me 8.20 (1H, d) thyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-1,1,2-trifluoro 2-(trifluoromethoxy)ethoxypyrazole. Example 55 55 H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.55 (3H, s), 3.38 (2H, q), 6.05 (1H, dt), 6.52(1H, s), 6.56(1H, t), 7.16 (1H, Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo d), 7.63 (1H, d) roethylthio)phenyl-5-fluoromethyl-3-1,1,2-trif luoro-2-(trifluoromethoxy)ethoxypyrazole (com Example 58 pound No. 1-1579 of the present invention) 60 Preparation of 5-difluoromethyl-1-(2-fluoro-4-me 0.22 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth thyl-5-(2,2,2-trifluoroethylsulfinyl)phenyl-3-1,1,2- ylthio)phenyl-5-hydroxymethyl-3-1,1,2-trifluoro-2-(trif trifluoro-2-(trifluoromethoxy)ethoxypyrazole (com luoromethoxy)ethoxypyrazole was dissolved in 10 mL of pound No. 1-1532 of the present invention) dichloromethane, and 85 mg of diethylaminosulfur trifluo 65 ride was dropwise added under cooling with ice, followed by 0.35 g of 5-difluoromethyl-1-(2-fluoro-4-methyl-5-(2.2, stirring for 3 hours under cooling with ice. Extraction with 2-trifluoroethylthio)phenyl-3-1,1,2-trifluoro-2-(trifluo US 8,802,713 B2 151 152 romethoxy)ethoxypyrazole was dissolved in 10 mL of chlo Example 61 roform, and 150 mg of m-chloroperbenzoic acid (purity: 75%) was added under cooling with ice. After stirring for one Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo hour under cooling with ice, the solution was washed with an roethylthio)phenyl-5-formylamino-3-(2,2,3.3.4.4.4- aqueous Sodium thiosulfate solution and then washed with an 5 heptafluorobutoxy)pyrazole (compound No. 1-1593 aqueous sodium hydrogen carbonate solution, and then dried of the present invention) over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, and the obtained residue 1.18 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo was purified by column chromatography (developing solvent roethylthio)phenyl)-3-(2.2.3.3.4.4.4-heptafluorobutoxy) ethyl acetate:hexane=1:2) to obtain 0.35 g of 5-difluorom 10 pyrazole was dissolved in 15 mL of formic acid, and 8mL of ethyl-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl) acetic anhydride was added under cooling with ice, followed phenyl)-3-1,1,2-trifluoro-2-(trifluoromethoxy) by stirring at room temperature for 12 hours. Then, extraction ethoxypyrazole. with ethyl acetate was carried out, the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.48 (3H, s), 15 off under reduced pressure, and the obtained residue was 3.38-3.59 (2H, m), 6.04 (1H, dt), 6.54 (1H, s), 6.62 (1H, t), purified by column chromatography (developing solvent 7.21 (1H, d), 8.14 (1H, d) ethyl acetate:hexane=1:2) to obtain 0.92 g of 1-2-fluoro-4- methyl-5-(2.2.2-trifluoroethylthio)phenyl-5-formylamino Example 59 3-(2,2,3,3,4,4,4-heptafluorobutoxy)pyrazole. Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.54 (3H, s), roethylthio)phenyl-5-methoxy-3-1,1,2-trifluoro-2- 3.40 (2H, q), 4.73 (2H, t), 6.30 (1H, s), 7.05 (1H, brs), 7.17 (trifluoromethoxy)ethoxypyrazole (compound No. (1H, d), 8,43 (1H, s) 1-794 of the present invention) Example 62 25 1.5g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo phenyl)-3-hydroxy-5-methoxypyrazole was dissolved in 30 roethylsulfinyl)phenyl-5-formylamino-3-(2,2,3,3,4, mL of N,N-dimethylformamide, 40 g of triethylamine was 4.4-heptafluorobutoxy)pyrazole (compound No. added, and stirring was carried out at 50° C. for 3 hours while 1-1594 of the present invention) trifluoromethyl trifluorovinyl ether was blown. To this solu 30 tion, ethyl acetate was added, followed by washing with a 0.7 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) saturated aqueous solution of citric acid, and then the organic phenyl-5-formylamino-3-(2.2.3.3.4.4.4-heptafluorobu layer was dried over anhydrous magnesium Sulfate, the Sol toxy)pyrazole was dissolved in 20 mL of chloroform, and 360 vent was distilled off under reduced pressure, and the mg of m-chloroperbenzoic acid (purity: 75%) was added obtained residue was purified by column chromatography 35 under cooling with ice. After stirring for one hour under (developing solvent ethyl acetate:hexane-1:4) to obtain 1.1 g cooling with ice, the Solution was washed with an aqueous of 1-2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phe Sodium thiosulfate solution and then washed with an aqueous nyl-5-methoxy-3-1,1,2-trifluoro-2-(trifluoromethoxy) Sodium hydrogen carbonate solution, and then dried over ethoxypyrazole. anhydrous magnesium Sulfate. Then, the solvent was distilled 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.51 (3H, s), 40 off under reduced pressure, and the obtained residue was 3.36 (2H, q), 3.92 (3H, s), 5.52 (1H, s), 6.07 (1H, dt), 7.09 purified by column chromatography (developing solvent (1H, d), 7.59 (1H, d) ethyl acetate:hexane=1:1) to obtain 0.72 g of 1-2-fluoro-4- methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-5-formy Example 60 lamino-3-(2.2.3.3.4.4.4-heptafluorobutoxy)pyrazole. 45 'H-NMR (d-DMSO/TMS 8 (ppm) value) 8: 2.47 (3H, s), Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 4.04-4.24 (2H, m), 4.95 (2H, t), 6.24 (1H, s), 7.58 (1H, d), roethylsulfinyl)phenyl-5-methoxy-3-1,1,2-trif 7.89 (1H, d), 8,15 (1H, s), 10.56 (1H, s) luoro-2-(trifluoromethoxy)ethoxypyrazole (com pound No. 1-795 of the present invention) Example 63 50 0.2 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo phenyl-5-methoxy-3-1,1,2-trifluoro-2-(trifluoromethoxy) roethylthio)phenyl-5-methyl-3-(4-trifluo ethoxypyrazole was dissolved in 10 mL of chloroform, and romethoxy)benzyloxypyrazole (compound No. 92 mg of m-chloroperbenzoic acid (purity: 75%) was added 1-1599 of the present invention) under cooling with ice. After stirring for one hour under 55 cooling with ice, the Solution was washed with an aqueous 0.7 g of 3-hydroxy 1-2-fluoro-4-methyl-5-(2.2.2-trifluo Sodium thiosulfate Solution and then washed with an aqueous roethylthio)phenyl-5-methylpyrazole was dissolved in 15 Sodium hydrogen carbonate solution, and then dried over mL of dimethylsulfoxide, and 0.36 g of potassium carbonate anhydrous magnesium Sulfate. Then, the solvent was distilled and 0.57 g of (4-trifluoromethoxy)benzyl bromide were off under reduced pressure, and the obtained residue was 60 added, followed by stirring at room temperature for 12 hours. purified by column chromatography (developing solvent After completion of the reaction, the reaction solution was ethyl acetate:hexane=1:2) to obtain 0.20 g of 1-2-fluoro-4- poured into water, extraction with ethyl acetate was carried methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-5-methoxy out, followed by washing with a saturated Salt Solution, and 3-1,1,2-trifluoro-2-(trifluoromethoxy)ethoxypyrazole. the organic layer was dried over anhydrous magnesium Sul H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.45 (3H, s), 65 fate. Then, the solvent was distilled off under reduced pres 3.35-3.59 (2H, m), 3.93 (3H, s), 5.54 (1H, s), 6.05 (1H, dt), sure, and the obtained residue was purified by column chro 7.14 (1H, d), 8.08 (1H, d) matography (ethyl acetate:hexane=1:10) to obtain 0.80 g of US 8,802,713 B2 153 154 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl-5- Example 66 methyl-3-(4-trifluoromethoxy)benzyloxypyrazole. Preparation of 4-cyano-1-(2-fluoro-4-methyl-5-(2.2, H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.18 (3H, s), 2-trifluoroethylthio)phenyl-3-1,1,2-trifluoro-2- 2.52 (3H, s), 3.72 (2H, q), 5.22 (2H, s), 5.70 (1H, s), 7.10 (1H, (trifluoromethoxy)ethoxypyrazole (compound No. d), 7.21 (2H, d), 7.57 (2H, d), 7.58 (1H, d) 5 1-1587 of the present invention) Example 64 1.20 g of ethyl-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroet hylthio)phenyl)-3-hydroxypyrazole-4-carboxylate was dis 10 solved in 40 mL of N,N-dimethylformamide, 25g of triethy Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo lamine was added, and stirring was carried out at 50° C. for 3 roethylsulfinyl)phenyl-5-methyl-3-(4-trifluo hours while trifluoromethyl trifluorovinyl ether was blown. romethoxy)benzyloxypyrazole (compound No. To this solution, ethyl acetate was added, followed by wash 1-1600 of the present invention) ing with a saturated aqueous solution of citric acid, and then 15 the organic layer was dried over anhydrous magnesium Sul 0.5g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) fate, and the solvent was distilled off under reduced pressure. phenyl-5-methyl-3-(4-trifluoromethoxy) The obtained residue was purified by column chromatogra benzyloxypyrazole was dissolved in 20 mL of chloroform, phy (developing solvent ethyl acetate:hexane=1:4) to obtain and 240mg of m-chloroperbenzoic acid (purity: 75%) was 0.73 g of ethyl-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroeth added under cooling with ice. After stirring for one hour 20 ylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) under cooling with ice, the solution was washed with an ethoxypyrazole-4-carboxylate ('H-NMR (CDCL/TMS 8 aqueous Sodium thiosulfate solution and then washed with an (ppm) value) 8: 1.36 (3H, t), 2.51 (3H, s), 3.41 (2H, q), 4.34 aqueous sodium hydrogen carbonate solution, and then dried (2H, q), 6.21 (1H,dt), 7.16 (1H, d), 7.97 (1H, d), 8.38(1H,d)). over anhydrous magnesium sulfate. Then, the solvent was Then, 0.73 g of ethyl-1-(2-fluoro-4-methyl-5-(2.2.2-trif distilled off under reduced pressure, and the obtained residue 25 luoroethylthio)phenyl)-3-1,1,2-trifluoro-2-(trifluo was purified by column chromatography (developing solvent romethoxy)ethoxypyrazole-4-carboxylate was dissolved in ethyl acetate:hexane=1:2) to obtain 0.50 g of 1-2-fluoro-4- 20mL of ethanol. To this solution, a solution having 0.25 g of methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-5-methyl-3- potassium hydroxide dissolved in 5 mL of water was added, {(4-trifluoromethoxy)benzyloxypyrazole. followed by stirring at room temperature for 30minutes. Con 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.15 (3H, s), 30 centrated hydrochloric acid was added to adjust the pH to 2, 2.45 (3H, s), 3.50 (2H, m), 5.25 (2H, s), 5.72(1H, s), 7.16 (1H, the solvent was distilled off under reduced pressure, and s), 7.26 (2H, d), 7.49 (2H, d), 8.10 (1H, d) extraction with ethyl acetate was carried out. The organic layer was dried over anhydrous sodium Sulfate, and the Sol vent was distilled off under reduced pressure. The obtained Example 65 35 residue was dissolved in 10 mL of dichloromethane, and 0.22 g of oxalyldichloride and N,N-dimethylformamide in a cata Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo lytic amount were added, followed by stirring at room tem roethylsulfinyl)phenyl)-3-(4-(trifluoromethyl) perature for 1 hour. Then, the solvent was distilled off under phenoxypyrazole (compound No. 1-1586 of the reduced pressure, and the resulting product was dissolved in present invention) 40 5 mL of tetrahydrofuran, and the solution was dropwise added to a mixed solution comprising 20 mL of a 25 mass % ammonia water and 30 mL of tetrahydrofuran at -30° C. 0.5g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) Then, stirring was carried out for 12 hours while the tempera phenyl)-3-hydroxypyrazole was dissolved in 20 mL of ture was slowly increased to room temperature. Then, the dichloromethane, and 0.44 g of 4-trifluoromethylbenzenebo- as solvent was distilled off under reduced pressure, extraction ronic acid, 0.47 g of triethylamine, 0.37 g of pyridine, 0.43g with ethyl acetate was carried out, the organic layer was dried of copper(II) acetate and 0.5g of powdery molecular sieves 4 over anhydrous sodium sulfate, the solvent was distilled off A were added, followed by stirring at room temperature for 12 under reduced pressure, and the obtained residue was purified hours. To this solution, ethyl acetate was added, followed by by column chromatography (developing solvent ethyl washing with a saturated aqueous solution of citric acid, and so acetate:hexane=1:3) to obtain 0.45 g of 1-2-fluoro-4-me then the organic layer was dried over anhydrous magnesium thyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-1,1,2-trifluoro sulfate, the solvent was distilled off under reduced pressure, 2-(trifluoromethoxy)ethoxypyrazole-4-carboxyamide ('H- the obtained residue was dissolved in 10 mL of chloroform, NMR (CDCL/TMS 8 (ppm) value) 8: 2.51 (3H, s), 3.40 (2H, and under cooling with ice, 80 mg of m-chloroperbenzoic q), 5.81 (1H, brs), 6.23 (1H, brs), 6.37 (1H, dt), 7.16 (1H, d), acid (purity: 75%) was added. After stirring for one hour ss 7.92 (1H, d), 8.45 (1H, d)). under cooling with ice, the solution was washed with an Then, 0.45 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroet aqueous Sodium thiosulfate solution and then washed with an hylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) aqueous sodium hydrogen carbonate solution, and then dried ethoxypyrazole-4-carboxyamide was dissolved in 20 mL of over anhydrous magnesium sulfate. Then, the solvent was tetrahydrofuran, 0.23g of triethylamine was added, and 0.28 distilled off under reduced pressure, the obtained residue was go g of trifluoroacetic anhydride was slowly dropwise added purified by Silica gel column chromatography (developing under cooling with ice. After stirring at room temperature for solvent ethyl acetate:hexane=1:2) to obtain 0.15 g of 1-2- 2 hours, the solvent was distilled off under reduced pressure, fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-3- and extraction with ethyl acetate was carried out. The organic {4-(trifluoromethyl)phenoxypyrazole. layer was dried over anhydrous magnesium sulfate, the Sol H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.43 (3H, s), 65 vent was distilled off under reduced pressure, and the 3.47 (2H, m), 6.13 (1H, d), 7.17 (1H, d), 7.29 (2H, d), 7.62 obtained residue was purified by column chromatography (2H, d), 7.94 (1H, d), 8.43 (1H, d) (developing solvent ethyl acetate:hexane=1:4) to obtain 0.30 US 8,802,713 B2 155 156 g of 4-cyano-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoroeth column chromatography (developing solvent ethyl acetate: ylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) hexane=1:3) to obtain 0.64 g of 5-acetylamino-1-(2-fluoro ethoxypyrazole. 4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-(1,1,2,2,3,3, H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.53 (3H, s), 4.4.5.5.5-undecafluoropentyloxy)pyrazole. 3.41 (2H, q), 6.15 (1H, dt), 7.19 (1H, d), 7.96 (1H, d), 8.30 5 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.11 (3H, s), (1H, d) 2.55 (3H, s), 3.41 (2H, q), 6.53 (1H, s), 7.09 (1H, brs), 7.18 (1H, d), 7.63 (1H, d) Example 67 Example 69 Preparation of 4-cyano-1-(2-fluoro-4-methyl-5-(2.2, 10 2-trifluoroethylsulfinyl)phenyl-3-1,1,2-trifluoro-2- Preparation of 5-acetylamino-1-(2-fluoro-4-methyl (trifluoromethoxy)ethoxypyrazole (compound No. 5-(2,2,2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2,2,3, 1-1588 of the present invention) 3.4.4.5.5.5-undecafluoropentyloxy)pyrazole (com pound No. 1-489 of the present invention) 0.2 g of 4-cyano-1-(2-fluoro-4-methyl-5-(2.2.2-trifluoro 15 ethylthio)phenyl-3-1,1,2-trifluoro-2-(trifluoromethoxy) 0.12 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2- ethoxypyrazole was dissolved in 10 mL of chloroform, and trifluoroethylthio)phenyl)-3-(1,1,2,2,3,3,4,4,5,5,5-undecaf 93 mg of m-chloroperbenzoic acid (purity: 75%) was added luoropentyloxy)pyrazole was dissolved in 10 mL of chloro under cooling with ice. After stirring for one hour under form, and 44 mg of m-chloroperbenzoic acid (purity: 75%) cooling with ice, the Solution was washed with an aqueous was added under cooling with ice. After stirring for 30 min Sodium thiosulfate Solution and then washed with an aqueous utes under cooling with ice, the Solution was washed with an Sodium hydrogen carbonate solution, and then dried over aqueous sodium thiosulfate solution and then washed with an anhydrous magnesium sulfate. The solvent was distilled off aqueous potassium carbonate solution, and then dried over under reduced pressure, the obtained residue was purified by anhydrous magnesium Sulfate. Then, the solvent was distilled silica gel column chromatography (developing solvent ethyl 25 off under reduced pressure, and the obtained residue was acetate:hexane=1:2) to obtain 0.19 g of 4-cyano-1-(2-fluoro purified by column chromatography (developing solvent 4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl)-3-(1,1,2- ethyl acetate:hexane=1:1) to obtain 0.095g of 5-acetylamino trifluoro-2-(trifluoromethoxy)ethoxypyrazole. 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylsulfinyl)phe H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.47 (3H, s), nyl)-3-(1.1.2.2.3.3.4.4.5.5.5-undecafluoropentyloxy)pyra 3.38-3.63 (2H, m), 6.13 (1H, dt), 7.25 (1H, d), 8.34 (1H, s), 30 Zole. 8.44 (1H, d) 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.10 (3H, s), 2.48 (3H, s), 3.42-3.60 (2H, m), 6.52 (1H, s), 7.23 (1H, d), Example 68 8.11 (1H, d)

Preparation of 5-acetylamino-1-(2-fluoro-4-methyl 35 Example 70 5-(2.2.2-trifluoroethylthio)phenyl)-3-(1,1,2,2,3,3,4, 4.5.5,5-undecafluoropentyloxy)pyrazole (compound Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo No. 1-488 of the present invention) roethylthio)phenyl-5-methylamino-3-(1,1,2,2,3,3,4, 4.5.5.5-undecafluoropentyloxy)pyrazole (compound To a mixed solution comprising 35 mL of trifluoroacetic 40 No. 1-524 of the present invention) acid and 103 mL of trifluoroacetic anhydride, 6.9 g of a 31 mass % hydrogen peroxide solution was added at -10°C., 0.45 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2- followed by stirring at -10°C. for 10 minutes. Then, 25g of trifluoroethylthio)phenyl)-3-(1,1,2,2,3,3,4,4,5,5,5-undecaf undecafluoropentane iodide was dropwise added at -10°C., luoropentyloxy)pyrazole was dissolved in 5 mL of N,N-dim and stirring was carried out for 12 hours while the tempera 45 ethylformamide, the solution was dropwise added to a ture was slowly increased to room temperature. The solvent Suspension having 40 mg of sodium hydride Suspended in 10 was distilled offunder reduced pressure at room temperature, mL of N,N-dimethylformamide under cooling with ice, and the obtained solid was dissolved in 70 mL of benzene and 70 after completion of the dropwise addition, stirring was carried mL of trifluoroacetic acid, and 9.4 g of trifluoromethane out at room temperature for 30 minutes. The reaction solution Sulfonic acid was dropwise added under cooling with ice, 50 was cooled with ice again, and 0.15g of methyl iodide was followed by stirring at room temperature for 12 hours. Then, added, followed by stirring at room temperature for one hour. the solvent was distilled off under reduced pressure at room Then, water was injected, extraction with ethyl acetate was temperature to obtain crude (perfluoropentyl)phenyliodo carried out, followed by washing with water, and the organic nium trifluoromethanesulfonate. layer was dried over anhydrous magnesium sulfate. Then, the 2.0 g of 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-tri 55 solvent was distilled offunder reduced pressure, the obtained fluoroethylthio)phenyl)-3-hydroxypyrazole was dissolved in residue was dissolved in 10 mL of ethanol, and 10 mL of a 35 30 mL of dichloromethane, 2.18 g of pyridine was added, and mass % hydrochloric acid aqueous solution was added, fol the above prepared crude (perfluoropentyl)phenyliodonium lowed by stirring under reflux with heating for one hour. trifluoromethanesulfonate was added at room temperature Then, the reaction mixture was poured into water, extraction until 5-acetylamino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo 60 with ethyl acetate was carried out, followed by washing with roethylthio)phenyl)-3-hydroxypyrazole disappeared (disap water, and the organic layer was dried over anhydrous mag pearance was confirmed by thin layer chromatography). nesium sulfate. Then, the solvent was distilled off under Then, the solvent was distilled off under reduced pressure, a reduced pressure, and the obtained residue was purified by saturated salt solution was added, extraction with ethyl column chromatography (developing solvent ethyl acetate: acetate was carried out, the organic layer was dried over 65 hexane=1:4) to obtain 0.39 g of 1-2-fluoro-4-methyl-5-(2, anhydrous sodium sulfate, the solvent was distilled off under 2.2-trifluoroethylthio)phenyl-5-methylamino-3-(1,1,2,2,3, reduced pressure, and the obtained residue was purified by 3.4.4.5.5.5-undecafluoropentyloxy)pyrazole. US 8,802,713 B2 157 158 H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.51 (3H, s), Example 73 2.85 (3H, d), 3.39 (2H, q), 3.64 (1H, brs), 5.36 (1H, s), 7.12 Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo (1H, d), 7.61 (1H, d) roethylthio)phenyl-3-methoxy-5-(2,2,3,3,3-pen Example 71 tafluoropropoxy)pyrazole (compound No. 1-1469 of the present invention) 0.14 g of 1-2-fluoro-4-me thyl-5-(2,2,2-trifluoroethylthio)phenyl-5-hydroxy Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 3-methoxypyrazole was dissolved in 100 mL of dim roethylsulfinyl)phenyl-5-methylamino-3-(1,1,2,2,3, ethylsulfoxide, and 63 mg of potassium carbonate 3.4.4.5.5.5-undecafluoropentyloxy)pyrazole (com was added, followed by stirring at room temperature pound No. 1-525 of the present invention) 10 for 5 minutes. To this solution, 0.20 g of 2,2,3,3,3- pentafluoropropylnonafluorobutanesulfonate was 0.25 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth added, followed by stirring at room temperature for ylthio)phenyl-5-methylamino-3-(1,1,2,2,3,3,4,4,5,5,5-un 12hours. Then, extraction with ethyl acetate was car decafluoropentyloxy)pyrazole was dissolved in 10 mL of ried out, the organic layer was dried over anhydrous chloroform, and 95 mg of m-chloroperbenzoic acid (purity: magnesium sulfate, the solvent was distilled off 75%) was added under cooling with ice. After stirring for 30 under reduced pressure, and the obtained residue was minutes under cooling with ice, the solution was washed with purified by column chromatography (developing an aqueous Sodium thiosulfate solution and then washed with solvent ethyl acetate:hexane=1:4) to obtain 0.16 g of an aqueous potassium carbonate solution, and then dried over 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) anhydrous magnesium Sulfate. Then, the solvent was distilled phenyl-3-methoxy-5-(2,2,3,3,3-pentafluoropro off under reduced pressure, and the obtained residue was poxy)pyrazole. purified by column chromatography (developing solvent ethyl acetate:hexane=1:1) to obtain 0.23g of 1-2-fluoro-4- 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.50 (3H, s), methyl-5-(2.2.2-trifluoroethylsulfinyl)phenyl-5-methy 3.36 (2H, q), 3.91 (3H, s), 4.44 (2H, t), 5.26 (1H, s), 7.08 (1H, lamino-3-(1,1,2,2,3,3,4,4,5,5,5-undecafluoropentyloxy) 25 d), 7.60 (1H, d) pyrazole. 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.45 (3H, s), Example 74 2.85 (3H, s), 3.36-3.62 (2H, m), 3.66 (1H, brs), 5.37 (1H, s), 7.18 (1H, d), 8.11 (1H, d) Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 30 roethylsulfinyl)phenyl-3-methoxy-5-(2,2,3,3,3- Example 72 pentafluoropropoxy)pyrazole (compound No. 1-1470 of the present invention) Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo roethylthio)phenyl-5-hydroxy-3-methoxypyrazole 0.16 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth (compound No. 1-1615 of the present invention) 35 ylthio)phenyl-3-methoxy-5-(2,2,3,3,3-pentafluoropro poxy)pyrazole was dissolved in 10 mL of chloroform, and 1.5 g of 2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) 0.079 g of m-chloroperbenzoic acid (purity: 75%) was added phenylhydrazine was dissolved in 70 mL of tetrahydrofuran, under cooling with ice. After stirring for 30 minutes under and 0.83 g of malonyl chloride was added under cooling with cooling with ice, the Solution was washed with an aqueous ice. Stirring was carried out under reflux with heating for 5 40 Sodium thiosulfate solution and then washed with an aqueous hours, and the solvent was distilled off under reduced pres potassium carbonate Solution, and then dried over anhydrous sure. To the obtained residue, 20 mL of dichloromethane and magnesium sulfate. Then, the solvent was distilled off under 2 mL of methanol were added, and 0.7 mL of a diethyl ether reduced pressure, and the obtained residue was purified by solution (2.0 mol/L) of trimethylsilyldiazomethane was column chromatography (developing solvent ethyl acetate: added under cooling with ice, followed by stirring at room 45 hexane=1:2) to obtain 0.13 g of 1-2-fluoro-4-methyl-5-(2, temperature for 5 hours. Then, the solvent was distilled off 2.2-trifluoroethylsulfinyl)phenyl-3-methoxy-5-(2,2,3,3,3- under reduced pressure, and the obtained residue was purified pentafluoropropoxy)pyrazole. by column chromatography (developing solvent ethyl 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.43 (3H, s), acetate:hexane=1:1) to obtain 0.14 g of 1-2-fluoro-4-me 3.39-3.54 (2H, m), 3.91 (3H, s), 4.46 (2H, t), 5.27 (1H, s), thyl-5-(2.2.2-trifluoroethylthio)phenyl-5-hydroxy-3-meth 50 7.12 (1H, d), 8.09 (1H, d) oxypyrazole. 'H-NMR (CDCL/TMS 8 (ppm)) values of compounds I H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.48 (3H, s), of the present invention prepared in accordance with the 3.35 (2H, q), 3.45 (2H, s), 3.92 (3H, s), 7.08 (1H,d), 7.64 (1H, above Examples are given below together with values in the d) above Examples. TABLE 39 m.p. (C.) or refractive indx Comp. No. H-NMR (CDC1/TMS d(ppm) value) (n') 1-1 2.50(3H, s), 3.37 (3H, s), 3.40(2H, q), 6.36(1H, d), 7.13(1H, d), 7.90(1H, t), 82-83 7.96(1H, d) 1-2 2.45(3H, s), 3.39(3H, s), 3.37-3.58(2H, m), 6.40(1H, d), 7.19(1H, d), 7.96(1H, t), 96-97 8.44(1H, d) 1-3 2.10(3H, s), 2.55 (3H, s), 3.41 (2H, q), 6.61 (1H, s), 7.20(1H, d), 7.21 (1H, brs), Measurement 7.61 (1H, d) impossible

US 8,802,713 B2 195 196 TABLE 62-continued m.p. (C.) or Comp. No. "H-NMR (CDCITMS d (ppm) value) refractive indx (n') -1605 2.48 (3H, s), 3.41 (2H, q), 5.32 (2H, s), 5.93 (1H, d), 7.07 (1H, d), 7.36 (1H, d), 78-80 7.80 (2H, m), 7.99 (1 H, d), 8.52 (1 H, d) -1606 2.41 (3H, s), 3.49 (2H, m), 5.34 (2H, s), 5.97 (1H, d), 7.12 (1H, d), 7.44 (1H, d), 102-103 7.49 (1H, d), 7.82 (1 H, d), 7.92 (1 H, d), 8.51 (1H, s) -1607 2.54 (3H, s), 3.40 (2H, q), 6.18 (1H, dt), 6.56 (1H, s), 7.18 (1H, d), 7.32 (1H, brs), 14631 7.63 (1H, d), 8.26 (1H, s) -1608 (d-DMSO, 100° C.) 2.48 (3H, s), 3.91-4.15 (2H, m), 6.39 (1H, s) 7.14 (1H, dt), 1SO-153 7.48 (1H, d), 7.94 (1 H, d), 8.21 (1H, brs), 10.27 (1H, brs) -1609 2.46 (3H, s), 3.40 (2H, q), 5.44 (2H, s), 6.00 (1H, d), 7.05 (1H, d), 7.23 (1H, d), 1.5585 7.56 (1H, d), 7.73 (1H, t), 7.86 (1H, d), 8.01 (1H, d), 8.61 (1H, d) -1610 2.41 (3H, s), 3.50 (2H, m), 5.45 (2H, s), 6.03 (1H, d), 7.10 (1 H, d), 7.23 (1 H, d), 102-105 7.55 (1H, d), 7.74 (1 H, t), 7.86 (1H, d), 8.47 (1H, d), 8.62 (1 H, d) -1611 0.60-1.1 (4H, br), 2.51 (3H, s), 3.32 (2H, q), 4.14 (1H, br), 5.06 (1H, br), 5.22 (2H, s), Measurement 5.61 (1H, s), 7.05 (1 H, d), 7.25 (2H, d), 7.47 (2H, d), 7.51 (1H, d) impossible -1613 2.44 (3H, s), 2.47 (3H, s), 3.41 (2H, q), 5.26 (2H, s), 5.92 (1H, d), 7.06 (1H, d), 1.5585 7.19 (2H, d), 7.39 (2H, d), 7.79 (1 H, d), 8.04 (1 H, d) -1614 2.36 (3H, s), 2.41 (3H, s), 3.49 (2H, m), 5.28 (2H, s), 5.96 (1 H, d), 7.10 (1 H, d), 157-160 7.18 (2H, d), 7.39 (2H, d), 7.85 (1 H, d), 8.52 (1 H, d) -1615 See Ex. 72

INTERMEDIATE PREPARATION EXAMPLES methanesulfonic acid was added, followed by reflux with heating for 3 hours. After cooling to room temperature, the Intermediate Preparation Example 1 25 solvent was distilled off under reduced pressure, the reaction solution was neutralized to pH-7 with sodium hydrogen car Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo bonate, and extraction with ethyl acetate was carried out. The roethylthio)phenyl)-3-hydroxypyrazole (compound organic layer was dried over anhydrous magnesium sulfate, No. 2-1 of the present invention) the solvent was distilled off under reduced pressure, and the 30 obtained residue was purified by column chromatography 12 g of 2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phe (developing solvent ethyl acetate:hexane:acetic acid=50:50: nylhydrazine was dissolved in 200 mL of tetrahydrofuran, 1) to obtain 20.2 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2, and 100 mL of water was added. To this solution, 16 g of 2-trifluoroethylthio)phenyl)-3-hydroxypyrazole in the form potassium carbonate and 8.1 g of 3-bromopropionyl chloride of brown crystals (melting point: 110-113°C.). were added, followed by stirring at room temperature for 5 35 H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.49 (3H, s), hours. The aqueous layer was neutralized to the vicinity of pH 3.49 (2H, q), 5.04 (1H, s), 7.10 (1H, d), 7.57 (1H, d) 2 with 6.Nhydrochloric acid. Then, the solvent was distilled off under reduced pressure, and the residue was subjected to extraction with ethyl acetate. The organic layer was dried over Intermediate Preparation Example 3 anhydrous magnesium Sulfate, and the solvent was distilled 40 off under reduced pressure to obtain a solid, which was Preparation of 5-acetylamino-1-(2-fluoro-4-methyl washed with hexane. Then, this solid was dissolved in 200 mL 5-(2.2.2-trifluoroethylthio)phenyl)-3-hydroxypyra of toluene, and 100mL of water was added. Then, 3.7 g of Zole (compound No. 2-4 of the present invention) potassium permanganate and tetra n-butyl ammonium bro mide in a catalytic amount were added, followed by stirring at 45 room temperature for 10 minutes. Then, an insoluble solid 10.6 g of 5-amino-1-(2-fluoro-4-methyl-5-(2.2.2-trifluo was removed by filtration, and the organic layer was dried roethylthio)phenyl)-3-hydroxypyrazole was dissolved in over anhydrous magnesium sulfate. Then, the solvent was 200 mL of toluene, and to this solution, 20.0 g of acetyl distilled offunder reduced pressure, and the solid was washed chloride was added, followed by reflux with heating for 12 with hexane to obtain 8.7 g of pale yellow crystals (melting 50 hours. After cooling to room temperature, the solvent was distilled off under reduced pressure, and the obtained residue point: 166-168° C.). was purified by column chromatography (developing solvent 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.46 (3H, s), ethyl acetate:hexane=1:4) to obtain 9.4 g of 3-acetoxy-5-(N, 3.69 (2H, q), 5.89 (1H, d), 7.08 (1H, d), 7.72 (1H, d), 7.77 N-diacetylamino)-1-(2-fluoro-4-methyl-5-(2,2,2-trifluoro (1H, d), 11.88 (1H, brs) ethylthio)phenylpyrazole. Then, 9.4 g of the obtained 3-ac 55 etoxy-5-(N,N-diacetylamino)-1-(2-fluoro-4-methyl-5-(2.2, Intermediate Preparation Example 2 2-trifluoroethylthio)phenylpyrazole was dissolved in 100 Preparation of 5-amino-1-(2-fluoro-4-methyl-5-(2.2, mL of ethanol, and 10 mL of a 25 mass % ammonia water was 2-trifluoroethylthio)phenyl)-3-hydroxypyrazole added, followed by stirring at room temperature for 30min (compound No. 2-2 of the present invention) 60 utes. Then, the solvent was distilled off under reduced pres sure, and the obtained solid was washed with diisopropyl 27.5 g of 2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) ether to obtain 7.0 g of 5-acetylamino-1-(2-fluoro-4-methyl phenylhydrazine was dissolved in 300 mL oftetrahydrofuran, 5-(2,2,2-trifluoroethylthio)phenyl)-3-hydroxypyrazole in and to this solution, 14 g of cyanoacetyl chloride was added, the form of white crystals (melting point: 223-225°C.). followed by stirring at room temperature for 5 minutes. Then, 65 H-NMR (d6-DMSO/TMS 8 (ppm) value) 8: 2.01 (3H, s), the solvent was distilled off under reduced pressure, the resi 2.50 (3H, s), 3.49 (2H, q), 5.91 (1H, s), 7.10 (1H,d), 7.60 (1H, due was dissolved in 300 mL of 1-propanol, and 10.6 g of d), 9.33 (1H, brs) US 8,802,713 B2 197 198 Intermediate Preparation Example 4 H-NMR (CDCL/TMS 8 (ppm) value) 8: 1.26 (3H, t), 2.52 (3H, s), 3.53 (2H, q), 4.66 (2H, q), 4.25 (2H, q), 6.31 (1H, Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo s), 7.07 (1H, d), 7.62 (1H, d) roethylthio)phenyl)-3-hydroxy-5-methylpyrazole Intermediate Preparation Example 6 (compound No. 2-11 of the present invention) Preparation of 1-2-fluoro-4-methyl-5-(2.2.2-trifluo 4.6 g of 1-(5-(2.2.2-trifluoroethylthio)-2-fluoro-4-meth roethylthio)phenyl)-3-hydroxy-5-methoxypyrazole ylphenyl)hydrazine was dissolved in 100 mL of diethyl ether, (compound No. 2-16 of the present invention) and 1.85g of acetic anhydride was dropwise added under 10 cooling with ice, followed by stirring at room temperature for 2.0 g of N'-(2-fluoro-4-methyl-5-(2.2.2-trifluoroeth one hour. The obtained crystals were collected by filtration ylthio)phenyl)acetohydrazide was dissolved in 100 mL of and washed with a solution of hexane:diisopropyl ether 3:1 tetrahydrofuran, 0.95g of malonyl chloride was added under (mass ratio) to obtain 4.41 g of N'-(2-fluoro-4-methyl-5-(2, cooling with ice, stirring was carried out under cooling with 2.2-trifluoroethylthio)phenyl)acetohydrazide in the form of 15 ice for one hour, and then stirring was carried out under reflux colorless crystals. Then, to 4.4 g of this hydrazide, 1.93 g of with heating for 5 hours. Then, the solvent was distilled off ethyl acetoacetate and 4.02 g of phosphorus tribromide were under reduced pressure, and the obtained crystals were added, followed by stirring at 50° C. for 2 hours. Then, after washed with isopropyl ether to obtain 1.74 g of 1-acetyl-2- stirring under cooling with ice for 10 minutes, ice was put, {2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) and the pH was adjusted to 5 with a 1N sodium hydroxide phenylpyrazolidine-3,5-dione. aqueous solution. Then, extraction with ethyl acetate was Then, 1.50 g of 1-acetyl-2-2-fluoro-4-methyl-5-(2.2.2- carried out, followed by washing with a saturated salt solu trifluoroethylthio)phenylpyrazolidine-3,5-dione was dis tion, the organic layer was dried over anhydrous sodium solved in 50 mL of dichloromethane, 5 mL of methanol was sulfate, the solvent was distilled off under reduced pressure, 25 added, and 2.1 mL of a diethyl ether solution (2.0 mol/L) of and the obtained residue was purified by column chromatog trimethylsilyldiazomethane was added under cooling with raphy (ethyl acetate:hexane=1:3) to obtain 2.03 g of 1-2- ice, followed by stirring at room temperature for 5 hours. fluoro-4-methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-hy Then, the solvent was distilled off under reduced pressure, droxy-5-methylpyrazole in the form of colorless solid. and the obtained residue was purified by column chromatog 30 raphy (developing solvent ethyl acetate:hexane-1:2) to 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.14 (3H, s), obtain 0.69 g of 2-acetyl-1-(2-fluoro-4-methyl-5-(2.2.2-trif 2.50 (3H, s), 3.55 (2H, q), 5.55 (1H, s), 7.09(1H,d), 7.58 (1H, luoroethylthio)phenyl-5-methoxypyrazol-3-one. d) 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.47 (3H, s), 2.53 (3H, s), 3.32 (2H, q), 3.88 (3H, s), 4.88 (1H, s), 7.03 (1H, Intermediate Preparation Example 5 35 d), 7.51 (1H, d) Then, 0.65 g of 2-acetyl-1-(2-fluoro-4-methyl-5-(2.2.2- trifluoroethylthio)phenyl-5-methoxypyrazol-3-one was dis Preparation of ethyl-1-(2-fluoro-4-methyl-5-(2.2.2- solved in 20 mL of tetrahydrofuran, and 0.2 g of potassium trifluoroethylthio)phenyl)-3-hydroxypyrazole-5- hydroxide was added, followed by stirring at room tempera carboxylate (compound No. 2-12 of the present 40 ture for 2 hours. Concentrated hydrochloric acid was added to invention) adjust pH to 3, the solvent was distilled off under reduced pressure, and extraction with ethyl acetate was carried out. 14 g of a 20 mass % sodium ethoxide ethanol solution was The organic layer was dried over anhydrous sodium sulfate, added to 20 mL of ethanol, and 10g of 2-fluoro-4-methyl-5- and the solvent was distilled off under reduced pressure to 45 obtain 0.57 g of 1-2-fluoro-4-methyl-5-(2.2.2-trifluoroeth (2.2.2-trifluoroethylthio)phenylhydrazine was rapidly added ylthio)phenyl)-3-hydroxy-5-methoxypyrazole. under reflux with heating. After stirring for 30 seconds, 7.8 g. 'H-NMR (CDCL/TMS 8 (ppm) value) 8: 2.48 (3H, s), of diethyl maleate was dropwise added, followed by stirring 3.46 (2H, q), 3.91 (3H, s), 5.15 (1H, s), 7.07 (1H,d), 7.53 (1H, under reflux with heating for 10minutes. The reaction solu d) tion was cooled to 50° C. or below, and 4.5g of acetic acid was 50 added. Then, the solvent was distilled offunder reduced pres Intermediate Preparation Example 7 Sure, extraction with ethyl acetate was carried out, the organic layer was dried over anhydrous sodium Sulfate, and the Sol Preparation of ethyl-1-(2-fluoro-4-methyl-5-(2.2.2- vent was distilled off under reduced pressure. The obtained trifluoroethylthio)phenyl)-3-hydroxypyrazole-4- residue was dissolved in 80 mL of toluene, 0.68 g of tetra 55 carboxylate (compound No. 2-17 of the present n-butyl ammonium bromide was added, and 3.5g of a 10 invention) mass % aqueous solution of potassium permanganate was gradually added. After completion of the reaction, ethyl 5.0 g of 2-fluoro-4-methyl-5-(2.2.2-trifluoroethylthio) acetate and 20 mL of a saturated aqueous solution of citric phenylhydrazine was dissolved in 50 mL of ethanol, and 5.0 acid were added, and the solution was washed with an aque 60 g of ethyl 2-cyano-3,3-diethoxyacrylate was added, followed ous sodium thiosulfate Solution and then dried over anhy by stirring under reflux with heating for 6 hours. Then, the drous magnesium sulfate. Then, the solvent was distilled off solvent was distilled off under reduced pressure, and extrac under reduced pressure, and the obtained residue was purified tion with ethyl acetate was carried out. The organic layer was by column chromatography (developing solvent ethyl dried over anhydrous magnesium sulfate, and the solvent was acetate:hexane=1:1) to obtain 3.80 g of ethyl 1-2-fluoro-4- 65 distilled offunder reduced pressure. The obtained residue was methyl-5-(2.2.2-trifluoroethylthio)phenyl)-3-hydroxypyra purified by column chromatography (developing solvent Zole-5-carboxylate. ethyl acetate:hexane=1:3) to obtain 1.48g of ethyl-5-amino