United States Patent (19) 11 Patent Number: 5,034,393 Hackler et al. (45) Date of Patent: Jul. 23, 1991

54 FUNGICIDALUSE OF OTHER PUBLICATIONS PYRIDOPYRIMIDINE, PTERIDINE, PYRIMIDOPYRIMIDINE, Sankyo Co., Chemical Abstracts, vol. 94: 1068f and PYRIMIDOPYRIDAZINE, AND attached 10th collected index, p. 46420CS. PYRIMIDO-1,2,4-TRIAZINE DERIVATIVES E. C. Taylor et al., 82 J.A.C.S. 5711-5718 (1960). S. Nishikawa et al., 50 Agric. Biol. Chem., 2243-2249 75) Inventors: Ronald E. Hackler, Indianapolis; (1986). Glen P. Jourdan, Morristown, both S. Nishikawa et al., 50 Agric. Biol. Chenn., 495-497 of Ind. (1986). H. Iwamura et al., 28 J. Med. Chem, 577-583 (1985). Derwent Abst. 86-001 168/01 (1986) abstracting EP (73) Assignee: Dowelanco, Indianapolis, Ind. 165,572A. Derwent Abst. 80-70448C/40 (1980) abstracting JP (21) Appl. No.: 385,840 55108806. (22 Filed: Jul. 27, 1989 Primary Examiner-Mukund J. Shah Assistant Examiner-M. V. Grumbling 51) Int. Cl...... A01N 43/90 Attorney, Agent, or Firm-Donald R. Stuart 52 U.S. Cl...... 514/258; 514/249; 57 ABSTRACT 514/248; 514/63; 514/278; 544/257; 544/258; Fungicidal compositions contain as active ingredient a 544/256; 544/238; 544/279 4-substituted-pyrido3,2-dipyrimidine, -pyrido4,3- (58) Field of Search ...... 514/249, 258, 248, 63, d)pyrimidine, -pyrido3,4-dpyrimidine, pyrido 2,3- 514/278; 546/345; 544/257, 258, 256, 238,279 dlpyrimidine, -pteridine, -pyrimido-4,5-d)pyrimidine, -pyrimido-4,5-cpyridazine, -pyrimido5,4-d)pyrimi (56) References Cited dine, -pyrimido5,4-c)pyridazine, pyrimido-4,5- U.S. PATENT DOCUMENTS d)pyridazine, or -pyrimido5,4-e-1,2,4-triazine, for ex ample 4-2-(4-chlorophenyl)ethoxypyrido2,3- 4, 101,554 7/1989 Tobin ...... 260/290 HC d)pyrimidine. FOREIGN PATENT DOCUMENTS 920267 5/1959 United Kingdom ...... 544/257 40 Claims, No Drawings 5,034,393 1 2 (C3-C4) branched alkyl, phenyl, or substituted phenyl, FUNGICIDALUSE OF PYRIDOPYRIMIDINE, and optionally substituted with (C1-C4) alkyl, (C2-C4) PTERIDINE, PYRIMIDOPYRIMIDINE, alkenyl or -alkynyl, branched (C3-C7) alkyl, C3-C7) PYRIMIDOPYRIDAZINE, AND cycloalkyl or -cycloalkenyl, halo, hydroxy, or acetyl, PYRIMIDO-1,2,4-TRIAZINE DERIVATIVES 5 and Z is FIELD OF THE INVENTION (a) a C1-C12 saturated or unsaturated hydrocarbon This invention provides new compounds that have chain, straight chain or branched optionally including a excellent plant fungicide activity. Some of the com hetero atom selected from O, S, SO, SO2, or SiR20R21, pounds have also demonstrated insecticidal and mitici 10 dal activity. The invention also provides compositions where R20 and R2 are as defined above and optionally and combination products that contain a compound of substituted with halo, halo (C1-C4) alkoxy, hydroxy, the invention as active ingredient, as well as providing (C3-C8) cycloalkyl or cycloalkenyl, or (C1-C4) acyl; fungicidal, miticidal, and insecticidal methods. (b) (C3-Cs) cycloalkyl or cycloalkenyl, optionally There is an acute need for new fungicides, insecti 15 substituted with (C1-C4) alkyl, (C1-C4) alkoxy, halo cides, and miticides, because target pathogens are rap (C1-C4) alkyl, halo (C1-C4) alkoxy, halo, hydroxy, or idly developing resistance to currently used pesticides. (C1-C4) acyl; Widespread failure of N-substituted azole fungicides to (c) a phenyl group of the formula (2) control barley mildew was observed in 1983, and has been attributed to the development of resistance. At 20 least 50 species of fungi have developed resistance to (2) the benzimidazole fungicides. The field performance of DMI (demethylation inhibitor) fungicides, which are now widely relied on to protect cereal crops from pow dery mildew, has declined since they were introduced 25 in the 1970's. Even recently introduced fungicides, like the acylalanines, which initially exhibited excellent con trol of potato late blight and grape downy mildew in the where field, have become less effective because of widespread R6 to R10 are independently H, halo, I, (C1-C10) alkyl, resistance. Similarly, and insects are developing 30 resistance to the miticides and insecticides in current (C3-C8) alkenyl or -alkynyl, branched (C3-C6) alkyl, use. Resistance to insecticides in is wide -alkenyl, or -alkynyl, (C3-C8) cycloalkyl or -cycloalke spread, with at least 400 species resistant to one or more nyl, halo (C1-C7) alkyl, (C1-C7) alkoxy, (C-C7) alkyl insecticides. The development of resistance to some of thio, halo (C1-C7) alkoxy, phenoxy, substituted phe the older insecticides, such as DDT, the carbamates, 35 noxy, phenylthio, substituted phenylthio, phenyl, sub and the organophosphates, is well known. But resis stituted phenyl, NO2, acetoxy, OH, CN, SiR11R2R3, tance has even developed to some of the newer pyre OSiR 11R12R13, NR14R15, S(O)R16, or SOR17 where throid insecticides and miticides. Therefore a need ex Ril, R12, and R3 are independently (C1-C4) alkyl, ists for new fungicides, insecticides, and miticides. (C3-C4) branched alkyl, phenyl, or substituted phenyl, 40 R“ and R1s are independently H, (C1-C4) alkyl, or SUMMARY OF THE INVENTION (C3-C4) acyl, and R6 and R 7 are (C1-C10) alkyl, This invention provides compounds of the formula phenyl, or substituted phenyl; (1): (d) a furyl group of formula (3) 45 X-Y-Z (1) (3) 2. N O s N 2. 50 where R8 is H, halo, halomethyl, CN, NO2, (C1-C4) wherein alkyl, (C3-C4) branched alkyl, phenyl, or (C1-C4) alk one or two of A, B, E, or D are N, and the others are Oxy; CR1 or A, E, and D are N and B is CR; where R and (e) a thienyl group of the formula (4) R2 are independently H, halo, (C1-C4) alkyl, (C3-C4) 55 branched alkyl, (C1-C4) alkoxy, halo (C1-C4) alkyl, (4) phenyl, or substituted phenyl; X is O, S, SO, SO2, NR3, or CR“R5, where R3 is H, (C1-C4) alkyl, or (C1-C4) acyl, and R and Rare inde S pendently H, (C1-C4) acyl, (C1-C4) alkyl, (C2-C4) alke nyl or -alkynyl, CN, or OH, or R* and R5 combine to where R8 is as defined in paragraph (d); form a carbocyclic ring containing four to six carbon (f) a group of formula (5) or (6) atoms; Y is a bond or an alkylene chain one to six carbon (5) atoms long, optionally including a carbocyclic ring, and 65 optionally including a hetero atom selected from O, NR3, S, SO, SO2, or SiR20R2, where R3 is as defined sy." above and R20 and R2 are independently (C1-C4) alkyl, 5,034,393 3 4. (l) to (3), in combination with a second insecticide or -continued Initicide. (6) The insecticide and Initicide compositions of the in vention comprise an insect- or -inactivating amount of a compound of formula (), including compounds of provisos (1) to (3), in combination with a carrier. Such where R8 is as defined in paragraph (d), J is N or CH, compositions may optionally contain additional active and G is O, NR19, or S, provided that if J is not N then ingredients, such as an additional fungicidal, miticidal, G is NR19, where R19 is H., (C1-C4) alkyl, (C1-C4) acyl, or insecticidal ingredient. phenylsulfonyl, or substituted phenylsulfonyl; 10 The insecticidal or miticidal method of the invention (g) a group selected from comprises applying to the locus to be protected an in optionally substituted naphthyl, dihydronaphthyl, sect- or mite-inactivating amount of a compound of tetrahydronaphthyl, and decahydronaphthyl; formula (1), including compounds of provisos (1) to (3), or of a combination described above. optionally substituted pyridyl; 15 optionally substituted indolyl; DETAILED DESCRIPTION OF THE and 1,3-benzodioxolyl; INVENTION or an acid addition salt of a compound of formula (1); provided that the following compounds are excluded: Throughout this document, all temperatures are 1) pyrido2,3-dipyrimidines of formula (1) wherein X given in degrees Celsius, and all percentages are weight is NR3 and -Y-Z is benzyl, or X is NR3, Y is an 20 percentages unless otherwise stated. alkylene chain containing an O or Saton adjacent to Z, The term "halo' refers to a F, C, or Br atom. The term "(C1-C7) alkoxy' refers to straight or and Z is either unsubstituted phenyl or a substituted branched chain alkoxy groups. phenyl group other than one substituted with The term "(C1-C7) alkylthio" refers to straight and branched (C3-C6) alkyl, 25 halo (C1-C4) alkyl, branched chain alkylthio groups. halo (C1-C4) alkoxy, The term "halo (C1-C7) alkyl" refers to a (C1-C7) phenyl, alkyl group, straight chain or branched, substituted with one or more halo atoms. substituted phenyl, The term "halo (C1-C7) alkoxy' refers to a (C1-C7) phenoxy, 30 alkoxy group substituted with one or more halo groups. substituted phenoxy, The term "halo (C1-C4) alkylthio" refers to a (C1-C4) phenylthio, alkylthio group, straight chain or branched, substituted substituted phenylthio, with one or more halo atoms. SiR11R12R13, or The term "substituted phenyl" refers to phenyl sub OSiR11R12R13; 35 stituted with up to three groups selected from halo, I, 2) pyrido 3,4-dpyrimidines of formula (1) wherein X (C1-C10) alkyl, branched (C3-C6) alkyl, halo (C1-C4) is NR3, Z is unsubstituted phenyl, and R is methyl; and alkyl, hydroxy (C1-C4) alkyl, (C1-C4) alkoxy, halo 3) pyrido3,4-dipyrimidines of formula (1) wherein X (C1-C4) alkoxy, phenoxy, substituted phenoxy, phenyl, is NR3 and -Y-Z is benzyl or isoamyl. substituted phenyl, NO2, OH, CN, (C1-C4) al Proviso (1) excludes compounds that are described as 40 kanoyloxy, or benzyloxy. fungicides in Japanese patent application 55108806 of The terms "substituted naphthyl', 'substituted pyri Sankyo. Proviso (2) excludes compounds for which dyl and "substituted indolyl" refer to these ring sys cytokinin activity is reported in Agri. Biol. Chem., 50, tems substituted with halo, halo (C1-C4) alkyl, CN, 2243-49 (1986). Proviso (3) excludes compounds for 45 NO2, (C1-C4) alkyl, (C3-C4) branched alkyl, phenyl, which cytokinin activity is reported in Agri. Biol. Substituted phenyl, (C1-C4) alkoxy, or halo (C1-C4) Chem. 50, 495-97 (1986). alkoxy, The fungicide combinations of the invention com The term "substituted phenoxy' refers to phenoxy prise at least 1% by weight of a compound of formula substituted with up to three groups selected from halo, (l), excluding compounds of proviso (l) but including 50 I, (C1-C10) alkyl, branched (C3-C6) alkyl, halo (C1-C7) those of provisos (2) and (3), in combination with a alkyl, hydroxy (C1-C7) alkyl, (C1-C7) alkoxy, halo second plant fungicide. (C1-C7) alkoxy, phenoxy, substituted phenoxy, phenyl, The fungicide compositions of the invention com substituted phenyl, NO2, OH, CN, (C1-C4) al prise a disease inhibiting and phytologically acceptable kanoyloxy, or benzyloxy. amount of compound of formula (1), excluding con The term "carbocyclic ring" refers to a saturated or pounds of proviso (1) but including those of provisos (2) unsaturated carbocyclic ring containing three to seven and (3), in combination with a phytologically-accepta carbon atoms. ble carrier. Such compositions may optionally contain The terms 'substituted phenylthio' and "substituted additional active ingredients, such as an additional fun phenyl Sulfonyl' refer to such groups substituted with gicidal, miticidal, or insecticidal ingredient. 60 up to three groups selected from halo, I, (C1-Co) alkyl, The fungicidal method of the invention comprises branched (C3-C6) alkyl, halo (C1-C7) alkyl, hydroxy applying to the locus of a plant pathogen a disease inhib (C-C7) alkyl, (C1-C7) alkoxy, halo (C-C) alkoxy, iting and phytologically acceptable amount of a com phenoxy, Substituted phenoxy, phenyl, substituted pound of formula (1), excluding compounds of proviso phenyl, NO2, OH, CN, (C1-C4) alkanoyloxy, or ben (1) but including those of provisos (2) and (3). 65 Zyloxy. The insecticide and miticide combinations of the The term "unsaturated hydrocarbon chain refers to invention comprise at least 1% by weight of a com a hydrocarbon chain containing one or two sites of pound of formula (1), including compounds of provisos unsaturation. 5,034,393 5 6 The term "HPLC" refers to a high-performance liq Y and Z are as previously defined. uid chromatography. For many of the examples, the reaction was carried COMPOUNDS out in toluene treated with dry HCI, at room tempera ture or with gentle heating. Compounds of formula (1) wherein A is N and B, E, and D are CR are pyrido (3,2-d)pyrimidines. Alternatively, and preferably, the reaction may be Compounds of formula (1) wherein B is N and A, E, carried out in the presence of a strong base, such as and D are CR are pyrido (4,3-dipyrimidines. sodium hydride, in a non-reactive organic solvent, such Compounds of formula (1) wherein E is N and A, B, as DMF, at a temperature in the range of 0 to 25 C. and D are CR are pyrido3,4-d)pyrimidines. 10 Compounds of formula (1) wherein D is N and A, B, Synthesis of Compounds Wherein X is NR3 and E are CR are pyrido2,3-d)pyrimidines. The compounds of formula (1) wherein X is NR3 are Compounds of formula (1) wherein A and D are N prepared by condensing a compound of formula (7) and B and E are CR are pteridines (or pyrazino(2,3- d)pyrimidines. 15 with an amine of the formula (9) Compounds of formula (1) wherein B and D are N and A and E are CR are pyrimido-4,5-d)pyrimidines. R3 (9) Compounds of formula (1) wherein E and D are N and A and B are CR are pyrimido-4,5-cpyridazines. Compounds of formula (1) wherein A and E are N 20 and B and D are CR are pyrimido5,4-dpyrimidines. where Compounds of formula (1) wherein A and B are N R3, is H or ((C1-C4) alkyl, and and E and D are CR are pyrimido5,4-cpyridazines. Y and Z are as previously defined. Compounds of formula () wherein B and E are N The chloride of formula (7) is allowed to react with and A and D are CR are pyrimido-4,5-dipyridazines. 25 an appropriate amine at a wide variety of temperatures Compounds of formula (1) wherein A, E, and D are N and B is CR are pyrimido5,4-e-1,2,4-triazines. (20-180° C.), preferably in the presence of an acid ac While all of the compounds of the invention are use ceptor, such as triethylamine. The reaction may be ful fungicides, certain classes are preferred for reasons carried out neat, or in a non-reactive organic solvent. of greater efficacy or ease of synthesis, viz: 30 Compounds where R is acyl are prepared from amines (a) compounds of formula (1) wherein one of A, B, E, where R3 is H, which were allowed to react with an and D is N and the rest are CR. acylating agent such as acetyl chloride or acetic anhy (b) compounds of class (a) wherein D is N and A, B, dride. In cases where the starting material of formula (7) and E are CR, i.e., pyrido2,3-dipyrimidine deriva 35 is one wherein R or R2 is Cl, a mixture of products is tlves; (c) compounds of formula (1) wherein Z is substituted obtained which are separable using liquid chromatogra phenyl; phy. (d) compounds of formula (1) wherein X is O; and Synthesis of Compounds Wherein X is CH2 (e) compounds of class (d) wherein Y is a chain at least two atoms long. The compounds of formula (1) wherein X is CH2 can be made using the process described in J. Heterocyclic SYNTHESIS Chemistry, Vol. 14, p. 1081–1083 (1977) by A. Scoville The compounds of this invention are made using well and F. X. Smith. This process entails preparation of a known chemical procedures. The required starting ma terials are commercially available, or they are readily 45 barbituric acid of the formula (10) synthesized using standard procedures. Z-Y CO-NH (10) Synthesis of Compounds Wherein X is O N / \ C CO The compounds of formula (1) wherein X is O are 50 V / made by condensing a compound of formula (7): A CO-NH

L (7) E rels 1 A SD N R2 B1 n 55 Ei el which is then hydrolyzed and decarboxylated by dis S D N R2 solving the intermediate in a solution of sodium hydrox where R2, A, B, E, and D are as previously defined, and ide and water, refluxing, then making the solution L is a leaving group such as F, Cl, Br, I., NO2, 1,2,4- slightly acidic with hydrochloric acid and again reflux triazol-1-yl, --O-Si(Me)3, arylthio, alkylthio, alkylsul ing. fonyl, arylsulfonyl, alkoxy, or arylsulfinyl with an alco The acid addition salts of compounds of formula (1) hol or phenol of the formula (8): are obtained in the usual way. Accordingly, the invention also provides a process 65 for preparing a compound of formula (1) which com H-Y-Z (8) prises where (a) condensing a compound of formula (7) 5,034,393 7 8 P. Gramaccioni, and A. Vaciago, Gazz. Chim. Ital, 99, (1969). L (7) 4-Hydroxypyrimido5,4-cpyridazines can be pre B21 A. N pared by the procedures described in R. N. Castle and i H. Murakami, J. Hetero. Chem., 5, 523 (1968). E S. els 4-Hydroxypyrimido-4,5-dipyridazines can be pre S D N R2 pared by the procedures described in R. N. Castle, J. Hetero, Chenn., 5, 845 (1968). wherein R, R2, A, B, E, and D are as previously de 4-Chloro derivatives of formula (7) wherein L is Cl fined, and L is a leaving group with an alcohol of the 10 are prepared by chlorodehydroxylation of the corre formula (8): sponding 4-keto compounds using conventional meth ods, for example by reaction with POCl3. Intermediates of formula (7) wherein L is 1,2,4- HO-Y-Z (8) triazol-1-yl, can be prepared, for example, by adding wherein Y and Z are as previously defined to produce a 15 POCl3 dropwise to a mixture of a 4-hydrox compound of formula (1) wherein X is ; or ypyridopyrimidine (1 equiv.) and 1,2,4-triazole (3 (b) condensing a compound of formula (7) as defined equiv.) in pyridine at a temperature from 20 to 100° C. above with an amine of the formula (9) EXAMPLES 1-72 The following examples are compounds actually pre R3 (9) pared by the above described general procedures. The melting point is given for each compound. In addition, although the data has not been included, each com where R is H or (C1-C4) alkyl, and Y and Z are as pound was fully characterized by NMR, IR, mass spec previously defined, to provide a compound of formula tra, and combustion analysis. Specific illustrative prepa (1) where X is NR3; or rations for the compounds of Examples follow the tabu (c) acylating a compound of formula (1) wherein X is lar listing. NR3 to provide a compound of formula (1) wherein X is NR3 and R is acyl; or 30 EXAMPLE (d) hydrolyzing and decarboxylating a compound of NUMBER COMPOUND M.P. formula (10) l 4-(4-fluorophenoxy)pyrido?,3-d- 142-144 C. pyrimidine 2 4-(2-[4-(i-propyl)phenyl)ethyl- 198-200 C. Z-Y CO-NH (10) aminolpyrido(2,3-dipyrimidine N / V 35 3 4-2-(4-chlorophenyl)ethoxypyrido- 126-128 C. C CO V / 2,3-dipyrimidine CO-NH 4 4-2-(4-chlorophenyl)ethoxypyrido- 86° C. a s 3,2-dpyrimidine B N 5 4-2-[4-(1-butyl)phenyl)ethylamino)- 77-78° C. pyrido3.2-d)pyrinidine EI 40 6 4-(2-chloro-4-fluorophenoxy)pyrido- 8-82 C. SD N 2. 2,3-dipyrimidine 7 4-2-(4-ethoxyphenyl)ethoxypyrido- 74-75 C. 3,2-d)pyrimidine to produce a compound of formula (1) wherein X is 8 N-(2-phenylethyl)pyrido2,3-d)- 252-254 C CH2. pyrimidin-4-amine 45 9 N-(2-(2-naphthalenyl)ethylpyrido- 247-251 C Preparation of Pyridopyrimidine, Pyrimidopyrimidine, 2,3-dipyrimidin-4-amine and Pteridine Starting Materials O 4-2-(2,4-difluorophenyl)ethoxy)- 84-85 C. pyrido(2,3-d)pyrinidine 4-Hydroxypyridopyrimidine starting materials are 11 4-2-(4-ethoxyphenyl)ethoxypyrido- 62-64 C. commercially available or readily prepared using con 2,3-d)pyrimidine 2 N-(2-3-(trifluoromethyl)phenyl)- 90-93 C, ventional procedures. For example, useful synthetic 50 ethyl)pyrido.2.3-dipyrimidin-4-amine procedures are described in 13 N-(4-phenylbutyl)pyrido2,3-d- 79-8 C. R. K. Robins & G. H. Hitchings, J. Am. Chem. Soc., pyrimidin-4-amine 77, 2256 (1955); 14 N-(3-phenylpropyl)pyrido(2,3-d- 195-98 C. pyrimidin-4-amine S. Gabriel & J. Colman, Chem. Ber., 35, 2831 (1902); 5 4-(2-phenylethoxy)pyrido2,3-d- O-102 C. and 55 pyrimidine C. C. Price & D. Y. Curtin, J. Am. Chem. Soc., 68,914 16 N-(2-(4-chlorophenyl)ethylpyrido- 27-275 C. (1946). 2,3-dipyrimidin-4-amine 7 4-2-(4-methoxy-3-methylphenyl)- 113-14 C. 4-Hydroxypyrimido4,5-dipyrimidines can be pre ethoxypyrido(2.3-dpyrimidine pared using the procedure described in E. C. Taylor, et 18 4-3-(4-phenoxyphenyl)propoxy- oil al., J. Anner. Chem. Soc., 82, 6058 (1960). 60 pyrido2,3-d)pyrinidine 4-Hydroxypteridines can be prepared using the pro 9 N-(4-chlorophenyl)methylpyrido- 252-255 C. 2,3-d)pyrimidin-4-amine cedures described in A. Albert, D. J. Brown and G. 2O N-(2-(2,6-difluorophenyl)ethyl)- 263-266 C. Cheesman, J. Chen. Soc., 474 (1951). pyrido2,3-d)pyrimidin-4-amine 4-Hydroxypyrimido-4,5-cpyridazines can be pre 2 4-2-4-(trimethylsilyl)phenyl)- 90° C. pared by the procedures described in J. L. Styles and R. 65 ethoxypyridio2.3-dipyrimidine 22 4-2-(2-naphthalenyl)ethoxypyrido- 108 C. W. Morrison, J. Org. Chem., 50, 346 (1985). (2,3-d)pyrinidine 4-Hydroxypyrimido5,4-dipyrimidines can be pre 23 4-2-(4-methoxyphenyl)ethoxy)- 109-10 C. pared by the procedures described in F. A. Gianturro, pyrido2,3-dipyrimidine

5,034,393 11 12 tallized from toluene/hexane to give 9.0 g first crop, uct were combined to give a thick oil which crystallized M.P. 206-210° C., 5.7g second crop, M.P. 218-220 C., from petroleum ether. Yield 1.4g. M.P. 59-60 C. 1.45 g third crop, M.P. 205-209 C. B. The title compound was also made by mixing 1.47 EXAMPLE 41 g of pyrido2,3-dipyrimidin-4(3H)one and 2.07 g of 5 4-(2-4-(t-butyl)phenyl)ethoxypyrido(2,3-dpyrimidine 1,2,4-triazole in 50 mL of pyridine and adding 1.12 mL A mixture consisting of 1.86 g (0.011 mole) of 4 of POCl3 while stirring the mixture at room tempera chloropyrido-2,3-dipyrimidine, 2.0 g (0.0ll mole) of ture. After stirring the mixture overnight, 500 mL of 2-4-(t-butyl)phenyl)ethanol, and 40 mL of toluene con CH2Cl2 was added, and the mixture was washed Succes taining a little HCl gas was stirred at room temperature. sively with 500 mL of 2% HCl and 500 mL of water, O The mixture was then cooled, and a yellow solid was and then dried over MgSO4. Solvent was evaporated collected. This was washed with hexane, then parti under vacuum to leave 0.4 of yellow solid, which was tioned between 1N NaOH and CH2Cl2. The CH2Cl2 recrystallized from toluene/hexane. M.P. 217-219 C. layer was dried over MgSO4, then the solvent was EXAMPLE 2 5 removed under vacuum to leave a yellow solid, which 4-2-4-(i-propyl)phenyl)ethylaminol-pyrido2,3-d}- was recrystallized from hexane. Yield 2.5 g. M.P. pyrimidine 77-79° C. A mixture consisting of 1.98 g (.01 mole) of 4-1'- EXAMPLE 50 (1,2,4-triazolyl)pyrido2,3-dipyrimidine, 1.63 g (0.01 4-2-[4-(t-butyl)phenyl)ethylaminolpyrido-4,3- mole) of 2-4-(i-propyl)phenyl)ethylamine, and 50 mL 20 d)pyrimidine of CHCl3 was stirred at reflux for two hours. Then l.0 A mixture consisting of 0.45 g of pyrido-4,3- g (0.01 mole) of triethyl amine was added, and the mix dpyrimidine-4-ol, 0.53 g of 2-4-(t-butyl)phenyl)ethyla ture was refluxed for four hours. After washing the mine, about 40 mg of (NH4)2SO4 in 4 mL of hexameth mixture with water, the CHCl3layer was dried over 25 yldisilazane was refluxed for about five hours. The MgSO4. The CHCl3 was removed using a vacuum and mixture was then cooled and excess disilaZane was re the product was recrystallized from EtOH/H2O. Yield moved in vacuo. The residue was dissolved in CH2Cl2, 1.5 g. This product was recrystallized from ethyl ace and the solution was washed with water and filtered tate. M.P. 200-203 C. through phase separating paper. Evaporated the EXAMPLE 3 30 CH2Cl2 and adsorbed the residue onto silica gel, which was applied to a thin silica pad and eluted with 4-2-(4-chlorophenyl)ethoxypyrido2,3-d)pyrimidine CH2Cl2-50% EtOAc/50% CH2Cl2 EtOAc. Fractions A mixture consisting of 1.48 g (7.5 mmole) of 4 containing the major product were combined and the 1'(1,2,4-triazolyl)-pyrido2,3-dipyrimidine, 1.20 g of product which crystallized was recrystallized from 2-(4-chlorophenyl)ethanol (7.5 mmole), and 50 mL of 35 hexane/EtOAc. Yield 0.2g. M.P. 157-158 C. toluene which had been treated with dry HCl gas was stirred at room temperature, heated gently for about EXAMPLE 55 one and one half hours, then cooled. TLC indicated that 4-2-4-(t-butyl)phenyl)ethoxypteridine the reaction was not complete, so additional alcohol To a suspension of 2 g of 4-hydroxypteridine in 20 was added and the mixture was warmed. After cooling mL of CH2Cl2 under nitrogen was added 1.2 g of 25 the mixture, it was diluted with water and made basic pyridine. The mixture was cooled to -30 C and over a with 1.0 N NaOH. The product was extracted from the 15 minute period a solution of 4.82 g of triphenyl phos mixture into toluene, which was then washed with Satu rated brine, filtered through phase separating paper, and phite in CH2Cl2 was added simultaneously with addi 45 tion of chlorine gas. The mixture was stirred for one and concentrated in vacuo. The oily residue that crystal one half hours while maintaining the temperature at lized was chromatographed (silica gel, CH2Cl2-70% - 15 to -20°C. The mixture was then allowed to warm CHCl2/30% EtOAc). The fractions containing the to 10° C., and a solution of 2.67 g of 2-4-(t-butyl)- major product were combined, and the product crystal phenyl)ethanol in CH2Cl2 was added. The resulting lized. The product was recrystallized from CH2Cl2/pe 50 mixture was refluxed for 45 minutes, then cooled and troleum ether. Yield 1.05 g. M.P. 126-128 C. diluted into toluene. The toluene solution was washed EXAMPLE 26 with dilute base, then filtered through phase separating paper and concentrated in vacuo. The resulting bluish 4-2-4-(t-butyl)phenyl)ethoxypyrido3,4-dpyrimidine oil was adsorbed onto Silica gel and chromatographed To a suspension of 300 mg of 60% NaH in 15 mL of 55 (silica gel, CH2Cl2-80% CH2Cl2, 20% EtOAc). Frac DMF was added 1.33 g of 2-4-(t-butyl)phenyl)ethanol. tions containing the major product were combined. The The mixture was stirred at room temperature for 30 product was then recrystallized from petroleum minutes. The 1.48g of 4-1'-(1,2,4-triazolyl)pyrido3,4- ether/CH2Cl2. Yield 60 mg. M.P. 149 C. d)pyrimidine was added and the mixture was stirred at room temperature overnight. Solvent was then re Fungicide Utility moved in vacuo, azeotroping with xylene. The residue The compounds of the present invention have been was diluted with water and the pH was adjusted to found to control fungi, particularly plant pathogens. neutral by adding dilute HC1. The product was ex When employed in the treatment of plant fungal dis tracted into CHCl2, which was then washed with eases, the compounds are applied to the plants in a dis brine, dried over Na2SO4, filtered, and concentrated. 65 ease inhibiting and phytologically acceptable amount. The residue was adsorbed onto silica gel and chromato The term "disease inhibiting and phytologically accept graphed, eluting with CH2Cl2 to 75/25 able amount,' as used herein, refers to an amount of a CH2Cl2/EtOAc. Fractions containing the major prod compound of the invention which kills or inhibits the 5,034,393 13 14 plant disease for which control is desired, but is not significantly toxic to the plant. This amount will gener PLANT PATHOLOGY SCREEN ally be from about 1 to 1000 ppm, with 10 to 500 ppm EXAMPLE POWD RICE LEAF GRAY DOWN being preferred. The exact concentration of compound NUMBER MDEW BLAST RUST MOLD MDEW required varies with the fungal disease to be controlled, - - - - - the type formulation employed, the method of applica 2 ------tion, the particular plant species, climate conditions and 3 ------4 ------the like. A suitable application rate is typically in the 5 ------range from 0.25 to 4 lb/A. The compounds of the inven O 6 ------tion may also be used to protect stored grain and other 7 ------8 ------non-plant loci from fungal infestation. 9 ------Greenhouse Tests 10 ------11 ------The following experiments were performed in the 12 ------5 13 ------laboratory to determine the fungicidal efficacy of the 14 ------compounds of the invention. 15 ------This screen was used to evaluate the efficacy of the 16 ------present compounds against a variety of different organ 7 ------8 ------isms that cause plant diseases. 9 ------The test compounds were formulated for application 20 ------by dissolving 50 mg of the compound into 1.25 ml of 2 ------22 ------solvent. The solvent was prepared by mixing 50 ml of 23 ------

"Tween 20' (polyoxyethylene (20) sorbitan monolau 24 ------rate emulsifier) with 475 ml of acetone and 475 ml of 25 25 ------ethanol. The solvent/compound solution was diluted to 26 ------27 ------125 ml with deionized water. The resulting formulation 28 ------contains 400 ppm test chemical. Lower concentrations 29 ------were obtained by serial dilution with the solvent-sur 30 ------factant mixture. 30 31 ------32 ------The formulated test compounds were applied by 33 ------foliar spray. The following plant pathogens and their 34 ------corresponding plants were employed. 35 ------36 ------35 37 ------Designation in 38 ------Pathogen Following Table Host 39 ------40 ------Erysiphe graminis tritici POWD wheat 41 ------(powdery mildew) MDEW 43 ------Pyricularia oryzae RICE rice 44 ------(rice blast) BLAS 45 ------Puccinia recondita tritici LEAF wheat 46 ------(leaf rust) RUST 47 ------Botrytis cinerea GRAY grape berries 48 ------(gray mold) MOLD 49 -- m ------Pseudoperonospora cubensis DOWN Squash 50 ------(downy mildew) MDEW 45 5 ------Cercospora beticola LEAF Sugar beet 52 ---- m ------(leaf spot) SPOT 53 - - -- O -- Venturia inaequalis APPL apple seedling 54 ------. O ---- (apple scab) SCAB 55 ------Septoria tritici LEAF wheat 61 ------50 65 -- m ------(leaf blotch) BLOT 67 ------72 ------The formulated technical compounds were sprayed on all foliar surfaces of the host plants (or cut berry) to Combinations past run-off. Single pots of each host plant were placed 55 on raised, revolving pedestals in a fume hood. Test Fungal disease pathogens are known to develop resis solutions were sprayed on all foliar surfaces. All treat tance to fungicides. When strains resistant to a fungicide ments were allowed to dry and the plants were inocu do develop, it becomes necessary to apply larger and lated with the appropriate pathogens within 2-4 hours. larger amounts of the fungicide to obtain desired results. The following Table presents the activity of typical 60 To retard the development of resistance to new fungi compounds of the present invention when evaluated in cides, it is desirable to apply the new fungicides in com this experiment. The effectiveness of test compounds in bination with other fungicides. Use of a combination controlling disease was rated using the following scale. product also permits the product's spectrum of activity O= not tested against specific organism to be adjusted. - = 0-19% control at 400 ppm 65 Accordingly, another aspect of the invention is a + = 20-89% control at 400 ppm fungicidal combination comprising at least 1% by + + =90-100% control at 400 ppm weight of a compound of formula (1) in combination ---|--|- =90-100% control at ppm with a second fungicide. 5,034,393 15 16 Contemplated classes of fungicides from which the Second fungicide may be selected include: Insecticide and Miticide Utility 1) N-substituted azoles, for example propiconazole, The compounds of the invention are also useful for triadenefon, flusilazol, diniconazole, ethyltrianol, my the control of insects and mites. Therefore, the present clobutanil, and prochloraz; 5 invention also is directed to a method for inhibiting an 2) pyrimidines, such as fenarimol and nuarimol; insect or mite which comprises applying to a locus of 3) morpholines, such as fenpropimorph and tride- the insect or mite an insect- or mite-inhibiting amount of morph; a compound of formula (1). 4) piperazines, such as triforine; and The compounds of the invention show activity 5) pyridines, such as pyrifenox. 10 against a number of insects and mites. More specifically, Fungicides in these five classes all function by inhibiting the compounds show activity against melon aphid, sterol biosynthesis. Additional classes of contemplated which is a member of the insect order Homoptera. fungicides, which have other mechanisms of action Other members of the Homoptera include leafhoppers, include: planthoppers, pear pyslla, apple sucker, Scale insects, 6) dithiocarbamates, such as maneb and mancozeb; 15 whiteflies, spittle bugs as well as numerous other host 7) phthalinides, such as captafol; specific aphid species. Activity has also been observed 8) isophthalonitrites, such as chlorothalonil; against greenhouse thrips, which are members of the 9) dicarboximides, such as iprodione; order Thysanoptera. The compounds also show activity 10) benzinidazoles, such as benomyl and carben- against Southern armyworm, which is a member of the dazim; 20 insect order Lepidoptera. Other typical members of this li) 2-aminopyrimidines, such as ethirimol; order are codling moth, cutworm, clothes moth, Indian 12) carboxamides, such as carboxin; meal moth, leaf rollers, corn earworm, European corn 13) dinitrophenols, such as dinocap; and borer, cabbage worm, cabbage looper, cotton boll 14) acylalanines, such as metalaxyl. worm, bagworm, eastern tent caterpillar, sod web The fungicide combinations of the invention contain 25 worm, and fall armyworm. at least 1%, ordinarily 20 to 80%, and more typically 50 Representative mite species with which it is contem to 75% by weight of a compound of formula (1). plated that the present invention can be practiced in clude those listed below.

FAMILY SCIENTIFIC NAME COMMON NAME ACARIDAE Aleurobius farinae Rhizoglyphus echinopus Bulb mite Rhizoglyphus elongatus Rhizoglyphus rhizophagus Rhizoglyphus Sagittatae Rhizoglyphus tarsalis Abacarus farinae Grain rust Inite Aceria brachytarsus Acalitus essigi Redberry mite Aceraficus Aceria fraaxinivorus .-ceria granati Aceria parapopuli sheldoni Citrus bud mite Aceria tulipae A cuius carnutus Peach silver inite - cuius schlechtendali Apple rust mite Colomerus vitis Grape erineum mite Eriophyes convolvens Eriophyes insidiosus Eriophyes malifoliae Eriophyes padi Eriophyes pruni Epitrimerus pyri Pear leaf blister mite Eriophyes ramosus Eriophyes sheldoni Citrus bud mite Eriophyes ribis Phylocoptes gracilis Dryberry mite Phylocoptruta oleiyora Citrus rust mite Phytoptus ribis Trisetacus pini Vasates amygdalina Vasates eurynotus Wasates quadripedes Maple bladdergall mite Vasaies schlechtendai EUPODIDAE Penthaleus major Winter grain mite Linopodes spp. NALEPELLIDAE Phylocoptella avellanae Filbert bud Inite PENTHALEIDAE Halotydeus destrustor PYEMOTIDAE Pyemotes tritici Straw itch mite Siteroptes cerealium TARSONEMIDAE Polyphagotarisonemus latus Broad mite Steneotarsonemus paidus Cyclamen mite TENUIPALPIDAE Brevipalpus californicus Brevipalpus obovatus Privet mite Brevipalpus lewisi Citrus fat inite 5,034,393 17 18 -continued FAMILY SCIENTIFIC NAME COMMON NAME Dolichotetranychus floridanus Pineapple flase spider inite Tenuipalpes granati Tenuipalpes pacificus TETRANYCHIDAE Bryobia arborea Bryobia practiosa Clover mite Bryobia rubrioculus Brown mite Eotetranychus coryli Eotetranychus hicoriae Pecan deaf scorch mite Eotetranychus lewisi Eotetranychus sexmaculatus Sixspotted spider mite Eotetranychus willametti Eotetranychus banksi Texas citrus mite Oligonychus ilicis Southern red mite Oligonychus pratensis Banks grass mite Oligonychus ununguis Spruce spider mite Panonychus citri Citrus red mite Panonychus ulmi European red mite Paratetranychus modestus Paratetranychus pratensis Paratetranychus viridis Petrobia latens Brown wheat nite Schizotetranychus cellarius Bamboo spider nite Schizotetranychus praiensis Tetranychus canadensis Fourspotted spider mite Tetranychus cinnabarinus Carmine spider mite Tetranychus mcdanieli McDaniel spider mite Tetranychus pacificus Pacific spider mite Tetranychus schoenei Schoene spider mite Tetranychus urticae Twospotted spider mite Tetranychus turkestani Strawberry spider mite Tetranychus desertorum Desert spider mite

MITE/INSECT SCREEN The compounds of Examples 1-10 were tested for miticidal and insecticidal activity in the following mite The compounds are useful for reducing populations 35 /insect screen. of insects and mites, and are used in a method of inhibit Each test compound was formulated by dissolving ing an insect or mite population which comprises apply the compound in acetone/alcohol (50:50) mixture con ing to a locus of the insect or an effective taining 23 g of "TOXIMUL R" (sulfonate/nonionic insect- or mite-inactivating amount of a compound of emulsifier blend) and 13 g of "TOXIMUL S" (sul formula (l). The "locus' of insects or mites is a term 40 fonate/nonionic emulsifier blend) per liter. These mix used herein to refer to the environment in which the tures were then diluted with water to give the indicated insects or mites live or where their eggs are present, concentrations. including the air surrounding them, the food they eat, or Twospotted spider mites (Tetranychus urticae Koch) objects which they contact. For example, plant-ingest and melon aphids (Aphis gossypii Glover) were intro ing insects or mites can be controlled by applying the 45 duced on squash cotyledons and allowed to establish on active compound to plant parts, which the insects or both leaf surfaces. Other plants in the same treatment mites eat, particularly the foliage. It is contemplated pot were left uninfested. The leaves were then sprayed that the compounds might also be useful to protect with 5 ml of test solution using a DeVilbiss atomizing textiles, paper, stored grain, or seeds by applying an sprayer at 10 psi. Both surfaces of the leaves were cov active compound to such substance. The term "inhibit 50 ered until runoff, and then allowed to dry for one hour. ing an insect or mite" refers to a decrease in the num Two uninfested leaves were then excised and placed bers of living insects or mites; or a decrease in the num into a Petri dish containing larval southern armyworm ber of viable insect or mite eggs. The extent of reduc (Spodopetra eridania Cramer). tion accomplished by a compound depends, of course, Activity on Southern corn rootworm (Diabrotica upon the application rate of the compound, the particu 55 undecimpuctata howardi Barber) was evaluated by add lar compound used, and the target insect or mite spe ing two ml of tap water, a presoaked corn seed, and 15 cies. At least an insect-inactivating or mite-inactivating g of dry sandy soil to a one ounce plastic container. The amount should be used. The terms "insect-inactivating soil was treated with 1 mL of test solution containing a amount' and "mite-inactivating amount' are used to predetermined concentration of test compound. After describe the amount, which is sufficient to cause a mea six to 12 hours of drying, five 2-3 instar corn rootworm surable reduction in the treated insect or mite popula larvae were added to the individual cups, which were tion. Generally an amount in the range from about 1 to then capped and held at 23° C. about 1000 ppm active compound is used. After standard exposure periods, percent mortality In a preferred embodiment, the present invention is and phytotoxicity were evaluated. Results for the com directed to a method for inhibiting a mite which com 65 pounds found to be active are reported in the following prises applying to a plant an effective mite-inactivating table. The remaining compounds showed no activity. amount of a compound of formula (1) in accordance The following abbreviations are used in the following with the present invention. table: 5,034,393 19 20 CRW refers to corn rootworn - contine SAW refers to Southern armyworm MITE AND INSECT SCREEN SM refers to twospotted spider mites SAW SM MA MA refers to melon aphids. EXAMPLE RATE RESULTS RESULTS RESULTS 5 NUMBER PPM % % MITE AND INSECT SCREEN OO 20 O O 39 2OO O 8O O SAW SM MA 400 O O O EXAMPLE RATE RESULTS RESULTS RESULTS 40 200 20 O O NUMBER PPM % 6. O 400 O O O 400 O O O 4. 200 O OO 100 2 200 O O O 400 O 100 100 400 8O O O 44 200 O O O 3 2OO O O O 400 40 O O 400 O O O 45 200 O O O 4. 2OO O O O 400 O O O 400 O O O 15 46 400 O O O 5 2OO O OO 90 47 200 O 20 90 400 O OO 100 400 O O O 6 400 O O O 48 2OO O 8O 60 7 200 O O 90 400 O O O 400 O O O 49 200 O O O 8 OO O O O 400 O O O 400 O O O SO 2OO O 90 70 9 2OO 8O O O 4OO O O O 400 70 O O 5 2OO SO 8O 8O O 2OO O 90 90 400 40 O O 2OO O 80 OO 52 2OO O O O 400 O OO OO 400 O 100 1OO 11 200 O OO OO 53 400 O O O OO O 100 100 54 400 O 100 OO 12 200 O O O 55 400 O O O 400 O O O 57 2OO O 90 90 13 OO 60 O O 400 O 8O 1OO 1OO O O O 30 6 400 O O N.A. l4 OO O O 50 64 400 O O O 400 O O O 65 2OO 90 O O ls OO O O O 400 OO O O OO O 8O SO 67 400 O O OO 6 OO 8O O O 68 OO O O O 400 O O O 35 72 200 O O O 17 OO O 80 8O 400 O O O OO O 60 8O 8 200 O 30 80 400 O 90 90 19 OO O O O Compositions 400 O O O 40 2O OO O O O The compounds of this invention are applied in the 400 O O O form of compositions which are important embodi 2 OO 70 OO OO ments of the invention, and which comprise a com OO O OO 60 pound of this invention and a phytologically-acceptable 200 90 OO OO 400 O 60 8O inert carrier. The compositions are either concentrated 23 OO O O 90 45 formulations which are dispersed in water for applica 4OO O 40 8O tion, or are dust or granular formulations which are 24 400 O O O applied without further treatment. The compositions 25 200 8O 50 60 are prepared according to procedures and formulae 400 O O O 26 OO O 100 8O which are conventional in the agricultural chemical art, 400 O O O but which are novel and important because of the pres 27 200 O O O ence therein of the compounds of this invention. Some 400 O O O description of the formulation of the compositions will 28 OO O 20 30 400 O O O be given, however, to assure that agricultural chemists 29 OO O OO 90 can readily prepare any desired composition. 400 O SO 8O 55 The dispersions in which the compounds are applied 30 200 O 100 1OO are most often aqueous suspensions or emulsions pre 400 O 100 OO 3. OO O O O pared from concentrated formulations of the com 32 200 60 OO 90 pounds. Such water-soluble, water-suspendable or 400 O O O emulsifiable formulations are either solids usually 33 OO O O O 60 known as wettable powders, or liquids usually known as OO O O O 34 200 60 O O emulsifiable concentrates or aqueous suspensions. Wet 400 O O O table powders, which may be compacted to form water 35 OO O O 60 dispersible granules, comprise an intimate mixture of OO O O O the active compound, an inert carrier and Surfactants. 36 200 O O O 65 OO O O O The concentration of the active compound is usually 37 OO O O O from about 10% to about 90% by weight. The inert 4OO O O O carrier is usually chosen from among the attapulgite 38 OO O O O clays, the montmorillonite clays, the diatomaceous 5,034,393 21 22 earths, or the purified silicates. Effective surfactants, The compounds of the invention can also be applied comprising from about 0.5% to about 10% of the wetta in the form of an aerosol composition. In such composi ble powder, are found among the sulfonated lignins, the tions the active compound is dissolved or dispersed in condensed naphthalenesulfonates, the naphthalenesul an inert carrier, which is a pressure-generating propel fonates, the alkylbenzenesulfonates, the alkyl sulfates, 5 lant mixture. The aerosol composition is packaged in a and non-ionic surfactants such as ethylene oxide ad container from which the mixture is dispensed through ducts of alkyl phenols. an atomizing valve. Propellant mixtures comprise either Emulsifiable concentrates of the compounds com low-boiling halocarbons, which may be mixed with prise a convenient concentration of a compound, such organic solvents, or aqueous suspensions pressurized as from about 50 to about 500 grams per liter of liquid, 10 with inert gases or gaseous hydrocarbons. equivalent to about 10% to about 50%, dissolved in an The actual amount of compound to be applied to loci inert carrier which is either a water miscible solvent or of insects and mites is not critical and can readily be a mixture of water-immiscible organic solvent and determined by those skilled in the art in view of the emulsifiers. Useful organic solvents include aromatics, examples above. In general, concentrations of from 10 especially the xylenes, and the petroleum fractions, 15 ppm to 5000 ppm of compound are expected to provide especially the high-boiling naphthalenic and olefinic good control. With many of the compounds, concentra portions of petroleum such as heavy aromatic naphtha. tions of from 100 to 1500 ppm will suffice. For field Other organic solvents may also be used, such as the crops, such as soybeans and cotton, a suitable applica terpenic solvents including rosin derivatives, aliphatic tion rate for the compounds is about 0.5 to 1.5 lb/A, ketones such as cyclohexanone, and complex alcohols typically applied in 50 gal/A of spray formulation con such as 2-ethoxyethanol. Suitable emulsifiers for emulsi taining 1200 to 3600 ppm of compound. For citrus fiable concentrates are chosen from conventional non crops, a suitable application rate is from about 100 to ionic surfactants, such as those discussed above. 1500 gal/A spray formulation, which is a rate of 100 to Aqueous suspensions comprise suspensions of water 1000 ppm. 25 The locus to which a compound is applied can be any insoluble compounds of this invention, dispersed in an locus inhabited by an insect or arachnid, for example, aqueous vehicle at a concentration in the range from vegetable crops, fruit and nut trees, grape vines, and about 5% to about 50% by weight. Suspensions are ornamental plants. Inasmuch as many mite species are prepared by finely grinding the compound, and vigor specific to a particular host, the foregoing list of mite ously mixing it into a vehicle comprised of water and 30 surfactants chosen from the same types discussed above. species provides exemplification of the wide range of Inert ingredients, such as inorganic salts and synthetic settings in which the present compounds can be used. or natural gums, may also be added, to increase the Because of the unique ability of mite eggs to resist density and viscosity of the aqueous vehicle. It is often toxicant action, repeated applications may be desirable most effective to grind and mix the compound at the 35 to control newly emerged larvae, as is true of other same time by preparing the aqueous mixture, and ho known acaricides. mogenizing it in an implement such as a sand mill, ball The following formulations of compounds of the mill, or piston-type homogenizer. invention are typical of compositions useful in the prac The compounds may also be applied as granular com tice of the present invention. positions, which are particularly useful for applications 40 to the soil. Granular compositions usually contain from A. 0.75 Emulsifiable Concentrate about 0.5% to about 10% by weight of the compound, Compound of Example 25 9.38% dispersed in an inert carrier which consists entirely or in 'TOXIMUL D' 2.50% (nonionic/anionic surfactant blend) large part of clay or a similar inexpensive substance. TOXIMUL H' 2.50% Such compositions are usually prepared by dissolving 45 (nonionic/anionic surfactant blend) the compound in a suitable solvent, and applying it to a *EXXON 200' 85.62% granular carrier which has been pre-formed to the ap (naphthalenic solvent) propriate particle size, in the range of from about 0.5 to B. 1.5 Emulsifiable Concentrate Compound of Example 25 18.50% 3 mm. Such compositions may also be formulated by "TOXIMUL D' 2.50% making a dough or paste of the carrier and compound, 50 TOXIMUL H' 2.50% and crushing and drying to obtain the desired granular "EXXON 200' 76.50% particle size. C. 0.75 Emulsifiable Concentrate Dusts containing the compounds are prepared simply Compound of Example 41 9.38% by intimately mixing the compound in powdered form "TOXIMUL D' 2.50% TOXIMUL H' 2.50% with a suitable dusty agricultural carrier, such as kaolin 55 "EXXON 200' 85.62% clay, ground volcanic rock and the like. Dusts can suit D. 1.0 Emulsifiable Concentrate ably contain from about 1% to about 10% of the com Compound of Example 41 2.50% pound. N-methylpyrrollidone 25,00% It is equally practical, when desirable for any reason, 'OXIMUL D' 2.50% TOXIMUL H' 250c to apply the compound in the form of a solution in an "EXXON 200' 57.50% appropriate organic solvent, usually a bland petroleum E. 1.0 Aqueous Suspension oil, such as the spray oils, which are widely used in Compound of Example 25 1200c agricultural chemistry. PLURONICP-O3' 1.50% Insecticides and miticides are generally applied in the (block copolymer of propylene oxide 65 and ethylene oxide, surfactant) form of a dispersion of the active ingredient in a liquid 'PROXEL GXL' .05% carrier. It is conventional to refer to application rates in (biocide/preservative) terms of the concentration of active ingredient in the "AF-100' 20% carrier. The most widely used carrier is water. (silicon based antifoam agent) 5,034,393 23 24 -continued 'REAX S8B' 100% X-Y-Z (1) (lignosulfonate dispersing agent) propylene glycol 0.00% 2^ n veegun 75% xanthan 25% f Water 74.25% s N 2. F. 10 Aqueous Suspension Compound of Example 25 2.50% wherein "MAKON 10" (10 moles ethyleneoxide 1.00% nonylphenol surfactant) O or A, C, and D are N and B is CR; "ZEOSYL 200' (silica) 1.00% a) A is N and B, E, and D are CR; "AF.OO' 0.20% b) B is N and E, E, and D are CR; 'AGRIWET FR" (surfactant) 3.00% c) E is N and A, B, and D are CR; 2% xanthan hydrate 0.00% Water 72.30% d) D is N and A, B, and E are CR; G. 1.0 Aqueous Suspension 15 e) A and D are N and B and E are CR; Compound of Example 41 2.50% f) B and D are N and A and E are CR; "MAKON O' 1.50% g) E and D are N and A and B are CR; "ZEOSYL 200' (silica) 1.00% h) A and E are N and B and D are CR; "AF-100' O.20% i) A and B are N and E and D are CR; “POLY FON H' 0.20% (ignosulfonate dispersing agent) j) A and B are N and E and D are CR; 2% xanthan hydrate 10.00% k) A, E, and D are N and B is CR; wa 74.60% where R1 and R2 are independently H, halo H. Wettable Powder (C1-C4) alkyl, (C3-C4) branched alkyl, (C1-C4) Compound of Example 25 25.80% alkoxy, halo (C1-C4 alkyl, phenyl, or substituted 'POLY FON H' 3.50% 25 phenyl: "SELLOGEN HR' 5.OOC 'STEPANOL ME DRY' O09. X is O, S, SO, SO2, NR3, or CRR5, where R3 is H, gun arabic O.50. (C1-C4) alkyl, or (C1-C4) acyl, and R* and R5 are 'HISL 233' 2.50% independently H, (C1-C4) acyl, (C1-C4) alkyl, Barden clay 61.707 (C2-C4) alkenyl or -alkynyl, CN, or OH, or R* and I. Aqueous Suspension 30 R5 combine to form a carbocyclic ring containing Compound of Example 25 1240. TERGITOL 58.7' 5.00% four to six carbon atoms; 'ZEOSYL 200' OO6. Y is a bond or an alkylene chain one to six carbon “AF.OO' O.2O6 atoms long, optionally including a carbocyclic “POLY FON H' O.50% ring, and optionally including a hetero atom se 2% xanthan solution 1O.OOc. 35 lected from O, NR3, S, SO, SO2, or SiR20R21, tap water 70.90% J. Emulsifiable Concentrate where R3 is as defined above and R20 and R2 are Compound of Example 25 2.40% independently (C1-C4) alkyl, (C3-C4) branched TOXIMUL D' 2.50% alkyl, phenyl, or substituted phenyl, and optionally TOXMU H' 2.50c. Substituted with (C1-C4) alkyl, (C2-Cs) alkenyl or *EXXON OO' 82.60% 40 -alkynyl, branched (C3-C7) alkyl, (C3-C7) cycloal K. Wettable Powder kyl or -cycloalkenyl, halo, hydroxy, or acetyl, and Compound of Example 41 25.806. Z is 'SELLOGEN HR S.OO7. POLY FON H' 4,006. (a) a (C1-C2) saturated or unsaturated hydrocarbon STEPANOL ME ERY' 2.00% chain, straight chain or branched optionally includ 'HISL 233' 3.00% 45 ing a hetero atom selected from O, S, SO, SO2, or Barden clay 60.20% SiROR2, where R20 and R2 are as defined above, L. Emulsifiable Concentrate and optionally Substituted with halo, haio (C1-C4) Compound of Example 25 6.19% alkoxy, hydroxy, (C3-C8) cycloalkyl or cycloalke TOXIMUL H' 3.60% TOXMUL D' 0.0% nyl, or (C1-C4) acyl; *EXXON 200' 89.8% 50 (b) (C3-C8) cycloalkyl or cycloalkenyl, optionally M. Wettable Powder Substituted with (C1-C4) alkyl, (C1-C4) alkoxy, Compound of Example 25 25.80% halo (C1-C4) alkyl, halo (C1-C4) alkoxy, halo, hy 'SELLOGEN HR 5.00% droxy, or (C1-C4) acyl; 'POLY FON H' 4.00% "STEPANOL ME DRY' 2.00% (c) a phenyl group of the formula (2) 'HISIL 233 3.00% 55 Barden clay 60.20% R6 R7 (2) N. Aqueous Suspension Compound of Example 41 2.0% “TERGITOL 58-7' SOO. R8 ZEOSYLOO' 100% 60 POLY FON H' 0.50 *AF-OO' O.20% Xanthan solution (2%) 10.00% R10 R9 tap water 70.90c where We claim: 65 R6 to R10 are independently H, halo, I, (C1-C10) alkyl, 1. A fungicidal composition comprising a compound (C3-Cs) alkenyl or -alkynyl, branched (C3-C6) of formula (i): alkyl, -alkenyl, or -alkynyl, (C3-Cs) cycloalkyl or -cycloalkenyl, halo (C-C7) alkyl, (C-C) alkoxy, 5,034,393 25 26 (C-C7) alkylthio, halo (C1-C7) alkoxy, phenoxy, 6. A composition of claim 3 wherein the compound of substituted phenoxy, phenylthio, substituted phe formula (l) is one wherein Y is a chain at least two nylthio, phenyl, substituted phenyl, NO2, acetoxy, atoms iong. OH, CN, SiR11R12R13, OSiR 11R12R13, NR 14R 15, 7. A composition of claim 3 wherein the compound of S(O)R16, or SOR17 where R11, R12, and R13 are formula (1) is one wherein Z is a group of formula (2). independently (C1-C4) alkyl, (C3-C4) branched 8. A composition of claim 7 wherein the compound of alkyl, phenyl, or substituted phenyl, R1 and Ris formula (1) is one wherein at least one of R6 to R10 is are independently H, (C1-C4) alkyl, or (C1-C4) branched (C3-C6) alkyl, halo (C1-C4) alkyl, halo acyl, and R6 and R17 are (C1-C10) alkyl, phenyl, or (C1-C4) alkoxy, phenyl, substituted phenyl, phenoxy, substituted phenyl; 10 substituted phenoxy, phenylthio, substituted phe (d) a furyl group of formula (3) nylthio, SiR11R12R13, or OSiR11R12R13. 9. A composition of claim 1 wherein the compound of formula (1) is 4-2-4-(t-butyl)phenyl)ethoxypyrido (3) 2,3-dipyrimidine. 5 10. A composition of claim 1 wherein the compound O of formula (1) is 4-2-(1, 1'-biphenyl)-4-ylethoxy)- pyrido2,3-d)pyrimidine. where R8 is H, halo, halomethyl, CN, NO2, 11. A composition of claim 1 wherein the compound (C1-C4) alkyl, (C3-C4) branched alkyl, phenyl, or of formula (1) is 4-2-(4-ethoxyphenyl)ethoxy)- (C1-C4) alkoxy; 20 pyrido2,3-d)pyrimidine. (e) a thienyl group of the formula (4) 12. A composition of claim 1 wherein the compound of formula (1) is one wherein X is NR3. (4) 13. A composition of claim 12 wherein the compound of formula (1) is one wherein X is NH. 25 14. A composition of claim 12 wherein the compound S of formula (1) is one wherein Z is a group of formula (2). 15. A composition of claim 14 wherein the compound where R8 is as defined in paragraph (d); of formula (1) is one wherein at least one of R6 to R10 is (f) a group of formula (5) or (6) branched (C3-C6) alkyl, halo (C1-C4) alkyl, halo 30 (C1-C4) alkoxy, phenyl, substituted phenyl, phenoxy, (5) substituted phenoxy, phenylthio, substituted phe nylthio, SiR11R12R13, or OSiR11R12R13. 16. A composition of claim 12 wherein the compound sts." of formula () is one wherein Y is a chain at least two (6) 35 atoms long. 17. A composition of claim 1 wherein the compound of formula () is one wherein Y is a chain at least two atoms long. 18. A composition of claim 1 wherein the compound where R8 is as defined in paragraph (d), J is N or of formula (1) is one wherein Z is a group of formula (2). CH, and G is O, NR19, or S, provided that if J is not 19. A composition of claim 1 wherein the compound N then G is NR19, where R19 is H, (C-C) alkyl, of formula (1) is one wherein at least one of R6 to R10 is (C1-C4) acyl, phenylsulfonyl, or substituted branched (C3-C6) alkyl, halo (C1-C4) alkyl, halo phenylsulfonyl; (C1-C4) alkoxy, phenyl, substituted phenyl, phenoxy, (g) a group selected from 45 optionally substituted naphthyl, dihydronaphthyl, substituted phenoxy, phenylthio, substituted phe tetrahydronaphthyi, and decahydronaphthyl; nylthio, SiR1|R12R13, or OSiR11R12R13. optionally substituted pyridyl; 20. A composition of claim 1 wherein the compound optionally substituted indolyl; of formula () is one of the formula (la) and 1,3-benzodioxolyl; 50 or an acid addition salt of a compound of formula R6 R7 (a) (l); provided that the following compounds are excluded: 1) pyrido(2,3-dipyrimidines of formula (1) wherein X X-Y R8 and NR3 in combination with a phytologically 55 acceptable carrier. 10 9 2. A plant fungicidal method which comprises apply 4 wa R R ing to the locus of a plant pathogen a disease inhibiting i and phytologically acceptable amount of a compound E Sa els of formula (l) as defined in claim 1. 60 S D N R2 3. A composition of claim 1 wherein the compound of formula (1) is one wherein X is O. wherein A, B, and E are CR1 and X, Y, R2, R6, R7, R8, 4. A composition of claim 3 wherein the compound of R9, and R10 are as defined in claim 1. formula (1) is one wherein A, G, and E are CR and D 21. A composition of claim 1 wherein the compound is N. 65 of formula (1) is one wherein 5. A composition of claim 4 wherein the compound of a) A is N and B, E, and D are CR; formula (l) is one wherein at least two of A, B, and E b) B is N and A, E, and D are CR; are CH. c) E is N and A, B, and D are CR; 5,034,393 27 28 d) D is N and A, B, and E are CRl; or 32. A composition of claim 21 wherein the compound of formula () is one wherein A and D are N and B and e) A and D are N and B and E are CRI. E are CR1. 22. A composition of claim 21 wherein the compound 33. A composition of claim 32 wherein X is O. of formula (1) is one wherein A is N and B, E, and D are 5 34. A composition of claim 32 wherein X is NR3. CR1. 35. A composition of claim 21 wherein the compound 23. A composition of claim 22 wherein X is O. of formula () is one wherein B and D are N and A and E are CR1. 24. A composition of claim 22 wherein X is NR3. 36. A composition of claim 21 wherein the compound 25. A composition of claim 21 wherein the compound O of formula (1) is one wherein E and D are N and A and of formula (1) is one wherein B is N and A, E, and D are B are CR1. CR 1. 37. A composition of claim 21 wherein the compound 26. A composition of claim 25 wherein X is O. of formula (1) is one wherein A and E are N and B and 27. A composition of claim 25 wherein X is NR3. D are CR 1. 5 38. A composition of claim 21 wherein the compound 28. A composition of claim 21 wherein the compound of formula (1) is one wherein A and B are N and E and of formula (1) is one wherein E is N and A, B, and D are D are CR1. CRl, 39. A composition of claim 21 wherein the compound 29. A composition of claim 28 wherein X is O. of formula (1) is one wherein B and E are N and A and D are CR 1. 30. A composition of claim 28 wherein X is NR3. 40. A composition of claim 21 wherein the compound 31. A composition of claim 21 wherein the compound of formula (1) is one wherein A, E, and D are N and B of formula (1) is one wherein D is N and A, B, and E are is CR. CR1. k k : : 25

35

40

45

50

55

65