USOO853.0667B2

(12) United States Patent (10) Patent No.: US 8,530,667 B2 Jeanmart et al. (45) Date of Patent: Sep. 10, 2013

(54) HERBICIDES (52) U.S. Cl. USPC ...... 548/100: 548/204:546/287.7: 549/60; (75) Inventors: Stephane André Marie Jeanmart, 549/459; 549/78; 54.4/318 Bracknell (GB); John Benjamin Taylor, (58) Field of Classification Search Bracknell (GB); Melloney Tyte, None Bracknell (GB); Christopher John See application file for complete search history. Mathews, Bracknell (GB); Stephen Christopher Smith, Bracknell (GB) (56) References Cited (73) Assignee: Syenta Limited, Guildford, Surrey U.S. PATENT DOCUMENTS (GB) 2005, 0164883 A1 7/2005 Maetzke (*) Notice: Subject to any disclaimer, the term of this 58-385 A. 585 May patent is extended or adjusted under 35 2012/0094832 A1 4/2012 Tyte et al. U.S.C. 154(b) by 116 days. 2012/0142529 A1 6/2012 Tyte et al. (21) Appl. No.: 12/675,975 FOREIGN PATENT DOCUMENTS WO 96.03366 2, 1996 (22) PCT Filed:1-1. Sep. 1, 2008 WO 9948869O17477O 10,9, 20011999 (86). PCT No.: PCT/EP2008/007 132 W. 3352 1358. S371 (c)(1), Primary Examiner — Nyeemah A Grazier (2), (4) Date: Jun. 15, 2010 (74) Attorney, Agent, or Firm — R. Kody Jones (87) PCT Pub. No.: WO2009/030450 (57) ABSTRACT PCT Pub. Date: Mar. 12, 2009 Compounds of formula (I) wherein the substituents are as (65) Prior Publication Data defined in claim 1, are suitable for use as herbicides. US 2010/O29814.0 A1 Nov. 25, 2010

(I) (30) Foreign Application Priority Data Sep. 3, 2007 (GB) ...... 07170822 (51) Int. Cl. C07D 293/00 (2006.01) C07D 277/30 (2006.01) CO7D 409/00 (2006.01) C07D 307/00 (2006.01) CO7D 333/6 (2006.01) CO7D 405/00 (2006.01) C07D 239/02 (2006.01) 13 Claims, No Drawings US 8,530,667 B2 1. 2 HERBCDES alkoxy, tri(C-C)alkylsilyl (C-C)alkoxy, C-C alkoxycar bonyl(C-C)alkoxy, C-Cohaloalkoxy, aryl(C-C)alkoxy This application is a 371 of International Application No. (where the aryl group is optionally Substituted), C-C, PCT/EP2008/007 132 filed Sep. 1, 2008, which claims prior cycloalkyloxy (where the cycloalkyl group is optionally Sub ity to GB 0717082.2 filed Sep. 3, 2007, the contents of which stituted with C-C alkyl or halogen), C-Co alkenyloxy, are incorporated herein by reference. Cs-Co alkynyloxy, mercapto, C-Co alkylthio, C-Co The present invention relates to novel, herbicidally active haloalkylthio, aryl (C-C)alkylthio (where the aryl group is cyclopentanedione compounds, and derivatives thereof, to optionally substituted), C-C, cycloalkylthio (where the processes for their preparation, to compositions comprising cycloalkyl group is optionally substituted with C-C alkyl or 10 halogen), tri(C-C)alkylsilyl(C-C)alkylthio, arylthio those compounds, and to their use in controlling weeds, espe (where the aryl group is optionally Substituted), C-C alkyl cially in crops of useful plants, or in inhibiting undesired plant Sulfonyl, C-Chaloalkylsulfonyl, C-C alkylsulfinyl, C-C, growth. haloalkylsulfinyl, arylsulfonyl (where the aryl group may be Cyclopentanedione compounds having herbicidal action optionally substituted), tri(C-C)alkylsilyl, aryldi(C-C) are described, for example, in WO 01/74770 and WO 15 alkylsilyl (C-C)alkyldiarylsilyl, triarylsilyl, aryl(C-C) 96/03366. alkylthio(C-C)alkyl, aryloxy(C-C)alkyl, formyl, C-Co Novel cyclopentanedione compounds, and derivatives alkylcarbonyl, HOC, C-C alkoxycarbonyl, aminocarbo thereof, having herbicidal and growth-inhibiting properties nyl, C-C alkylaminocarbonyl, di(C-C alkyl)aminocarbo have now been found. nyl, N-(C-C alkyl)-N-(C-C alkoxy)aminocarbonyl, The present invention accordingly relates to compounds of C-C alkylcarbonyloxy, arylcarbonyloxy (where the aryl formula (I) group is optionally substituted), di(C-C)alkylaminocarbo nyloxy, C-Calkyliminooxy, C-Calkenyloxyimino, ary loxyimino, aryl (itself optionally substituted), heteroaryl (it (I) self optionally substituted), heterocyclyl (itself optionally 25 substituted with C-C alkyl or halogen), aryloxy (where the aryl group is optionally Substituted), heteroaryloxy, (where the heteroaryl group is optionally Substituted), heterocycly loxy (where the heterocyclyl group is optionally substituted with C-C alkyl or halogen), amino, C-C alkylamino, 30 di(C-C)alkylamino, C-C alkylcarbonylamino, N-(C- C.)alkylcarbonyl-N-(C-C)alkylamino, C-C alkenylcar bonyl, C-C alkynylcarbonyl, C-C alkenyloxycarbonyl, C-C alkynyloxycarbonyl, aryloxycarbonyl (where the aryl wherein group is optionally Substituted) and arylcarbonyl (where the R" and R are independently of each other hydrogen, 35 aryl group is optionally Substituted). C-C alkyl, C-Chaloalkyl, C-Calkoxy, C-C alkylthio. Alkenyl and alkynyl moieties can be in the form of straight halogen or C-Calkoxycarbonyl, or branched chains, and the alkenyl moieties, where appro R. R. R. R. R. and R7 are independently of each other priate, can be of either the (E)- or (Z)-configuration. hydrogen or a Substituent, or Examples are vinyl, allyl and propargyl. Alkenyl and alkynyl R" and R. RandR, or RandR together with the carbon 40 moieties can contain one or more double and/or triple bonds atoms to which they are attached form an optionally Substi in any combination. It is understood, that allenyl and alkyli tuted ring, optionally containing a heteroatom, or nylalkenyl are included in these terms. RandR together with the carbon atoms to which they are When present, the optional substituents on alkenyl or alky attached form a keto, imino or alkenyl unit, or nyl include those optional Substituents given above for an RandR together form a bond, 45 alkyl moiety. G is hydrogen or an alkali metal, alkaline earth metal, Sulfo Halogen is fluorine, chlorine, bromine or iodine. nium, ammonium or a latentiating group, Haloalkyl groups are alkyl groups which are substituted Het is an optionally substituted monocyclic or bicyclic het with one or more of the same or different halogen atoms and eroaromatic ring, and agronomically acceptable salts thereof. are, for example, CF, CFC, CFH, CC1H, FCH, CICH, In the substituent definitions of the compounds of the for 50 BrCH, CHCHF (CH),CF, CFCH or CHFCH. mula (I), each alkyl moiety either alone or as part of a larger In the context of the present specification the terms “aryl'. group (Such as alkoxy, alkoxycarbonyl, alkylcarbonyl, alky 'aromatic ring and 'aromatic ring system’ refer to ring laminocarbonyl, dialkylaminocarbonyl) is a straight or systems which may be mono-, bi- or tricyclic. Examples of branched chain and is, for example, methyl, ethyl, n-propyl. Such rings include phenyl, naphthalenyl, anthracenyl, indenyl n-butyl, n-pentyl, n-hexyl, iso-propyl. n-butyl, sec-butyl, iso 55 or phenanthrenyl. A preferred aryl group is phenyl. In addi butyl, tert-butyl or neopentyl. The alkyl groups are suitably tion, the terms "heteroaryl, "heteroaromatic ring or “het C to C alkyl groups, but are preferably C-C alkyl groups. eroaromatic ring system” refer to an aromatic ring system Ring forming alkylene, and alkenylene groups can option containing at least one heteroatom and consisting either of a ally be further substituted by one or more halogen, single ring or of two or more fused rings. Preferably, single C-C alkyl and/or C-Calkoxy groups. When present, the 60 rings will contain up to three and bicyclic systems up to four optional Substituents on an alkyl moiety (alone or as part of a heteroatoms which will preferably be chosen from nitrogen, larger group Such as alkoxy, alkoxycarbonyl, alkylcarbonyl, oxygen and Sulphur. Suitable examples of heteroaromatic alkylaminocarbonyl, dialkylaminocarbonyl) include one or rings are, for example, thienyl, furyl, pyrrolyl, isoxazolyl, more of halogen, nitro, cyano, C-C, cycloalkyl (itself oxazolyl, isothiazolyl, thiazolyl pyrazolyl, imidazolyl, tria optionally Substituted with C-C alkyl or halogen), Cs-C, 65 Zolyl, tetrazolyl pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, cycloalkenyl (itself optionally substituted with C-C alkyl or triazinyl, oxadiazolyl and thiadiazolyl, and, where appropri halogen), hydroxy, C-Co alkoxy, C-Co alkoxy(C-Co) ate, N-oxides and salts thereof. US 8,530,667 B2 3 4 The terms heterocycle and heterocyclyl preferably refer to C.)alkylamino (where the aryl group is substituted by C-C, a non-aromatic preferably monocyclic or bicyclic ring sys alkyl or halogen), aryl-N-(C-C)alkylamino (where the tems containing up to 7 atoms including one or more (pref aryl group is substituted by C-C alkyl or halogen), ary erably one or two) heteroatoms selected from O, S and N. lamino (where the aryl group is Substituted by C-C alkyl or Examples of Such rings include 1,3-dioxolane, oxetane, tet halogen), heteroaryl amino (where the heteroaryl group is rahydrofuran, morpholine, thiomorpholin and piperazine. Substituted by C-C alkyl or halogen), heterocyclylamino When present, the optional substituents on heterocyclyl (where the heterocyclyl group is substituted by C-C alkyl or include C-C alkyl and C-C haloalkyl as well as those halogen), aminocarbonylamino, C-C alkylaminocarbony optional Substituents given above for an alkyl moiety. lamino, di(C-C)alkylaminocarbonylamino, arylaminocar Cycloalkyl includes preferably cyclopropyl, cyclobutyl, 10 cyclopentyl and cyclohexyl. Cycloalkylalkyl is preferentially bonylamino where the aryl group is Substituted by C-C, cyclopropylmethyl. Cycloalkenyl includes cyclopentenyl alkyl or halogen), aryl-N-(C-C)alkylamino-carbony and cyclohexenyl. lamino where the aryl group is Substituted by C-C alkyl or When present, the optional substituents on cycloalkyl or halogen). C-Calkylaminocarbonyl-N-(C-C)alky cycloalkenyl include C-C alkyl as well as those optional 15 lamino, di(C-C)alkylaminocarbonyl-N-(C-C)alky Substituents given above for an alkyl moiety. lamino, arylaminocarbonyl-N-(C-C)alkylamino where Carbocyclic rings include aryl, cycloalkyl and cycloalk the aryl group is substituted by C-C alkyl or halogen) and enyl groups. aryl-N-(C-C)alkylaminocarbonyl-N-(C-C)alky When present, the optional substituents on aryl or het lamino where the aryl group is Substituted by C-C alkyl or eroaryl are selected independently, from halogen, nitro, halogen). cyano, rhodano, isothiocyanato, C-C alkyl, C-C, For substituted phenyl moieties, heterocyclyl and het haloalkyl, C-C alkoxy-(C-C)alkyl, C-C alkenyl, C-C, eroaryl groups it is preferred that one or more Substituents are haloalkenyl, C-C alkynyl, C-C, cycloalkyl (itself option independently selected from halogen, C-C alkyl, C-C, ally substituted with C-C alkylorhalogen), Cs-C7 cycloalk haloalkyl, C-C alkoxy, C-C haloalkoxy, C-C alkylthio. enyl (itself optionally substituted with C-C alkyl or halo 25 C-C alkylsulfinyl, C-C alkylsulfonyl, nitro and cyano. It is gen), hydroxy, C1-Coalkoxy, C-Coalkoxy(C-Co.)alkoxy, to be understood that dialkylamino substituents include those tri(C-C)alkylsilyl (C-C)alkoxy, C-C alkoxycarbonyl where the dialkyl groups together with the Natom to which (C-C)alkoxy, C-C haloalkoxy, aryl(C-C)alkoxy they are attached form a five, six or seven-membered hetero (where the aryl group is optionally Substituted with halogen cyclic ring which may contain one or two further heteroatoms or C-C alkyl), C-C, cycloalkyloxy (where the cycloalkyl 30 group is optionally Substituted with C-C alkyl or halogen), selected from O, NorS and which is optionally substituted by Cs-Co alkenyloxy, C-Co alkynyloxy, mercapto, C-Co one or two independently selected (C-C)alkyl groups. alkylthio, C-C haloalkylthio, aryl (C-C)alkylthio, C-C, When heterocyclic rings are formed by joining two groups on cycloalkylthio (where the cycloalkyl group is optionally Sub an Natom, the resulting rings are Suitably pyrrolidine, pip stituted with C-C alkyl or halogen), tri(C-C)-alkylsilyl 35 eridine, thiomorpholine and morpholine each of which may (C-C)alkylthio, arylthio, C-C alkylsulfonyl, C-C, be substituted by one or two independently selected (C-C) haloalkylsulfonyl, C-C alkylsulfinyl, C-Chaloalkylsulfi alkyl groups. nyl, arylsulfonyl, tri(C-C)alkylsilyl, aryldi(C-C)-alkylsi The term “ring includes corresponding aryls, heteroaryls, lyl, (C-C)alkyldiarylsilyl, triarylsilyl, C-Co alkylcarbo cycloalkyls, cycloalkenyls and heterocycles, optionally Sub nyl, HOC, C-C alkoxycarbonyl, aminocarbonyl, C-C, 40 stituted as described above. alkylaminocarbonyl, di(C-C alkyl)-aminocarbonyl, Preferably, in the compounds of the formula (I), R and R' N-(C-C alkyl)-N-(C-C alkoxy)aminocarbonyl, C-C, are independently of each other hydrogen, halogen, formyl. alkylcarbonyloxy, arylcarbonyloxy, di(C-C)alkylamino cyano or nitro or carbonyloxy, aryl (itself optionally substituted with C-C, R° and R are independently of each other C-Calkyl, alkyl or halogen), heteroaryl (itself optionally substituted 45 C-Calkenyl, C-Calkynyl, C-Calkoxy, C-C, with C-C alkyl or halogen), heterocyclyl (itself optionally cycloalkyl, C-C cycloalkenyl, phenyl, heteroaryl or a 3-7 substituted with C-C alkyl or halogen), aryloxy (where the membered heterocyclyl, where all these substituents are aryl group is optionally Substituted with C-C alkyl or halo optionally substituted, or gen), heteroaryloxy (where the heteroaryl group is optionally R° and R7 are independently of each other a group COR. Substituted with C-C alkyl or halogen), heterocyclyloxy 50 COR' or CONR'R'2, CR NOR, CR's NNR'R'7, (where the heterocyclyl group is optionally substituted with NHR', NR'R' or OR, wherein C-C alkyl or halogen), amino, C-C alkylamino, di(C-C) R is C-Calkyl, Ca-Calkenyl, Ca-Calkynyl, C-C, alkylamino, C-C alkylcarbonylamino, N-(C-C)alkyl cycloalkyl, Cs-C,cycloalkenyl, phenyl, heteroaryl or a 3-7 carbonyl-N-(C-C)alkylamino, arylcarbonyl, (where the membered heterocyclyl, where all these substituents are aryl group is itself optionally Substituted with halogen or 55 optionally substituted, C-C alkyl) or two adjacent positions on an aryl or heteroaryl R" is hydrogen, C-Calkyl, Cs-Coalkenyl, Ca-Calkynyl, system may be cyclised to form a 5, 6 or 7-membered car C-C cycloalkyl, Cs-C,cycloalkenyl, phenyl, heteroaryloris bocyclic or heterocyclic ring, itself optionally substituted 3-7 membered heterocyclyl, where all these substituents are with halogen or C-C alkyl. Further substituents for aryl or optionally substituted, heteroaryl include arylcarbonylamino (where the aryl group 60 R'' is hydrogen, C-Calkyl, Cs-Coalkenyl, Ca-Calkynyl, is substituted by C-C alkyl or halogen), (C-C)alkoxycar C-C, cycloalkyl, Cs-C,cycloalkenyl, phenyl, heteroaryl or a bonylamino(C-C)alkoxycarbonyl-N-(C-C)alkylamino, 3-7 membered heterocyclyl, where all these substituents are aryloxycarbonylamino (where the aryl group is Substituted by optionally substituted, C-C alkyl or halogen), aryloxycarbonyl-N-(C-C)alky R" is hydrogen, C-Calkyl, Cs-Coalkenyl, Ca-Calkynyl, lamino, (where the aryl group is Substituted by C-C alkyl or 65 C-Calkoxy, C-Chaloalkoxy, C-C cycloalkyl, halogen), arylsulphonylamino (where the aryl group is Sub Cs-C,cycloalkenyl, C-Calkylsulfonyl, phenylsulfonyl, het stituted by C-C alkyl or halogen), arylsulphonyl-N-(C- eroarylsulfonyl, amino, C-Calkylamino, diC US 8,530,667 B2 5 6 Calkylamino, phenyl, heteroaryl or a 3-7 membered hetero R is C-Calkyl, Ca-Calkenyl, Ca-Calkynyl, C-C, cyclyl, where all these substituents are optionally substituted, cycloalkyl, Cs-C,cycloalkenyl, phenyl, heteroaryl or a 3-7 O membered heterocyclyl, where all these substituents are R'' and R' may be joined to form an optionally substituted optionally substituted, 3-7 membered ring, optionally containing an oxygen, Sulfur 5 R" is hydrogen, C-Calkyl, Cs-Coalkenyl, Ca-Calkynyl, or nitrogen atom, C-C cycloalkyl, Cs-C,cycloalkenyl, phenyl, heteroaryloris R" and R' are independently of each other hydrogen, 3-7 membered heterocyclyl, where all these substituents are C-C alkyl or C-C cycloalkyl, optionally substituted, R'', R'' and R'' are independently of each other hydrogen, R'' is hydrogen, C-Calkyl, Cs-Coalkenyl, Ca-Calkynyl, C-Calkyl, C-Calkenyl, C-Calkynyl, C-C, cycloalkyl, 10 C-Calkoxy, C-Chaloalkoxy, C-C cycloalkyl, C-Calkylcarbonyl, C-Calkoxycarbonyl, C-C cycloalkenyl, phenyl, heteroaryl or a 3-7 membered C-Calkylthiocarbonyl, aminocarbonyl, heterocyclyl, where all these substituents are optionally sub C-Calkylaminocarbonyl, diC-Calkylaminocarbonyl, stituted, phenyl or heteroaryl, where all these substituents are option 15 R" is hydrogen, C-Calkyl, Cs-Coalkenyl, Ca-Calkynyl, ally substituted, C-Calkoxy, C-Chaloalkoxy, C-C cycloalkyl, R" is C-Calkylcarbonyl, C-Calkoxycarbonyl, Cs-C,cycloalkenyl, C-Calkylsulfonyl, amino, C-Calkylthiocarbonyl, C-Calkylaminocarbonyl, diC C-Calkylamino, diC-Calkylamino, phenyl, heteroaryl or Calkylaminocarbonyl, C-Calkylsulfonyl, phenylcarbonyl, a 3-7 membered heterocyclyl, where all these substituents are phenoxycarbonyl, phenylaminocarbonyl, phenylthiocarbo optionally substituted, or nyl, phenylsulfonyl, heteroarylcarbonyl, heteroaryloxycar R'' and R' may be joined to form an optionally substituted bonyl, heteroarylaminocarbonyl, heteroarylthiocarbonyl or 3-7 membered ring, optionally containing an oxygen, Sulfur heteroarylsulfonyl, where all these substituents are optionally or nitrogen atom, substituted, R" and R' are independently of each other hydrogen, R" is C1-Calkyl, Ca-Calkenyl, Ca-Calkynyl, C-C, 25 C-C alkyl or C-Cacycloalkyl, cycloalkyl, C-Calkylcarbonyl, C-Calkoxycarbonyl, R'', R'' and R7 are independently of each other hydrogen, C-Calkylthiocarbonyl, C-Calkylaminocarbonyl, diC C-Calkyl, C-Calkenyl, C-Calkynyl, C-C, cycloalkyl, Calkylaminocarbonyl, C-Calkylsulfonyl, phenyl or het C-Calkylcarbonyl, C-Calkoxycarbonyl, eroaryl, where all these substituents are optionally substi C-Calkylthiocarbonyl, C-Calkylaminocarbonyl, diC 30 Calkylaminocarbonyl, phenyl or heteroaryl, where all these tuted, or Substituents are optionally substituted, R" and R' may be joined to form an optionally substituted R" and R' are independently of each other C-Calkyl, 3-7 membered ring, optionally containing an oxygen, Sulfur C-Calkenyl, C-Calkynyl, C-C, cycloalkyl, or nitrogen atom, where all these Substituents are optionally C-Calkylcarbonyl, C-Calkoxycarbonyl, Substituted, and 35 C-Calkylthiocarbonyl, C-Calkylaminocarbonyl, diC R" is C-Calkyl, C.-Calkenyl, Cs-Coalkynyl, C-C, Calkylaminocarbonyl, C-Calkylsulfonyl, phenyl or het cycloalkyl, C-Calkylcarbonyl, C-Calkoxycarbonyl, eroaryl or C-Calkylthiocarbonyl, aminocarbonyl, RandR' may bejoined to forman optionally substituted C-Calkylaminocarbonyl, diC-Calkylaminocarbonyl, 3-7 membered ring, optionally containing an oxygen, Sulfur C-Calkylsulfonyl, tri(C-Calkyl)silyl phenyl or het 40 or nitrogen atom, where all these Substituents are optionally eroaryl, where all these substituents are optionally substi Substituted, and tuted. R" is C-C alkyl, Ca-Calkenyl, Ca-Calkynyl, C-C, More preferably, RandR are independently of each other cycloalkyl, C-Calkylcarbonyl, C-Calkoxycarbonyl, hydrogen, halogen, cyano, optionally Substituted C-Calkyl C-Calkylthiocarbonyl, C-Calkylaminocarbonyl, diC or a group COR, CORO or CONR'R'?, CR NOR' or 45 Calkylaminocarbonyl, C-Calkylsulfonyl, tri(C-Calkyl) CR'—NNR'R'7, wherein silyl phenyl or heteroaryl, where all these substituents are R. R', R'' and Rare C-Calkyl, optionally substituted. R" and Rare hydrogen or C-C alkyl, More preferably, R. R. Rand Rare independently of R'' is C-C alkyl, and each other hydrogen, cyano, C-Calkyl, C-Calkenyl, R'' and R'' are independently of each other hydrogen or 50 C-Calkoxy, C-CalkoxyC-Calkyl, 3-7 membered het C-C alkyl, where erocyclyl or CR'—NOR'', wherein R° and R being independently of each other hydrogen, R" is hydrogen or C-C alkyl and methyl or methyl substituted by C-Calkoxy is particularly R" is C-C alkyl. preferred. In a group of preferred compounds of the formula (I) R 55 and R together form a unit=O, or forma unit=CR'R'', or Preference is given to compounds of formula (I) wherein form a unit=NR, or form together with the carbon atom to R. R. Rand Rare independently of each other hydrogen, which they are attached a 3-8 membered ring, optionally halogen, hydroxyl, formyl, amino, cyano or nitro, or containing a heteroatom selected from O.S or N and option R. R. RandR are independently of each other C-Calkyl, ally Substituted by C-C alkyl, C-Calkoxy, C-C alkylthio. C-Calkenyl, C-Calkynyl, C-Calkoxy, C-Calkylthio. 60 C-C alkylsulfinyl, C-C alkylsulfonyl, C-Chaloalkyl, C-Calkylsulfinyl, C-Calkylsulfonyl, C-C, cycloalkyl, halogen, phenyl, phenyl substituted by C-C alkyl, C-C cycloalkenyl, tri(C-Calkyl)silyl phenyl, heteroaryl C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, or a 3-7 membered heterocyclyl, where all these substituents C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, are optionally substituted, or C-C alkylcarbonyl, C-C alkoxycarbonyl, aminocarbonyl, R. R. Rand Rare independently of each other a group 65 C-Calkylaminocarbonyl, diC-Calkylaminocarbonyl, COR, CORO or CONR'R'2, CR NOR, halogen, cyano or by nitro, heteroaryl or heteroaryl Substi CR's NNR'R'7, NR'R' or OR2, wherein tuted by C-Calkyl, C-Chaloalkyl, C-Calkoxy, US 8,530,667 B2 7 8 C-Chaloalkoxy, C-C alkylthio, C-C alkylsulfinyl, The group G denotes hydrogen, an alkali metal cation such C-C alkylsulfonyl, C-C alkylcarbonyl, halogen, cyano or as Sodium or potassium, alkaline earth metal cation Such as by nitro, wherein calcium, Sulfonium cation (preferably —S(C-Calkyl)") or R" and R’ are independently of each other hydrogen, halo ammonium cation (preferably —NH" or —N(C-C, gen, cyano or nitro, or alkyl)a), or C-Calkyl, C-Calkenyl or C-Calkynyl or a R" and R' are independently of each other C-Calkyl, latentiating group. The latentiating group G is preferably C-Calkoxy, C-Calkylamino, diC-Calkylamino, selected from the groups were G is C-C alkyl, C-Cs C-Calkylcarbonyl, C-Calkoxycarbonyl, haloalkyl, phenylC-Csalkyl (wherein the phenyl may C-Calkylaminocarbonyl, diC-Calkylaminocarbonyl, optionally be substituted by C-C alkyl, C-Chaloalkyl, 10 C-Calkoxy, C-Chaloalkoxy, C-C alkylthio. N-phenyl-N-C-Calkylaminocarbonyl, N-phenylC C-C alkylsulfinyl, C-C alkylsulfonyl, halogen, cyano or Calkyl-N-C-Calkylaminocarbonyl, N-heteroaryl-N- by nitro), heteroarylC-Calkyl (wherein the heteroaryl may C-Calkylaminocarbonyl, N-heteroarylC-Calkyl-N-C- optionally be substituted by C-C alkyl, C-Chaloalkyl, Calkylaminocarbonyl, phenyl, heteroaryl, C-C scycloalkyl C-Calkoxy, C-Chaloalkoxy, C-C alkylthio. or 3-7 membered heterocyclyl, where all these substituents 15 C-C alkylsulfinyl, C-C alkylsulfonyl, halogen, cyano or are optionally substituted, or by nitro), C-C alkenyl, C-C haloalkenyl, C-C alkynyl. R" and R’ may be joined together to form a 5-8 membered CCX) R, C(X) X R, CCX) N(R) R', SO ring optionally containing a heteroatom selected from O.S or R, PCX)(R) Rs or CH X R' wherein X, X, X, N and optionally substituted by C-C alkyl or C-Calkoxy, X, X and X are independently of each other oxygen or R’ is nitro or cyano, or sulfur, R’ is C-Calkylamino, diC-Calkylamino, C-Calkoxy, R" is H. C-C salkyl, C-C salkenyl, C-C alkynyl, C-Calkenyloxy, C-Calkynyloxy, phenoxy, phenylamino, C-Cohaloalkyl, C-Cocyanoalkyl, C-Conitroalkyl, N-phenyl-N-C-Calkylamino, N-phenylC-Calkyl-N- C-Caminoalkyl, C-C alkylaminoC-Calkyl, C-Calkylamino heteroaryloxy, heteroarylamino, N-het C-CsdialkylaminoC-Csalkyl, C-C,cycloalkylC-Csalkyl, eroaryl-N-C-Calkylamino or N-heteroarylC-Calkyl 25 C-CalkoxyC-Calkyl, C-CsalkenyloxyC-Calkyl, N—C-Calkylamino, where all these substituents are C-C alkynylC-Coxyalkyl, C-CsalkylthioC-Csalkyl, optionally substituted, where C-C alkylsulfinylC-Csalkyl, C-CalkylsulfonylC It is particularly preferred, when RandR togetherform a Calkyl, C-CalkylideneaminoxyC-Calkyl, unit=O or -NR, C-C alkylcarbonylC-Csalkyl, C-CsalkoxycarbonylC wherein R’ is C-Calkoxy. 30 Calkyl, aminocarbonylC-Calkyl, Preference is given to compounds of the formula (I), C-C alkylaminocarbonylC-Calkyl, wherein R and R together with the carbon atoms to which C-C dialkylaminocarbonylC-Calkyl, they are attached forma Saturated 3-4 membered ring, option C-C alkylcarbonylaminoC-Calkyl, N C ally containing a heteroatom or group selected from O, S or Calkylcarbonyl-N-C-CsalkylaminoC-Csalkyl, C-C- NR, and optionally substituted by C-C alkyl, 35 trialkylsilylC-Calkyl, phenylC-Calkyl (wherein the phe C-C alkoxy, C-C alkylthio, halogen, C-C alkylcarbonyl nyl may optionally be substituted by C-C alkyl, or C-C alkoxycarbonyl, or C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, RandR together with the carbon atoms to which they are C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, attached form a 5-8 membered ring, optionally containing a halogen, cyano, or by nitro), heteroarylC-Calkyl, (wherein heteroatom selected from O, S or N, and optionally substi 40 the heteroaryl may optionally be substituted by C-C alkyl, tuted by C-C alkyl, C-Calkoxy, C-C alkylthio. C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, C-C alkylsulfinyl, C-C alkylsulfonyl, C-Chaloalkyl, C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, halogen, phenyl, phenyl Substituted by C-C alkyl, halogen, cyano, or by nitro), C-Chaloalkenyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, C-C scycloalkyl, phenyl orphenyl Substituted by C-C alkyl, C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, 45 C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen, C-C alkylcarbonyl, C-C alkoxycarbonyl, aminocarbonyl, cyano or nitro, heteroaryl or heteroaryl substituted by C-C, C-Calkylaminocarbonyl, diC-Calkylaminocarbonyl, alkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halo halogen, cyano or by nitro, heteroaryl or heteroaryl Substi gen, cyano or nitro, R is C1-Cisalkyl, Ca-Cisalkenyl, tuted by C-C alkyl, C-Chaloalkyl, C-C alkoxy, C-C salkynyl, C-Cohaloalkyl, C-Clocyanoalkyl, C-Chaloalkoxy, C-C alkylthio, C-C alkylsulfinyl, 50 C-Conitroalkyl, C-Coaminoalkyl, C-C alkylaminoC C-C alkylsulfonyl, C-C alkylcarbonyl, halogen, cyano or Calkyl, C-CsdialkylaminoC-Csalkyl, C-C,cycloalkylC by nitro, or Calkyl, C-CsalkoxyC-Calkyl, C-CsalkenyloxyC RandR together form a bond, wherein Calkyl, C-CsalkynyloxyC-Csalkyl, C-C alkylthioC R is hydrogen, C-Calkyl, Cs-Coalkenyl, Ca-Calkynyl, Calkyl, C-C alkylsulfinylC-Calkyl, C-Calkoxy, C-Calkylcarbonyl, C-Calkoxycarbonyl, 55 C-C alkylsulfonylC-Calkyl, C-Calkylaminocarbonyl, diC-Calkylaminocarbonyl, C-CalkylideneaminoxyC-Calkyl, phenoxycarbonyl C-Calkylsulfonyl, phenylsulfonyl or het C-C alkylcarbonylC-Csalkyl, C-CsalkoxycarbonylC eroaryloxycarbonyl, where all these Substituents are option Calkyl, aminocarbonylC-Csalkyl, ally substituted. C-C alkylaminocarbonylC-Calkyl, More preferably, RandR together form a bond. 60 C-CsdialkylaminocarbonylC-Calkyl, In preferred compounds of the formula (I) R' and Rare C-C alkylcarbonylaminoC-Calkyl, N C independently of each other hydrogen or C-C alkyl, where, Calkylcarbonyl-N-C-CsalkylaminoC-Csalkyl, C-C- more preferably, R' and Rare hydrogen. trialkylsilylC-Calkyl, phenylC-Calkyl (wherein the phe In another preferred group of compounds of formula (I), R' nyl may optionally be substituted by C-C alkyl, and R together with the carbon atoms to which they are 65 C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, attached form a 3-7 membered ring, optionally containing an C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, oxygen or Sulphur atom. halogen, cyano, or by nitro), heteroarylC-Calkyl, (wherein US 8,530,667 B2 9 10 the heteroaryl may optionally be substituted by C-C alkyl, C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen, cyano, or by nitro), heteroarylC-Calkyl (wherein C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, the heteroaryl may optionally be substituted by C-C alkyl, halogen, cyano, or by nitro), C-Chaloalkenyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, C-C scycloalkyl, phenyl orphenyl Substituted by C-C alkyl, C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen, halogen, cyano, or by nitro), C-Chaloalkenyl, cyano or nitro, heteroaryl or heteroaryl substituted by C-C, C-C cycloalkyl, phenyl orphenyl substituted by C-C alkyl, alkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halo C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen, gen, cyano or nitro, cyano or nitro, heteroaryl or heteroaryl substituted by C-C, R and Rare each independently of each other hydrogen, 10 alkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halo C-Coalkyl, Cs-Coalkenyl, Cs-Coalkynyl, gen, cyano or by nitro, heteroarylamino or heteroarylamino C-Cohaloalkyl, C-Cocyanoalkyl, C-Conitroalkyl, Substituted by C-C alkyl, C-Chaloalkyl, C-Calkoxy, C-Caminoalkyl, C-C alkylaminoC-Calkyl, C-Chaloalkoxy, halogen, cyano or by nitro, diheteroary C-C dialkylaminoC-Calkyl, C-C,cycloalkylC-Calkyl, lamino or diheteroarylamino substituted by C-C alkyl, C-CsalkoxyC-Csalkyl, C-CsalkenyloxyC-Calkyl, 15 C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen, C-C alkynyloxyC-Calkyl, C-C alkylthioC-Calkyl, cyano or nitro, phenylamino or phenylamino Substituted by C-CsalkylsulfinylC-Csalkyl, C-CsalkylsulfonylC C-C alkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, Calkyl, C-CsalkylideneaminoxyC-Csalkyl, halogen, cyano or nitro, diphenylamino, or diphenylamino C-CsalkylcarbonylC-Csalkyl, C-CsalkoxycarbonylC Substituted by C-C alkyl, C-Chaloalkyl, C-Calkoxy, Calkyl, aminocarbonylC-Csalkyl, C-Chaloalkoxy, halogen, cyano or nitro, or C-C alkylaminocarbonylC-Calkyl, C-C,cycloalkylamino, diC-C,cycloalkylamino O C-CsdialkylaminocarbonylC-Calkyl, C-C cycloalkoxy, C-Coalkoxy, C-Cohaloalkoxy, C-C alkylcarbonylaminoC-Calkyl, N C C-C alkylamino or C-C dialkylamino Calkylcarbonyl-N-C-Csalkylaminoalkyl, C-C-trialkyl R and R are each independently of each other C-Coalkyl, silylC-Csalkyl, phenylC-Csalkyl (wherein the phenyl may 25 C-Coalkenyl, C-Coalkynyl, C-Coalkoxy, optionally be substituted by C-C alkyl, C-Chaloalkyl, C-Cohaloalkyl, C-Cocyanoalkyl, C-Conitroalkyl, C-Calkoxy, C-Chaloalkoxy, C-C alkylthio. C-Coaminoalkyl, C-C alkylaminoC-Calkyl, C-C alkylsulfinyl, C-C alkylsulfonyl, halogen, cyano, or C-C dialkylaminoC-Calkyl, C-C,cycloalkylC-Calkyl, by nitro), heteroarylC-Calkyl, (wherein the heteroaryl may C-CalkoxyC-Calkyl, C-CsalkenyloxyC-Calkyl, optionally be substituted by C-C alkyl, C-Chaloalkyl, 30 C-C alkynyloxyC-Calkyl, C-C alkylthioC-Calkyl, C-Calkoxy, C-Chaloalkoxy, C-C alkylthio. CalkylsulfinylC-Csalkyl, C-CalkylsulfonylC-Csalkyl, C-C alkylsulfinyl, C-C alkylsulfonyl, halogen, cyano, or C-CalkylideneaminoxyC-Calkyl, by nitro), C-Chaloalkenyl, C-C cycloalkyl, phenyl orphe C-C alkylcarbonylC-Calkyl, C-CalkoxycarbonylC nyl Substituted by C-C alkyl, C-Chaloalkyl, C-Calkoxy, Calkyl, aminocarbonylC-Csalkyl, C-Chaloalkoxy, halogen, cyano or nitro, heteroaryl or het 35 C-C alkylaminocarbonylC-Calkyl, eroaryl substituted by C-C alkyl, C-Chaloalkyl, C-CsdialkylaminocarbonylC-Calkyl, C-Calkoxy, C-Chaloalkoxy, halogen, cyano or nitro, het C-C alkylcarbonylaminoC-Calkyl, N C eroarylamino or heteroarylamino Substituted by C-C alkyl, Calkylcarbonyl-N-C-Csalkylaminoalkyl, C-C-trialkyl C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen, silylC-Csalkyl, phenylC-Csalkyl (wherein the phenyl may cyano or nitro, diheteroarylamino or diheteroarylamino Sub 40 optionally be substituted by C-C alkyl, C-Chaloalkyl, stituted by C-C alkyl, C-Chaloalkyl, C-Calkoxy, C-Calkoxy, C-Chaloalkoxy, C-C alkylthio. C-Chaloalkoxy, halogen, cyano or nitro, phenylamino or C-C alkylsulfinyl, C-C alkylsulfonyl, halogen, cyano, or phenylamino Substituted by C-C alkyl, C-Chaloalkyl, by nitro), heteroarylC-Calkyl (wherein the heteroaryl may C-Calkoxy, C-Chaloalkoxy, halogen, cyano or by nitro, optionally be substituted by C-C alkyl, C-Chaloalkyl, diphenylamino or diphenylamino Substituted by C-C alkyl, 45 C-Calkoxy, C-Chaloalkoxy, C-C alkylthio. C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen, C-C alkylsulfinyl, C-C alkylsulfonyl, halogen, cyano, or cyano or by nitro or C-C,cycloalkylamino, di-C- by nitro), C-Chaloalkenyl, C-C cycloalkyl, phenyl orphe C,cycloalkylamino or C-C,cycloalkoxy or R and R may nyl Substituted by C-C alkyl, C-Chaloalkyl, C-Calkoxy, join together to form a 3-7 membered ring, optionally con C-Chaloalkoxy, halogen, cyano or nitro, heteroaryl or het taining one heteroatom selected from O or S, 50 eroaryl substituted by C-C alkyl, C-Chaloalkyl, R is C-Coalkyl, C-Coalkenyl, C-Coalkynyl, C-Calkoxy, C-Chaloalkoxy, halogen, cyano or by nitro, C-Cohaloalkyl, C-Cocyanoalkyl, C-Conitroalkyl, heteroarylamino or heteroarylamino substituted by C-C, C-Caminoalkyl, C-C alkylaminoC-Calkyl, alkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halo C-C dialkylaminoC-Calkyl, C-C,cycloalkylC-Calkyl, gen, cyano or by nitro, diheteroarylamino or diheteroary C-CsalkoxyC-Csalkyl, C-CsalkenyloxyC-Calkyl, 55 lamino Substituted by C-C alkyl, C-Chaloalkyl, C-C alkynyloxyC-Calkyl, C-C alkylthioC-Calkyl, C-Calkoxy, C-Chaloalkoxy, halogen, cyano or nitro, phe C-CsalkylsulfinylC-Csalkyl, C-CsalkylsulfonylC nylamino or phenylamino Substituted by C-C alkyl, Calkyl, C-CsalkylideneaminoxyC-Csalkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen, C-CsalkylcarbonylC-Csalkyl, C-CsalkoxycarbonylC cyano or nitro, diphenylamino, or diphenylamino Substituted Calkyl, aminocarbonylC-Csalkyl, 60 by C-C alkyl, C-Chaloalkyl, C-Calkoxy, C-C alkylaminocarbonylC-Calkyl, C-Chaloalkoxy, halogen, cyano or nitro, or C-CsdialkylaminocarbonylC-Calkyl, C-C cycloalkylamino, diC-C,cycloalkylamino O C-C alkylcarbonylaminoC-Calkyl, N C C-C,cycloalkoxy, C-Chaloalkoxy, C-C alkylamino or Calkylcarbonyl-N-C-CsalkylaminoC-Csalkyl, C-C- C-Csdialkylamino, benzyloxy or phenoxy, wherein the ben trialkylsilylC-Calkyl, phenylC-Calkyl (wherein the phe 65 Zyl and phenyl groups may in turn be substituted by nyl may optionally be substituted by C-C alkyl, C-C alkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen, cyano or nitro, and US 8,530,667 B2 11 12 R" is C1-Coalkyl, Cs-Coalkenyl, Cs-Coalkynyl, -continued C-Cohaloalkyl, C-Cocyanoalkyl, C-Conitroalkyl, (R4) C-Co-aminoalkyl, C-C alkylaminoC-Calkyl, 27 C-CsdialkylaminoC-Csalkyl, C-C,cycloalkylC-Csalkyl, N-N C-CalkoxyC-Calkyl, C-CalkenyloxyC-Calkyl, X-R C-CsalkynyloxyC-Calkyl, C-CsalkylthioC-Csalkyl, Aus Z (Rs) C-CsalkylsulfinylC-Csalkyl, C-CsalkylsulfonylC R28 Csalkyl, C-CalkylideneaminoxyC-Calkyl, R2 C-CsalkylcarbonylC-Csalkyl, C-CsalkoxycarbonylC NN N Calkyl, aminocarbonylC-Csalkyl, 10 R26 C-C alkylaminocarbonylC-Calkyl, A-N Z C-CsdialkylaminocarbonylC-Calkyl, (R6) C-CsalkylcarbonylaminoC-Calkyl, N C R28 Csalkylcarbonyl-N-C-C-alkylaminoC-Calkyl, C-C- 15 R23 trialkylsilylC-Calkyl, phenylC-Calkyl (wherein the phe e nyl may optionally be substituted by C-C alkyl, N-R30 S. C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, A C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, R29 halogen, cyano or by nitro), heteroarylC-Csalkyl (wherein (R) the heteroaryl may optionally be substituted by C-C alkyl, R28 C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, R23 e C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, N-R30 halogen, cyano or by nitro), phenoxyC-Calkyl (wherein the S. M phenyl may optionally be substituted by C-C alkyl, 25 A N C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, (Rs) C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, R23 N e N halogen, cyano or by nitro), heteroaryloxyC-Csalkyl N-R30 (wherein the heteroaryl may optionally be substituted by S. M C-C alkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, 30 A Z C-C alkylthio, C-C alkylsulfinyl, C-C alkylsulfonyl, (Ro) R23 Z halogen, cyano or by nitro), C-Chaloalkenyl, e C-C scycloalkyl, phenyl orphenyl Substituted by C-C alkyl, 1) . C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, halogen or N / 35 A1 by nitro, or heteroaryl, or heteroaryl substituted by C-C alkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, R29 halogen, cyano or by nitro. (R10) R23 Z In particular, the latentiating group G is a group —C(X)— e R" or—C(X) X R', and the meanings of X", R, X, X” 40 X and Rare as defined above. A1 N4 It is preferred that G is hydrogen, analkali metal or alkaline (R1) earth metal, where hydrogen is especially preferred. R23 Z Het is preferably an optionally substituted monocyclic e N 6-membered or, preferably, 5-membered sulfur or, prefer 45 N-N / ably, nitrogen containing heteroaromatic ring. More prefer A1 -K ably, Het is a monocyclic 5-membered Sulfur and nitrogen R29 containing heteroaromatic ring, and even more preferably, (R12) Het is a group of the formula R to R. R23 50 Sp M (R) -N. 25 R 'sw. wherein 2W. 55 A designates the point of attachment to the ketoenol moiety, A W4 (R) W is N or CR2, 25 W° and Ware independently of each other N or CR. R X W is N or CRP, X- R26 60 with the proviso that at least one of W, W, W or W is N, A Z X is O, S, Se, or NR', (R3) Z is N or CR, R25 Z wherein R is hydrogen, halogen, C-C alkyl, C-Chaloalkyl, X- R26 65 C-C-cycloalkyl, C-C-halocycloalkyl, C-C alkenyl, A X C-Chaloalkenyl, C-C alkynyl, C-C alkoxy, C-Chaloalkoxy, C-C alkylthio, C-C alkylsulfinyl, US 8,530,667 B2 13 14 C-C alkylsulfonyl, nitro or cyano, preferably halogen, sium. The compounds of formula (I) according to the inven C-C alkyl, C-Chaloalkyl, vinyl, ethynyl, or methoxy, and tion also include hydrates which may be formed during the even more preferably methyl or ethyl, salt formation. R" is hydrogen, C-Coalkyl, C-Chaloalkyl, Ca-Calkenyl, Examples of amines Suitable for ammonium salt formation C-Chaloalkenyl, C-Calkynyl, C-C cycloalkyl, include ammonia as well as primary, secondary and tertiary Cs-Cecycloalkenyl, halogen, C-Calkoxy, C-Calkoxy-C- C-C salkylamines, C-Chydroxyalkylamines and C-C- Calkyl, C-Chaloalkoxy, optionally Substituted aryl, alkoxyalkylamines, for example methylamine, ethylamine, optionally substituted aryloxy, optionally substituted het n-propylamine, isopropylamine, the four butylamine iso eroaryl or optionally substituted heteroaryloxy, preferably mers, n-amylamine, isoamylamine, hexylamine, hepty 10 lamine, octylamine, nonylamine, decylamine, pentadecy optionally substituted aryl or optionally substituted het lamine, hexadecylamine, heptadecylamine, octadecylamine, eroaryl wherein the substituents are selected from halogen, methylethylamine, methylisopropylamine, methylhexy C-C2-alkyl, C-C2-alkoxy, C-C haloalkyl, C-C, lamine, methylnonylamine, methylpentadecylamine, methy haloalkoxy, cyano or nitro, and even more preferably phenyl, loctadecylamine, ethylbutylamine, ethylheptylamine, ethy Substituted once, twice or three times, by halogen, C-C- 15 loctylamine, hexylheptylamine, hexyloctylamine, alkyl, C-C2-alkoxy, C-C haloalkyl, C-C haloalkoxy or dimethylamine, diethylamine, di-n-propylamine, diisopropy cyano, lamine, di-n-butylamine, di-n-amylamine, diisoamylamine, R’ is hydrogen, C-C alkyl, C-C haloalkyl, C-C-cy dihexylamine, diheptylamine, dioctylamine, ethanolamine, cloalkyl, C-C-halocycloalkyl, C-Calkenyl, n-propanolamine, isopropanolamine, N,N-diethanolamine, C-C alkynyl, C-Chaloalkyl or C-C haloalkenyl, prefer N-ethylpropanolamine, N-butylethanolamine, allylamine, ably methyl or ethyl, n-but-2-enylamine, n-pent-2-enylamine, 2,3-dimethylbut-2- R’ is hydrogen, methyl, halomethyl or halogen, preferably enylamine, dibut-2-enylamine, n-hex-2-enylamine, propy hydrogen, lenediamine, trimethylamine, triethylamine, tri-n-propy R’ is hydrogen, halogen, C-C alkyl, C-C haloalkyl, lamine, triisopropylamine, tri-n-butylamine, C-C alkenyl, C-C haloalkenyl, C-C alkynyl, C-C, 25 triisobutylamine, tri-sec-butylamine, tri-n-amylamine, meth alkoxy, C-Chaloalkoxy, C-C alkylthio, C-C alkylsulfi oxyethylamine and ethoxyethylamine; heterocyclic amines, nyl, C-C alkylsulfonyl or cyano, preferably hydrogen, halo for example pyridine, quinoline, isoquinoline, morpholine, gen, methyl or ethyl, piperidine, pyrrolidine, indoline, quinuclidine and azepine; R" is hydrogen, methyl, ethyl, halomethyl, haloethyl, primary arylamines, for example anilines, methoxyanilines, optionally substituted aryl or optionally substituted het 30 ethoxyanilines, o-, m- and p-toluidines, phenylenediamines, eroaryl, preferably optionally substituted aryl or optionally benzidines, naphthylamines and o-, m- and p-chloroanilines; substituted heteroaryl wherein the substituents are selected but especially triethylamine, isopropylamine and diisopropy from halogen, C-C-alkyl, C-C-alkoxy, C-C haloalkyl, lamine. C-C haloalkoxy, cyano or nitro, even more preferably phe Preferred quaternary ammonium bases suitable for salt nyl, Substituted once, twice or three times, by halogen, C-C- 35 formation correspond, for example, to the formula alkyl, C-C2-alkoxy, C-C haloalkyl, C-C haloalkoxy or N(R'R'R'R')OH wherein R. R. R. and R', are each cyano, independently of the others C-C alkyl. Further suitable tet R" is hydrogen, methyl, ethyl or halomethyl, and raalkylammonium bases with other anions can be obtained, R is hydrogen, methyl, ethyl, halomethyl, haloethyl, halo for example, by anion exchange reactions. gen, cyano or nitro. 40 Depending on the nature of the Substituents, compounds of More preferably, Het is a group of the formula (R), formula (I) may exist in different isomeric forms. When G is wherein X is S and Z is N and R and R are as defined hydrogen, for example, compounds of formula (I) may exist above. in different tautomeric forms. This invention covers all such It is also preferred that Het is a group of the formula (R), isomers and tautomers and mixtures thereof in all propor wherein X is S and Z is CR and R, R and Rare as 45 tions. Also, when Substituents contain double bonds, cis- and defined above. trans-isomers can exist. These isomers, too, are within the Those compounds of the formula (I) are particularly pre Scope of the claimed compounds of the formula (I). ferred, wherein R' to Rand Garehydrogen, Hetis a group R, Compounds of formula (I) wherein G is C-C alkyl, C-Cs haloalkyl, phenylC-Calkyl (wherein the phenyl may 50 optionally be substituted by C-C alkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, C-C alkylthio. C-C alkylsulfinyl, C-C alkylsulfonyl, halogen, cyano or by nitro), heteroarylC-Calkyl (wherein the heteroaryl may optionally be substituted by C-C alkyl, C-Chaloalkyl, 55 C-Calkoxy, C-Chaloalkoxy, C-C alkylthio. C-C alkylsulfinyl, C-C alkylsulfonyl, halogen, cyano or by nitro), C-C alkenyl, C-Cs haloalkenyl, C-C alkynyl, wherein X is S. Z is N, R is methyl or ethyl and R is CCX) R, C(X) X R, CCX) N(R) R', SO 4-chlorophenyl or 4-bromophenyl. R, PCX)(R) R8 or CH X R' where X, X, X, X, The invention relates also to the agronomically acceptable 60 X, X, R. R. R. R. R. R. R8 and Rareas defined above salts which the compounds of formula (I) preferably are able may be prepared by treating compounds of formula (A), to form with amines, alkali metal and alkaline earth metal which are compounds of formula (I) wherein G is H, with a bases or quaternary ammonium bases. reagent G-Z, wherein G-Z is alkylating agent such as an alkyl Among the alkali metal and alkaline earth metal hydrox halide (the definition of alkyl halides includes simple C-Cs ides as salt formers, special mention should be made of the 65 alkyl halides such as methyl iodide and ethyl iodide, substi hydroxides of lithium, Sodium, potassium, magnesium and tuted alkyl halides such as chloromethyl alkyl ethers, calcium, but especially the hydroxides of Sodium and potas C1 CH X R", wherein X is oxygen, and chloromethyl US 8,530,667 B2 15 16 alkyl sulfides C1-CH X R", wherein X is sulfur), a al., Tetrahedron Lett. (2004), 45,7187 and by B. Zwanenburg C-C alkyl sulfonate, or a di-C-C-alkyl sulfate, or with a et al., Tetrahedron (2005), 45 (22), 71.09. C-Cs alkenylhalide, or with a C-C alkynyl halide, or with The acylation of cyclic 1,3-diones may be effected by an acylating agent such as a carboxylic acid, HO C(X)R. procedures similar to those described, for example, in U.S. wherein X* is oxygen, an acid chloride, Cl—C(X)R’, Pat. No. 4,551,547, U.S. Pat. No. 4,175,135, U.S. Pat. No. wherein X* is oxygen, or acid anhydride, RC(X)].O. 4,422,870, U.S. Pat. No. 4,659,372 and U.S. Pat. No. 4,436, wherein X* is oxygen, or an isocyanate, RN=C=O, or a 666. Typically diones of formula (A) may be treated with the carbamoyl chloride, C1 C(X) N(R) R' (wherein X is acylating agent in the presence of at least one equivalent of a oxygen and with the proviso that neither R or R is hydro suitable base, optionally in the presence of a suitable solvent. gen), or a thiocarbamoyl chloride C1 C(X) N(R) R' 10 The base may be inorganic, such as an alkali metal carbonate (whereinX is sulfurand with the proviso that neither R or R' or hydroxide, or a metal hydride, or an organic base Such as a is hydrogen) or a chloroformate, C1 C(X) X R', tertiary amine or metal alkoxide. Examples of suitable inor (wherein X and X are oxygen), or a chlorothioformate ganic bases include sodium carbonate, Sodium or potassium C1 C(X) X R' (whereinX is oxygen and X is sulfur), hydroxide, Sodium hydride, and Suitable organic bases or a chlorodithioformate C1 C(X) X R., (wherein X 15 include trialkylamines, such as trimethylamine and triethy and X are sulfur), or an isothiocyanate, RN=C=S, or by lamine, pyridines or other amine bases such as 1,4-diazobi sequential treatment with carbon disulfide and an alkylating cyclo[2.2.2]octane and 1,8-diazabicyclo[5.4.0]undec-7-ene. agent, or with a phosphorylating agent such as a phosphoryl Preferred bases include triethylamine and pyridine. Suitable chloride, Cl- P(X)(R)-R or with a sulfonylating agent solvents for this reaction are selected to be compatible with such as a sulfonyl chloride C1 SO. R. preferably in the the reagents and include ethers such as tetrahydrofuran and presence of at least one equivalent of base. 1.2-dimethoxyethane and halogenated solvents such as Depending on the nature of the substituents R* to R, and of dichloromethane and chloroform. Certain bases, such as pyri the group G, isomeric compounds of formula (I) may be dine and triethylamine, may be employed Successfully as formed. For example, compounds of formula (A) wherein R' both base and solvent. For cases where the acylating agent is and Rare different may give rise to compounds of formula (I) 25 a carboxylic acid, acylation is preferably effected in the pres or to compounds of formula (IA), or to a mixture of com ence of a coupling agent Such as 2-chloro-1-methylpyri pounds of formula (I) and formula (IA). This invention covers dinium iodide, N,N-dicyclohexycarbodiimide, 1-(3-dim both compounds of formula (I) and compounds of formula ethylaminopropyl)-3-ethylcarbodiimide and N,N'- (IA), together with mixtures of these compounds in any ratio. carbodiimidazole, and optionally a base Such as triethylamine 30 or pyridine in a Suitable solvent Such as tetrahydrofuran, dichloromethane or acetonitrile. Suitable procedures are described, for example, by W. Zhang and G. Pugh, Tetrahe dron Lett. (1999), 40 (43), 75.95 and T. Isobe and T. Ishikawa, J. Org. Chem. (1999), 64 (19) 6984. Phosphorylation of cyclic-1,3-diones may be effected using a phosphorylhalide or thiophosphorylhalide and a base by procedures analogous to those described in U.S. Pat. No. 4,409,153. Sulfonylation of compounds of formula (A) may be achieved using an alkyl or aryl Sulfonylhalide, preferably in the presence of at least one equivalent of base, for example by the procedure of C. J. Kowalski and K. W. Fields, J. Org. Chem. (1981), 46, 197. Certain compounds of formula (I) are alkenes, and as Such undergo further reactions typical of alkenes to give additional compounds of formula (I) according to known procedures. Examples of Such reactions include, but are not restricted to, halogenation, epoxidation, cyclopropanation, dihydroxyla tion and hydration of alkenes. In turn, these products may be transformed into additional compounds of formula (I) by methods described, for example, by Michael B. Smith and Jerry March, March's Advanced Organic Chemistry (Sixth Edition), John Wiley and Sons. Compounds of formula (I) wherein RandR form a bond and R or Rare C-Calkoxy are enol ethers, and these may be hydrolysed to the corre sponding ketone using standard procedures to give additional compounds of formula (I). Compounds of formula (I) (IA) wherein R and R form a bond and R' or R are halogen, preferably chloride or bromide, may undergo a cross-cou The O-alkylation of cyclic 1,3-diones is known; suitable 60 pling reaction with a suitable coupling partner under condi methods are described, for example, in U.S. Pat. No. 4,436, tions described in the literature for Suzuki-Miyaura, Sono 666. Alternative procedures have been reported by M. T. gashira, Stille and related cross-coupling reactions to give Pizzorno and S. M. Albonico, Chem. Ind. (London) (1972), additional compounds of formula (I) (see, for example, C. J. 425; H. Bornet al., J. Chem. Soc. (1953), 1779; M. G. Con O’Brien, M. G. Organ Angew. Chem. Int. Ed. 2007, 46. stantino et al., Synth. Commun., (1992), 22 (19), 2859; Y. 65 2768-2813: A. Suzuki, Journal of Organometallic Chemistry Tianet al., Synth. Commun. (1997), 27 (9), 1577; S. Chandra (2002), 653, 83; N. Miyaura and A. Suzuki Chem. Rev. Roy et al., Chem. Lett. (2006), 35 (1), 16: P. K. Zubaidha et (1995), 95, 2457-2483). US 8,530,667 B2 18

R7 R8 OG R base, solvent --- then acid R4 RI R2 O

(I) 10

where R and R form a bond

R Het 15 R4

(B) Compounds of formula (B), wherein R is H may be esteri fied to compounds of formula (B), wherein R is alkyl, under Compounds of formula (A) may be prepared via the cycli standard conditions. sation of compounds of formula (B), preferably in the pres Compounds of formula (C) wherein R is alkyl may be ence of an acid or base, and optionally in the presence of a prepared by treating compounds of formula (D) with suitable Suitable solvent, by analogous methods to those described in 25 carboxylic acid chlorides of formula (E) wherein R is alkyl U.S. Pat. No. 4,209,532. The compounds of the formula (B) under basic conditions. Suitable bases include potassium tert have been particularly designed as intermediates in the Syn butoxide, sodium bis(trimethylsilyl)amide and lithium diiso thesis of the compounds of the formula (I). Compounds of propylamide and the reaction is preferably conducted in a formula (B) wherein R is hydrogen may be cyclised under suitable solvent (such as tetrahydrofuran or toluene) at a acidic conditions, preferably in the presence of a strong acid 30 temperature of between -80° C. and 30° C.: such as Sulfuric acid, polyphosphoric acid or Eaton's reagent, O optionally in the presence of a Suitable solvent Such as acetic base acid, toluene or dichloromethane. R No --- Het 35 (D)

Het acid He solvent 40

7 R v R, OH 45 R5 Het R4 (C) 50 Alternatively, compounds of formula (C), wherein R is H. R2 R O may be prepared by treating compounds of formula (D) with (A) a suitable base (such as potassium tert-butoxide, sodium bis (trimethylsilyl)amide and lithium diisopropylamide) in a Compounds of formula (B) wherein R is alkyl (preferably suitable solvent (such as tetrahydrofuran or toluene) at a methyl or ethyl), may be cyclised under acidic or basic con suitable temperature (between -80° C. and 0°C.) and react ditions, preferably in the presence of at least one equivalent of ing the resulting anion with a suitable anhydride of formula a strong base Such as potassium tert-butoxide, lithium diiso (F):

propylamide or Sodium hydride and in a solvent such as (F) tetrahydrofuran, dimethylsulfoxide or N,N-dimethylforma 60 mide. Compounds of formula (B), wherein R is H. may be pre pared by Saponification of compounds of formula (C) wherein R' is alkyl (preferably methyl or ethyl), under stan dard conditions, followed by acidification of the reaction 65 mixture to effect decarboxylation, by similar processes to those described, for example, in U.S. Pat. No. 4,209,532. US 8,530,667 B2 19 20 Compounds of formula (D) are known, or may be made by Compounds of formula (G) may be prepared by reacting known methods from known compounds (see, for example, compounds of formula (H) with maleic anhydrides of for E. Bellur and P. Langer, Synthesis (2006), 3, 480-488; E. mula (J), optionally in the presence of a Lewis acid catalyst, Bellur and P. Langer, Eur. J. Org. Chem. (2005), 10, 2074 and according to procedures described, for example, by O. 2090; G. Bartolo et al., J. Org. Chem. (1999), 64 (21), 7693- 5 Diels and K. Alder, Liebigs Ann. Chem. (1931), 490, 257; K. 7699; R. Kranich et al., J. Med. Chem. (2007), 50 (6), 1101 T. Potts and E. B. Walsh, J. Org. Chem. (1984), 49 (21), 4099: 1115: I. Freifeld et al., J. Org. Chem. (2006), 71 (13), 4965 J. Jurczak, T. Kozluk, S. Filipek and S. Eugster, Helv. Chim. 4968; S. Hermann et al., WO2006/087120; R. Fischer et al. Acta (1982), 65, 1021; W. G. Dauben, C. R. Kessel and K. H. WO96/16061; H. A. Staab and G. A. Schwalbach, Justus Takemura, J. Am. Chem. Soc. (1980), 102, 6893: A. Pelter Liebigs Annalender Chemie (1968), 715, 128-34; J-L Brayer 10 et al., EP402246: P. Chemla et al., WO99/32464; A. Dornow and B. Singaram, Tetrahedron Lett. (1982), 23, 245; M. W. and G. Petsch, Chem. Ber. (1953), 86, 1404-1407; E. Y-H Lee and C. W. Herndon, J. Org. Chem. (1978), 43,518; B. E. Chao et al., WO2001/000603: D. B. Lowe et al., WO2003/ Fisher and J. E. Hodge, J. Org. Chem. (1964), 29, 776; G. F. 01 1842; R. Fischer et al., WO2001/096333; J. Ackermann et D'Alelio, C. J. Williams and C. L. Wilson, J. Org. Chem. al., WO2005/049572; B. Li et al., Bioorg. Med. Chem. Lett. 15 (1960), 25, 1028; Z.Z. Song, M. S. Ho and H. N. C. Wong, J. (2002), 12, 2141-2144, G. P. Rizzi, J. Org. Chem. (1968), 33 Org. Chem. (1994), 59 (14) 3917-3926; W. Tochtermann, S. (4) 13333-13337; M. Okitsu and K. Yoshid, JP63230670: F. Bruhn and C. Wolff, Tetrahedron Lett. (1994), 35.(8) 1165 Bohlmann et al., Chem. Ber. (1955), 88, 1831-1838: R. Fis 1168; W. G. Dauben, J. Y. L. Lam and Z. R. Guo, J. Org. cher et al., WO2003/035463; R. Fischer er al., WO2005/ Chem. (1996), 61 (14) 4816-4819; M. Sodeoka, Y. Baba, S. 005428; D O'Mant, GB1226981). Kobayashi and N. Hirukawa, Bioorg. Med. Chem. Lett. Compounds of formula (E) may be prepared from com (1997), 7(14), 1833; M. Avalos, R. Babiano, J. L. Bravo, P. pounds of formula (F) by treatment with an alkyl alcohol, Cintas, J. L. Jimenez and J. C. Palacios, Tetrahedron Lett. R-OH, in the presence of a base, Such as an alkaline metal (1998), 39(50), 9301; J. Auge, R. Gil, S. Kalsey and N. alkoxide (see, for example, S. Buser and A. Vasella, Helv. Lubin-Germain, Synlett (2000), 6, 877: I. Hemeon, C. Chim. Acta (2005), 88,3151; M. E. Hartet al., Bioorg. Med. 25 Deamicis, H. Jenkins, P. Scammells and R. D. Singer, Synlett Chem. Lett. (2004), 14, 1969), followed by treatment of the (2002), 11, 1815; M. Essers, B. Wibbeling and G. Haufe, resulting acid with a chlorinating reagent such as oxalyl chlo Tetrahedron Lett. (2001), 42 (32), 5429; P. Vogel et al., Tet ride or thionyl chloride under known conditions (see, for rahedron: Asymmetry (1996), 7 (11), 3153; Y. Baba, N. example, C. Santelli-Rouvier. Tetrahedron Lett. (1984), 25 Hirukawa, N. Tanohira and M. Sodeoka, J. Am. Chem. Soc. (39), 4371; D. M. Walba and M. D. Wand, Tetrahedron Lett. (2003), 125,9740; L. Ghosezet al., Tetrahedron Lett. (1988), (1982), 23 (48), 4995; J. Cason, Org. Synth. Coll. Vol. III, 30 29 (36), 4573 (and references therein); H. Kotsuki, S. Kita (1955), 169). gawa and H. Nishizawa, J. Org. Chem. (1978), 43 (7) 1471;Y.

Liet al., J. Org. Chem. (1997), 62 (23), 7926; M. Drew et al., J. Chem. Soc. Perkin Trans. 1 (1985), 1277: R. N. McDonald 35 and C. E. Reineke, J. Org. Chem. (1967), 32, 1878; R. H. ROH Fleming and B. M. Murray, J. Org. Chem. (1979), 44 (13), Her 2280; M. J. Goldstein and G. L. Thayer Jr. J. Am. Chem. Soc. Chlorinating agent (1965), 87(9), 1925 and G. Keglevich et al., J. Organomet. Chem. (1999), 579, 182 and references therein.

O R8

O 7 R7 RI R R8 - R O R e J S. Compounds of formula (F) wherein R and Rare hydro 50 R4 R4 RI gen may be prepared by the reduction of compounds of for R2 R2 O mula (G) under known conditions (see, for example, Y. Baba, (H) N. Hirukawa and M. Sodeoka, Bioorg. Med. Chem. (2005), (G) 13 (17), 5164; M. E. Hart et al., Bioorg. Med. Chem. Lett. (2004), 14(18), 1969;Y. Baba, N. Hirukawa, N. Tanohira and 55 Compounds of formula (H) and formula (J) are known M. Sodeoka, J. Am. Chem. Soc. (2003), 125,9740). compounds, or may be made from known compounds by R7 R7 known methods. 5 R8 O R8 O Certain compounds of formula (G) are alkenes, and as Such R R undergo further reactions typical of alkenes to give additional compounds of formula (F) according to known procedures. C O reduction O 60 Examples of Such reactions include, but are not restricted to, R4 R4 halogenation, epoxidation, cyclopropanation, dihydroxyla R R1 R2 O R2 O tion and hydration of alkenes. In turn, these products may be transformed into additional compounds of formula (F) by (G) (F) 65 methods described, for example, by Michael B. Smith and wherein R and R = H Jerry March, March's Advanced Organic Chemistry (Sixth Edition), John Wiley and Sons. US 8,530,667 B2 21 22 Compounds of formula (G) may also be prepared by react -continued ing compounds of formula (H) with compounds of formula (K), wherein R" is hydrogen or an alkyl group, to give com pounds of formula (L) and cyclising compounds of formula (L) under known conditions (see, for example, P. W. Sprague et al., J. Med. Chem. (1985), 28, 1580; A. P. Guzaev and M Manoharan, J. Am. Chem. Soc. (2003), 125, 2380; and A. P. Marchand and R. W. Allen, J. Org. Chem. (1975), 40 (17), 2551. 10 (N) COR"

R7 Preferably, the rearrangement is effected by heating com R1DC COR" R pounds of formula (O) at temperatures of between 120-250° e (K) 15 C., optionally in a Suitable solvent such as 1,2-dimethoxy O He S. ethane, diethylene glycol methyl ether, triglyme, tetraglyme, R4 xylene, mesitylene or DowthermR), and optionally under R2 microwave irradiation. (H) Similarly, compounds of formula (P), which are com R 7 R 7 pounds of formula (A) wherein Het is (R) when R is R8 R8 O CHR" and R" is hydrogen, alkyl or halogenoalkyl (prefer R COR" R ably hydrogen, methyl or trifluoromethyl), may be prepared O from compounds of formula (Q) using similar methods. C ---cyclisation C R4 COR" R4 25 R1 R O R2 R2 ( L) ( G)

solvent 7 ision 26 R R7 X R R8 R8 O R COR" R cyclisation O He

R4 COR" R4 RI RI R2 R2 O (M) (F) wherein RandR = H 40 Compounds of formula (L) may also be reduced to com pounds of formula (M), and compounds of formula (M) cyc lised to compounds of formula (F) wherein R and R are (P) hydrogen, under conditions similar to those described previ 45 ously. Compounds of formula (O) may be prepared from com Compounds of formula (K) are known compounds, or may pounds of formula (R) by alkylation with compounds of be prepared from known compounds by known methods. formula (S), wherein L is a Suitable leaving group Such as a In a further approach to compounds of formula (A), com halogen or an alkyl- or aryl-sulfonate, optionally in the pres pounds of formula (N), which are compounds of formula (A) 50 ence of a suitable base and optionally in a suitable solvent as wherein Het is (R) when R’ is CHR" and R" is hydrogen, described above for the alkylation of compounds of formula alkyl or halogenoalkyl (preferably hydrogen, methyl or trif (A) luoromethyl), may be prepared by thermal rearrangement of compounds of formula (O), optionally in the presence of a Suitable solvent and optionally under microwave irradiation. 55 R'

R'' X L 26 X 6 R8 O R R7 ZX-R 60 / -- R5 (S) ZX-R solventA base, solvent R4 R3 R2 R O 65 US 8,530,667 B2 23 24 -continued -continued R'

X X-R26 Z

10 (O) Similarly, compounds of formula (Q) may be prepared from compounds of formula (R) by alkylation with com pounds of formula (T), wherein L is a suitable leaving group 15 Such as a halogen oran alkyl- or aryl-sulfonate, under similar Alternatively, the condensation may be effected in the pres conditions. ence of Suitable coupling agents such as 2-chloro-1-meth ylpyridinium iodide, N,N'-dicyclohexylcarbodiimide, 1.(3- dimethylaminopropyl)-3-ethylcarbodiimimde and N.N- Z carbodiimidazole and optionally a Suitable base Such a I N triethylamine or pyridine in a Suitable solvent such as tetrahy R 7 R8 O X- R26 drofuran, acetonitrile or dichloromethane, or in the presence X of a triarylphosphine (Such as triphenylphosphine) and a (T) dialkyl azidodicarboxylate (preferably diethyl azidodicar base, solvent 25 boxylate or diisopropyl azidodicarboxylate) and in a suitable solvent such as diethyl ether, tetrahydrofuran or 1,4-dioxane as described, for example, by O. Mitsunobu, Synthesis (1981), 1, 1-28. Using similar processes, compounds of formula (Q) may be prepared by reaction of compounds of formula (R) with compounds of formula (V).

35

(Q) HO Z N R26 O In an alternative approach, compounds of formula (O) may X be prepared from compounds of formula (R) by condensation 40 with alcohols of formula (U), optionally in the presence of a (V) Suitable acid catalyst Such as p-toluenesulfonic acid, or a catalyst solvent Lewis acid catalyst, for example, ytterbium (III) trifluo romethanesulfonate, lanthanum (III) trifluoromethane R3 R2 R1 O sulfonate, sodium tetrachloroaurate (III) dihydrate, titanium 45 (IV) chloride, indium (III) chloride or aluminium chloride, (R) and optionally in a suitable solvent. Suitable solvents are R' selected to be compatible with the reagents used, and include, R6 R7 R8 O for example, toluene, ethanol or acetonitrile. Similar approaches have been described by, for example, M. Curini, F. Epifano, S. Genovese, Tetrahedron Lett. (2006), 47, 4697 50 R5 } { 700 and A. Arcadi, G. Bianchi, S. Di Giuseppe, F. Marinelli, R4 C) s Green Chemistry (2003), 5, 64-7. R3 R2 R1 O

55 (Q)

X HO 26 Additional compounds of formula (O) wherein R is an R aromatic or heteroaromatic moiety, or is an alkyl, alkenyl or Z 60 alkynyl group, may be prepared by the reaction of compounds (U) of formula (W), wherein Q is an atom or group suitable for catalyst solvent undergoing cross-coupling reactions (for example Q is chlo rine, bromine or iodine, or a haloalkylsulfonate such as trif luoromethanesulfonate), and R" is as defined for compound 65 of formula (N), with a suitable coupling partner under con ditions described in the literature for Suzuki-Miyaura, Sono gashira, Stille and related cross-coupling reactions. US 8,530,667 B2 26 -continued

Suzuki-Miyaura coupling Stille coupling 5 Sonogashira coupling or similar

10 (O)

Alternatively, compounds of formula (O), wherein R is an optionally Substituted acetylene, may be prepared from compounds of formula (W) by reacting with a terminal 15 alkyne, R H, in the presence of a suitable palladium cata lyst and optionally in the presence of a suitable copper co catalyst, a suitable ligand, a Suitable base and a suitable addi tive under conditions known to effect the Sonogashira coupling (see, for example, U. Sorenson and E Pombo-Villar, Tetrahedron (2005), 2697-2703; N. Leadbeater and B. Tomi For example, compounds of formula (W) may be treated nack, Tetrahedron Lett. (2003), 44, 8653-8656: K. Sonogash with aryl-, heteroaryl-, alkyl-, alkenyl- or alkynylboronic ira, J. Organomet. Chem. (2002), 653, 46–49). acids, R. B(OH), boronate esters, R. B(OR"), In a further approach, compounds of formula (O), wherein 25 R’ is alkyl, optionally substituted vinyl, optionally substi wherein R" is C-Calkyl or R B(OR") represents tuted ethynyl, optionally substituted aryl or optionally sub cyclic boronate esters derived from a C-C diol (especially stituted heteroaryl, may be prepared from compounds of for preferred are cyclic boronate esters derived from pinacol), or mula (W) by reaction with a suitable organnostannane under a metal (especially potassium) aryl-, heteroaryl, alkyl-, alk Stille conditions (see, for example, R. Bedford, C. Cazin and enyl- and alkynyltrifluoroborate salts, MR BFI in the S. Hazlewood (2002), 22, 2608-2609; S. Ley et al., Chem. presence of a Suitable palladium catalyst, a Suitable ligand 30 Commun. (2002), 10, 1134-1135; G. Grasa and S. Nolan, and a Suitable base in the presence of a Suitable solvent, under Org. Lett. (2001), 3 (1), 119-122; T. Weskamp, V. Boehm, J. Suzuki-Miyaura conditions Organomet. Chem. (1999),585 (2),348-352: A. Littke and G. Fu, Angew. Chem. Int. Ed. (1999), 38 (16), 2411-2413: J. (see, for example K. Billingsley and S. Buchwald, J. Am. Stille et al., Org. Synth. (1992), 71,97). Chem. Soc. (2007), 129, 3358-3366; H. Stefani, R. Cella and 35 Compounds of formula (Q) may be prepared from com A. Vieira, Tetrahedron (2007), 63,3623-3658; N. Kudo, M. pounds of formula (X), wherein Q and R" are as defined for Perseghini and G. Fu, Angew. Chem. Int. Ed. (2006), 45, compounds of formula (W), by analogous methods using 1282-1284; A. Roglans, A. Pla-Quintana and M. Moreno appropriate starting materials. Mafias, Chem. Rev. (2006), 106, 4622-4643; J-H Li, Q-M Zhu and Y-X Xie, Tetrahedron (2006), 10888-10895; S. 40 Nolanet al., J. Org. Chem. (2006), 71, 685-692; M. Lysén and R' R7 K. Köhler, Synthesis (2006), 4, 692-698; K. Anderson and S. R6 R8 O Buchwald, Angew. Chem. Int. Ed. (2005), 44, 6173-61.77;Y. Wang and D. Sauer, Org. Lett. (2004), 6 (16), 2793-2796: I. R5 W Z Suzuki-Miyaura coupling 45 > Stille coupling Kondolff, H. Doucet and M, Santelli, Tetrahedron, (2004), R4 X Q Sonogashira coupling or 60,3813-3818; F. Bellina, A. Carpita and R. Rossi, Synthesis R3 RI related reaction (2004), 15, 2419-2440; H. Stefani, G. Molander, C-SYun, M. R2 O Ribagorda and B. Biolatto, J. Org. Chem. (2003), 68,5534 (X) 5539; A. Suzuki, Journal of Organometallic Chemistry R' (2002), 653, 83; G. Molander and C-S Yun, Tetrahedron 50 (2002), 58, 1465-1470; G. Zou, Y. K. Reddy and J. Falck, Tetrahedron Lett. (2001), 42, 4213-7215; S. Darses, G. W Z Michaud and J.-P. Genet, Eur. J. Org. Chem. (1999), 1877 1883). 55 X R26

(Q)

Compounds of formula (W) may be prepared from com MR-BF Her pounds of formula (R), by reaction with compounds of for catalyst, base, mula (Y) wherein L is a suitable leaving group Such as a solvent halogen oran alkyl- oraryl-sulfonate, by processes analogous to those described above for the preparation of compounds of 65 formula (O) from compounds of formula (R). Alternatively, compounds of formula (W) may be prepared by reaction of compounds of formula (R) with compounds of formula (Z) by US 8,530,667 B2 27 28 processes analogous to those described above for the prepa- abromide, phosphorus oxybromide, oxalyl chloride or oxalyl ration of compounds of formula (O) from compounds of bromide, optionally in a suitable solvent such as toluene, formula (R). chloroform, dichloromethane with optionally the presence of

R''

X I X-Q Z (Y) base, solvent R''

X HO X-Q (Z) Z catalyst, solvent

By analogous processes to those described above, com- dimethylformamide, and the resulting vinyl halides of for pounds of formula (X) may be prepared from compounds of mula (AC), wherein Hal is chlorine or bromine may be con formula (R) by alkylation with compounds of formula (AA), 35 verted by reaction with alcohols of formula (U), or of formula wherein L is a suitable leaving group Such as a halogen oran (V), or of formula (Z) or of formula (AB) optionally in the alkyl- or aryl-sulfonate, or by alkylation with compounds of presence of a Suitable base such as Sodium hydride, sodium formula (AB). tert-butoxide, potassium tert-butoxide and a suitable solvent

R''

Z L X-Q X (AA) base, solvent R'

Z (R) HO X-Q X (AB) catalyst, solvent

In an alternative approach, compounds of formula (R) may 65 Such as tetrahydrofuran, 1.4-dioxane, diethylene glycol dim be treated with a halogenating agent such as phosphorus ethyl ether to give compounds of formula (O), formula (Q), oxychloride, phosphorus pentachloride, phosphorus pent- formula (W) and formula (X) respectively: US 8,530,667 B2 29 30

halogenation He

R'

X HO 26 2- R Z (U) base, solvent

HO Z

7 X- R26 R6 v Rs Hal X 5 (V) R base, solvent R4 3 R R2 R1 O (AC) R'

HO X ill X-Q R Z (Z) X base, solvent W 22. Z Q R'

HO Z y Q R' X (AB) base, solvent

R2 RI O (X) Compound of formula (R) wherein Rand Rare hydrogen Certain compounds of formula (AD) are alkenes, and as may be prepared by reduction of compounds of formula (AD) 55 Such undergo further reactions typical of alkenes to give under known conditions. additional compounds of formula (R) according to known R7 procedures. Examples of Such reactions include, but are not R8 S restricted to, halogenation, epoxidation, cyclopropanation, R dihydroxylation and hydration of alkenes. In turn, these prod reduction, go ucts may be transformed into additional compounds of for mula (R) by methods described, for example, by Michael B. R4 Smith and Jerry March, March's Advanced Organic Chem R2 R O istry (Sixth Edition), John Wiley and Sons. Compounds of (AD) (R) formula (R) wherein R or R are C-Calkoxy are enol 65 ethers, and these may be hydrolysed to the corresponding wherein R and R = H ketone using standard procedures. In turn, the ketone may be further transformed, for example by ketalisation, oximation, US 8,530,667 B2 31 32 reduction and the like under known conditions to give addi ranging compounds of formula (W) under conditions similar tional compounds of formula (R). Compounds of formula to those used to convert compounds of formula (O) to com (AD) wherein R or R are halogen, preferably chloride or pounds of formula (N): bromide, may undergo a cross-coupling reaction with a Suit able coupling partner under conditions described in the lit erature for Suzuki-Miyaura, Sonogashira, Stille and related cross-coupling reactions to give additional compounds of formula (AD) (see, for example, C.J. O’Brien, M. G. Organ Angew. Chem. Int Ed. 2007, 46,2768-2813: A. Suzuki, Jour 4.2 -– nal of Organometallic Chemistry (2002), 653, 83; N. Miyaura 10 and A Suzuki Chem. Rev. (1995), 95, 2457-2483). Compounds of formula (AD) may be prepared by reacting

compounds of formula (AE) with a cyclopentenediones of formula (AF), optionally in the presence of a Lewis acid catalyst, according to procedures described, for example by B. Zwanenburg et al., Tetrahedron (1989), 45 (22), 7109 and by M. Oda et al., Chem. Lett. (1977), 307. O R8 (AG) 7 R * Rs 9 Suzuki-Miyaua, R O R2 O 5 R 25 Sonogashira Stille or \ f ---(AF) CO related reaction R5 R4 R4 2 R1 O (AE) R 30 (AD) Compounds of formula (AE) and formula (AF) are known compounds or may be made from known compounds by known methods. Compounds of formula (S), formula (T), formula (U), for 35 mula (V), formula (Y), formula (Z), formula (AA) and for (N) mula (AB) are known or may be prepared by known methods wherein R is aryl, heteroaryl, from known compounds (see, for example T. T. Denton, X. alkenyl, alkynyl or similar Zhang, J. R. Cashman, J.Med. Chem. (2005), 48, 224-239; J. Reinhard, W. E. Hull, C.-W. von der Lieth, U. Eichhorn, H.-C. 40 Those skilled in the art will appreciate that transformations Kliem, J. Med. Chem. (2001), 44, 4050-4061; H. Kraus and of this type are not restricted to compounds of formula (AG), H. Fiege, DE 19547076; M. L. Boys, L.A. Schretzman, N. S. but may in general be applied to any compound of formula (I) Chandrakumar, M. B. Tollefson, S. B. Mohler, V. L. Downs, where Het is a heterocycle substituted by an atom or group T. D. Penning, M. A. Russell, J. A. Wendt, B. B. Chen, H. G. suitable for further derivatisation. Stenmark, H. Wu, D. P. Spangler, M. Clare, B. N. Desai, I. K. 45 Khanna, M. N. Nguyen, T. Duffin, V. W. Engleman, M. B. Those skilled in the art will appreciate that compounds of Finn, S.K. Freeman, M.L. Hanneke, J. L. Keene, J. A. Klover, formula (I) may contain a heteroaromatic moiety bearing one G. A. Nickols, M.A. Nickols, C. N. Steininger, M. Westlin, W. or more Substituents capable of being transformed into alter Westlin, Y. X. Yu, Y. Wang, C. R. Dalton, S. A. Norring, native substituents under known conditions, and that these Bioorg. Med. Chem. Lett. (2006), 16,839-844; A. Silberg, A. 50 compounds may themselves serve as intermediates in the Benko, G. Csavassy, Chem. Ber. (1964), 97, 1684-1687: K. preparation of additional compounds of formula (I). For Brown and R. Newbury, Tetrahedron Lett. (1969), 2797; A. example, a heterocycle of formula (N) wherein Risalkenyl Jansen and M. Szelke, J. Chem. Soc. (1961), 405; R. Diaz or alkynyl, may be reduced to compounds of formula (N) Cortes, A. Silva and L. Maldonado, Tetrahedron Lett. (1997), wherein R is alkyl under known conditions. 38(13), 2007-2210; M. Friedrich, A. Waechtler and A De 55 Meijure, Synlett. (2002), 4,619-621; F. Kerdesky and L. Seif, Synth. Commun. (1995), 25 (17), 2639-2645; Z. Zhao, G. Scarlato and R. Armstrong. Tetrahedron Lett. (1991), 32 H2, catalyst (13), 1609-1612. K-T. Kang and S. Jong, Synth. Commun. -e- (1995), 25 (17), 2647-2653; M. Altamura and E. Perrotta, J. solvent Org. Chem. (1993), 58 (1), 272-274). Furthermore, compounds of formula (AG) wherein Q is an atom or group Suitable for cross-coupling chemistry (such as (N) a halogen or a haloalkylsulfonate) may undergo Suzuki Miyaura, Stille, Sonogashira and related reactions under 65 wherein R is known conditions to give additional compounds of formula alkyl or alkenyl N. Compounds of formula (AG) may be prepared by rear US 8,530,667 B2 33 34 -continued -continuedsR6 R

(A) where Het is (R) 10 X is Sand Z is N Alternatively, compounds of formula (AH) may be treated wherein R is alkyl with thiourea, by known procedures (see, for example, V. 15 Pshenichniya, O. Gulyakevich and V. Kripach, Chemistry of Heterocyclic Compounds (1990), 10, 1409-1412), and the In a further approach to compounds of formula (A), resulting products of formula (AK) may be converted into wherein Het is a group of formula (R), X is S. and Y is N. additional compounds of formula (A) by conversion to compounds of formula (AH) wherein Lisa suitable leaving halides of formula (AL), wherein Hal is chlorine, bromine or group Such as a halogen or an alkyl- or haloalkylsulfonate, may be treated with compounds of formula (AJ) in the pres iodine, under Sandmeyer conditions, and compounds of for ence of a suitable base (such as triethylamine or pyridine), and mula (AL) may be converted to compounds of formula (A) by optionally in a Suitable solvent (such as water, acetone, etha cross-coupling under known conditions for the Suzuki nol or isopropanol) according to known procedures, (see, for Miyaura, Sonogashira, Stille and related reactions, as example, E. Knott, J. Chem. Soc. (1945), 455; H. Brederick, described previously.

COSS coupling

(A) where Het is (R) X is Sand Z is N

50 R. Gompper, Chem. Ber. (1960), 93, 723: B. Friedman, M. Compounds of formula (AH) may be prepared from com Sparks and R. Adams, J. Am. Chem. Soc. (1937), 59, 2262). pounds of formula (R) under known conditions (see, for example, V. Pshenichniya, O. Gulyakevich and V. Kripach, Chemistry of Heterocyclic Compounds (1990), 10, 1409 55 1412: V. Pshenichniya, O. Gulyakevich and V. Kripach, Rus sian Journal of Organic Chemistry (1989), 25 (9), 1882 1888). In a further approach, compounds of formula (A) may be prepared by reaction of compounds of formula (R) with a 60 heteroaryl lead tricarboxylates under conditions described in the literature (for example see, J.T. Pinhey, B. A. Rowe, Aust. J. Chem. (1979), 32, 1561-6:J. Morgan, J.T. Pinhey, J. Chem. (AJ) Soc. Perkin Trans. 1 (1990), 3, 715-20 and J. T. Pinhey, base, solvent Roche, E. G. J. Chem. Soc. Perkin Trans. 1 (1988), 2415-21). 65 Preferably the heteroaryl lead tricarboxylates are heteroaryl triacetates of formula (AM) and the reaction is conducted in the presence of a suitable ligand (for example N,N-dimethy US 8,530,667 B2 35 36 laminopyridine, pyridine, imidazole, bipyridine, and 1.10 -continued phenanthroline, preferably one to ten equivalents of N.N- (AN) dimethylaminopyridine with respect to compound (R)) and in a suitable solvent (for example chloroform, dichloromethane and toluene, preferably chloroform and optionally in the pres ence of a co-solvent such as toluene) at 25° C. to 100° C. (preferably 60-90° C.). (AN4) 10

OAc ligand, solvent + AcO-Pb-Het -> 25° C. to 100° C. 15 OAc (ANs) (AM)

Het (AN) 25

Compounds of formula (AM) may be prepared from com pounds of formula (AN) by treatment with lead tetraacetate in 30 a suitable solvent (for example chloroform) at 25°C. to 100° (AN) C. (preferably 25-50° C.), optionally in the presence of a catalyst Such as mercury diacetate, according to procedures described in the literature (for example see, K. Shimi, G. 35 Boyer, J.-P. Finet and J.-P. Galy, Letters in Organic Chemistry (2005), 2,407-409; J. Morgan and J.T. Pinhey, J. Chem. Soc. Perkin Trans. 1 (1990), 3, 715-20). (ANs) 40 HO OAc Pb(OAc)4 B-Het -> AcO-Pb-Het Hg(OAc)2, solvent HO OAc 45 (AN) (AM) Heteroarylboronic acids of formula (AN) are known com Preferred coupling partners include heteroarylboronic pounds, or may be prepared from known compounds by acids, (AN) to (ANs), wherein R, R2, R7, R. R. R. 50 known methods (see for example A. Voisinet al., Tetrahedron X, W, W. W. W. and Z are as defined above. (2005), 1417-1421: A. Thompson et al, Tetrahedron (2005), 61, 5131-5135; K. Billingsley and S. Buchwald, J. Am. (AN) Chem. Soc. (2007), 129, 3358-3366; N. Kudo, M. Pauro and R23 W G. Fu, Angew. Chem. Int. Ed. (2006), 45, 1282-1284; A. 55 Ivachtchenko et al., J. Heterocyclic Chem. (2004), 41(6), 931-939; H. Matondo et al., Synth. Commun. (2003), 33 (5) HO DC Sw22W. W4 795-800; A. Bouillon et al., Tetrahedron (2003), 59, 10043 10049; W. Liet al., J. Org. Chem. (2002), 67,5394-5397: C. OH Enguehardet al., J. Org. Chem. (2000), 65,6572-6575; H N (AN) 60 25 Nguyen, X. Huang and S. Buchwald, J. Am. Chem. Soc. R X (2003), 125, 11818-11819, and references therein). R26 In a further approach, compounds of formula (A) may be HON B D Z2 prepared from compounds of formula (AO) by reaction with 65 heteroarylboronic acids of formula (AN), in the presence of OH a Suitable palladium catalyst and a base, and preferably in a suitable solvent. US 8,530,667 B2 37 38 -continued Het

(AN) Her "Pol" base, additive, solvent

(AO) 10

In a further approach, compounds of formula (A) may be prepared from compounds of formula (I) or IA (wherein G is C-C alkyl) by hydrolysis, preferably in the presence of an acid catalyst Such as hydrochloric acid and optionally in the Het 15 presence of a suitable solvent such as tetrahydrofuran or 1,4-dioxane. Compounds of formula (I) (wherein G is C-C, alkyl) may be prepared by reacting compounds of formula (AP) (wherein G is C-C alkyl, and Hai is a halogen, prefer ably bromine or iodine), with a heteroarylboronic acid, Het B(OH), of formula (AN) in the presence of a suitable palla dium catalyst (for example 0.001-50% palladium(II) acetate Suitable palladium catalysts are generally palladium(II) or with respect to compound (AP)) and a base (for example 1 to palladium(0) complexes, for example palladium(II) diha 10 equivalents potassium phosphate with respect to com lides, palladium(II) acetate, palladium(II) sulfate, bis(triph pound (AP)) and preferably in the presence of a suitable enylphosphine)palladium(II) dichloride, bis(tricyclopen ligand (for example 0.001-50% (2-dicyclohexylphosphino)- tylphosphine)palladium(II) dichloride, bis 25 2,6'-dimethoxybiphenyl with respect to compound (AP)), (tricyclohexylphosphine)palladium(II) dichloride, bis and in a suitable solvent (for example toluene), preferably (dibenzylideneacetone)palladium(0) O tetrakis between 25°C. and 200° C. Similar couplings are known in (triphenylphosphine)palladium(0). The palladium catalyst the literature (see for example, Y. S. Song, B.T. Kim and J.-N. can also be prepared in situ from palladium(II) or palladium Heo, Tetrahedron Letters (2005), 46 (36), 5987-5990). (0) compounds by complexing with the desired ligands, by, 30 for example, combining the palladium(II) salt to be com Het-B(OH) plexed, for example palladium(II) dichloride (PdCl) or pal formula (Y) "Pd", ligand ladium(II) acetate (Pd(OAc)), together with the desired H ligand, for example triphenylphosphine (PPh3), tricyclopen base, solvent tylphosphine or tricyclohexylphosphine and the selected Sol 35 vent, with compounds of formula (AO), a heteroaromatic boronic acid of formula (AN) and a base. Also suitable are bidendate ligands, for example 1, 1'-bis(diphenylphosphino) ferrocene or 1.2-bis(diphenylphosphino)ethane. By heating 40 the reaction medium, the palladium(II) complex or palladium hydrolysis (O) complex desired for the C C coupling reaction is thus Het -e- formed “in situ', and then initiates the C C coupling reac tion. The palladium catalysts are used in an amount of from 0.001 to 50 mol%, preferably in an amount of from 0.1 to 15 mol %, based on the compound of formula (AO). More pref 45 erably the palladium source is palladium acetate, the base is lithium hydroxide and the solvent is a mixture of 1.2- dimethoxyethane and water in a ratio of 4:1 to 1:4. The reaction may also be carried out in the presence of other Het additives, such as tetralkylammonium salts, for example, tet 50 rabutylammonium bromide: Compounds of formula (AO) may be prepared from com pounds of formula (R) by treatment with (diacetoxy)iodoben Zene according to the procedures of K. Schank and C. Lick, (A) Synthesis (1983),392; or of ZYana et al., Ora. Lett. (2002), 4 55 (19), 3333. Compounds of formula (AP) may be prepared by haloge nating compound of formula (R), followed by alkylation of

the resulting halides of formula (AQ) with a C-C alkyl halide or tri-C-C-alkylorthoformate under known condi tions, for example by the procedures of R. G. Shepherd and A. 60 PhI(OAc) C. White (J. Chem. Soc. Perkin Trans. 1 (1987), 2153-2155) -e- and Y.-L. Lin et al. (Bioorg. Med. Chem. (2002), 10, 685 base, solvent 690). Alternatively, compounds of formula (AP) may be pre pared by alkylating compounds of formula (R) with a C-C, alkyl halide or a tri-C-C-alkylorthoformate, and halogenat 65 ing the resulting enone of formula (AR) under known condi tions (see for example Y. S. Song, B. T. Kim and J.-N. Heo, Tetrahedron Letters (2005), 46 (36), 5987-5990). US 8,530,667 B2 39

halogenation

(R)

alkylation

In a further approach, compounds of formula (A) may be -continued prepared by reacting compounds of formula (R) with Suitable 30 heteroaryl halides (Het-Hal where Hal is, for example, an R7 iodide or bromide), in the presence of a suitable palladium R6 R8 O catalyst (for example 0.001-50% palladium(II) acetate with R5 respect to compound (R)) and a base (for example 1 to 10 Het equivalents potassium phosphate with respect to compound 35 R4 (R)) and preferably in the presence of a suitable ligand (for R3 example 0.001-50% (2-dicyclohexylphosphino)-2',4',6'- R2 R O thisopropylbiphenyl with respect to compound (R)), and in a suitable solvent (for example 1,4-dioxane), preferably (A) between 25°C. and 200° C. Similar couplings are known in 40 the literature (see for example, J. M. Fox, X. Huang, A. Additional compounds of formula (A) may be prepared by Chieffi, and S. L. Buchwald, J. Am. Chem. Soc. (2000), 122, hydrolysing compounds of formula (I), wherein G is C-C, 1360-1370; B. Hong et al. WO 2005/000233). Alternatively, alkyl under aqueous acidic conditions. Compounds of for compounds of formula (A) may be prepared by reacting com 45 mula (I), wherein G is C-Calkyland RandR form a bond, pounds of formula (R) with suitable heteroaryl halides (Het may be prepared by reacting compounds of formula (AS), Hal where Hal is, for example, an iodide or bromide) in the wherein G is C-Calkyl, X is halogen or other suitable leav presence of a suitable copper catalyst (for example 0.001 ing group (such as an alkyl or arylsulfonate, or an arylsele 50% copper(I) iodide with respect to compound (R)) and a noxide), with compounds of formula (AE), neat or in a Suit base (for example 1 to 10 equivalents potassium carbonate 50 able solvent, and optionally in the presence of a suitable base. with respect to compound (R)) and preferably in the presence of a suitable ligand (for example 0.001-50% L-proline with respect to compound (R)), and in a suitable solvent (for G example dimethylsulfoxide), preferably between 25°C. and V R8 O 200° C. Similar couplings are known in the literature for aryl 55 halides (see for example, Y. Jiang, N.Wu, H. Wu, and M. He, H Synlett (2005), 18, 2731-2734). Het X 7 5 R RI O 60 R catalyst, ligand e (AS) + Het-hal -e- O -- base, solvent S. base, solvent R4 R2 65 US 8,530,667 B2 41 42

-continued -continued R' OH R8 7 X

R1 Z ls R26 O (AU) (I) wherein G is C1-C alkyl 10 and RandR form a bond Preferably, the rearrangement is effected by heating com Suitable solvents include toluene, and suitable bases pounds of formula (AV) attemperatures of between 120-300 include organic bases Such as 1,8-diazabicyclo5.4.0]undec 15 C., optionally in a Suitable solvent such as 1,2-dimethoxy 7-ene. ethane, diethylene glycol methyl ether, triglyme, tetraglyme, Compounds of formula (AS), wherein G is C-Calkyl and xylene, mesitylene or DowthermR), and optionally under X is halogen may be prepared from compounds of formula microwave irradiation. Similarly, compounds of formula (AW), which are com (AT), wherein G is C-Calkyl, under known conditions. pounds of formula (AT) wherein G is hydrogen and Het is (R) when R is CHR" and R" is hydrogen, alkyl or halo genoalkyl (preferably hydrogen, methyl or trifluoromethyl), V v may be prepared from compounds of formula (AX) using R8 O R8 O similar methods. H H 25 Het -- Het H X R'

R O R O O (AT) (AS) 30 R8 W Z A > solvent - For example, compounds of formula (AS) wherein X is X R26 chlorine may be prepared by reacting compounds of formula R1 (AT) with copper(II) chloride and lithium chloride according O 35 to the procedure of E. M. Kosower et al., J. Org. Chem. (AX) (1963), 28, 630-633. R' Compounds of formula (AT) are known compounds or may be made from known compounds by known methods (see, for OH example, Y. S. S. Song, B. T. Kim and J-N Heo, Tetrahedron R8 Lett., 46 (2005) 5977-5990). Alternatively, compounds of 40 formula (AT) wherein G is C-Calkyl may be prepared by ( alkylation of compounds of formula (AT), wherein G is R1 x-s. hydrogen under known conditions. Compounds of formula O (AT), wherein G is hydrogen, are known, or may be prepared (AW) from known compounds by known methods (see, for 45 example, DE 10118310). Alternatively, in a further approach to compounds of for Compounds of formula (AV) may be prepared from com mula (AT), compounds of formula (AU), which are com pounds of formula (AY) by alkylation with compounds of pounds of formula (AT) wherein G is hydrogen and Het is formula (S), wherein L is a Suitable leaving group Such as a (R) when R is CHR" and R" is hydrogen, alkyl or halo 50 halogen or an alkyl- or aryl-sulfonate, optionally in the pres genoalkyl (preferably hydrogen, methyl or trifluoromethyl), ence of a suitable base and optionally in a suitable solvent as may be prepared by thermal rearrangement of compounds of described above for the alkylation of compounds of formula formula (AV), optionally in the presence of a suitable solvent (A) and optionally under microwave irradiation. 55 R' R' X R26 L O O 1 R8 X A 60 R8 Z Her 2 R26 solvent (S) Z base, solvent RI R1 O O 65 (AV) (AY) US 8,530,667 B2 43 44 -continued -continued R' R''

O O X R / X R8 / 2. 2s. 4 R26 R1 RI O O 10 (AV) (AV)

Similarly, compounds of formula (AX) may be prepared from compounds of formula (AY) by alkylation with com pounds of formula (T), wherein L is a suitable leaving group 15 Such as a halogen oran alkyl- or aryl-sulfonate, under similar Alternatively, the condensation may be effected in the pres conditions. ence of Suitable coupling agents such as 2-chloro-1-meth ylpyridinium iodide, N,N'-dicyclohexylcarbodiimide, 1.(3- R' dimethylaminopropyl)-3-ethylcarbodiimimde and N.N- carbodiimidazole and optionally a Suitable base Such a Z R26 triethylamine or pyridine in a Suitable solvent such as tetrahy O L \ y drofuran, acetonitrile or dichloromethane, or in the presence R8 X of a triarylphosphine (Such as triphenylphosphine) and a (T) dialkyl azidodicarboxylate (preferably diethyl azidodicar 25 base, solvent boxylate or diisopropyl azidodicarboxylate) and in a suitable RI solvent such as diethyl ether, tetrahydrofuran or 1,4-dioxane as described, for example, by O. Mitsunobu, Synthesis O (1981), 1, 1-28. (AY) R'' Using similar processes, compounds of formula (AX) may be prepared by reaction of compounds of formula (AY) with O compounds of formula (V). R8 / y X R26 R' R1 Z R26 O O HO \ Y (AX) R8 X (V) In an alternative approach, compounds of formula (AV) 40 may be prepared from compounds of formula (AY) by con catalyst densation with alcohols of formula (U), optionally in the R1 solvent presence of a suitable acid catalyst Such as p-toluenesulfonic O acid, or a Lewis acid catalyst, for example, ytterbium (III) trifluoromethanesulfonate, lanthanum(III) trifluoromethane (AY) sulfonate, sodium tetrachloroaurate (III) dihydrate, titanium 45 R'' (IV) chloride, indium (III) chloride or aluminium chloride, and optionally in a suitable solvent. Suitable solvents are O selected to be compatible with the reagents used, and include, R8 / y for example, toluene, ethanol or acetonitrile. Similar approaches have been described by, for example, M. Curini; 50 X R26 F. Epifano, S. Genovese, Tetrahedron Lett. (2006), 47, 4697 RI 700 and A. Arcadi, G. Bianchi, S. Di Giuseppe, F. Marinelli, O Green Chemistry (2003), 5, 64-7. (AX) 55 R' Additional compounds of formula (AV) wherein R is an X R26 aromatic or heteroaromatic moiety, or is an alkyl, alkenyl or O HO 1 alkynyl group, may be prepared by the reaction of compounds R8 Z 60 of formula (AZ), wherein Q is an atom or group suitable for (U) undergoing cross-coupling reactions (for example Q is chlo catalyst rine, bromine or iodine, or a haloalkylsulfonate such as trif RI solvent luoromethanesulfonate), and R" is as defined for compound 65 of formula (AW), with a suitable coupling partner under (AY) conditions described in the literature for Suzuki-Miyaura, Sonogashira, Stille and related cross-coupling reactions. US 8,530,667 B2 45 46 -continued R' R''

O Suzuki-Miyaura coupling O R8 W X Stille coupling X 2. HerSonogashira coupling R8 / 2. Z Q or similar 4 R26 RI RI O O 10 (AZ) (AV) R''

O Alternatively, compounds of formula (AV), wherein R is an optionally Substituted acetylene, may be prepared from R8 / X 15 compounds of formula (AZ) by reacting with a terminal alkyne, R H, in the presence of a suitable palladium cata -> R26 lyst and optionally in the presence of a suitable copper co R1 catalyst, a suitable ligand, a Suitable base and a suitable addi O tive under conditions known to effect the Sonogashira (AV) coupling (see, for example, U. Sorenson and E Pombo-Villar, Tetrahedron (2005), 2697-2703; N. Leadbeater and B. Tomi nack, Tetrahedron Lett. (2003), 44, 8653-8656: K. Sonogash For example, compounds of formula (AZ) may be treated ira, J. Organomet. Chem. (2002), 653, 46–49). with aryl-, heteroaryl-, alkyl-, alkenyl- or alkynylboronic In a further approach, compounds of formula (AV), acids, R. B(OH), boronate esters, R. B(OR"), 25 wherein R is alkyl, optionally substituted vinyl, optionally wherein R" is C-Calkyl or R B(OR"), represents substituted ethynyl, optionally substituted aryl or optionally cyclic boronate esters derived from a C-Cadiol (especially Substituted heteroaryl, may be prepared from compounds of preferred are cyclic boronate esters derived from pinacol), or formula (AZ) by reaction with a Suitable organnostannane a metal (especially potassium) aryl-, heteroaryl, alkyl-, alk under Stille conditions (see, for example, R. Bedford, C. enyl- and alkynyltrifluoroborate salts, M'R' BFI in the 30 Cazin and S. Hazlewood (2002), 22, 2608-2609; S. Ley et al., presence of a Suitable palladium catalyst, a Suitable ligand Chem. Commun. (2002), 10, 1134-1135; G. Grasa and S. and a Suitable base in the presence of a Suitable solvent, under Nolan, Org. Lett. (2001), 3 (1), 119-122; T. Weskamp, V. Suzuki-Miyaura conditions Boehm, J. Organomet. Chem. (1999), 585 (2), 348-352: A. (see, for example K. Billingsley and S. Buchwald, J. Am. Littke and G. Fu, Angew. Chem. Int. Ed. (1999), 38 (16), 35 2411-2413: J. Stille et al., Org. Synth. (1992), 71,97). Chem. Soc. (2007), 129, 3358-3366; H. Stefani, R. Cella and Compounds of formula (AX) may be prepared from com A. Vieira, Tetrahedron (2007), 63,3623-3658; N. Kudo, M. pounds of formula (BA), wherein Q and R" areas defined for Perseghini and G. Fu, Angew. Chem. Int. Ed. (2006), 45, compounds of formula (AZ), by analogous methods using 1282-1284; A. Roglans, A. Pla-Quintana and M. Moreno appropriate starting materials. Mafias, Chem. Rev. (2006), 106, 4622-4643; J-H Li, Q-M Zhu and Y-X Xie, Tetrahedron (2006), 10888-10895; S. 40 Nolanet al., J. Org. Chem. (2006), 71, 685-692; M. Lysén and K. Köhler, Synthesis (2006), 4, 692-698; K. Anderson and S. Buchwald, Angew. Chem. Int. Ed. (2005), 44, 6173-61.77;Y. Wang and D. Sauer, Org. Lett. (2004), 6 (16), 2793-2796: I. Suzuki-Miyaura coupling 45 Stille coupling Kondolff, H. Doucet and M, Santelli, Tetrahedron, (2004), HeSonogashira coupling 60,3813-3818; F. Bellina, A. Carpita and R. Rossi, Synthesis X Q or related reaction (2004), 15, 2419-2440; H. Stefani, G. Molander, C-SYun, M. Ribagorda and B. Biolatto, J. Org. Chem. (2003), 68,5534 5539; A. Suzuki, Journal of Organometallic Chemistry so (2002), 653, 83; G. Molander and C-S Yun, Tetrahedron 50 (BA) (2002), 58, 1465-1470; G. Zou, Y. K. Reddy and J. Falck, Tetrahedron Lett. (2001), 42, 4213-7215; S. Darses, G. Michaud and J.-P. Genet, Eur. J. Org. Chem. (1999), 1877 1883). 55 ( y R26 R' O O 60 (AX) R W 2n or MR-BF 4. Q catalyst, base, Solvent Compounds of formula (AZ) may be prepared from com pounds of formula (AY), by reaction with compounds of RI formula (Y) wherein L is a suitable leaving group Such as a O 65 halogen oran alkyl- oraryl-sulfonate, by processes analogous (AZ) to those described above for the preparation of compounds of formula (AV) from compounds of formula (AY). Alterna US 8,530,667 B2 47 48 tively, compounds of formula (AZ) may be prepared by reac R' tion of compounds of formula (AY) with compounds of for Z mula (Z) by processes analogous to those described above for I V Q the preparation of compounds of formula (AV) from com y pounds of formula (AY). (AA) R' base, solvent

L X Q R'' ZX1 10 (Y) O O Z base, solvent R8 "N-V8 4 y X Q 15 RI RI R'' O R'' O O O (AY) (BA) R8 R8 W X HO y- Q Z2. Q X RI RI (AB) O R'' O catalyst, solvent (AY) (AZ) In an alternative approach, compounds of formula (AY) HO may be treated with a halogenating agent such as phosphorus X 25 oxychloride, phosphorus pentachloride, phosphorus pent Z abromide, phosphorus oxybromide, oxalyl chloride or oxalyl (Z) bromide, optionally in a suitable solvent such as toluene, catalyst, solvent chloroform, dichloromethane with optionally the presence of dimethylformamide, and the resulting vinyl halides of for 30 mula (BB), wherein Hal is chlorine or bromine may be con By analogous processes to those described above, com verted by reaction with alcohols of formula (U), or of formula pounds of formula (BA) may be prepared from compounds of (V), or of formula (Z) or of formula (AB) optionally in the formula (AY) by alkylation with compounds of formula presence of a Suitable base such as Sodium hydride, sodium tert-butoxide, potassium tert-butoxide and a suitable solvent (AA), wherein L is a suitable leaving group Such as a halogen Such as tetrahydrofuran, 1.4-dioxane, diethylene glycol dim or an alkyl- or aryl-sulfonate, or by alkylation with com 35 ethyl ether to give compounds of formula (AV), formula pounds of formula (AB). (AX), formula (AZ) and formula (BA) respectively: O R halogenation --es R1 O (AY) HO X- R26 A O (U)

base, solvent Z R'' R O Z HO Ny- R26 (AV)R'' X C O R (V) 8 Z base, solvent R / > 26 R' X R R1 R1 O X HO Q O (BB) X1 (AX) US 8,530,667 B2 49 50 -continued

(Z) base, solvent O R'' R8 / X

Z N Q 2s, RI X O (AB) base, solvent

O R8 Z

( X ) Q RI O

Compounds of formula (AY) are known compounds or -continued may be made from known compounds by known methods. R' Furthermore, compounds of formula (BC) wherein Q is an atom or group Suitable for cross-coupling chemistry (such as O a halogen or a haloalkylsulfonate) may undergo Suzuki 30 R8 Miyaura, Stille, Sonogashira and related reactions under / X known conditions to give additional compounds of formula N. Compounds of formula (BC) may be prepared by rearrang RI Z als R26 ing compounds of formula (AZ) under conditions similar to O 35 those used to convert compounds of formula (AV) to com (AU) pounds of formula (AU): wherein R is aryl, heteroaryl, alkenyl, alkynyl or similar

40 Those skilled in the art will appreciate that transformations of this type are not restricted to compounds of formula (BC), R but may in general be applied to any compound of formula (I) where Het is a heterocycle substituted by an atom or group suitable for further derivatisation. 45 Those skilled in the art will appreciate that compounds of formula (AT) may contain a heteroaromatic moiety bearing one or more Substituents capable of being transformed into alternative Substituents under known conditions, and that these compounds may themselves serve as intermediates in the preparation of additional compounds of formula (AT). For 50 example, a heterocycle of formula (AU) wherein R is alk enyl or alkynyl, may be reduced to compounds of formula (AU) wherein R is alkyl under known conditions.

55

H2, catalyst -- solvent (BC) Suzuki-Miyaua, Sonogashira (AU) Stille or 65 wherein R is related reaction alkyl or alkenyl US 8,530,667 B2 51 -continued OH S R8 O ls HN NH2 He base, solvent R1 R25 O L. (BD) 10 (AU) OH R25 wherein R is alkyl R8 / S 15 R1 N als NH2 In a further approach to compounds of formula (AT), O wherein Het is a group of formula (R), X is S. and Y is N. (BE) compounds of formula (BD) wherein L is a suitable leaving group Such as a halogen or an alkyl- or haloalkylsulfonate, may be treated with compounds of formula (AJ) in the pres unse ence of a suitable base (such as triethylamine or pyridine), and optionally in a Suitable solvent (such as water, acetone, etha OH R25 OH R25 nol or isopropanol) according to known procedures, (see, for 25 R8 R8 example, E. Knott, J. Chem. Soc. (1945), 455; H. Brederick, M alsS couplingSt. M alsS R. Gompper, Chem. Ber. (1960), 93, 723: B. Friedman, M. RI N R26 RI N Hal Sparks and R. Adams, J. Am. Chem. Soc. (1937), 59, 2262). O O (AT) (BF) 30 where G is Hand S Het is (R2) OH l X is Sand Z is N R O HN R26

--(AJ) 35 base, solvent RI R25 O L. Compounds of formula (BD) may be prepared from com (BD) pounds of formula (AY) under known conditions (see, for OH R25 40 example, V. Pshenichniya, O. Gulyakevich and V. Kripach, R Chemistry of Heterocyclic Compounds (1990), 10, 1409 7 S 1412: V. Pshenichniya, O. Gulyakevich and V. Kripach, Rus sian Journal of Organic Chemistry (1989), 25 (9), 1882 RI N als R26 1888). 45 O Furthermore, compounds of formula (I), wherein G is H (AT) and RandR form a bond, may be prepared by the reaction of compounds of formula (BG), with compounds of formula wherein G is Hand (H), optionally in the presence of a suitable solvent and a Het is (R) X is Sand Z is N 50 Suitable catalyst.

O Alternatively, compounds of formula (BD) may be treated 55 R8 with thiourea, by known procedures (see, for example, V. Het Pshenichniya, O. Gulyakevich and V. Kripach, Chemistry of Heterocyclic Compounds (1990), 10, 1409-1412), and the R7 R R O resulting products of formula (BE) may be converted into 60 e additional compounds of formula (AT) by conversion to O (BG) halides of formula (BF), wherein Hal is chlorine, bromine or S. iodine, under Sandmeyer conditions, and compounds of for R4 mula (BF) may be converted to compounds of formula (AT) R2 by cross-coupling under known conditions for the 65 formula (H) Suzuki Miyaura, Sonogashira, Stille and related reactions, as described previously. US 8,530,667 B2 53 54

-continued

Het Het reduction

(BK) (BJ)

(I) 10 Compounds of formula (BK) are known, or may be made where G is Hydrogen by known methods from known compounds (see, for and RandR form a bond example, Y. Shigetaka, T., Akira, Y. Katsumi, Yakugaku Zasshi (1968), 88(8),997-1002: Leditschke, H. Arch. Pharm. (1952), 295,323-30). Compounds of formula (BG), may be prepared by oxidis Alternatively compounds of formula (BJ) may be prepared ing compounds of formula (BH) in a suitable solvent such as 15 by the addition of a Suitable organometallic reagent such as a heteroarylmagnesium halide of formula (BL) wherein Hal is toluene, acetone, chloroform, dichloromethane or 1,4-diox a halide such as chloride, bromide or iodide, or a heteroaryl ane. A wide range of oxidants are Suitable for effecting this lithium reagent of formula (BM) or a diheteroarylzinc reagent transformation, including inorganic oxidants such as chro of formula (BN) to a furan-2-carboxaldehyde of formula mium trioxide, pyridinium dichromate, manganese dioxide (BO) according to known procedures (see, for example G. and aluminium alkoxides such as aluminium isopropoxide, as Panda et al, Tetrahedron Lett., 46, 2005, 3097-3102: D. J. well as organic oxidants such as 2,3-dichloro-5,6-dicyano-p- Dixon, M. S. Scott, C. A. Luckhurst, Synlett (2003), (15), 2317-2320; I. Gupta, M. Ravikanth, Tetrahedron (2003), benzoquinone and hypervalent iodine oxidants such as 1.1, 59(32), 6131-6139; M. Sanchez, O. Diallo, A. Oussaid, B. 1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one Oussaid, B. Garrigues, Phosphorus, Sulfur and Silicon and (Dess-Martin periodinane), Suitable procedures are 25 the Related Elements (2001), 173235-242: B. Garrigues, M. described, for example, in U.S. Pat. No. 4.371,711 and by G. Sanchez, O. Diallo, F. Chemat, Journal of Nature (2000), Piancatelli et al. Tetrahedron (1978), 34(18), 2775-2778. 12(1), 25-28; C. M. Shafer, T. F. Molinski, J. Org. Chem. (1998), 63(3), 551-555).

O O Y Het Het 30 8 Mg Or 1 R8 R8 R R Hall 1. Li Het oxidation Het / \ (BL) (BM) or (Het-is-Zn RI R1 O CHO (BN) OH O 35 (BO) (BH) (BG) Het Compounds of formula (BH) may be prepared from com pounds of formula (BJ) by treatment with a suitable acid 40 catalyst in the presence of water and optionally in the pres ence of a suitable solvent, according to known procedures. (BJ)

O 45 Additional compounds of formula (BJ) may be prepared 8 from compounds of formula (BP) by reaction with an alkyl Het R lithium reagent, Such as n-butyllithium, optionally in the aqueous acid Het presence of an additive such as tetramethylethylenediamine, or ZnCl2, water and in a suitable solvent such as diethyl ether or tetrahydro R1 furan, followed by reaction with a benzaldehyde of formula OH 50 (BQ) as described, for example by I. Gupta and M. Ravikanth, (BH) J. Org. Chem., 2004, 69,6796-6811, A. M. Echavarren et al., J. Am. Chem. Soc., 125 (19), 5757-5766, 2003 and by T. K. Chandrashekar et al., J. Org. Chem., 2002, 67, 6309-6319. For example, compounds of formula (BJ) may be con verted to compounds of formula (BH) in the presence of an 55 aqueous Solution of an acid Such as polyphosphoric acid as described, for example in U.S. Pat. No. 4,371.711. Alterna tively compounds of formula (BH) may be prepared from RI R8 Het compounds of formula (BJ) by rearrangement in the presence W \ 1. alkyl lithium of a Lewis acid catalyst Such as Zinc chloride according to the 60 procedure of G. Piancatelli et al., Tetrahedron (1978), 34(18), O 2. OHC - Het 2775-2778. Compounds of formula (BJ) may be prepared by the reduc tion of compounds of formula (BK) by known conditions (see, for example R Silvestri et al., J. Med. Chem. 2005, 48, 65 Compounds of formula (BP) and compounds of formula 4378-4388: B-L Yin et al., Synthesis (2003), (13), 1995 (BQ) are known compounds, or may be prepared from known 2000). compounds by known methods. US 8,530,667 B2 55 56 The compounds of formula (I) according to the invention diacetate, glycerol triacetate, hexadecane, hexylene glycol, can be used as herbicides in unmodified form, as obtained in isoamyl acetate, isobornyl acetate, isooctane, isophorone, the synthesis, but they are generally formulated into herbi isopropylbenzene, isopropyl myristate, lactic acid, laury cidal compositions in a variety of ways using formulation lamine, mesityl oxide, methoxypropanol, methyl isoamyl adjuvants, such as carriers, solvents and Surface-active Sub ketone, methyl isobutyl ketone, methyl laurate, methyl stances. The formulations can be in various physical forms, octanoate, methyl oleate, methylene chloride, m-Xylene, for example in the form of dusting powders, gels, wettable n-hexane, n-octylamine, octadecanoic acid, octylamine powders, water-dispersible granules, water-dispersible tab acetate, oleic acid, oleylamine, o-Xylene, phenol, polyethyl lets, effervescent compressed tablets, emulsifiable concen ene glycol (PEG 400), propionic acid, propyl lactate, propy trates, microemulsifiable concentrates, oil-in-water emul 10 lene carbonate, propylene glycol, propylene glycol methyl sions, oil flowables, aqueous dispersions, oily dispersions, ether, p-Xylene, toluene, triethyl phosphate, triethylene gly Suspoemulsions, capsule Suspensions, emulsifiable granules, col, Xylenesulfonic acid, paraffin, mineral oil, trichloroethyl soluble liquids, water-soluble concentrates (with water or a ene, perchloroethylene, ethyl acetate, amyl acetate, butyl water-miscible organic solvent as carrier), impregnated poly acetate, propylene glycol methyl ether, diethylene glycol mer films or in other forms known, for example, from the 15 methyl ether, methanol, ethanol, isopropanol, and higher Manual on Development and Use of FAO Specifications for molecular weight alcohols, such as amyl alcohol, tetrahydro Plant Protection Products, 5th Edition, 1999. Such formula furfuryl alcohol, hexanol, octanol, ethylene glycol, propylene tions can either be used directly or are diluted prior to use. glycol, glycerol, N-methyl-2-pyrrolidone and the like. Water Diluted formulations can be prepared, for example, with is generally the carrier of choice for the dilution of the con water, liquid fertilisers, micronutrients, biological organisms, centrates. Suitable Solid carriers are, for example, talc, tita oil or solvents. nium dioxide, pyrophyllite clay, silica, attapulgite clay, kie The formulations can be prepared, for example, by mixing Selguhr, limestone, calcium carbonate, bentonite, calcium the active ingredient with formulation adjuvants in order to montomorillonite, cottonseed husks, wheatmeal, soybean obtain compositions in the form of finely divided solids, flour, pumice, wood flour, ground walnut shells, lignin and granules, Solutions, dispersions or emulsions. The active 25 similar materials, as described, for example, in CFR ingredients can also be formulated with other adjuvants, for 180.1001. (c) & (d). example finely divided solids, mineral oils, vegetable oils, A large number of Surface-active Substances can advanta modified vegetable oils, organic solvents, water, Surface-ac geously be used both in Solid and in liquid formulations, tive substances or combinations thereof. The active ingredi especially in those formulations which can be diluted with a ents can also be contained in very fine microcapsules consist 30 carrierprior to use. Surface-active Substances may be anionic, ing of a polymer. Microcapsules contain the active cationic, non-ionic or polymeric and they may be used as ingredients in a porous carrier. This enables the active ingre emulsifying, wetting or suspending agents or for other pur dients to be released into their surroundings in controlled poses. Typical Surface-active substances include, for amounts (e.g. slow release). Microcapsules usually have a example, salts of alkyl Sulfates, such as diethanolammonium diameter of from 0.1 to 500 microns. They contain active 35 lauryl Sulfate; salts of alkylarylsulfonates, such as calcium ingredients in an amount of about from 25 to 95% by weight dodecylbenzenesulfonate; alkylphenol-alkylene oxide addi of the capsule weight. The active ingredients can be present in tion products, such as nonylphenol ethoxylate; alcohol-alky the form of a monolithic solid, in the form of fine particles in lene oxide addition products, such as tridecyl alcohol ethoxy solid or liquid dispersion or in the form of a suitable solution. late: Soaps, such as sodium Stearate; salts of The encapsulating membranes comprise, for example, natu 40 alkylnaphthalenesulfonates, such as Sodium dibutylnaphtha ral and synthetic gums, cellulose, styrene-butadiene copoly lenesulfonate; dialkyl esters of SulfoSuccinate salts, such as mers, polyacrylonitrile, polyacrylate, polyester, polyamides, sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such polyureas, polyurethane or chemically modified polymers as Sorbitol oleate; quaternary amines, such as lauryl trimethy and starch Xanthates or other polymers that are known to the lammonium chloride, polyethylene glycol esters of fatty person skilled in the art in this connection. Alternatively it is 45 acids, such as polyethylene glycol Stearate; block copolymers possible for very fine microcapsules to be formed wherein the of ethylene oxide and propylene oxide; and salts of mono- and active ingredient is present in the form of finely divided di-alkyl phosphate esters; and also further substances particles in a solid matrix of a base Substance, but in that case described e.g. in “McCutcheon's Detergents and Emulsifiers the microcapsule is not encapsulated. Annual, MC Publishing Corp., Ridgewood, N.J., 1981. The formulation adjuvants suitable for the preparation of 50 Further adjuvants which can usually be used in pesticidal the compositions according to the invention are known perse. formulations include crystallisation inhibitors, viscosity As liquid carriers there may be used: water, toluene, Xylene, modifying Substances, Suspending agents, dyes, anti-oxi petroleum ether, vegetable oils, acetone, methyl ethyl ketone, dants, foaming agents, light absorbers, mixing aids, anti cyclohexanone, acid anhydrides, acetonitrile, acetophenone, foams, complexing agents, neutralising or pH-modifying amyl acetate, 2-butanone, butylenes carbonate, chloroben 55 Substances and buffers, corrosion-inhibitors, fragrances, wet Zene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, ting agents, absorption improvers, micronutrients, plasticis diacetone alcohol. 1,2-dichloropropane, diethanolamine, ers, glidants, lubricants, dispersants, thickeners, anti-freezes, p-diethylbenzene, diethylene glycol, diethylene glycol abi microbiocides, and also liquid and Solid fertilisers. etate, diethylene glycol butyl ether, diethylene glycol ethyl The formulations may also comprise additional active Sub ether, diethylene glycol methyl ether, N,N-dimethylforma 60 stances, for example further herbicides, herbicide safeners, mide, dimethyl Sulfoxide, 1,4-dioxane, dipropylene glycol, plant growth regulators, fungicides or insecticides. dipropylene glycol methyl ether, dipropylene glycol diben The compositions according to the invention can addition Zoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhex ally include an additive comprising an oil of vegetable or anol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, animal origin, a mineral oil, alkyl esters of Such oils or mix alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, eth 65 tures of such oils and oil derivatives. The amount of oil ylene glycol butyl ether, ethylene glycol methyl ether, additive used in the composition according to the invention is gamma-butyrolactone, glycerol, glycerol acetate, glycerol generally from 0.01 to 10%, based on the spray mixture. For US 8,530,667 B2 57 58 example, the oil additive can be added to the spray tank in the The herbicidal formulations generally contain from 0.1 to desired concentration after the spray mixture has been pre 99% by weight, especially from 0.1 to 95% by weight, of a pared. Preferred oil additives comprise mineral oils or an oil compound of formula (I) and from 1 to 99.9% by weight of a of vegetable origin, for example rapeseed oil, olive oil or formulation adjuvant, which preferably includes from 0 to sunflower oil, emulsified vegetable oil, such as AMIGOR) 25% by weight of a surface-active substance. Whereas com (Rhône-Poulenc Canada Inc.), alkyl esters of oils of vegetable mercial products will preferably be formulated as concen origin, for example the methyl derivatives, oran oil of animal trates, the end user will normally employ dilute formulations. origin, such as fish oil or beef tallow. A preferred additive The rate of application of the compounds of formula (I) contains, for example, as active components essentially 80% may vary within wide limits and depends upon the nature of by weight alkyl esters of fish oils and 15% by weight methy 10 the soil, the method of application (pre- or post-emergence; lated rapeseed oil, and also 5% by weight of customary emul seed dressing; application to the seed furrow; no tillage appli sifiers and pH modifiers. Especially preferred oil additives cation etc.), the crop plant, the weed or grass to be controlled, comprise alkyl esters of Cs-C fatty acids, especially the the prevailing climatic conditions, and other factors governed methyl derivatives of C-C fatty acids, for example the by the method of application, the time of application and the methyl esters of lauric acid, palmitic acid and oleic acid, 15 target crop. The compounds of formula (I) according to the being important. Those esters are known as methyl laurate invention are generally applied at a rate of 1-2000 g/ha, pref (CAS-111-82-0), methyl palmitate (CAS-1 12-39-0) and erably 1-1000 g/ha and most preferably at 1-500 g/ha. methyl oleate (CAS-1 12-62-9). A preferred fatty acid methyl Preferred formulations have especially the following com ester derivative is Emery(R) 2230 and 2231 (Cognis GmbH). positions: Those and other oil derivatives are also known from the (% percent by weight): Compendium of Herbicide Adjuvants, 5th Edition, Southern Emulsifiable Concentrates: Illinois University, 2000. active ingredient: 1 to 95%, preferably 60 to 90% The application and action of the oil additives can be fur surface-active agent: 1 to 30%, preferably 5 to 20% ther improved by combining them with surface-active sub liquid carrier: 1 to 80%, preferably 1 to 35% stances, such as non-ionic, anionic or cationic Surfactants. 25 Dusts: Examples of suitable anionic, non-ionic and cationic Surfac active ingredient: 0.1 to 10%, preferably 0.1 to 5% tants are listed on pages 7 and 8 of WO97/34485. Preferred solid carrier: 99.9 to 90%, preferably 99.9 to 99% Surface-active Substances are anionic Surfactants of the dode Suspension Concentrates: cylbenzylsulfonate type, especially the calcium salts thereof, active ingredient: 5 to 75%, preferably 10 to 50% and also non-ionic Surfactants of the fatty alcohol ethoxylate 30 water: 94 to 24%, preferably 88 to 30% type. Special preference is given to ethoxylated C-C fatty surface-active agent: 1 to 40%, preferably 2 to 30% alcohols having a degree of ethoxylation of from 5 to 40. Wettable Powders: Examples of commercially available surfactants are the active ingredient: 0.5 to 90%, preferably 1 to 80% Genapol types (Clariant AG). Also preferred are silicone sur surface-active agent: 0.5 to 20%, preferably 1 to 15% factants, especially polyalkyl-oxide-modified heptamethyl 35 solid carrier: 5 to 95%, preferably 15 to 90% trisiloxanes, which are commercially available e.g. as Silwet Granules: L-77(R), and also perfluorinated surfactants. The concentra active ingredient: 0.1 to 30%, preferably 0.1 to 15% tion of surface-active substances in relation to the total addi solid carrier: 99.5 to 70%, preferably 97 to 85% tive is generally from 1 to 30% by weight. Examples of oil The following Examples further illustrate, but do not limit, additives that consist of mixtures of oils or mineral oils or 40 the invention. derivatives thereof with surfactants are Edenor ME SUR, Turbocharge(R) (Syngenta AG, CH) and Actipron(R) (BP Oil UK Limited, GB). The said Surface-active Substances may also be used in the F1. Emulsifiable formulations alone, that is to say without oil additives. 45 concentrates a) b) c) d) Furthermore, the addition of an organic solvent to the oil active ingredient 59% 10% 25% additive/surfactant mixture can contribute to a further calcium dodecylbenzene 6% 8% 6% enhancement of action. Suitable solvents are, for example, Sulfonate castor oil polyglycol ether 4% 4% 4% Solvesso(R) (ESSO) and Aromatic Solvent(R) (Exxon Corpo (36 mol of ethylene oxide) ration). The concentration of such solvents can be from 10 to 50 octylphenol polyglycol 4% 296 80% by weight of the total weight. Such oil additives, which ether (7-8 mol of ethylene oxide) may be in admixture with solvents, are described, for NMP 10% 20% example, in U.S. Pat. No. 4,834,908. A commercially avail arom. hydrocarbon 85% 78% 55% 16% able oil additive disclosed therein is known by the name mixture Co-C2 MERGE(R) (BASF Corporation). A further oil additive that is 55 preferred according to the invention is SCORE(R) (Syngenta Crop Protection Canada.) Emulsions of any desired concentration can be prepared In addition to the oil additives listed above, in order to from such concentrates by dilution with water. enhance the activity of the compositions according to the invention it is also possible for formulations of alkylpyrroli 60 dones, (e.g. Agrimax(R) to be added to the spray mixture. F2. Solutions a) b) c) d) Formulations of synthetic latices. Such as, for example, poly acrylamide, polyvinyl compounds or poly-1-p-menthene active ingredient 59% 10% SO% 90% 1-methoxy-3-(3-methoxy 20% 20% (e.g. BondR, CourierR) or Emerald(R) can also be used. Solu propoxy)-propane tions that contain propionic acid, for example Eurogkem Pen 65 polyethylene glycol 20% 10% e-trate R, can also be mixed into the spray mixture as activity MW 400 enhancing agents. US 8,530,667 B2 59 -continued F2. Solutions a) b) c) d) F7. Dusts a) b) c) NMP 30% 10% active ingredient O.1% 196 59 arom. hydrocarbon 75% 60% talcum 39.9% 49% 359 mixture Co-C12 kaolin 60.0% SO% 60%

The solutions are suitable for application in the form of Ready-to-use dusts are obtained by mixing the active microdrops. ingredient with the carriers and grinding the mixture in a 10 suitable mill.

F3. Wettable powders b) d) active ingredient 59% 25% SO% 80% F8. Suspension concentrates b) d) 15 sodium lignoSulfonate 4% 3% active ingredient 3% 10% 25% SO% sodium lauryl Sulfate 2% 3% 4% ethylene glycol 59 59 59% 59 sodium 6% 59% 6% nonylphenol polyglycol ether 196 2% disobutylnaphthalene (15 mol of ethylene oxide) Sulfonate Sodium lignoSulfonate 3% 3% 4% 59 octylphenol polyglycol 196 2% carboxymethylcellulose 196 196 190 196 ether (7-8 mol of 37% aqueous formaldehyde O.2% O.2% O.2% O.2% ethylene oxide) Solution highly disperse silicic acid 190 3% 59% 10% silicone oil emulsion O.8% O.8% O.8% O.8% kaolin 88% 62% 35% Water 87% 79% 62% 38%

The active ingredient is thoroughly mixed with the adju 25 The finely ground active ingredient is intimately mixed vants and the mixture is thoroughly ground in a Suitable mill, with the adjuvants, yielding a suspension concentrate from yielding wettable powders which can be diluted with water to which Suspensions of any desired concentration can be pre give Suspensions of any desired concentration. pared by dilution with water. The invention relates also to a method for the selective 30 control of grasses and weeds in crops of useful plants, and for F4. Coated granules a) b) c) non-selective weed control, which comprises treating the use ful plants or the area under cultivation or the locus thereof active ingredient O.1% 59% 15% highly disperse silicic acid O.9% 2% 2% with a compound of formula (I). inorg. carrier 99.0% 93% 83% 35 Crops of useful plants in which the compositions according (diameter 0.1-1 mm) to the invention can be used include especially cereals, in e.g. CaCO3 or SiO2 particular wheat and barley, rice, corn, rape, Sugarbeet, Sug arcane, soybean, cotton, Sunflower, peanut and plantation The active ingredient is dissolved in methylene chloride, CropS. the Solution is sprayed onto the carrier and the solvent is 40 The term “crops” is to be understood as also including Subsequently evaporated offin vacuo. crops that have been rendered tolerant to herbicides or classes of herbicides (for example ALS, GS, EPSPS, PPO and HPPD inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been F5. Coated granules a) b) c) 45 rendered tolerant e.g. to imidazolinones, such as imaZamox, active ingredient O.1% 59% 15% by conventional methods of breeding is Clearfield(R) summer polyethylene glycol MW 200 1.0% 2% 3% rape (Canola). Examples of crops that have been rendered highly disperse silicic acid O.9% 190 296 tolerant to herbicides by genetic engineering methods include inorg. carrier 98.0% 92% 80% e.g. glyphosate- and glufosinate-resistant maize varieties (diameter 0.1-1 mm) 50 commercially available under the trade names Roundu e.g. CaCO or SiO2 pReady(R) and LibertyLink R. The weeds to be controlled may be both monocotyledonous and dicotyledonous weeds, such The finely ground active ingredientis applied uniformly, in as, for example, Stellaria, Nasturtium, Agrostis, Digitaria, a mixer, to the carrier moistened with polyethylene glycol. Avena, Setaria, Sinapis, Lolium, Solanum, Echinochloa, Scir Non-dusty coated granules are obtained in this manner. 55 pus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum, Rottboelia, Cyperus, Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum, Galium, Viola and Veronica. Control of monocotyledonous weeds, in particular F6. Extruder granules a) b) c) d) Agrostis, Avena, Setaria, Lolium, Echinochloa, Bromus, active ingredient O.1% 3% 59 15% 60 Alopecurus and Sorghum is very extensive. sodium lignoSulfonate 1.5% 2% 3% 4% Crops are also to be understood as being those which have carboxymethylcellulose 1.4% 2% 296 296 been rendered resistant to harmful insects by genetic engi kaolin 97.0% 93% 90% 79% neering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton bollweevil) and also The active ingredient is mixed and ground with the adju 65 Bt potatoes (resistant to Colorado beetle). Examples of Bt vants and the mixture is moistened with water. The resulting maize are the Bt-176 maize hybrids of NKR (Syngenta mixture is extruded and then dried in a stream of air. Seeds). The Bt toxin is a protein that is formed naturally by US 8,530,667 B2 61 62 Bacillus thuringiensis soil bacteria. Examples of toxins and of formula (I)+chlorimuron-ethyl, compound of formula (I)+ transgenic plants able to synthesise Such toxins are described chloroacetic acid, compound of formula (I)+chlorotoluron, in EP-A-451 878, EP-A-374 753, WO 93/07278, WO compound of formula (I)+chlorpropham, compound of for 95/34656, WO 03/052073 and EP-A-427 529. Examples of mula (I)+chlorsulfuron, compound of formula (I)+chlorthal, transgenic plants that contain one or more genes which code 5 compound of formula (I)+chlorthal-dimethyl, compound of for an insecticidal resistance and express one or more toxins formula (I)+cinidon-ethyl, compound of formula (I)+cinm are KnockCut(R) (maize), Yield Gard(R) (maize), ethylin, compound of formula (I)+cinosulfuron, compound NuCOTIN33B(R) (cotton), Bollgard R. (cotton), NewLeafR) of formula (I)+cisanilide, compound of formula (I)+ (potatoes), NatureGard(R) and ProtexctaR). Plant crops and clethodim, compound of formula (I)+clodinafop, compound their seed material can be resistant to herbicides and at the 10 of formula (I)+clodinafop-propargyl, compound of formula same time also to insect feeding ('stacked' transgenic (I)+clomaZone, compound of formula (I)+clomeprop, com events). Seed can, for example, have the ability to express an pound of formula (I)+clopyralid, compound of formula (I)+ insecticidally active Cry3 protein and at the same time be cloranSulam, compound of formula (I)+cloranSulam-methyl, glyphosate-tolerant. The term “crops” is to be understood as compound of formula (I)+CMA, compound of formula (I)+ also including crops obtained as a result of conventional 15 4-CPB, compound of formula (I)+CPMF, compound of for methods of breeding or genetic engineering which contain mula (I)+4-CPP compound of formula (I)+CPPC, compound so-called output traits (e.g. improved flavour, storage stabil of formula (I)+cresol, compound of formula (I)+cumyluron, ity, nutritional content). compound of formula (I)+cyanamide, compound of formula Areas under cultivation are to be understood as including (I)+cyanazine, compound of formula (I)+cycloate, com land where the crop plants are already growing as well as land pound of formula (I)+cyclosulfamuron, compound of for intended for the cultivation of those crop plants. mula (I)+cycloxydim, compound of formula (I)+cyhalofop, The compounds of formula (I) according to the invention compound of formula (I)+cyhalofop-butyl, compound of for can also be used in combination with other herbicides. The mula (I)+2,4-D, compound of formula (I)+3,4-DA, com following mixtures of the compound of formula (I) are espe pound of formula (I)+daimuron, compound of formula (I)+ cially important. Preferably, in these mixtures, the compound 25 dalapon, compound of formula (I)+dazomet, compound of of the formula (I) is one of those compounds listed in Tables formula (I)+2,4-DB, compound of formula (I)+3,4-DB.com 1 to 360 below: pound of formula (I)+2,4-DEB, compound of formula (I)+ compound of formula (I)+acetochlor, compound of formula desmedipham, compound of formula (I)+desmetryn, com (I)+acifluorfen, compound of formula (I)+acifluorfen-so pound of formula (I)+dicamba, compound of formula (I)+ dium, compound of formula (I)+aclonifen, compound of for 30 dichlobenil, compound of formula (I)+ortho mula (I)+acrolein, compound of formula (I)+alachlor, com dichlorobenzene, compound of formula (I)+para pound of formula (I)--alloxydim, compound of formula (I)+ dichlorobenzene, compound of formula (I)--dichlorprop, allyl alcohol, compound of formula (I)+ametryn, compound compound of formula (I)+dichlorprop-P, compound of for of formula (I)+amicarbazone, compound of formula (I)+ami mula (I)+diclofop, compound of formula (I)+diclofop-me dosulfuron, compound of formula (I)+aminopyralid, com 35 thyl, compound of formula (I)+dicloSulam, compound of for pound of formula (I)+amitrole, compound of formula (I)+ mula (I)+difenZoquat, compound of formula (I)+difenZoquat ammonium sulfamate, compound of formula (I)+anilofos, metilsulfate, compound of formula (I)+diflufenican, com compound of formula (I)+asulam, compound of formula (I)+ pound of formula (I)+diflufenzopyr, compound of formula atrazine, compound of formula (I)+aviglycine, compound of (I)+dimefuron, compound of formula (I)+dimepiperate, formula (I)+aZafenidin, compound of formula (I)+aZimsul 40 compound of formula (I)+dimethachlor, compound of for furon, compound of formula (I)+BCPC, compound of for mula (I)+dimethametryn, compound of formula (I)+dimeth mula (I)+beflubutamid, compound of formula (I)--benazolin, enamid, compound of formula (I)+dimethenamid-P, com compound of formula (I)+bencarbazone, compound of for pound of formula (I)+dimethipin, compound of formula (I)+ mula (I)--benfluralin, compound of formula (I)--benfuresate, dimethylarsinic acid, compound of formula (I)+dinitramine, compound of formula (I)+benSulfuron, compound of formula 45 compound of formula (I)+dinoterb, compound of formula (I)--bensulfuron-methyl, compound of formula (I)--ben (I)+diphenamid, compound of formula (I)+dipropetryn, Sulide, compound of formula (I)+bentaZone, compound of compound of formula (I)+diquat, compound of formula (I)+ formula (I)--benzfendizone, compound of formula (I)--ben diquat dibromide, compound of formula (I)+dithiopyr, com Zobicyclon, compound of formula (I)+benzofenap, com pound of formula (I)+diuron, compound of formula (I)+ pound of formula (I)+bifenox, compound of formula (I)+ 50 DNOC, compound of formula (I)+3,4-DP, compound of bilanafos, compound of formula (I)+bispyribac, compound formula (I)+DSMA, compound of formula (I)+EBEP, com of formula (I)+bispyribac-Sodium, compound of formula (I)+ pound of formula (I)+endothal, compound of formula (I)+ borax, compound of formula (I)+bromacil, compound of for EPTC, compound of formula (I)--esprocarb, compound of mula (I)+bromobutide, compound of formula (I)+bromophe formula (I)+ethalfluralin, compound of formula (I)+ethamet noxim, compound of formula (I)+bromoxynil, compound of 55 Sulfuron, compound of formula (I)+ethametSulfuron-methyl, formula (I)+butachlor, compound of formula (I)+butafenacil, compound of formula (I)+ethephon, compound of formula compound of formula (I)+butamifos, compound of formula (I)+ethofumesate, compound of formula (I)+ethoxyfen, com (I)+butralin, compound of formula (I)+butroxydim, com pound of formula (I)+ethoxysulfuron, compound of formula pound of formula (I)--butylate, compound of formula (I)+ (I)+etobenzanid, compound of formula (I)+fenoxaprop-P, cacodylic acid, compound of formula (I)+calcium chlorate, 60 compound of formula (I)+fenoxaprop-P-ethyl, compound of compound of formula (I)+cafenstrole, compound of formula formula (I)+fentraZamide, compound of formula (I)+ferrous (I)+carbetamide, compound of formula (I)+carfentraZone, Sulfate, compound of formula (I)+flamprop-M, compound of compound of formula (I)+carfentraZone-ethyl, compound of formula (I)+flazasulfuron, compound of formula (I)+florasu formula (I)+CDEA, compound of formula (I)+CEPC, com lam, compound of formula (I)+fluaZifop, compound of for pound of formula (I)+chlorflurenol, compound of formula 65 mula (I)+fluazifop-butyl, compound of formula (I)+fluazi (I)+chlorflurenol-methyl, compound of formula (I)+chlo fop-P, compound of formula (I)+fluazifop-P-butyl, ridazon, compound of formula (I)+chlorimuron, compound compound of formula (I)+fluaZolate, compound of formula US 8,530,667 B2 63 64 (I)+flucarbazone, compound of formula (I)+flucarbazone-so (I)+MSMA, compound of formula (I)+naproanilide, com dium, compound of formula (I)+flucetosulfuron, compound pound of formula (I)+napropamide, compound of formula of formula (I)+fluchloralin, compound of formula (I)+flufen (I)+naptalam, compound of formula (I)+NDA-402989, com acet, compound of formula (I)+flufenpyr, compound of for pound of formula (I)+neburon, compound of formula (I)+ mula (I)+flufenpyr-ethyl, compound of formula (I)+flumetra- 5 nicosulfuron, compound of formula (I)+nipyraclofen, com lin, compound of formula (I)+flumetSulam, compound of pound of formula (I)+n-methyl glyphosate, compound of formula (I)+flumiclorac, compound of formula (I)+flumiclo formula (I)+nonanoic acid, compound of formula (I)+norflu rac-pentyl, compound of formula (I)+flumioxazin, com razon, compound of formula (I)+oleic acid (fatty acids), com pound of formula (I)+flumipropin, compound of formula (I)+ pound of formula (I)+orbencarb, compound of formula (I)+ fluometuron, compound of formula (I)+fluoroglycofen, 10 orthosulfamuron, compound of formula (I)+ory Zalin, compound of formula (I)+fluoroglycofen-ethyl, compound compound of formula (I)+OXadiargyl, compound of formula of formula (I)+fluoxaprop, compound of formula (I)+ (I)+oxadiazon, compound of formula (I)+Oxasulfuron, com flupoxam, compound of formula (I)+flupropacil, compound pound of formula (I)+Oxaziclomefone, compound of formula of formula (I)+flupropanate, compound of formula (I)+ (I)+oxyfluorfen, compound of formula (I)+paraquat, com fluipyrsulfuron, compound of formula (I)+flupyrsulfuron-me 15 pound of formula (I)+paraquat dichloride, compound of for thyl-Sodium, compound of formula (I)+flurenol, compound mula (I)+pebulate, compound of formula (I)+pendimethalin, of formula (I)+fluridone, compound of formula (I)+fluoro compound of formula (I)+penoXSulam, compound of formula chloridone, compound of formula (I)+fluoroxypyr, com (I)+pentachlorophenol, compound of formula (I)+pen pound of formula (I)+flurtamone, compound of formula (I)+ tanochlor, compound of formula (I)+pentoxazone, com fluthiacet, compound of formula (I)+fluthiacet-methyl, pound of formula (I)+pethoxamid, compound of formula (I)+ compound of formula (I)+fomesafen, compound of formula petrolium oils, compound of formula (I)+phenmedipham, (I)+foramsulfuron, compound of formula (I)+fosamine, compound of formula (I)+phenmedipham-ethyl, compound compound of formula (I)+glufosinate, compound of formula of formula (I)+picloram, compound of formula (I)+picolin (I)+glufosinate-ammonium, compound of formula (I)+gly afen, compound of formula (I)+pinoxaden, compound of for phosate, compound of formula (I)+halosulfuron, compound 25 mula (I)+piperophos, compound of formula (I)+potassium of formula (I)+halosulfuron-methyl, compound of formula arsenite, compound of formula (I)+potassium azide, com (I)+haloxyflop, compound of formula (I)+haloxyfop-P, com pound of formula (I)+pretilachlor, compound of formula (I)+ pound of formula (I)+HC-252, compound of formula (I)+ primisulfuron, compound of formula (I)+primisulfuron-me hexaZinone, compound of formula (I)+imazamethabenz, thyl, compound of formula (I)+prodiamine, compound of compound of formula (I)+imazamethabenZ-methyl, com 30 formula (I)+profluaZol, compound of formula (I)+profoxy pound of formula (I)+imaZamox, compound of formula (I)+ dim, compound of formula (I)+prohexadione-calcium, com imazapic, compound of formula (I)+imazapyr, compound of pound of formula (I)+prometon, compound of formula (I)+ formula (I)+imaZaquin, compound of formula (I)+ prometryn, compound of formula (I)+propachlor, compound imazethapyr, compound of formula (I)+imaZoSulfuron, com of formula (I)+propanil, compound of formula (I)+pro pound of formula (I)+indanofan, compound of formula (I)+ 35 paquizafop, compound of formula (I)+propazine, compound iodomethane, compound of formula (I)+iodosulfuron, of formula (I)+propham, compound of formula (I)+prop compound of formula (I)+iodosulfuron-methyl-Sodium, isochlor, compound of formula (I)+propoxycarbazone, com compound of formula (I)+ioxynil, compound of formula (I)+ pound of formula (I)+propoxycarbazone-sodium, compound isoproturon, compound of formula (I)+isouron, compound of of formula (I)+propyZamide, compound of formula (I)+pro formula (I)+isoxaben, compound of formula (I)+isoxachlor- 40 Sulfocarb, compound of formula (I)+proSulfuron, compound tole, compound of formula (I)+isoxaflutole, compound of of formula (I)+pyraclonil, compound of formula (I)+ formula (I)+isoxapyrifop, compound of formula (I)+karbuti pyraflufen, compound of formula (I)+pyraflufen-ethyl, com late, compound of formula (I)+lactofen, compound of for pound of formula (I)+pyrasulfotole, compound of formula mula (I)+lenacil, compound of formula (I)+linuron, com (I)+pyrazolynate, compound of formula (I)+pyrazosulfuron, pound of formula (I)+MAA, compound of formula (I)+ 45 compound of formula (I)+pyrazosulfuron-ethyl, compound MAMA, compound of formula (I)+MCPA, compound of of formula (I)+pyrazoxyfen, compound of formula (I)+py formula (I)+MCPA-thioethyl, compound of formula (I)+ ribenzoxim, compound of formula (I)+pyributicarb, com MCPB, compound of formula (I)+mecoprop, compound of pound of formula (I)+pyridafol, compound of formula (I)+ formula (I)+mecoprop-P, compound of formula (I)+mefen pyridate, compound of formula (I)+pyriftalid, compound of acet, compound of formula (I)+mefluidide, compound of for 50 formula (I)+pyriminobac, compound of formula (I)+pyrimi mula (I)+mesosulfuron, compound of formula (I)+mesosul nobac-methyl, compound of formula (I)+pyrimisulfan, com furon-methyl, compound of formula (I)+mesotrione, pound of formula (I)+pyrithiobac, compound of formula (I)+ compound of formula (I)+metam, compound of formula (I)+ pyrithiobac-Sodium, compound of formula (I)+ metamifop, compound of formula (I)+metamitron, com pyroxasulfone (KIN-485), compound of formula (I)+ pound of formula (I)+metaZachlor, compound of formula 55 pyroxulam, compound of formula (I)+quinclorac, compound (I)+methabenzthiaZuron, compound of formula (I)+meth of formula (I)+quinmerac, compound of formula (I)+quinoc azole, compound of formula (I)+methylarsonic acid, com lamine, compound of formula (I)+quizalofop, compound of pound of formula (I)+methyldymron, compound of formula formula (I)+quizalofop-P, compound of formula (I)+rimsul (I)+methyl isothiocyanate, compound of formula (I)+meto furon, compound of formula (I)+Sethoxydim, compound of benZuron, compound of formula (I)+metobromuron, com 60 formula (I)+siduron, compound of formula (I)+simazine, pound of formula (I)+metolachlor, compound of formula (I)+ compound of formula (I)+simetryn, compound of formula S-metolachlor, compound of formula (I)+metoSulam, (I)+SMA, compound of formula (I)+Sodium arsenite, com compound of formula (I)+metoxuron, compound of formula pound of formula (I)+Sodium azide, compound of formula (I)+metribuzin, compound of formula (I)+metSulfuron, com (I)+Sodium chlorate, compound of formula (I)+Sulcotrione, pound of formula (I)+metSulfuron-methyl, compound of for 65 compound of formula (I)+SulfentraZone, compound of for mula (I)+MK-616, compound of formula (I)+molinate, com mula (I)+Sulfometuron, compound of formula (I)+Sulfometu pound of formula (I)+monolinuron, compound of formula ron-methyl, compound of formula (I)+Sulfosate, compound US 8,530,667 B2 65 66 of formula (I)+sulfosulfuron, compound of formula (I)+sul mula (I)+dymron, compound of the formula (I)+MCPA, com furic acid, compound of formula (I)+tar oils, compound of pound of the formula (I)+mecopropand compound of the formula (I)+2.3.6-TBA, compound of formula (I)+TCA, formula (I)+mecoprop-P. compound of formula (I)+TCA-Sodium, compound of for mula (I)+tebutam, compound of formula (I)+tebuthiuron, 5 The above-mentioned safeners and herbicides are compound of formula (I)+tefuryltrione, compound of for described, for example, in the Pesticide Manual, Twelfth Edi mula 1+tembotrione, compound of formula (I)+tepraloxy tion, British Crop Protection Council, 2000. R-29148 is dim, compound of formula (I)+terbacil, compound of for described, for example by P. B. Goldsbrough et al., Plant mula (I)+terbumeton, compound of formula (I)+ Physiology, (2002), Vol. 130 pp. 1497-1505 and references terbuthylazine, compound of formula (I)+terbutryn, 10 therein and PPG-1292 is known from WOO921 1761. compound of formula (I)+thenylchlor, compound of formula The rate of application of safener relative to the herbicide is (I)+thiazafluoron, compound of formula (I)+thiazopyr, com largely dependent upon the mode of application. In the case of pound of formula (I)+thifensulfuron, compound of formula field treatment, generally from 0.001 to 5.0 kg of safener?ha, (I)+thiencarbazone, compound of formula (I)+thifensulfu preferably from 0.001 to 0.5 kg of safener/ha, and generally ron-methyl, compound of formula (I)+thiobencarb, com 15 from 0.001 to 2 kg of herbicide/ha, but preferably from 0.005 pound of formula (I)+tiocarbazil, compound of formula (I)+ to 1 kg/ha, are applied. toprameZone, compound of formula (I)+tralkoxydim, compound of formula (I)+tri-allate, compound of formula The herbicidal compositions according to the invention are (I)+triasulfuron, compound of formula (I)+triaziflam, com Suitable for all methods of application customary in agricul pound of formula (I)+tribenuron, compound of formula (I)+ ture, Such as, for example, pre-emergence application, post tribenuron-methyl, compound of formula (I)+tricamba, com emergence application and seed dressing. Depending upon pound of formula (I)+triclopyr, compound of formula (I)+ the intended use, the safeners can be used for pretreating the trietazine, compound of formula (I)+trifloxysulfuron, seed material of the crop plant (dressing the seed or seedlings) compound of formula (I)+trifloxysulfuron-Sodium, com or introduced into the soil before or after sowing, followed by pound of formula (I)+trifluralin, compound of formula (I)+ 25 the application of the (unsafened) compound of the formula triflusulfuron, compound of formula (I)+triflusulfuron-me (I), optionally in combination with a co-herbicide. It can, thyl, compound of formula (I)+trihydroxytriazine, however, also be applied alone or together with the herbicide compound of formula (I)+trinexapac-ethyl, compound of for before or after emergence of the plants. The treatment of the mula (I)+tritosulfuron, compound of formula (I)+3-2- plants or the seed material with the safener can therefore take chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1, 30 place in principle independently of the time of application of 2,3,4-tetrahydropyrimidin-3-yl)phenoxy-2-pyridyloxy the herbicide. The treatment of the plant by simultaneous acetic acid ethyl ester (CAS RN353292-31-6), compound of application of herbicide and safener (e.g. in the form of a tank formula (I)+4-hydroxy-3-2-(2-methoxyethoxy)methyl mixture) is generally preferred. The rate of application of 6-(trifluoro-methyl)-3-pyridinylcarbonyl-bicyclo[3.2.1 safener relative to herbicide is largely dependent upon the oct-3-en-2-one (CAS RN 352010-68-5), and compound of 35 formula (I)+4-hydroxy-3-2-(3-methoxypropyl)-6-(difluo mode of application. In the case of field treatment, generally romethyl)-3-pyridinylcarbonyl-bicyclo[3.2.1]oct-3-en-2- from 0.001 to 5.0 kg of safener/ha, preferably from 0.001 to OC. 0.5 kg of safener/ha, are applied. In the case of seed dressing, The mixing partners for the compound of formula (I) may generally from 0.001 to 10g of safener/kg of seed, preferably also be in the form of esters or salts, as mentioned e.g. in The 40 from 0.05 to 2 g of safener/kg of seed, are applied. When the Pesticide Manual, 12th Edition (BCPC) 2000. safener is applied in liquid form, with seed soaking, shortly The compounds of formula (I) according to the invention before Sowing, it is advantageous to use Safener Solutions can also be used in combination with safeners. Preferably, in which contain the active ingredient in a concentration of from these mixtures, the compound of the formula (I) is one of 1 to 10 000 ppm, preferably from 100 to 1000 ppm. those compounds listed in Tables 1 to 360 below. The follow- 45 The following Examples illustrate the invention further but ing mixtures with Safeners, especially, come into consider do not limit the invention. ation: compound of formula (I)+cloquintocet-mexyl, compound of formula (I)+cloquintocet acid and salts thereof, compound of PREPARATION EXAMPLES formula (I)+fenchlorazole-ethyl, compound of formula (I)+ 50 fenchlorazole acid and salts thereof, compound of formula Those skilled in the art will appreciate that certain com (I)+mefenpyr-diethyl, compound of formula (I)+mefenpyr pounds described below are B-ketoenols, and as Such may diacid, compound of formula (I)+isoxadifen-ethyl, com exist as a single tautomer or as a mixture of keto-enol and pound of formula (I)+isoxadifen acid, compound of formula diketone tautomers, as described, for example by J. March, (I)+furilazole, compound of formula (I)+furilazole R isomer, 55 compound of formula (I)+benoxacor, compound of formula Advanced Organic Chemistry, third edition, John Wiley and (I)+dichlormid, compound of formula (I)+AD-67, compound Sons. The compounds are shown in Table T1 as a single enol of formula (I)+oxabetrinil, compound of formula (I)+cyo tautomer, but it should be inferred that this description covers metrinil, compound of formula (I)+cyometrinil Z-isomer, both the diketone form and any possible enols which could compound of formula (I)+fenclorim, compound of formula 60 arise through tautomerism. Furthermore, Some of the com (I)+cyprosulfamide, compound of formula (I)+naphthalic pounds in Table T1 and Table P1 are drawn as single enanti anhydride, compound of formula (I)+flurazole, compound of omers for the purposes of simplicity, but unless specified as formula (I)+CL 304,415, compound of formula (I)+dicy single enantiomers these structures should be construed as clonon, compound of formula (I)+fluxofenim, compound of representing a mixture of enantiomers. Within the detailed formula (I)+DKA-24, compound of formula (I)+R-291.48 65 experimental section the diketone tautomer is chosen for and compound of formula (I)+PPG-1292. A safening effect naming purposes, even if the predominant tautomer is the can also be observed for the mixtures compound of the for enol form. US 8,530,667 B2 67 68 Where more than one tautomer observed in proton NMR, reaction mixture is then filtered through a plug of silica and the data shown are for the mixture of tautomers. washed with ethyl acetate, and the filtrate is concentrated to give a brown solid. The crude product is purified by flash Example 1 chromatography on silica gel to give 2-(4-chlorophenyl)sel 5 enazole-5-carbaldehyde (162 mg). Preparation of 4-2-(4-chloro-phenyl)-5-methyl-sel enazol-4-yl)-10-Oxa-tricyclo5.2.1.0*2.6*decane-3, 5-dione Step 3 10 Preparation of 2-(4-chlorophenyl)selenazol-5-yl)methanol

15 OH

Se

Cl

Step 1 C Preparation of 5-chloro-10-Oxa-tricyclo[5.2.1.02, 25 To a Suspension of 2-(4-chlorophenyl)selenazole-5-carbal 6*dec-4-en-3-one dehyde (130 mg, 0.48 mmol) in methanol (5 ml) is added sodium borohydride (19 mg, 0.5 mmol) at 0°C. The reaction mixture is stirred at 0°C. for 0.5 hour. The reaction mixture is

30 quenched with Saturated aqueous ammonium chloride solu tion (10 ml), and extracted with dichloromethane (3x25ml). The combined organic extracts are dried over anhydrous magnesium Sulfate, filtered and the filtrate is evaporated to dryness to give 2-(4-chlorophenyl)selenazol-5-yl)methanol 35 (127 mg).

To a solution of 10-Oxa-tricyclo5.2.1.0*2.6*decane-3,5- Step 4 dione (1.66 g, 10 mmol) in chloroform (20 ml) is added PCls (1.04 g. 5 mmol) in one portion. The reaction mixture is 40 Preparation of 5-2-(4-chloro-phenyl)-selenazol-5- stirred and heated at reflux for 5 hours. The reaction mixture ylmethoxy-10-Oxa-tricyclo5.2.1.02.6*dec-4-en is evaporated to dryness. The crude product is purified by 3-one flash chromatography to give 5-chloro-10-Oxa-tricyclo 5.2.1.0*2.6* dec-4-en-3-one (1.29 g). 45 Step 2 C Preparation of

2-(4-chlorophenyl)selenazole-5-carbaldehyde 50

55

To a solution of 2-(4-chlorophenyl)selenazol-5-yl)metha nol (300 mg, 1.1 mmol) in dry tetrahydrofuran (5 ml) is 60 added, in one portion, sodium hydride (60% dispersion in C mineral oil, 44 mg, 1.1 mmol). The reaction mixture is stirred for 5 minutes at room temperature and 5-chloro-10-Oxa-tri To a Suspension of 4-chloroselenobenzamide (219 mg, 1 cyclo[5.2.1.0-2.6*dec-4-en-3-one (203 mg, 1.1 mmol) is mmol) and 2-chloromalonaldehyde (160 mg, 1.5 mmol) in added in one-portion. The reaction mixture is stirred at room 1.2-dimethoxyethane (1.5 ml) is added magnesium carbonate 65 temperature overnight. Silica gel is added to the crude reac (42 mg, 0.5 mmol) and the resulting mixture is stirred at 60° tion mixture, the solvent is evaporated under reduced pressure C. under an atmosphere of nitrogen for 3 hours. The crude and the residue is purified by flash chromatography on silica US 8,530,667 B2 69 70 gel to give 5-2-(4-chloro-phenyl)-selenazol-5-ylmethoxy collected and dried on a Buchner funnel to give 1-methyl-10 10-Oxa-tricyclo[5.2.1.0-2.6*dec-4-en-3-one (360 mg). oxa-tricyclo[5.2.1.02.6*dec-8-ene-3,5-dione (14.3 g) Step 5 Step 2 Preparation of 4-2-(4-chloro-phenyl)-5-methyl-sel Preparation of 1-methyl-10-Oxa-tricyclo5.2.1.02, enazol-4-yl)-10-Oxa-tricyclo5.2.1.0*2.6*decane-3, 6*decane-3,5-dione 5-dione

10

15

The 10-Oxa-tricyclo[5.2.1.0*2.6*dec-8-ene-3,5-dione (10.5 g) is dissolved in methanol (700 ml). The methanol Solution is passed at a rate of 1.5 ml/min through a Thalis 5-2-(4-chloro-phenyl)-selenazol-5-ylmethoxy-10-oxa H-cube apparatus (from Thalis nanotec) set-up at 40° C. and tricyclo5.2.1.0*2.6*dec-4-en-3-one (233 mg 0.55 mmol) 40 bar and fitted with a 10% Pd/C cartridge. The so obtained is placed in a microwave vial and dissolved in diethylene Solution is evaporated to give 1-methyl-10-Oxa-tricyclo glycol dimethyl ether (8 ml). 1-Butyl-3-methylimidazolium 5.2.1.0*2.6* decane-3,5-dione (9.2g). bis(trifluoromethylsulfonyl)imide (0.1 ml) is added and the 2s reaction mixture is heated at 210° C. for 30 minutes under Step 3 microwave irradiation. Silica gel is added to the crude reac tion mixture, the solvent is evaporated under reduced pressure Preparation of 5-chloro-1-methyl-10-Oxa-tricyclo and the residue is purified by flash chromatography on silica 5.2.1.0*2.6*dec-4-en-3-one gel to give 4-2-(4-chloro-phenyl)-5-methyl-selenazol-4-yl)- 30 10-Oxa-tricyclo[5.2.1.0-2.6* decane-3,5-dione (146 mg).

Example 2 Preparation of 4-2-(4-chloro-phenyl)-5-ethyl-thia zol-4-yl)-1-1-methyl-10-oxa-tricyclo5.2.1.0*2.6* 35 decane-3,5-dione

To a solution of 1-methyl-10-oxa-tricyclo[5.2.1.02.6* 40 decane-3,5-dione (3 g, 16.6 mmol) in chloroform (8 ml) is added PCls portionwise. The reaction mixture is stirred and heated at reflux for 5 hours. The reaction mixture is evapo rated to dryness The crude product is purified by flash chro matography on silica gel to give 5-chloro-1-methyl-10-Oxa 45 tricyclo5.2.1.0*2.6*dec-4-en-3-one (1.39 g). Step 4

Cl Preparation of 50 1-2-(4-chloro-phenyl)-thiazol-5-yl)ethanol Step 1 Preparation of 1-methyl-10-oxa-tricyclo[5.2.1.02, 6*dec-8-ene-3,5-dione OH 55

60

C

To a suspension of 1-2-(4-chloro-phenyl)-thiazol-5-yl) A mixture of 4-cyclopentene-1,3-dione (10g, 104 mmol) 65 ethanone (5 g, 21 mmol) in methanol (100 ml) is added and 2-methylfuran (15 ml) are stirred at room temperature for Sodium borohydride (832 mg, 22 mmol) at room temperature. 3 days. Methanol (50 ml) is then added and the solid is The reaction mixture is stirred at room temperature for 0.5 US 8,530,667 B2 71 72 hour. The reaction mixture is quenched with 100 ml of an on silica gel to give 4-2-(4-chloro-phenyl)-5-ethyl-thiazol aqueous saturated solution of ammonium chloride, extracted 4-yl)-1-methyl-10-oxa-tricyclo[5.2.1.02.6*decane-3,5-di with dichloromethane (2x150 ml). The combined organic one (175 mg). extracts are dried over magnesium Sulphate, filtered and evaporated to dryness to give 1-2-(4-chloro-phenyl)-thiazol 5 Example 3 5-yl)ethanol (4.88 g). Preparation of 5-1-2-(4-Bromo-2-methyl-phenyl)- Step 5 thiazol-5-yl-ethoxy)-10-Oxa-tricyclo[5.2.1.0*2.6* dec-4-en-3-one Preparation of 5-2-(4-chloro-phenyl)-thiazol-5-yl 10 methoxy-1-methyl-10-Oxa-tricyclo[5.2.1.02.6* Br dec-4-en-3-one

C 15

25

To a solution of 1-2-(4-chloro-phenyl)-thiazol-5-yl)etha Step 1 nol (264mg, 1.1 mmol) in tetrahydrofuran (5 ml) is added in one portion the sodium hydride (60% dispersion in mineral 30 Preparation of 4-bromo-2-methyl-thiobenzamide oil, 44 mg, 1.1 mmol). The reaction mixture is stirred for five minutes at room temperature and 5-Chloro-1-methyl-10-oxa tricyclo5.2.1.0*2.6*dec-4-en-3-one (219 mg, 1.1 mmol) is added in one-portion. The reaction mixture is stirred at room temperature overnight. Silica gel is added to the crude reac 35 NH2 tion mixture, the solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel to give 5-2-(4-chloro-phenyl)-thiazol-5-ylmethoxy)-1- Br methyl-10-Oxa-tricyclo[5.2.1.0*2.6*dec-4-en-3-one (410 To a slurry solution of sodium hydrosulphide (2.80 g, 50 mg). 40 mmol) and magnesium chloride hexahydrate (5.05 g, 25 mmol) in dimethylformamide (50 ml) is added 4-bromo-2- Step 6 methylbenzonitrile (4.90 g, 50 mmol) in one portion and the resulting green slurry is stirred at room temp for 90 minutes. Preparation of 4-2-(4-chloro-phenyl)-5-ethyl-thia The reaction mixture is poured onto water (200 ml) and the Zol-4-yl)-methyl-10-Oxa-tricyclo[5.2.1.02.6*de 45 resultant precipitate filtered and washed with water. This cane-3,5-dione yellow solid is then suspended in 2NHCl (200 ml) and stirred for 1 hour, then filtered, washed with water and hexane and dried in vacuo to give 4-bromo-2-methyl-thiobenzamide (820 mg). 50 Step 2 Preparation of 2-(4-bromo-2-methyl-phenyl)-thiaz ole-5-carbaldehyde 55

Cl 5-2-(4-chloro-phenyl)-thiazol-5-ylmethoxy-1-methyl 10-Oxa-tricyclo[5.2.1.0-2.6*dec-4-en-3-one (410 mg 0.56 60 mmol) is placed in a microwave vial and dissolved in dieth M Br ylene glycol dimethyl ether (8 ml). 1-Butyl-3-methylimida Zolium bis(trifluoromethylsulfonyl)imide (0.1 ml) is added N and the reaction mixture is heated at 210°C. for 30 minutes under microwave irradiation. Silica gel is added to the crude 65 reaction mixture, the solvent is evaporated under reduced To a suspension of 4-bromo-2-methyl-thiobenzamide pressure and the residue is purified by flash chromatography (3.11 g, 13.5 mmol) and 2-chloromalonaldehyde (2.16 g. 20.3 US 8,530,667 B2 73 74 mmol) in dimethoxyethane (20 ml) is added magnesium car mixture is vacced down and purified by flash chromatography bonate (567 mg, 6.75 mmol) and the resulting mixture stirred on silica gel to give a yellow solid. The solid is washed with at 60° C. under N for 3 hours. The crude reaction is then iso-hexane to give 5-1-2-(4-bromo-2-methyl-phenyl)-thia filtered through a plug of silica, washed with EtOAc and the zol-5-yl-ethoxy-10-Oxa-tricyclo[5.2.1.0*2.6*dec-4-en-3- filtrate concentrated to give 2-(4-bromo-2-methyl-phenyl)- 5 one (490 mg). thiazole-5-carbaldehyde (3.8 g). Step 3 Example 4 Preparation of 1-2-(4-bromo-2-methyl-phenyl)- 10 Preparation of 4-5-(4-chloro-phenyl)-2-ethyl thiazol-5-yl-ethanol thiophen-3-yl)-10-oxa-tricyclo5.2.1.0*2.6* decane 3,5-dione

OH 15

Br

A suspension of 2-(4-bromo-2-methyl-phenyl)-thiazole-5- carbaldehyde (1.9 g, 6.7 mmol) in ether at 0°C. is treated with 3.0 M MeMgBr (5 ml, 15 mmol) in diethylether (50 ml). The 25 reaction mixture is stirred for 2 hours then carefully diluted with water. Acidified with aq. sat. NHC1. The aqueous layer is extracted with DCM (2x100 ml). The combined organic layers are dried over magnesium Sulphate, filtered and evapo rated to dryness to give 1.80 g of crude product. The crude 30 product is purified by flash chromatography on silica gel to give 1-2-(4-bromo-2-methyl-phenyl)-thiazol-5-yl-ethanol (1.40 g). Step 1 Step 4 35 Preparation of 5-1-2-(4-bromo-2-methyl-phenyl)- Preparation of thiazol-5-yl-ethoxy)-10-Oxa-tricyclol5.2.1.0*2.6* 3-bromo-5-(4-chloro-phenyl)-2-ethyl-thiophene dec-4-en-3-one 40

Br C S 45

Br

50 To a solution of 3,5-dibromo-2-ethyl-thiophene (3.28 g. 12.15 mmol) in diethyl ether (50 ml) at -78°C. under N is added, slowly, 2.5M butyl lithium in hexane solution (4.86 ml, 12.15 mmol) over 10 minutes and the reaction stirred at -78°C. for a further 30 minutes. The reaction is then cooled 55 to -78° C. before the dropwise addition of trimethylborate (1.64 ml, 14.6 mmol) over 5 minutes. The reaction is stirred at -78°C. for 30 minutes, then allowed to warm to room tem To a solution of 2-(4-bromo-2-methyl-phenyl)-thiazol-5- perature and stirred for a further 60 minutes. Palladium yl-ethanol (450 mg, 1.5 mmol) and 5-chloro-10-oxa-tricyclo 60 acetate (68 mg, 0.3 mmol), triphenylphosphine (314 mg, 1.2 5.2.1.02.6*dec-4-en-3-one (277 mg, 1.5 mmol) in tetrahy mmol) and 4-chloro-iodobenzene (4.9 g, 12.15 mmol) is then drofuran (10 ml) is added in one portion the sodium hydride added to the reaction, followed by THF (50 ml) and 1N (60% dispersion in mineral oil, 60 mg, 1.5 mmol). The reac sodium carbonate solution (20 ml) and the reaction is heated tion mixture is stirred at room temperature for 24 hours. The to reflux for 3 hours. The cooled reaction mixture is parti crude reaction mixture is vacced down under reduced pres 65 tioned between ether (250 ml) and water (300 ml). The sure and 10 ml of triglyme are added. The reaction mixture is organic layer is separated, dried over magnesium Sulphate, therefore heated to reflux for 30 minutes. The crude reaction filtered and evaporated under reduced pressure. The residue is US 8,530,667 B2 75 76 therefore purified by flash chromatography on silica gel to Step 4 give 3-bromo-5-(4-chlorophenyl)-2-ethyl-thiophene as a white solid (2.75 g). Preparation of 2-5-(4-chloro-phenyl)-2-ethyl thiophen-3-yl-cyclopent-4-ene-1,3-dione Step 2

Preparation of 5-(4-chloro-phenyl)-2-ethyl thiophen-3-ylfuran-2-yl-methanol 10

C S 15

OH

e O S. To a solution of 5-5-(4-chloro-phenyl)-2-ethyl-thiophen 3-yl)-4-hydroxy-cyclopent-2-enone (300 mg. 0.95 mmol) in To a solution of 3-bromo-5-(4-chlorophenyl)-2-ethyl 25 acetone (5 ml) at 0°C. is added, dropwise, Jones reagent and thiophene (2.62g, 8.67 mmol) in diethyl ether (30 ml) at -78° the resulting yellow solution stirred at 0°C. for 80 minutes. C. under N is added, slowly, 2.5Mbutyl lithium in hexane Reaction is quenched by the addition of propan-2-ol (1 ml) solution (4.86 ml, 12.15 mmol) over 10 minutes and the and stirred for a further 2 hours. Brine (50 ml) is added and the reaction stirred at -78°C. for a further 30 minutes. 2-Fufural reaction is extracted with ethyl acetate (2x50 ml). The com dehyde (1 ml, 12.14 mmol) is then added dropwise over a 30 bined organics are then washed with brine, dried over mag period of 5 minutes, and the reaction is allowed to stir at -78° nesium Sulphate and concentrated in vacuo to give 2-5-(4- C. for 15 minutes before being allowed to warm to room chloro-phenyl)-2-ethyl-thiophen-3-yl)-cyclopent-4-ene-1,3- temperature and stirred for 1 hour. Reaction is quenched with dione as an orange Solid (248 mg). aqueous Saturated ammonium chloride (100 ml) and extracted with ether (100 ml). The organic layer separated is 35 dried over magnesium Sulphate, filtered and evaporated to Step 5 dryness. The residue is therefore purified by flash chromatog raphy on silica gel to give 5-(4-chloro-phenyl)-2-ethyl Preparation of 4-5-(4-chloro-phenyl)-2-ethyl thiophen-3-ylfuran-2-yl-methanol as a yellow oil (2.52 g). 40 thiophen-3-yl)-10-oxa-tricyclo[5.2.1.0*2.6*dec-8- ene-3,5-dione Step 3

Preparation of 5-5-(4-chloro-phenyl)-2-ethyl thiophen-3-yl)-4-hydroxy-cyclopent-2-enone 45

50

55

To a solution of 5-(4-chloro-phenyl)-2-ethyl-thiophen-3- 60 To a stirred solution of 2-5-(4-chloro-phenyl)-2-ethyl yl)-furan-2-yl-methanol (2.52 g, 7.9 mmol) in acetone (30 thiophen-3-yl)-cyclopent-4-ene-1,3-dione (248 mg, 0.78 ml) and water (5 ml) is added polyphosphoric acid (0.5 ml) mmol) in furan (3 ml) is added magnesium iodide (44 mg. and the resulting solution heated at 60° C. for 5 hours. The 0.15 mmol) and the reaction allowed to stir at room tempera resulting black solution is concentrated in vacuo and purified ture for 4 days. The crude reaction mixture is purified by flash by flash chromatography on silica gel to give 5-5-(4-chloro 65 chromatography to give 4-5-(4-chloro-phenyl)-2-ethyl phenyl)-2-ethyl-thiophen-3-yl)-4-hydroxy-cyclopent-2- thiophen-3-yl)-10-oxa-tricyclo[5.2.1.0*2.6*dec-8-ene-3,5- enone as a clear gum (320 mg) dione as a white solid (180 mg). US 8,530,667 B2 77 78 Step 6 before the slow addition of DMF (2 ml) over 2 minutes and the resulting solution is stirred at room temp for 1 hour. The Preparation of 4-5-(4-chloro-phenyl)-2-ethyl reaction is quenched with aqueous Saturated ammonium thiophen-3-yl)-10-oxa-tricyclo5.2.1.0*2.6* decane chloride (100 ml) and extracted with chloroform (100 ml). 3,5-dione The organic layer is washed with brine, dried over magne sium Sulphate and concentrated to give 4-ethylthiophene-2- carbaldehyde as a light brown oil (2.48 g).

10 Step 2

Preparation of (4-ethyl-thiophen-2-yl)methanol

15

S OH A solution of 4-5-(4-chloro-phenyl)-2-ethyl-thiophen-3- yl)-10-oxa-tricyclo[5.2.1.0*2.6* dec-8-ene-3,5-dione (180 mg, 0.47 mmol) in methanol (5 ml) is stirred under hydrogen (3 bars) for 7 hours. The reaction solution is filtered through a Celite pad and the filtrate concentrated to give 4-5-(4- 25 chloro-phenyl)-2-ethyl-thiophen-3-yl)-10-Oxa-tricyclo To a stirred solution of 4-ethylthiophene-2-carbaldehyde (2.48 g. 17.7 mmol) in methanol (10 ml) at 0°C. is added 5.2.1.0*2.6* decane-3,5-dione (51 mg). sodium borohydride (707 mg, 18.7 mmol) in one portion. The Example 5 resultant solution is allowed to warm to ambient and stirred at 30 room temperature for 40 minutes. Reaction is concentrated in Preparation of 4-(5-bromo-4-ethyl-2-methyl vacuo, quenched with Saturated aqueous ammonium chloride thiophen-3-yl)-10-Oxa-tricyclo[5.2.1.0*2.6* decane solution (100 ml) and extracted with chloroform (100 ml). 3,5-dione The organics are dried over magnesium Sulphate, filtered and concentrated to give a light brown oil, which is purified by 35 flash chromatography on silica gel to give (4-ethyl-thiophen

2-yl)methanol as a clear oil (1.87 g).

Step 3 40 Preparation of 5-(4-ethyl-thiophen-2-ylmethoxy)-10 oxa-tricyclo5.2.1.02.6*dec-4-en-3-one

45

Step 1 50 Preparation of 4-ethyl-thiophene-2-carbaldehyde

55 To a solution of (4-ethyl-thiophen-2-yl)methanol (369 mg, S 2 mmol) in THF (10 ml) is added sodium hydride, 60% \ / YI dispersion in mineral oil, (88 mg, 2.2 mmol) in one portion 60 and the reaction stirred at room temp for 3 hours. The result ing dark yellow solution is then cooled to 0°C., and 5-Chloro 10-Oxa-tricyclo[5.2.1.02.6*dec-4-en-3-one (341 mg, 2.4 To a solution of 3-ethylthiophene (2g, 17.7 mmol) in ether mmol) is added and the resulting brown solution allowed to (20 ml) under N at room temp is added butyl lithium, 2.5M warm to ambient over 30 minutes, then stirred at room temp in hexane solution (8.15 ml, 21.4 mmol) and the resulting 65 for 17 hours. Crude reaction is purified by flash chromatog straw coloured solution is heated to reflux for 20 minutes. The raphy to give 5-(4-ethyl-thiophen-2-ylmethoxy)-10-oxa-tri resulting cloudy solution is then cooled to room temperature cyclo[5.2.1.0-2.6*dec-4-en-3-one as a white solid (515 mg). US 8,530,667 B2 79 80 Step 4 Example 6

Preparation of 4-(4-ethyl-2-methyl-thiophen-3-yl)- Preparation of 4-(6-chloro-4-methyl-pyridin-3-yl)- 10-Oxa-tricyclo[5.2.1.02.6*decane-3,5-dione 10-oxa-tricyclo[5.2.1.02.6*decane-3,5-dione

10

15

A solution of 5-(4-ethyl-thiophen-2-ylmethoxy)-10-oxa tricyclo5.2.1.0*2.6*dec-4-en-3-one (515 mg, 1.77 mmol) in dimethoxyethane (5 ml) is heated to 200° C. for 30 minutes Step 1 using microwave irradiation. Silica gel is added to the crude reaction mixture, the solvent is evaporated under reduced 25 Preparation of 5-methoxy-10-Oxa-tricyclo5.2.1.02, pressure and the residue is purified by flash chromatography 6*dec-4-en-3-one on silica gel to give 4-(4-ethyl-2-methyl-thiophen-3-yl)-10 oxa-tricyclo5.2.1.02.6* decane-3,5-dione as a white solid (105 mg).

30 Step 5

Preparation of 4-(5-bromo-4-ethyl-2-methyl thiophen-3-yl)-10-oxa-tricyclo5.2.1.0*2.6* decane 35 3,5-dione To a suspension of 10-Oxa-tricyclo[5.2.1.0*2.6*decane 3,5-dione (9.97 g. 60 mmol) in methanol (200 ml) is added

sodium tetrachloroaurate (597 mg, 1.5 mmol) and the reac 40 tion mixture is heated to 60° C. for 7 hours. The reaction mixture is allowed to cool down to room temperature and left to stand overnight. The reaction mixture is concentrated under reduced pressure, dissolved in ethyl acetate (200 ml) and washed with aqueous 2N sodium carbonate (100 ml), 45 followed by saturated brine (100 ml). The organic layer is then dried over magnesium Sulphate and concentrated under reduced pressure to give 5-methoxy-10-Oxa-tricyclo 5.2.1.0*2.6* dec-4-en-3-one (8.62 g) 50 Step 2 Preparation of 4-Iodo-5-methoxy-10-oxa-tricyclo To a suspension of 4-(4-ethyl-2-methyl-thiophen-3-yl)-10 5.2.1.0*2.6*dec-4-en-3-one oxa-tricyclo5.2.1.02.6* decane-3,5-dione (73 mg, 0.25 mmol) in DCM (2 ml), at 0°C., is added bromine (26 ul, 0.5 55 mmol) in one portion, and the reaction allowed to warm to ambient and stirred at room temperature for 3 hours. The reaction is concentrated in vacuo, re-dissolved in methanol (10 ml), potassium carbonate (250mg) added and the result ing Suspension stirred at room temperature for a further 17 60 hours. The reaction is quenched by the addition if 2Naqueous HCl (10 ml) and extracted with DCM (2x10 ml). The com bined organics extracts are dried, filtered, concentrated in vacuo, and purified by flash chromatography on silica gel to give 4-(5-bromo-4-ethyl-2-methyl-thiophen-3-yl)-10-Oxa 65 tricyclo5.2.1.0*2.6*decane-3,5-dione as a brown solid (43 A flask is charged with 5-methoxy-10-Oxa-tricyclo mg). 5.2.1.02.6*dec-4-en-3-one (3.96 g. 22 mmol), cerium US 8,530,667 B2 81 82 ammonium nitrate (13.3g, 24.2 mmol) and iodine (6.73 mg, To a solution of 4-(6-chloro-4-methyl-pyridin-3-yl)-5- 26.5 mmol) and then purged with nitrogen. Anhydrous aceto methoxy-10-Oxa-tricyclo[5.2.1.0*2.6*dec-4-en-3-one (119 nitrile (120 ml) is added, and the reaction heated to 40° C. with stirring for 2 hours. The crude reaction mixture is poured mg) in acetone (1 ml) in a microwave vial is added 2N HCl onto a saturated aqueous solution of sodium metabisulphite 5 (0.6 ml) and the resultant solution is heated to 130° C. by (250 ml) and extracted with dichloromethane (2x250 ml). microwave irradiation, with stirring, for 30 minutes. The The combined organics are dried over magnesium Sulphate, crude reaction mixture is quenched with sodium hydrogen filtered, and the solvent is removed under reduced pressure to carbonate until the cessation of effervescence, and the reac give 4-Iodo-5-methoxy-10-Oxa-tricyclo5.2.1.0*2.6*dec-4- tion partitioned between ethyl acetate (40 ml) and saturated en-3-one (5.70 g) 10 aqueous ammonium chloride (40 ml). The organic layer is Step 3 removed, washed with saturated brine solution, dried over magnesium Sulphate, filtered, and the solvent is removed Preparation of 4-(6-chloro-4-methyl-pyridin-3-yl)-5- from the filtrate under reduced pressure to give 4-(6-chloro methoxy-10-Oxa-tricyclo[5.2.1.0*2.6*dec-4-en-3- 15 4-methyl-pyridin-3-yl)-10-Oxa-tricyclo5.2.1.02.6*de O cane-3,5-dione (104 mg).

Example 7

Preparation of 4-(5-Methyl-2-methylsulfanyl-pyrimi 25 din-4-yl)-10-Oxa-tricyclo5.2.1.0-2,6-decane-3,5- dione

30

A microwave vial is charged with 4-iodo-5-methoxy-10 oxa-tricyclo5.2.1.02.6*dec-4-en-3-one (184 mg. 0.6 mmol), 6-chloro-4-methylpyridine-3-boronic acid (103 mg, 35 0.6 mmol) and bis(triphenylphosphine)palladium dichloride (21 mg, 0.03 mmol). DME (1 ml) is added, followed by 2N aqueous sodium carbonate solution (0.6 ml, 1.2 mmol) and the reaction is heated to 130° C. by microwave irradiation, with stirring, for 30 minutes. The reaction is then diluted with 40 2N HCl (20 ml), extracted with ethyl acetate (20 ml), and the organic layer is removed and purified by flash chromatogra phy on silica gel to give 4-(6-chloro-4-methyl-pyridin-3-yl)- 5-methoxy-10-Oxa-tricyclo5.2.1.0*2.6*dec-4-en-3-one (119 mg). 45 Step 4 A microwave vial is charged with 4-chloro-5-methyl-2- Preparation of 4-(6-chloro-4-methyl-pyridin-3-yl)- methylsulfanylpyrimidine (174 mg, 1 mmol), 10-Oxa-tricy 10-Oxa-tricyclo[5.2.1.02.6*decane-3,5-dione 50 cloS.2.1.0*2.6*decane-3,5-dione (166 mg, 1 mmol), palla dium acetate (12 mg, 0.05 mmol), X-Phos (48 mg 0.1 mmol) and potassium phosphate (424 mg, 2 mmol). 1,2-dimethoxy

ethane (3 ml) is added and the reaction heated to 160°C., with stirring, for 30 minutes. Silica gel is added to the crude reac 55 tion mixture, the solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel to give 4-(5-methyl-2-methylsulfanyl-pyrimidin-4-yl)- 10-Oxa-tricyclo[5.2.1.02.6* decane-3,5-dione (34 mg). 60 Additional compounds in Table T1 below are prepared by similar methods using appropriate starting materials.

65 Where more than one tautomer or rotational conformer is observed in the proton NMR spectrum, the data shown below are for the mixture of isomers and conformers.

US 8,530,667 B2

TABLE T1-continued

Compound "H nmr (CDCls unless stated) or other Number Structure physical data

T58 8 ppm 1.52-1.70 (m, 2 H), 1.81-1.91 (m, 2 H), 2.01 (s.3 H), 2.25 (s.3 H), 2.81 (s, 2 H), 4.68-4.72 (m, 2 H)

Example 8 To a solution of 4-2-(4-chloro-phenyl)-5-ethyl-thiazol-4- Preparation of cyclopropanecarboxylic acid-4-2-(4- yl)-10-Oxa-tricyclo[5.2.1.02.6* decane-3,5-dione (100 mg. chloro-phenyl)-5-ethyl-thiazol-4-yl)-5-oxo-10-oxa 0.18 mmol) in DCM (5 ml) and triethylamine (140 ul. 1 tricyclo[5.2.1.0*2.6* dec-3-en-3-yl ester mmol) is added the cyclopropane carbonyl chloride (91 ul. 1 25 mmol) at room temperature. The reaction mixture is stirred C overnight at room temperature. Silica gel is added to the crude reaction mixture, the solvent is evaporated under reduced pressure and the residue is purified by flash chromatography on silica gel to give cyclopropanecarboxylic acid-4-2-(4- 30 chloro-phenyl)-5-ethyl-thiazol-4-yl)-5-oxo-10-Oxa-tricyclo 5.2.1.0*2.6* dec-3-en-3-yl ester (102 mg). Additional compounds in Table P1 below are prepared by similar methods using appropriate starting materials. 35 Where more than one tautomer or rotational conformer is observed in the proton NMR spectrum, the data shown below are for the mixture of isomers and conformers.

40

TABLE P1

Compound "H nmr (CDCls unless stated) Number Structure or other physical data

P1 8 ppm 1.30 (s, 9H), 1.62-1.71 (m, 2H), 1.85-1.96 (m, 2H), 2.37 (s.3H), 2.81 (d. 1H), 3.56 (d. 1H), 4.57 (d. 1H), 4.79 (d. 1H), 7.08 (s, 1H), 7.33-7.38 (m, 2H), 7.44-7.52 (m, 2H)

US 8,530,667 B2 127 128 TABLE 1-continued TABLE 1-continued

This table covers 272 compounds of the structural type T-1: This table covers 272 compounds of the structural type T-1:

10

wherein X is S. Z is wherein X is S. Z is C-H. R', R. R. R. R. R. R. and Rare hydrogen C H., R, R2, R, R, R. R. R. and Rare hydrogen Compound Number R25 15 Compound Number R’ R26 121 2-methylpyridin-4-yl 183 CHC 2,3-dichlorophenyl 122 3-methylpyridin-4-yl 184 CHC 2,4-dichlorophenyl 123 2-methylpyridin-5-yl 18S CHC 2,5-dichlorophenyl .124 3-methylpyridinyl-5-yl 186 CHC 2,6-dichlorophenyl 12S 2-trifluoromethylpyridin-5-yl 187 CHC 3,4-dichlorophenyl 126 3-trifluoromethylpyridin-5-yl 188 CHC 3,5-dichlorophenyl 127 2,6-dichloropyridin-3-yl 189 CHC 2,3,4-trichlorophenyl 128 2-chloro-4-methylpyridin-5-yl 190 CHC 2,3,5-trichlorophenyl 129 6-chloro-2-methylpyridin-3-yl 191 CHC 2,3,6-trichlorophenyl 130 3,4-methylenedioxyphenyl 192 CHC 2,4,5-trichlorophenyl 131 benzo(1,3diox-5-yl 25 193 CHC 2,4,6-trichlorophenyl 132 2,3-dihydrobenzo.14dioxin-6-yl 194 CHC 3,4,5-trichlorophenyl 133 4-chloropyrazol-1-yl 195 CHC 4-bromo-2-fluorophenyl 134 2-thiophenyl 196 CHC 4-bromo-3-fluorophenyl 13S 5-chlorothiophen-2-yl 197 CHC 4-bromo-2-chlorophenyl 136 hiophen-2-yl 198 CHC 4-bromo-3-chlorophenyl 137 3-thiophenyl 4-bromo-2-cyanophenyl 30 199 CHC 138 5-chlorothiophen-3-yl 2OO CHC 4-bromo-3-cyanophenyl 139 5-bromothiophen-3-yl 2O1 CHC 4-bromo-2-methoxyphenyl 140 5-chloro-thiazolyl 2O2 CHC 4-bromo-3-methoxyphenyl .141 5-bromo-thiazolyl 2O3 CHC 4-bromo-2-methylphenyl .142 2-chloro-thiazolyl 204 CHC 4-bromo-3-methylphenyl 143 2-bromo-thiazolyl 2OS CHC 4-chloro-2-cyanophenyl .144 Phenyl 35 2O6 CHC 4-chloro-3-cyanophenyl 145 2-fluorophenyl 2O7 CHC 4-chloro-2-fluorophenyl .146 3-fluorophenyl 2O8 CHC 4-chloro-3-fluorophenyl 147 4-fluorophenyl 209 CHC 4-chloro-2-methoxyphenyl 148 2-chlorophenyl 210 CHC 4-chloro-3-methoxyphenyl 149 3-chlorophenyl 211 CHC 4-chloro-2-methylphenyl 1SO 4-chlorophenyl 40 212 CHC 4-chloro-3-methylphenyl 151 2-bromophenyl 213 CHC 4-chloro-2-trifluoromethylphenyl 152 3-bromophenyl .214 CHC 4-chloro-3-trifluoromethylphenyl 153 4-bromophenyl 215 CHC 2-chloro-4-methoxyphenyl 154 2-iodophenyl 216 CHC 3-chloro-4-methoxyphenyl 155 3-iodophenyl 217 CHC 2-chloro-4-methylphenyl 156 4-iodophenyl 45 218 CHC 3-chloro-4-methylphenyl 157 2-methylphenyl 219 CHC 4-fluoro-2-chlorophenyl 158 3-methylphenyl 22O CHC 4-fluoro-3-chlorophenyl 159 4-methylphenyl 221 CHC 4-fluoro-2-methylphenyl 160 2-cyanophenyl 222 CHC 4-fluoro-3-methylphenyl 161 3-cyanophenyl 223 CHC 4-fluoro-2-trifluoromethylphenyl 162 4-cyanophenyl 4-fluoro-3-trifluoromethylphenyl 50 .224 CHC 163 2-methoxyphenyl 225 CHC 2-fluoro-4-methoxyphenyl .164 3-methoxyphenyl 226 CHC 3-fluoro-4-methoxyphenyl 16S 4-methoxyphenyl 227 CHC 2-fluoro-4-methylphenyl 166 2-trifluoromethylphenyl 228 CHC 2-fluoro-4-methylphenyl 167 3-trifluoromethylphenyl 229 CHC 2-fluoro-4-trifluoromethylphenyl 168 4-trifluoromethylphenyl 230 CHC 3-fluoro-4-trifluoromethylphenyl 169 4-trifluoromethoxyphenyl 55 231 CHC 2-pyridyl 170 4-difluoromethoxyphenyl 232 CHC 3-pyridyl 171 hylthiophenyl 233 CHC 4-pyridyl 172 hylsulfinylphenyl 234 CHC 3-chloropyridin-2-yl 173 hylsulfonylphenyl 235 CHC 4-chloropyridin-2-yl 174 4-trifluoromethylthiophenyl 236 CHC 5-chloropyridin-2-yl 175 4-trifluoromethylsulfinylphenyl 60 237 CHC 6-chloropyridin-2-yl 176 4-trifluoromethylsulfonylphenyl .238 CHC 2-chloropyridin-3-yl 177 ifluorophenyl 239 CHC 4-chloropyridin-3-yl 178 ifluorophenyl 240 CHC 2-chloropyridin-4-yl 179 ifluorophenyl .241 CHC 3-chloropyridin-4-yl 18O ifluorophenyl .242 CHC 2-chloropyridin-5-yl 181 ifluorophenyl 65 243 CHC 3-chloropyridin-5-yl 182 ifluorophenyl .244 CHC 3-methylpyridin-2-yl US 8,530,667 B2 129 130 TABLE 1-continued Table 7: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1: wherein X is S. Z is C H., R is CHCHOCH R', R. R. T1 R. R. Rand Rare hydrogen and RandR areas defined

in Table 1. Table 8: This table covers 272 compounds of the structural type T-1, whereinX is S. Zis C. H. R7 is OCH R', R,R,R,R,R and Rare hydrogen and Rand Rare as defined in Table 10 1. Table 9: wherein X is S. Z is This table covers 272 compounds of the structural type T-1, C-H. R', R. R. R. R. R. R. and Rare hydrogen wherein X is S. Z is C H., R is OCHCH. R. R. R. R. 15 R. Rand Rare hydrogen and Rand Rare as defined in Compound Number R’ R26 Table 1. 245 CHCH 4-methylpyridin-2-yl Table 10: 246 CHCH 5-methylpyridin-2-yl .247 CHCH 6-methylpyridin-2-yl This table covers 272 compounds of the structural type T-1, 248 CHCH-, 2-methylpyridin-3-yl wherein X is S. Zis C. H. RandR are CH. R. R. R. R. 249 CHCH 4-methylpyridin-3-yl R and Rare hydrogen and R and Rare as defined in 2SO CHCH 2-methylpyridin-4-yl Table 1. 251 CHCH 3-methylpyridin-4-yl .252 CHCH-, 2-methylpyridin-5-yl Table 11: 253 CHCH 3-methylpyridinyl-5-yl This table covers 272 compounds of the structural type T-1, 254 CHCH 2-trifluoromethylpyridin-5-yl wherein X is S. Z is C H., R is CH, R', R,R,R,R, R7 255 CHCH 3-trifluoromethylpyridin-5-yl 25 .256 CHCH 2,6-dichloropyridin-3-yl and Rare hydrogen and Rand Rare as defined in Table 257 CHCH 2-chloro-4-methylpyridin-5-yl 1. 258 CHCH 6-chloro-2-methylpyridin-3-yl Table 12: 259 CHCH 3.4-methylenedioxyphenyl 260 CHCH benzo(1,3diox-5-yl This table covers 272 compounds of the structural type T-1, 261 CHCH 2,3-dihydrobenzo.14dioxin-6-yl whereinX is S. Zis C H., R is CHCH, R', R,R,R,R, 262 CHCH 4-chloropyrazol-1-yl 30 R7 and Rare hydrogen and R and Rare as defined in 263 CHCH-, 2-thiophenyl Table 1. .264 CHCH 5-chlorothiophen-2-yl 26S CHCH 5-bromothiophen-2-yl Table 13: 266 CHCH 3-thiophenyl This table covers 272 compounds of the structural type T-1, .267 CHCH 5-chlorothiophen-3-yl 268 CHCH 5-bromothiophen-3-yl 35 wherein X is S. Z is C H., R is CHOCH R', R. R. R. 269 CHCH 5-chloro-thiazolyl R. R7 and Rare hydrogen and Rand Rare as defined in 270 CHCH 5-bromo-thiazolyl Table 1. 271 CHCH-, 2-chloro-thiazolyl Table 14: 272 CHCH 2-bromo-thiazolyl This table covers 272 compounds of the structural type T-1, 40 wherein X is S. Z is C H., R is CHOCHCH. R. R. R. Table 2: R. R. R7 and Rare hydrogen and RandR areas defined This table covers 272 compounds of the structural type T-1, in Table 1. wherein X is S. Z is C H., R is CH, R', R,R,R,R, R Table 15: and Rare hydrogen and Rand Rare as defined in Table This table covers 272 compounds of the structural type T-1, 1 45 wherein X is S. Z is C H., R is CHCHOCH R', R. R. Table 3: R. R. R7 and Rare hydrogen and RandR areas defined in Table 1. This table covers 272 compounds of the structural type T-1, Table 16: wherein X is S. Z is C. H. R7 is CHCH. R. R. R. R. R. This table covers 272 compounds of the structural type T-1, R and R are hydrogen and R and Rare as defined in 50 Table 1. wherein X is S. Z is C CH, R', R. R. R. R. R. R7 and Table 4: Rare hydrogen This table covers 272 compounds of the structural type T-1, Table 17: wherein X is S. Z is C. H. R7 is cyclopropyl R. R. R. R. This table covers 272 compounds of the structural type T-1, R. Rand Rare hydrogen and Rand Rare as defined in 55 wherein X is S. Z is C CH R is CH. R. R. R. R. R. Table 1. R and Rare hydrogen and R and Rare as defined in Table 1. Table 5: Table 18: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C H., R is CHOCH. R. R. R. R. 60 wherein X is S. Z is C CH, R7 is CHCH. R. R. R. R. R. Rand Rare hydrogen and Rand Rare as defined in R. Rand Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 6: Table 19: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C H., R is CHOCHCH. R. R. R. 65 wherein X is S. Z is C CH, R7 is cyclopropyl, R', R. R. R. R. RandR are hydrogen and RandR areas defined R. R. RandR are hydrogen and RandR areas defined in Table 1. in Table 1. US 8,530,667 B2 131 132 Table 20: Table 33: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, whereinX is S. Zis C CH R is CHOCH R',R,R,R, wherein X is S. Z is C CHCH, R7 is CHCH. R. R. R. R. Rand Rare hydrogen and Rand Rare as defined in R. R. Rand Rare hydrogen and RandR areas defined Table 1. in Table 1. Table 21: Table 34: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CH, R7 is CHOCHCH. R. R. wherein X is S. Z is C CHCH. R7 is cyclopropyl, R. R. R. R. R. Rand Rare hydrogen and R and Rare as R. R. R. R. and Rare hydrogen and R and Rare as defined in Table 1. 10 defined in Table 1. Table 22: Table 35: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CH R is CHCHOCH R', R, wherein X is S. Z is C CHCH, R7 is CHOCH R', R, R. R. R. Rand Rare hydrogen and Rand Rare as 15 R. R. R. R. and Rare hydrogen and Rand Rare as defined in Table 1. defined in Table 1. Table 23: Table 36: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CH, R7 is OCH R', R. R. R. R. wherein X is S. Z is C CHCH, R7 is CHOCHCH. R', R and R are hydrogen and R and R are as defined in R. R. R. R. RandR are hydrogen and RandR areas Table 1. defined in Table 1. Table 24: Table 37: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CH, R7 is OCHCHR,R,R,R, wherein X is S. Z is C CHCH, R7 is CHCHOCH R', R. Rand Rare hydrogen and Rand Rare as defined in 25 R. R. R. R. RandR are hydrogen and RandR areas Table 1. defined in Table 1. Table 25: Table 38: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CH, R7 and Rare CH. R. R. R. wherein X is S. Z is C CHCH, R7 is OCH R',R,R,R, R. Rand Rare hydrogen and Rand Rare as defined in 30 R. Rand Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 26: Table 39: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CH R is CH. R. R. R. R. R. wherein X is S. Z is C CHCH, R7 is OCHCH. R. R. R7 and R are hydrogen and R and Rare as defined in 35 R. R. R. R. and Rare hydrogen and Rand Rare as Table 1. defined in Table 1. Table 27: Table 40: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CH, R is CHCH. R. R. R. R. 40 wherein X is S. Z is C CHCH. RandR are CH, R', R, R. R7 and Rare hydrogen and Rand Rare as defined in R. R. Rand Rare hydrogen and RandR areas defined Table 1. in Table 1. Table 28: Table 41: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CH R is CHOCH R',R,R,R, 45 wherein X is S. Z is C CHCH R is CH. R. R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in R. R7 and Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 29: Table 42: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CH R is CHOCHCH. R. R. 50 wherein X is S. Z is C CHCH R is CHCH. R. R. R. R. R. R. R7 and Rare hydrogen and Rand Rare as R. R. R7 and Rare hydrogen and RandR areas defined defined in Table 1. in Table 1. Table 30: Table 43: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, 55 wherein X is S. Z is C CHCH, R is CHOCH R', R, wherein X is S. Z is C CH R is CHCHOCH R', R, R. R. R. R7 and Rare hydrogen and Rand Rare as R. R. R. R7 and Rare hydrogen and Rand Rare as defined in Table 1. defined in Table 1. Table 44: Table 31: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, 60 wherein X is S. Z is C CHCH, R is CHOCHCH. R', wherein X is S. Z is C CHCH. R. R. R. R. R. R. R7 R. R. R. R. RandR are hydrogen and RandR areas and Rare hydrogen. defined in Table 1. Table 32: Table 45: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is C CHCH R is CH. R. R. R. R. 65 wherein X is S. Z is C CHCH, R is CHCHOCH R', R. Rand Rare hydrogen and Rand Rare as defined in R. R. R. R. RandR are hydrogen and RandR areas Table 1. defined in Table 1. US 8,530,667 B2 133 134 Table 46: Table 60: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is N, R. R. R. R. R. R. R7 and Rare wherein X is S. Z is N, R is CHCHOCH R', R. R. R. hydrogen R. R7 and Rare hydrogen and Rand Rare as defined in Table 47: Table 1. This table covers 272 compounds of the structural type T-1, wherein X is S. Z is N, R is CH, R', R. R. R. R. Rand TABLE 61 Rare hydrogen and Rand Rare as defined in Table 1. Table 48: This table covers 272 compounds of the structural type T-2: This table covers 272 compounds of the structural type T-1, 10 wherein X is S. Z is N, R7 is CHCH, R', R. R. R. R. R. and Rare hydrogen and Rand Rare as defined in Table 1. Table 49: 15 This table covers 272 compounds of the structural type T-1, wherein X is S. Z is N, R is cyclopropyl, R', R. R. R. R. R and R are hydrogen and R and Rare as defined in Table 1. wherein X is S. Z is Table 50: C. H. R. R. R. R. R. R. R7 and Rare hydrogen This table covers 272 compounds of the structural type T-1, wherein X is S. Z is N, R is CHOCH R',R,R,R,R, R Table 62: and Rare hydrogen and Rand Rare as defined in Table This table covers 272 compounds of the structural type T-2, 1. wherein X is S. Z is C H, R7 is CH, R', R,R,R,R, R Table 51: 25 and Rare hydrogen and Rand Rare as defined in Table This table covers 272 compounds of the structural type T-1, wherein X is S. Z is N, R is CHOCHCH. R. R. R. R. 1. R. Rand Rare hydrogen and Rand Rare as defined in Table 63: Table 1. This table covers 272 compounds of the structural type T-2, Table 52: 30 wherein X is S. Z is C. H. R7 is CHCH. R. R. R. R. R. This table covers 272 compounds of the structural type T-1, R and Rare hydrogen and R and Rare as defined in wherein X is S. Z is N, R is CHCHOCH R', R. R. R. Table 1. R. Rand Rare hydrogen and Rand Rare as defined in Table 64: Table 1. This table covers 272 compounds of the structural type T-2, Table 53: 35 wherein X is S. Z is C. H. R7 is cyclopropyl, R', R. R. R. This table covers 272 compounds of the structural type T-1, R. Rand Rare hydrogen and Rand Rare as defined in wherein X is S. Z is N, R is OCH R', R,R,R,R, R and Table 1. Rare hydrogen and Rand Rare as defined in Table 1. Table 65: Table 54: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-1, 40 wherein X is S. Z is C. H. R7 is CHOCH R', R. R. R. wherein X is S. Z is N, R is OCHCHR,R,R,R,R, R R. Rand Rare hydrogen and Rand Rare as defined in and Rare hydrogen and Rand Rare as defined in Table Table 1. 1. Table 66: Table 55: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-1, 45 wherein X is S. Z is C H., R is CHOCHCH. R. R. R. wherein X is S. Z is N, R7 and Rare CH, R', R. R. R. R. R. R. Rand Rare hydrogen and RandR areas defined and Rare hydrogen and Rand Rare as defined in Table in Table 1. 1. Table 67: Table 56: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-1, 50 wherein X is S. Z is C H., R is CHCHOCH. R. R. R. wherein X is S. Z is N, R is CH, R', R. R. R. R. R7 and R. R. Rand Rare hydrogen and RandR areas defined Rare hydrogen and Rand Rare as defined in Table 1. in Table 1. Table 57: Table 68: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is N, R is CHCH. R. R. R. R. R. R7 55 wherein X is S. Zis C H., R7 is OCH R', R. R. R. R. R. and Rare hydrogen and Rand Rare as defined in Table and Rare hydrogen and Rand Rare as defined in Table 1. 1. Table 58: Table 69: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is N, R is CHOCH R',R,R,R,R, R7 60 wherein X is S. Z is C H., R is OCHCH. R. R. R. R. and Rare hydrogen and Rand Rare as defined in Table R. Rand Rare hydrogen and Rand Rare as defined in 1. Table 1. Table 59: Table 70: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is N, R is CHOCHCH. R. R. R. R. 65 wherein X is S. Zis C. H. RandR are CH. R. R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in R and Rare hydrogen and R and Rare as defined in Table 1. Table 1. US 8,530,667 B2 135 136 Table 71: Table 84: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C H., R is CH. R. R. R. R. R. R7 whereinX is S. Zis C CH R is OCHCHR,R,R,R, and Rare hydrogen and Rand Rare as defined in Table R. Rand Rare hydrogen and Rand Rare as defined in 1. Table 1. Table 72: Table 85: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Zis C H., R is CHCH, R', R,R,R,R, wherein X is S. Z is C CH, R7 and Rare CH, R', R. R. R7 and R are hydrogen and R and R are as defined in R. Rand Rare hydrogen and Rand Rare as defined in Table 1. 10 Table 1. Table 73: Table 86: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C H., R is CHOCH R', R. R. R. wherein X is S. Z is C CH R is CH. R. R. R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in 15 R7 and Rare hydrogen and R and Rare as defined in Table 1. Table 1. Table 74: Table 87: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C H., R is CHOCHCH. R. R. R. wherein X is S. Z is C CH, R is CHCH. R. R. R. R. R. R. R7 and Rare hydrogen and RandR areas defined R. R7 and Rare hydrogen and Rand Rare as defined in in Table 1. Table 1. Table 75: Table 88: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C H., R is CHCHOCH R', R. R. wherein X is S. Z is C CH R is CHOCH R',R,R,R, R. R. R7 and Rare hydrogen and RandR areas defined 25 R. R7 and Rare hydrogen and Rand Rare as defined in in Table 1. Table 1. Table 76: Table 89: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C CH, R', R. R. R. R. R. R7 and wherein X is S. Z is C CH R is CHOCHCH. R. R. Rare hydrogen 30 R. R. R. R7 and Rare hydrogen and Rand Rare as Table 77: defined in Table 1. This table covers 272 compounds of the structural type T-2, Table 90: wherein X is S. Z is C CH R is CH. R. R. R. R. R. This table covers 272 compounds of the structural type T-2, R and R are hydrogen and R and R are as defined in 35 wherein X is S. Z is C CH R is CHCHOCH R', R, Table 1. R. R. R7 and Rare hydrogen and RandR areas defined Table 78: in Table 1. This table covers 272 compounds of the structural type T-2, Table 91: wherein X is S. Z is C CH, R7 is CHCH. R. R. R. R. This table covers 272 compounds of the structural type T-2, R. Rand Rare hydrogen and Rand Rare as defined in 40 wherein X is S. Z is C CHCH. R. R. R. R. R. R. R7 Table 1. and Rare hydrogen Table 79: Table 92: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C CH R is cyclopropyl, R', R. R. wherein X is S. Z is C CHCH R is CH. R. R. R. R. R. R. RandR are hydrogen and RandR areas defined 45 R. Rand Rare hydrogen and Rand Rare as defined in in Table 1. Table 1. Table 80: Table 93: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C CH R is CHOCH R',R,R,R, wherein X is S. Z is C CHCH R is CHCH. R. R. R. R. Rand Rare hydrogen and Rand Rare as defined in 50 R. R. Rand Rare hydrogen and RandR areas defined Table 1. in Table 1. Table 81: Table 94: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C CH R is CHOCHCH. R. R. wherein X is S. Z is C CHCH. R7 is cyclopropyl, R. R. R. R. R. Rand Rare hydrogen and R and Rare as 55 R. R. R. R. and Rare hydrogen and R and Rare as defined in Table 1. defined in Table 1. Table 82: Table 95: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C CH, R7 is CHCHOCH R', R, 60 wherein X is S. Z is C CHCH, R7 is CHOCH R', R, R. R. R. Rand Rare hydrogen and R and Rare as R. R. R. R. and Rare hydrogen and R and Rare as defined in Table 1. defined in Table 1. Table 83: Table 96: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C CH, R7 is OCH R', R. R. R. R. 65 wherein X is S. Z is C CHCH, R7 is CHOCHCH. R', R and R are hydrogen and R and Rare as defined in R. R. R. R. RandR are hydrogen and RandR areas Table 1. defined in Table 1. US 8,530,667 B2 137 138 Table 97: Table 110: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C CHCH, R7 is CHCHOCH R', wherein X is S. Z is N, R is CHOCH R',R,R,R,R, R R. R. R. R. RandR are hydrogen and RandR areas and Rare hydrogen and Rand Rare as defined in Table defined in Table 1. 1. Table 98: Table 111: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C CHCHR is OCH R',R,R,R, wherein X is S. Z is N, R is CHOCHCH. R. R. R. R. R. Rand Rare hydrogen and Rand Rare as defined in R. Rand Rare hydrogen and Rand Rare as defined in Table 1. 10 Table 1. Table 112: Table 99: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is N, R is CHCHOCH R', R. R. R. wherein X is S. Z is C CHCH, R7 is OCHCH. R. R. R. Rand Rare hydrogen and Rand Rare as defined in R. R. R. Rand Rare hydrogen and Rand Rare as 15 Table 1. defined in Table 1. Table 113: Table 100: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is S. Z is N, R is OCH R', R. R. R. R. Rand wherein X is S. Z is C CHCH, R7 and Rare CH, R', R, Rare hydrogen and Rand Rare as defined in Table 1. R. R. Rand Rare hydrogen and RandR areas defined Table 114: in Table 1. This table covers 272 compounds of the structural type T-2, Table 101: wherein X is S. Z is N, R is OCHCH. R',R,R,R,R, R This table covers 272 compounds of the structural type T-2, and Rare hydrogen and Rand Rare as defined in Table wherein X is S. Z is C CHCH R is CH. R. R. R. R. 1. 25 Table 115: R. R7 and Rare hydrogen and Rand Rare as defined in This table covers 272 compounds of the structural type T-2, Table 1. wherein X is S. Z is N, R7 and Rare CH, R', R. R. R. R. Table 102: and Rare hydrogen and Rand Rare as defined in Table This table covers 272 compounds of the structural type T-2, 1. wherein X is S. Z is C CH-CH R is CHCH. R. R. R. 30 Table 116: R. R. R7 and Rare hydrogen and RandR areas defined This table covers 272 compounds of the structural type T-2, in Table 1. wherein X is S. Z is N, R is CH, R', R. R. R. R. R7 and Table 103: Rare hydrogen and Rand Rare as defined in Table 1. This table covers 272 compounds of the structural type T-2, Table 117: wherein X is S. Z is C CHCH., R is CHOCH R', R, 35 This table covers 272 compounds of the structural type T-2, R. R. R. R7 and Rare hydrogen and R and Rare as wherein X is S. Z is N, R is CHCH. R. R. R. R. R. R7 defined in Table 1. and Rare hydrogen and Rand Rare as defined in Table Table 104: 1. This table covers 272 compounds of the structural type T-2, Table 118: wherein X is S. Z is C CHCH R is CHOCHCH. R', 40 This table covers 272 compounds of the structural type T-2, R. R. R. R. RandR are hydrogen and RandR areas wherein X is S. Z is N, R is CHOCH R',R,R,R,R, R7 defined in Table 1. and Rare hydrogen and Rand Rare as defined in Table Table 105: 1. Table 119: This table covers 272 compounds of the structural type T-2, 45 This table covers 272 compounds of the structural type T-2, wherein X is S. Z is C CHCH R is CHCHOCH R', wherein X is S. Z is N, R is CHOCHCH. R. R. R. R. R,R,R,R,R7 and Rare hydrogen and RandR areas R. R7 and Rare hydrogen and Rand Rare as defined in defined in Table 1. Table 1. Table 106: Table 120: This table covers 272 compounds of the structural type T-2, 50 This table covers 272 compounds of the structural type T-2, wherein X is S. Z is N, R. R. R. R. R. R. R7 and Rare wherein X is S. Z is N, R is CHCHOCH R', R. R. R. hydrogen R. R7 and Rare hydrogen and Rand Rare as defined in Table 107: Table 1. This table covers 272 compounds of the structural type T-2, Table 121: wherein X is S. Z is N, R7 is CH. R. R. R. R. R. Rand 55 This table covers 272 compounds of the structural type T-1, Rare hydrogen and Rand Rare as defined in Table 1. wherein X is O, Z is C. H. R. R. R. R. R. R. R7 and R' Table 108: are hydrogen Table 122: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is N, R7 is CHCH. R. R. R. R. R. R. 60 wherein X is O, Z is C H., R is CH, R', R. R. R. R. R. and Rare hydrogen and Rand Rare as defined in Table and Rare hydrogen and Rand Rare as defined in Table 1 1. Table 109: Table 123: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-1, wherein X is S. Z is N, R is cyclopropyl, R', R. R. R. R. 65 wherein X is O, Z is C H., R is CHCH. R. R. R. R. R. R and R are hydrogen and R and Rare as defined in R and Rare hydrogen and R and Rare as defined in Table 1. Table 1. US 8,530,667 B2 139 140 Table 124: Table 137: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C H., R is cyclopropyl, R', R. R. R. wherein X is O, Z is C CH R is CH. R. R. R. R. R. R. Rand Rare hydrogen and Rand Rare as defined in R and Rare hydrogen and R and Rare as defined in Table 1. Table 1. Table 125: Table 138: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C. H. R7 is CHOCH R', R. R. R. wherein X is O, Z is C CH, R7 is CHCH. R. R. R. R. R. Rand Rare hydrogen and Rand Rare as defined in R. Rand Rare hydrogen and Rand Rare as defined in Table 1. 10 Table 1. Table 126: Table 139: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C H., R is CHOCHCH. R. R. R. wherein X is O, Z is C CH, R7 is cyclopropyl, R', R. R. R. R. RandR are hydrogen and RandR areas defined 15 R. R. RandR are hydrogen and RandR areas defined in Table 1. in Table 1. Table 127: Table 140: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C H., R is CHCHOCH. R. R. R. whereinX is O. Zis C CHR’ is CHOCH R',R,R,R, R. R. Rand Rare hydrogen and RandR areas defined R. Rand Rare hydrogen and Rand Rare as defined in in Table 1. Table 1. Table 128: Table 141: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, whereinX is O, Zis C. H. R7 is OCH, R,R,R,R,R,R wherein X is O, Z is C CH, R7 is CHOCHCH. R', R, and Rare hydrogen and Rand Rare as defined in Table 25 R. R. R. R. and Rare hydrogen and R and Rare as 1. defined in Table 1. Table 129: Table 142: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C. H. R7 is OCHCH. R. R. R. R. wherein X is O, Z is C CH, R7 is CHCHOCH R', R, R. Rand Rare hydrogen and Rand Rare as defined in 30 R. R. R. R. and Rare hydrogen and Rand Rare as Table 1. defined in Table 1. Table 130: Table 143: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Zis C. H. R7 and Rare CHR,R,R,R, wherein X is O, Z is C CH, R7 is OCH R', R. R. R. R. R and R are hydrogen and R and Rare as defined in 35 R and Rare hydrogen and R and Rare as defined in Table 1. Table 1. Table 131: Table 144: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C H., R is CH, R', R. R. R. R. R7 40 whereinX is O. Zis C CHR’ is OCHCHR,R,R,R, and Rare hydrogen and Rand Rare as defined in Table R. Rand Rare hydrogen and Rand Rare as defined in 1. Table 1. Table 132: Table 145: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, whereinX is O, Zis C H., R is CHCH, R', R,R,R,R, 45 wherein X is O, Z is C—CH, R7 and R7 and R are hydrogen and R and R are as defined in Rare CH, R',R,R,R,RandR are hydrogen and R' Table 1. and Rare as defined in Table 1. Table 133: Table 146: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C H., R is CHOCH R', R. R. R. 50 wherein X is O, Z is C CH R is CH, R', R. R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in R7 and Rare hydrogen and R and Rare as defined in Table 1. Table 1. Table 134: Table 147: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, 55 wherein X is O, Z is C CH R is CHCH. R. R. R. R. wherein X is O, Z is C H., R is CHOCHCH. R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in R. R. R7 and Rarehydrogen and RandR areas defined Table 1. in Table 1. Table 148: Table 135: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, 60 whereinX is O. Zis C CHR is CHOCH R',R,R,R, wherein X is O, Z is C H., R is CHCHOCH. R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in R. R. R7 and Rare hydrogen and RandR areas defined Table 1. in Table 1. Table 149: Table 136: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, 65 wherein X is O, Z is C CH, R is CHOCHCH. R', R, wherein X is O, Z is C CH R', R. R. R. R. R. R7 and R. R. R. R7 and Rare hydrogen and Rand Rare as Rare hydrogen defined in Table 1. US 8,530,667 B2 141 142 Table 150: Table 163: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C CH R is CHCHOCH R', R, wherein X is O, Z is C CHCH R is CHOCH R', R, R. R. R. R7 and Rare hydrogen and R and Rare as R. R. R. R7 and Rare hydrogen and R and Rare as defined in Table 1. defined in Table 1. Table 151: Table 164: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C CHCH, R',R,R,R,R,R, R7 wherein X is O, Z is C CHCH R is CHOCHCH. R', and Rare hydrogen R. R. R. R7 and Rare hydrogen and R and Rare as Table 152: 10 defined in Table 1. This table covers 272 compounds of the structural type T-1, Table 165: wherein X is O, Z is C CHCH. R7 is CH. R. R. R. R. This table covers 272 compounds of the structural type T-1, R. Rand Rare hydrogen and Rand Rare as defined in wherein X is O, Z is C CHCH R is CHCHOCH R', Table 1. 15 R. R. R7 and Rare hydrogen and RandR areas defined Table 153: in Table 1. This table covers 272 compounds of the structural type T-1, Table 166: wherein X is O, Z is C CHCH, R7 is CHCH. R. R. R. This table covers 272 compounds of the structural type T-1, R. R. Rand Rare hydrogen and RandR areas defined wherein X is O, Z is N, R. R. R. R. R. R. R7 and Rare in Table 1. hydrogen Table 154: Table 167: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is C CH-CH, R is cyclopropyl, R', R, wherein X is O, Zis N, R7 is CH, R', R,R,R,R, R and R. R. R. Rand Rare hydrogen and Rand Rare as Rare hydrogen and Rand Rare as defined in Table 1. defined in Table 1. 25 Table 168: Table 155: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is N, R is CHCH. R. R. R. R. R. R. wherein X is O, Z is C CHCH R is CHOCH R', R, and Rare hydrogen and Rand Rare as defined in Table R. R. R. Rand Rare hydrogen and Rand Rare as 1. defined in Table 1. 30 Table 169: This table covers 272 compounds of the structural type T-1, Table 156: wherein X is O, Z is N, R is cyclopropyl R. R. R. R. R. This table covers 272 compounds of the structural type T-1, R and Rare hydrogen and R and Rare as defined in wherein X is O, Z is C CHCH R is CHOCHCH. R', Table 1. R. R. R. R. RandR are hydrogen and RandR areas 35 Table 170: defined in Table 1. This table covers 272 compounds of the structural type T-1, Table 157: wherein X is O, Z is N, R is CHOCH R', R. R. R. R. This table covers 272 compounds of the structural type T-1, R and Rare hydrogen and R and Rare as defined in wherein X is O, Z is C CHCH, R7 is CHCHOCH R', Table 1. R. R. R. R. RandR are hydrogen and RandR areas 40 Table 171: defined in Table 1. This table covers 272 compounds of the structural type T-1, Table 158: wherein X is O, Z is N, R7 is CHOCHCH, R', R. R. R. This table covers 272 compounds of the structural type T-1, R. Rand Rare hydrogen and Rand Rare as defined in whereinX is O. Zis C CHCHR is OCH R',R,R,R, Table 1. R. Rand Rare hydrogen and Rand Rare as defined in 45 Table 172: Table 1. This table covers 272 compounds of the structural type T-1, Table 159: wherein X is O, Z is N, R7 is CHCHOCH, R', R. R. R. This table covers 272 compounds of the structural type T-1, R. Rand Rare hydrogen and Rand Rare as defined in wherein X is O, Z is C CHCH R is OCHCH. R', R, Table 1. 50 Table 173: R. R. R. Rand Rare hydrogen and R and Rare as This table covers 272 compounds of the structural type T-1, defined in Table 1. wherein X is O, Z is N, R7 is OCH R', R,R,R,R,R and Table 160: Rare hydrogen and Rand Rare as defined in Table 1. This table covers 272 compounds of the structural type T-1, Table 174: whereinX is O, Z is C CHCH. R7 and Rare CH, R', R, 55 This table covers 272 compounds of the structural type T-1, R. R. Rand Rare hydrogen and RandR areas defined wherein X is O, Z is N, R7 is OCHCH. R. R. R. R. R. in Table 1. R and Rare hydrogen and R and Rare as defined in Table 161: Table 1. This table covers 272 compounds of the structural type T-1, Table 175: wherein X is O, Z is C CHCH R is CH. R. R. R. R. 60 This table covers 272 compounds of the structural type T-1, R. R7 and Rare hydrogen and Rand Rare as defined in wherein X is O, Z is N, R7 and Rare CH, R,R,R,R,R Table 1. and Rare hydrogen and Rand Rare as defined in Table Table 162: 1. This table covers 272 compounds of the structural type T-1, Table 176: wherein X is O, Z is C CHCH R is CHCH. R. R. R. 65 This table covers 272 compounds of the structural type T-1, R. R. R7 and Rarehydrogen and RandR areas defined wherein X is O, Z is N, R is CH. R. R. R. R. R. R7 and in Table 1. Rare hydrogen and Rand Rare as defined in Table 1. US 8,530,667 B2 143 144 Table 177: Table 190: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is N, R is CHCH. R. R. R. R. R. R7 whereinX is O, Zis C H., RandR are CH, R', R,R,R, and Rare hydrogen and Rand Rare as defined in Table R and Rare hydrogen and R and Rare as defined in 1. Table 1. Table 178: Table 191: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is N, R is CHOCH R', R. R. R. R. wherein X is O, Z is C H., R is CH, R', R,R,R,R, R7 R7 and R are hydrogen and R and R are as defined in and Rare hydrogen and Rand Rare as defined in Table Table 1. 10 1. Table 179: Table 192: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is N, R is CHOCHCH. R. R. R. R. wherein X is O, Z is C H., R is CHCH. R. R. R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in 15 R7 and Rare hydrogen and R and Rare as defined in Table 1. Table 1. Table 180: Table 193: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is N, R is CHCHOCH R', R. R. R. wherein X is O, Z is C H., R is CHOCH R', R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in R. R7 and Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 181: Table 194: This table covers 272 compounds of the structural type T-2: This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C. H. R. R. R. R. R. R. R7 and R' wherein X is O, Z is C H., R is CHOCHCH. R. R. R. are hydrogen 25 R. R. R7 and Rare hydrogen and RandR areas defined Table 182: in Table 1. This table covers 272 compounds of the structural type T-2, Table 195: wherein X is O, Z is C H., R is CH, R', R. R. R. R. R. This table covers 272 compounds of the structural type T-2, and Rare hydrogen and Rand Rare as defined in Table wherein X is O, Z is C H., R is CHCHOCH. R. R. R. 1. 30 R. R. R7 and Rare hydrogen and RandR areas defined Table 183: in Table 1. This table covers 272 compounds of the structural type T-2, Table 196: wherein X is O, Z is C H., R is CHCH. R', R,R,R,R, This table covers 272 compounds of the structural type T-2, R and R are hydrogen and R and R are as defined in 35 wherein X is O, Z is C CH R', R. R. R. R. R. R7 and Table 1. Rare hydrogen Table 184: Table 197: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C H., R is cyclopropyl, R', R. R. R. wherein X is O, Z is C CH, R7 is CH, R', R. R. R. R. R. Rand Rare hydrogen and Rand Rare as defined in 40 R and Rare hydrogen and R and Rare as defined in Table 1. Table 1. Table 185: Table 198: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C H., R is CHOCH R', R. R. R. wherein X is O, Z is C CH R is CHCH. R. R. R. R. R. Rand Rare hydrogen and Rand Rare as defined in 45 R. Rand Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 186: Table 199: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C H., R is CHOCHCH. R. R. R. wherein X is O, Z is C CH, R7 is cyclopropyl, R', R. R. R. R. Rand Rare hydrogen and RandR areas defined 50 R. R. Rand Rare hydrogen and RandR areas defined in Table 1. in Table 1. Table 187: Table 200: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C. H. R7 is CHCHOCH. R. R. R. whereinX is O. Zis C CHR" is CHOCH R',R,R,R, R. R. Rand Rare hydrogen and RandR areas defined 55 R. Rand Rare hydrogen and Rand Rare as defined in in Table 1. Table 1. Table 188: Table 201: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, whereinX is O, Zis C. H. R7 is OCH, R,R,R,R,R,R 60 wherein X is O, Z is C CH, R7 is CHOCHCH. R', R, and Rare hydrogen and Rand Rare as defined in Table R. R. R. R. and Rare hydrogen and R and Rare as 1. defined in Table 1. Table 189: Table 202: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C H., R is OCHCH. R. R. R. R. 65 wherein X is O, Z is C CH, R7 is CHCHOCH R', R, R. Rand Rare hydrogen and Rand Rare as defined in R. R. R. R. and Rare hydrogen and Rand Rare as Table 1. defined in Table 1. US 8,530,667 B2 145 146 Table 203: Table 216: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C CH, R7 is OCH R', R,R,R,R, wherein X is O, Z is C CHCH, R7 is CHOCHCH. R', R and R are hydrogen and R and R are as defined in R. R. R. R. RandR are hydrogen and RandR areas Table 1. 5 defined in Table 1. Table 204: Table 217: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, whereinX is O. Zis C CH, R7 is OCHCHR,R,R,R, wherein X is O, Z is C CHCH R is CHCHOCH R', R. Rand Rare hydrogen and Rand Rare as defined in R. R. R. R. RandR are hydrogen and RandR areas Table 1. 10 defined in Table 1. Table 205: Table 218: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C CH, R7 and Rare CH. R. R. R. whereinX is O. Zis C CHCHR is OCH R',R,R,R, R. Rand Rare hydrogen and Rand Rare as defined in 15 R. Rand Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 206: Table 219: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C CH R is CH. R. R. R. R. R. wherein X is O, Z is C CHCH, R7 is OCHCH. R', R, R7 and R are hydrogen and R and R are as defined in R. R. R. R. and Rare hydrogen and R and Rare as Table 1. defined in Table 1. Table 207: Table 220: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C CH R is CHCH. R. R. R. R. wherein X is O, Z is C CHCH, R7 and Rare CH, R', R, R. R7 and Rare hydrogen and Rand Rare as defined in 25 R. R. RandR are hydrogen and RandR areas defined Table 1. in Table 1. Table 208: Table 221: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, whereinX is O. Zis C CHR is CHOCH R',R,R,R, wherein X is O, Z is C CHCH R is CH. R. R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in 30 R. R7 and Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 209: Table 222: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C CH, R is CHOCHCH. R', R, 35 wherein X is O, Z is C CHCH R is CHCH. R. R. R. R. R. R. R7 and Rare hydrogen and Rand Rare as R. R. R7 and Rare hydrogen and RandR areas defined defined in Table 1. in Table 1. Table 210: Table 223: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C CH, R is CHCHOCH R', R, 40 wherein X is O, Z is C CHCH R is CHOCH R', R, R. R. R. R7 and Rare hydrogen and R and Rare as R. R. R. R7 and Rare hydrogen and Rand Rare as defined in Table 1. defined in Table 1. Table 211: Table 224: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C CHCH, R',R,R,R,R,R, R7 45 wherein X is O, Z is C CHCH R is CHOCHCH. R', and Rare hydrogen R. R. R. R. R7 and Rare hydrogen and RandR areas Table 212: defined in Table 1. This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C CHCH. R7 is CH. R. R. R. R. Table 225: 50 This table covers 272 compounds of the structural type T-2, R. Rand Rare hydrogen and Rand Rare as defined in wherein X is O, Z is C CHCH R is CHCHOCH R', Table 1. R. R. R. R. R7 and Rare hydrogen and RandR areas Table 213: defined in Table 1. This table covers 272 compounds of the structural type T-2, wherein X is O. Zis C CHCH R is CHCH. R. R. R. Table 226: R. R. Rand Rare hydrogen and RandR areas defined 55 This table covers 272 compounds of the structural type T-2, in Table 1. wherein X is O, Z is N, R. R. R. R. R. R. R7 and Rare Table 214: hydrogen This table covers 272 compounds of the structural type T-2, Table 227: wherein X is O, Z is C CHCH. R7 is cyclopropyl, R', R. 60 This table covers 272 compounds of the structural type T-2, R. R. R. Rand Rare hydrogen and R and Rare as wherein X is O, Z is N, R is CH. R. R. R. R. R. Rand defined in Table 1. Rare hydrogen and Rand Rare as defined in Table 1. Table 215: Table 228: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is O, Z is C CHCH R is CHOCH R', R, 65 wherein X is O, Z is N, R is CHCH. R. R. R. R. R. R. R. R. R. Rand Rare hydrogen and Rand Rare as and Rare hydrogen and Rand Rare as defined in Table defined in Table 1. 1. US 8,530,667 B2 147 148 Table 229: Table 243: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is N, R is cyclopropyl, R', R. R. R. R. whereinX is Se, Zis C. H. R7 is CHCH. R',R,R,R,R, R and R are hydrogen and R and R are as defined in R and Rare hydrogen and R and Rare as defined in Table 1. Table 1. Table 230: Table 244: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-1, wherein X is O, Z is N, R is CHOCH R', R. R. R. R. whereinX is Se, Z is C H., R is cyclopropyl, R', R. R. R. R and R are hydrogen and R and Rare as defined in R. Rand Rare hydrogen and Rand Rare as defined in Table 1. 10 Table 1. Table 231: This table covers 272 compounds of the structural type T-2, Table 255: wherein X is O, Z is N, R is CHOCHCH. R. R. R. R. This table covers 272 compounds of the structural type T-1, R. Rand Rare hydrogen and Rand Rare as defined in wherein X is Se, Z is C H., R is CHOCH. R. R. R. R. Table 1. 15 R. Rand Rare hydrogen and Rand Rare as defined in Table 232: Table 1. This table covers 272 compounds of the structural type T-2, Table 246: wherein X is O, Z is N, R is CHCHOCH R', R. R. R. This table covers 272 compounds of the structural type T-1, R. Rand Rare hydrogen and Rand Rare as defined in wherein X is Se, Z is C H., R is CHOCHCH. R. R. R. Table 1. R. R. Rand Rare hydrogen and RandR areas defined Table 233: in Table 1. This table covers 272 compounds of the structural type T-2, Table 247: whereinX is O, Zis N, R7 is OCH R',R,R,R,R,Rand This table covers 272 compounds of the structural type T-1, Rare hydrogen and Rand Rare as defined in Table 1. wherein X is Se, Z is C. H. R7 is CHCHOCH. R. R. R. Table 234: 25 R. R. Rand Rare hydrogen and RandR areas defined This table covers 272 compounds of the structural type T-2, in Table 1. wherein X is O, Z is N, R is OCHCH. R. R. R. R. R. Table 248: R and R are hydrogen and R and Rare as defined in This table covers 272 compounds of the structural type T-1, Table 1. Table 235: 30 wherein X is Se, Z is C. H. R7 is OCH R', R. R. R. R. This table covers 272 compounds of the structural type T-2, R and Rare hydrogen and R and Rare as defined in wherein X is O, Z is N, R and Rare CHR, R. R. R. R. Table 1. and Rare hydrogen and Rand Rare as defined in Table Table 249: 1. This table covers 272 compounds of the structural type T-1, Table 236: 35 wherein X is Se, Z is C H., R is OCHCH. R. R. R. R. This table covers 272 compounds of the structural type T-2, R. Rand Rare hydrogen and Rand Rare as defined in wherein X is O, Z is N, R is CH. R. R. R. R. R. R7 and Table 1. Rare hydrogen and Rand Rare as defined in Table 1. Table 250: Table 237: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, 40 whereinX is Se, Zis C. H. RandR are CHR,R,R,R, wherein X is O, Z is N, R is CHCH. R. R. R. R. R. R7 R and Rare hydrogen and R and Rare as defined in and Rare hydrogen and Rand Rare as defined in Table Table 1. 1. Table 251: Table 238: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, 45 wherein X is Se, Z is C H., R is CHR,R,R,R,R, R7 wherein X is O, Z is N, R is CHOCH R', R. R. R. R. and Rare hydrogen and Rand Rare as defined in Table R7 and R are hydrogen and R and Rare as defined in 1. Table 1. Table 252: Table 239: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, 50 whereinX is Se, Z is C H., R is CHCHR,R,R,R,R, wherein X is O, Z is N, R is CHOCHCH. R. R. R. R. R7 and Rare hydrogen and R and Rare as defined in R. R7 and Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 253: Table 240: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, 55 wherein X is Se, Z is C H., R is CHOCH. R. R. R. R. wherein X is O, Z is N, R is CHCHOCH, R', R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in R. R7 and Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 254: Table 241: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, 60 wherein X is Se, Z is C H., R is CHOCHCH. R. R. R. wherein X is Se, Z is C. H. R. R,R,R,R,R, R7 and R' R. R. R7 and Rare hydrogen and RandR areas defined are hydrogen in Table 1. Table 242: Table 255: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C H., R is CH. R. R. R. R. R. R. 65 wherein X is Se, Z is C H., R is CHCHOCH. R. R. R. and Rare hydrogen and Rand Rare as defined in Table R. R. R7 and Rare hydrogen and RandR areas defined 1. in Table 1. US 8,530,667 B2 149 150 Table 256: Table 269: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH. R. R. R. R. R. R. R7 and wherein X is Se, Z is C CH R is CHOCHCH. R', R, Rare hydrogen R. R. R. R7 and Rare hydrogen and R and Rare as Table 257: defined in Table 1. This table covers 272 compounds of the structural type T-1, Table 270: wherein X is Se, Z is C CH, R7 is CH. R. R. R. R. R. This table covers 272 compounds of the structural type T-1, R and R are hydrogen and R and Rare as defined in wherein X is Se, Z is C CH R is CHCHOCH R', R, Table 1. R. R. R. R7 and Rare hydrogen and R and Rare as Table 258: 10 defined in Table 1. This table covers 272 compounds of the structural type T-1, Table 271: wherein X is Se, Z is C CH, R7 is CHCH. R. R. R. R. This table covers 272 compounds of the structural type T-1, R. Rand Rare hydrogen and Rand Rare as defined in wherein X is Se, Z is C CHCH. R', R,R,R,R,R, R7 Table 1. 15 and Rare hydrogen Table 259: Table 272: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH, R7 is cyclopropyl, R', R. R. wherein X is Se, Z is C CHCH, R7 is CH, R', R,R,R, R. R. Rand Rare hydrogen and RandR areas defined R. Rand Rare hydrogen and Rand Rare as defined in in Table 1. Table 1. Table 260: Table 273: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH, R7 is CHOCH R', R. R. wherein X is Se, Z is C CHCHR is CHCHR,R,R, R. R. RandR are hydrogen and RandR areas defined R. R. RandR are hydrogen and RandR areas defined in Table 1. 25 in Table 1. Table 261: Table 274: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH, R7 is CHOCHCH. R. R. whereinX is Se, Z is C CHCH, R is cyclopropyl, R', R, R. R. R. Rand Rare hydrogen and Rand Rare as R. R. R. R. and Rare hydrogen and Rand Rare as defined in Table 1. 30 defined in Table 1. Table 262: Table 275: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH, R7 is CHCHOCH R', R, wherein X is Se, Z is C CHCH R is CHOCH R', R, R. R. R. Rand Rare hydrogen and R and Rare as 35 R. R. R. R. and Rare hydrogen and R and Rare as defined in Table 1. defined in Table 1. Table 263: Table 276: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, whereinX is Se, Zis C CH, R7 is OCH R',R,R,R,R, wherein X is Se, Z is C CHCH, R7 is CHOCHCH. R', R and R are hydrogen and R and R are as defined in 40 R. R. R. R. RandR are hydrogen and RandR areas Table 1. defined in Table 1. Table 264: Table 277: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH, R7 is OCHCH. R. R. R. wherein X is Se, Z is C CHCH, R7 is CHCHOCH R', R. R. RandR are hydrogen and RandR areas defined 45 R. R. R. R. RandR are hydrogen and RandR areas in Table 1. defined in Table 1. Table 265: Table 278: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH, Rand wherein X is Se, Z is C CHCH R is OCH R', R. R. Rare CHR,R,R,R,RandR are hydrogen and R' 50 R. R. Rand Rare hydrogen and RandR areas defined and Rare as defined in Table 1. in Table 1. Table 266: Table 279: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH R is CH. R. R. R. R. R. wherein X is Se, Z is C CHCH R is OCHCH. R', R, R7 and R are hydrogen and R and R are as defined in 55 R. R. R. R. and Rare hydrogen and R and Rare as Table 1. defined in Table 1. Table 267: Table 280: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH R is CHCH. R. R. R. R. 60 whereinX is Se, Zis C CHCH, R7 and Rare CHR,R, R. R7 and Rare hydrogen and Rand Rare as defined in R. R. Rand Rare hydrogen and RandR areas defined Table 1. in Table 1. Table 268: Table 281: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CH R is CHOCH R', R. R. 65 wherein X is Se, Z is C CHCH R is CH. R. R. R. R. R. R. R7 and Rarehydrogen and RandR areas defined R. R7 and Rare hydrogen and Rand Rare as defined in in Table 1. Table 1. US 8,530,667 B2 151 152 Table 282: Table 296: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Zis C CHCHR is CHCHR,R,R, wherein X is Se, Z is N, R is CH, R', R,R,R,R,R7 and R. R. R7 and Rare hydrogen and RandR areas defined Rare hydrogen and Rand Rare as defined in Table 1. in Table 1. Table 297: Table 283: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is N, R is CHCH. R. R. R. R. R. R7 wherein X is Se, Z is C CHCH R is CHOCH R', R, and Rare hydrogen and Rand Rare as defined in Table R. R. R. R7 and Rare hydrogen and Rand Rare as 1. defined in Table 1. 10 Table 284: Table 298: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CHCH R is CHOCHCH. R', wherein X is Se, Z is N, R is CHOCH, R', R. R. R. R. R. R. R. R. RandR are hydrogen and RandR areas R7 and Rare hydrogen and R and Rare as defined in defined in Table 1. 15 Table 1. Table 285: Table 299: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is C CHCH R is CHCHOCH R', wherein X is Se, Z is N, R is CHOCHCH. R. R. R. R. R. R. R. R. RandR are hydrogen and RandR areas R. R7 and Rare hydrogen and Rand Rare as defined in defined in Table 1. Table 1. Table 286: Table 300: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is N, R. R,R,R,R,R, R7 and Rare wherein X is Se, Z is N, R is CHCHOCH. R. R. R. R. hydrogen R. R7 and Rare hydrogen and Rand Rare as defined in Table 287: 25 Table 1. This table covers 272 compounds of the structural type T-1, wherein X is Se, Z is N, R is CH, R', R. R. R. R. Rand Table 301: Rare hydrogen and Rand Rare as defined in Table 1. This table covers 272 compounds of the structural type T-2: Table 288: wherein X is Se, Z is C. H. R. R,R,R,R,R, R7 and R' This table covers 272 compounds of the structural type T-1, 30 are hydrogen wherein X is Se, Z is N, R is CHCH. R. R. R. R. R. R. Table 302: and Rare hydrogen and RandR areas defined in Table This table covers 272 compounds of the structural type T-2, 1. wherein X is Se, Z is C H., R7 is CHR,R,R,R,R, R Table 289: and Rare hydrogen and Rand Rare as defined in Table This table covers 272 compounds of the structural type T-1, 35 1 wherein X is Se, Z is N, R is cyclopropyl, R', R. R. R. R. Table 303: R and R are hydrogen and R and R are as defined in This table covers 272 compounds of the structural type T-2, Table 1. whereinX is Se, Z is C. H. R7 is CHCHR,R,R,R,R, Table 290: R and Rare hydrogen and R and Rare as defined in This table covers 272 compounds of the structural type T-1, 40 Table 1. wherein X is Se, Z is N, R is CHOCH R', R. R. R. R. R and R are hydrogen and R and Rare as defined in Table 304: Table 1. This table covers 272 compounds of the structural type T-2, Table 291: wherein X is Se, Z is C H., R is cyclopropyl, R',R,R,R, This table covers 272 compounds of the structural type T-1, 45 R. Rand Rare hydrogen and Rand Rare as defined in wherein X is Se, Z is N, R is CHOCHCH. R. R. R. R. Table 1. R. Rand Rare hydrogen and Rand Rare as defined in Table 305: Table 1. This table covers 272 compounds of the structural type T-2, Table 292: wherein X is Se, Z is C H., R is CHOCH R', R. R. R. This table covers 272 compounds of the structural type T-1, 50 R. Rand Rare hydrogen and Rand Rare as defined in wherein X is Se, Z is N, R is CHCHOCH. R. R. R. R. Table 1. R. Rand Rare hydrogen and Rand Rare as defined in Table 306: Table 1. This table covers 272 compounds of the structural type T-2, Table 293: wherein X is Se, Z is C H., R is CHOCHCH. R. R. R. This table covers 272 compounds of the structural type T-1, 55 R. R. RandR are hydrogen and RandR areas defined whereinX is Se, Zis N, R7 is OCH,R,R,R,R,R,R° and in Table 1. Rare hydrogen and Rand Rare as defined in Table 1. Table 307: Table 294: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is N, R is OCHCH. R. R. R. R. R. 60 wherein X is Se, Z is C H., R is CHCHOCH R', R. R. R and R are hydrogen and R and Rare as defined in R. R. Rand Rare hydrogen and RandR areas defined Table 1. in Table 1. Table 295: Table 308: This table covers 272 compounds of the structural type T-1, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is N, R and Rare CH. R. R. R. R. R. 65 wherein X is Se, Z is C H., R is OCH R', R. R. R. R. and Rare hydrogen and Rand Rare as defined in Table R and Rare hydrogen and R and Rare as defined in 1. Table 1. US 8,530,667 B2 153 154 Table 309: Table 322: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C. H. R7 is OCHCH. R. R. R. R. wherein X is Se, Z is C CH, R7 is CHCHOCH R', R, R. Rand Rare hydrogen and Rand Rare as defined in R. R. R. R. and Rare hydrogen and R and Rare as Table 1. 5 defined in Table 1. Table 310: Table 323: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, whereinX is Se, Zis C. H. R7 and Rare CHR,R,R,R, whereinX is Se, Z is C CH, R7 is OCH R,R,R,R,R, R and R are hydrogen and R and R are as defined in R and Rare hydrogen and R and Rare as defined in Table 1. 10 Table 1. Table 311: Table 324: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C H., R is CH. R. R. R. R. R. R7 wherein X is Se, Z is C CH, R7 is OCHCH. R. R. R. and Rare hydrogen and Rand Rare as defined in Table 15 R. R. RandR are hydrogen and RandR areas defined 1. in Table 1. Table 312: Table 325: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, whereinX is Se, Zis C H., R is CHCHR,R,R,R,R, wherein X is Se, Z is C CH, R7 and Rare CHR,R,R, R7 and R are hydrogen and R and R are as defined in R. Rand Rare hydrogen and Rand Rare as defined in Table 1. Table 1. Table 313: Table 326: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C H., R is CHOCH R', R. R. R. wherein X is Se, Z is C CH R is CH, R', R. R. R. R. R. R7 and Rare hydrogen and Rand Rare as defined in 25 R7 and Rare hydrogen and R and Rare as defined in Table 1. Table 1. Table 314: Table 327: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C H., R is CHOCHCH. R. R. R. wherein X is Se, Z is C CH R is CHCH. R. R. R. R. R. R. R7 and Rarehydrogen and RandR areas defined 30 R. R7 and Rare hydrogen and Rand Rare as defined in in Table 1. Table 1. Table 315: Table 328: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C H., R is CHCHOCH. R. R. R. wherein X is Se, Z is C CH R is CHOCH R', R. R. R. R. R7 and Rarehydrogen and RandR areas defined 35 R. R. R7 and Rare hydrogen and RandR areas defined in Table 1. in Table 1. Table 316: Table 329: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C CH. R. R. R. R. R. R. R7 and 40 wherein X is Se, Z is C CH, R is CHOCHCH. R. R. Rare hydrogen R. R. R. R7 and Rare hydrogen and R and Rare as Table 317: defined in Table 1. This table covers 272 compounds of the structural type T-2, Table 330: wherein X is Se, Z is C CH, R7 is CH. R. R. R. R. R. This table covers 272 compounds of the structural type T-2, R and R are hydrogen and R and Rare as defined in 45 wherein X is Se, Z is C CH R is CHCHOCH R', R, Table 1. R. R. R. R7 and Rare hydrogen and R and Rare as Table 318: defined in Table 1. This table covers 272 compounds of the structural type T-2, Table 331: wherein X is Se, Z is C CH, R7 is CHCH. R. R. R. R. This table covers 272 compounds of the structural type T-2, R. Rand Rare hydrogen and Rand Rare as defined in 50 wherein X is Se, Z is C CHCH. R', R,R,R,R,R, R7 Table 1. and Rare hydrogen Table 319: Table 332: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C CH R is cyclopropyl, R', R. R. whereinX is Se, Z is C CHCH R is CH. R. R. R. R. R. R. Rand Rare hydrogen and RandR areas defined 55 R. Rand Rare hydrogen and Rand Rare as defined in in Table 1. Table 1. Table 320: Table 333: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C CH, R7 is CHOCH R', R. R. 60 wherein X is Se, Z is C CHCH, R7 is CHCHR,R,R, R. R. Rand Rare hydrogen and RandR areas defined R. R. Rand Rare hydrogen and RandR areas defined in Table 1. in Table 1. Table 321: Table 334: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C CH, R7 is CHOCHCH. R. R. 65 whereinX is Se, Z is C CHCH, R is cyclopropyl, R', R, R. R. R. Rand Rare hydrogen and Rand Rare as R. R. R. R. and Rare hydrogen and Rand Rare as defined in Table 1. defined in Table 1. US 8,530,667 B2 155 156 Table 335: Table 348: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C CHCH, R7 is CHOCH R', R, wherein X is Se, Z is N, R is CHCH. R. R. R. R. R. R. R. R. R. Rand Rare hydrogen and R and Rare as and Rare hydrogen and Rand Rare as defined in Table defined in Table 1. 1. Table 349: Table 336: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is N, R is cyclopropyl, R', R,R,R,R, wherein X is Se, Z is C CHCH, R7 is CHOCHCH. R', R and Rare hydrogen and R and Rare as defined in R. R. R. R. RandR are hydrogen and RandR areas Table 1. defined in Table 1. 10 Table 350: Table 337: This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is N, R is CHOCH R', R. R. R. R. This table covers 272 compounds of the structural type T-2, R and Rare hydrogen and R and Rare as defined in wherein X is Se, Z is C CHCH, R7 is CHCHOCH R', Table 1. R. R. R. R. RandR are hydrogen and RandR areas 15 Table 351: defined in Table 1. This table covers 272 compounds of the structural type T-2, Table 338: wherein X is Se, Z is N, R is CHQCHCI's, R, R2, R, R, This table covers 272 compounds of the structural type T-2, R. Rand Rare hydrogen and RandR areas defined in wherein X is Se, Z is C CHCH, R7 is OCH R', R. R. Table 1. R. R. Rand Rare hydrogen and RandR areas defined Table 352: in Table 1. This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is N, R is CHCHOCH. R. R. R. R. Table 339: R. Rand Rare hydrogen and Rand Rare as defined in This table covers 272 compounds of the structural type T-2, Table 1. wherein X is Se, Z is C CHCH R is OCHCH. R. R. 25 Table 353: R. R. R. Rand Rare hydrogen and Rand Rare as This table covers 272 compounds of the structural type T-2, defined in Table 1. whereinX is Se, Zis N, R is OCH,R,R,R,R,R,R° and Table 340: Rare hydrogen and Rand Rare as defined in Table 1. This table covers 272 compounds of the structural type T-2, Table 354: whereinX is Se, Z is C CHCH, R7 and Rare CHR,R, This table covers 272 compounds of the structural type T-2, R. R. Rand Rare hydrogen and RandR areas defined 30 wherein X is Se, Z is N, R7 is OCHCH. R. R. R. R. R. in Table 1. R and Rare hydrogen and R and Rare as defined in Table 341: Table 1. Table 355: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is C CHCH R is CH, R', R. R. R. 35 wherein X is Se, Z is N, RandR are CH, R,R,R,R,R) R. R7 and Rare hydrogen and Rand Rare as defined in and Rare hydrogen and Rand Rare as defined in Table Table 1. 1. Table 342: Table 356: This table covers 272 compounds of the structural type T-2, This table covers 272 compounds of the structural type T-2, 40 wherein X is Se, Z is N, R is CH, R', R. R. R. R. R7 and wherein X is Se, Zis C CHCHR is CHCHR,R,R, Rare hydrogen and Rand Rare as defined in Table 1. R. R. R7 and Rarehydrogen and RandR areas defined Table 357: in Table 1. This table covers 272 compounds of the structural type T-2, Table 343: wherein X is Se, Z is N, R is CHCH. R. R. R. R. R. R7 This table covers 272 compounds of the structural type T-2, 45 and Rare hydrogen and Rand Rare as defined in Table wherein X is Se, Z is C CHCH R is CHOCH R', R, 1. R. R. R. R7 and Rare hydrogen and R and Rare as Table 358: defined in Table 1. This table covers 272 compounds of the structural type T-2, Table 344: wherein X is Se, Z is N, R is CHOCH R', R. R. R. R. R7 and Rare hydrogen and R and Rare as defined in This table covers 272 compounds of the structural type T-2, 50 Table 1. wherein X is Se, Z is C CHCH R is CHOCHCH. R', Table 359: R,R,R,R,R7 and Rare hydrogen and RandR areas This table covers 272 compounds of the structural type T-2, defined in Table 1. wherein X is Se, Z is N, R is CHOCHCH. R. R. R. R. Table 345: R. R7 and Rare hydrogen and Rand Rare as defined in This table covers 272 compounds of the structural type T-2, 55 Table 1. wherein X is Se, Z is C CHCH R is CHCHOCH R', Table 360: R. R. R. R. RandR are hydrogen and RandR areas This table covers 272 compounds of the structural type T-2, defined in Table 1. wherein X is Se, Z is N, R is CHCHOCH. R. R. R. R. Table 346: R. R7 and Rare hydrogen and Rand Rare as defined in 60 Table 1. This table covers 272 compounds of the structural type T-2, wherein X is Se, Z is N, R. R,R,R,R,R, R7 and Rare Biological Examples hydrogen Table 347: Example A This table covers 272 compounds of the structural type T-2, 65 wherein X is Se, Z is N, R7 is CH, R', R. R. R. R. Rand Seeds of a variety of test species were sown instandard soil Rare hydrogen and Rand Rare as defined in Table 1. in pots. After cultivation for one day (pre-emergence) or after US 8,530,667 B2 157 158 10 days cultivation (post-emergence) under controlled con Example B ditions in a glasshouse, the plants were sprayed with an aque ous spray solution derived from the formulation of the tech Seeds of a variety of test species were sown instandard soil nical active ingredient in 0.6 ml acetone and 45 ml in pots. After cultivation for one day (pre-emergence) or after formulation Solution containing 10.6% Emulsogen EL (Reg 8 days cultivation (post-emergence) under controlled condi istry number 61791-12-6), 42.2% N-methylpyrrolidone, tions in a glasshouse (at 24/16°C., day/night; 14 hours light; 42.2% dipropylene glycol monomethyl ether (Registry num 65% humidity), the plants were sprayed with an aqueous ber 34590-94-8) and 0.2%X-77 (Registry number 11097-66 spray solution derived from the formulation of the technical 8). The test plants were then grown in a greenhouse under 10 active ingredient in acetone/water (50:50) solution contain optimum conditions until, 14 or 15 days later for post-emer ing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, gence and 19 or 20 days for pre-emergence, the test was CAS RN 9005-64-5). evaluated (100-total damage to plant; 0 no damage to plant). The test plants were then grown in a glasshouse under controlled conditions in a glasshouse (at 24/16°C., day/night; Test Plants: 15 14 hours light: 65% humidity) and watered twice daily. After 13 days for pre and post-emergence, the test was evaluated Alopecurus myosuroides (ALOMY), Avena fatua (100 total damage to plant; 0 no damage to plant). (AVEFA), Lolium perenne (LOLPE), Setaria faberi Test Plants: (SETFA), Digitaria sanguinalis (DIGSA), Echinochloa Alopecurus myosuroides (ALOMY), Avena fatua crus-galli (ECHCG) (AVEFA), Setaria faberi (SETFA), Echinochloa crus-galli Pre-Emergence Activity (ECHCG) and Amaranthus retoflexus (AMARE)

Compound Number Rate g/ha ALOMY AVEFA LOLPE SETFA DIGSA ECHCG T4 500 70 70 70 70 30 70 T5 500 O 2O O O O O T6 500 O 60 O O O O T7 500 10 10 10 O 2O O T10 250 10 10 2O O 30 30 T12 500 10 2O 10 2O O 30 T14 250 90 60 1OO 1OO 70 90 T15 250 70 10 10 2O 30 90 T21 250 90 70 90 1OO 100 100 T22 250 100 100 1OO 1OO 100 100 T23 500 100 90 90 1OO 100 100 T24 250 90 60 90 1OO 100 100 T25 250 90 90 1OO 1OO 100 100 T26 250 90 60 70 1OO 100 8O T27 250 70 60 90 1OO 100 70 T28 250 100 100 1OO 1OO 100 100 T30 250 10 30 40 70 60 8O P1 250 30 O 30 O O 2O P2 250 30 O 50 O O 50

Post-Emergence Activity

Compound Number Rate g/ha ALOMY AVEFA LOLPE SETFA DIGSA ECHCG T4 25 10 30 40 40 60 8O T5 25 10 10 O 10 30 O T6 25 10 10 10 40 2O 30 T7 25 O O O O O 50 T10 25 10 40 2O 60 40 60 T12 25 8O 8O 30 70 8O 8O T14 25 90 100 8O 8O 60 100 T15 25 50 40 40 70 40 90 T21 25 50 2O 40 8O 8O 100 T22 25 70 70 2O 60 100 100 T23 25 100 100 1OO 1OO 100 100 T24 25 70 70 30 8O 90 100 T25 25 100 100 50 90 100 100 T26 25 10 O O O 30 O T27 25 8O 90 40 8O 100 100 T28 25 70 70 50 8O 100 100 T30 25 O 10 2O 40 70 70 P1 25 70 8O 60 90 8O 100 P2 25 90 90 70 8O 8O 100 US 8,530,667 B2 159 160 Pre-Emergence Activity -continued

Compound Rate Number g/ha AMARE SETFA ALOMY ECHCG AVEFA Compound Rate 5 P9 250 O 1OO 1OO 1OO 90 Number g/ha AMARE SETFA ALOMY ECHCG AVEFA P10 250 2O 1OO 1OO 1OO 100 T20 250 O 8O 50 70 60 T29 250 2O 90 50 90 90 T31 250 2O 90 60 90 70 T32 250 O 40 O O O 10 What is claimed is: T33 250 O OO 90 1OO O T34 250 O 90 40 70 2O 1. A compound of the formula (I) T35 250 O OO 1OO 1OO 100 T36 250 O OO 90 1OO 8O T37 250 O 90 30 40 O (I)

T38 250 O 90 O 40 O T39 250 O 90 70 8O 90 15 T40 250 O OO 90 1OO 40 T41 250 O OO 1OO 1OO 30 T42 250 O OO 90 90 30 T43 250 O 60 O 8O O Het, T45 250 O OO 90 1OO 60 T47 250 O OO 90 90 80 20 T48 250 O 90 40 70 2O T49 250 O 90 2O 70 O TSO 250 O 90 40 90 O T51 250 O OO 8O 1OO 90 T52 250 O OO 70 1OO 90 and tautomeric forms thereof, T53 250 90 90 50 8O 25 wherein T54 250 O OO 90 1OO 100 8 P4 250 O 90 60 90 90 R" and R are independently of each other hydrogen, P5 250 O OO 50 90 70 C-C alkyl, C-Chaloalkyl, C-Calkoxy, p 3. g O 18 is 18 C-C alkylthio, halogen or C-Calkoxycarbonyl, P8 250 O OO 90 1OO 30 R° and R7 are independently of each other hydrogen, halo P9 250 O 90 70 90 50 30 gen, cyano, C-Calkyl or a group COR, CO.R' or P10 250 O OO 90 1OO 100 CONR'R'4,11t 12 CR -3. NOR'"14 or CR's15 NNR'R'':1617. R. R. Rand Rare independently of each other hydro Post-Emergence Activity gen, cyano, C1-Calkyl, Ca-Calkenyl, C-C alkoxy, 35 CCoality-Coalkyl, 3-7 membered heterocycyl or CR' NOR'"; wherein Spid t AMARE SETFA. ALOMY ECHCG AVEFA R. R. R'' and Rare C-Calkyl, le gna R" and Rare hydrogen or C-C alkyl, P34 250 O OO OO OO O 40 R'' is C-C alkyl, and f g ig 3. g g o R" and R7 are independently of each other hydrogen or T19 1OOO 20 30 10 O O C-C alkyl, T20 250 O OO 90 OO OO O 15 g g g g g g RandR together with the carbonatoms to which they are T31 250 O 70 60 8O 50 45 attached form a keto, imino or alkenyl unit, or T32 250 O 70 O 30 O RandR together form a bond, T33 250 60 OO OO OO OO T35 250 O OO OO OO OO G is hydrogen or an alkali metal, alkaline earth metal, T36 250 30 OO OO OO OO Sulfonium, ammonium or a latentiating group, T37 250 O 90 50 90 10 Het is a group of the formula R to R. T38 250 O OO 90 OO 90 50 T39 250 O OO OO OO OO T40 250 O OO OO OO 70 T41 250 O OO OO OO 90 (R) T42 250 O OO OO OO OO R23 W. T43 250 O OO 90 OO OO W2 T45 250 O OO OO OO 00 55 T47 250 O OO OO OO OO 2W. T48 250 40 90 60 OO 40 A W4 T49 250 O 90 50 OO 30 (R) TSO 250 O OO 90 OO 90 R23 X T51 250 O 90 90 OO 8O T52 250 O OO OO OO 60 / R26 T53 250 O OO 60 90 70 Z T54 250 40 OO OO OO OO A P3 250 O OO OO OO OO (R3) P4 250 O OO OO OO OO R23 Z P5 250 O OO 90 OO 90 N P6 250 O OO 90 OO 90 X-R P7 250 O OO OO OO OO 65 P8 250 O OO OO OO OO A X US 8,530,667 B2 161 162 -continued C-Chaloalkoxy, C-C alkylthio, C-C alkylsulfinyl, 27 (R4) C-C alkylsulfonyl, nitro or cyano, preferably halogen, RN-N C-C alkyl, C-Chaloalkyl, vinyl, ethynyl, or methoxy, N \ R’ is optionally substituted aryl or optionally substituted S. heteroaryl wherein the substituents are selected from A ZX-r halogen C-C2-alkyl, C-C2-alkoxy, C-C haloalkyl, (Rs) R28 C-C haloalkoxy, cyano or nitro, R2 R’ is hydrogen, C-C alkyl, C-C haloalkyl, C-C-cy n N N cloalkyl, C-C-halocycloalkyl, C-Calkenyl, 10 C-C alkynyl, C-Chaloalkyl or C-C haloalkenyl, S. A Z R’ is hydrogen, methyl, halomethyl or halogen, (R6) R’ is hydrogen, halogen, C-C alkyl, C-C haloalkyl, R28 C-C alkenyl, C-Chaloalkenyl, C-C alkynyl, C-C R23 15 alkoxy, C-Chaloalkoxy, C-C alkylthio, C-C alkyl e Sulfinyl, C-C alkylsulfonyl or cyano, N-R30 R" is optionally substituted aryl or optionally substituted S. A heteroaryl wherein the substituents are selected from R29 halogen C-C2-alkyl, C-C2-alkoxy, C-C haloalkyl, 28 (R) C-C haloalkoxy, cyano or nitro, R R" is hydrogen, methyl, ethyl or halomethyl, and R23 R is hydrogen, methyl, ethyl, halomethyl, haloethyl, e N-R30 halogen, cyano or nitro: N / and A N 25 agronomically acceptable salts of compounds of formula I 25 (Rs) and of said tautomeric forms. R 2. A compound according to claim 1, wherein R and R' eNN-R30 together form a bond. S. M 3. A compound according to claim 1, wherein R' and Rare A Z 30 independently of each other hydrogen or C-C alkyl. 25 (Ro) 4. A compound according to claim 1, wherein R' and R' R together with the carbon atoms to which they are attached N R26 form a 3-7 membered ring, optionally containing an oxygen -N4 or Sulphur atom. A 35 5. A compound according to claim 1, wherein G denotes R29 hydrogen, an alkali metal cation, alkaline earth metal cation, 25 (R10) R Sulfonium cation or ammonium cation, or C-Calkyl, C-Calkenyl or C-Calkynyl or a latentiating group. R26 40 6. A compound according to claim 1, wherein R' to Rand A1 N4 Gare hydrogen, Het is a group R. 25 (R) R

N 25 N-7\ 45 R X A1 NN-K / R29 A Z 25 (R12) R 50 N wherein A designates the point of attachment to the ketoenol N M moiety, X is S. Z is N, R is methyl or ethyl and R is A1 NS, 4-chlorophenyl or 4-bromophenyl. 7. A herbicidal composition comprising; a formulation wherein 55 assistant, and a herbicidally effective amount of a compound A designates the point of attachment to the ketoenol moi of formula (I), according to claim 1. ety, 8. A composition according to claim 7 further comprising W is N or CR2, a second herbicide, optionally a third herbicide, and option W° and Ware independently of each other N or CR. ally a safener. W is N or CR2, 60 9. A method of controlling grasses and weeds in crops of with the proviso that at least one of W, W, W or W is N, useful plants, which comprises applying a herbicidally effec X is O, S, Se, or NR', tive amount of a compound of formula (I) according to claim Z is N or CR, 1, or of a composition comprising Such a compound, to the wherein plants or to a locus thereof. R is hydrogen, halogen, C1-Calkyl, C-Chaloalkyl, 65 10. A compound according to claim 1 wherein R and R' C-C-cycloalkyl, C-C-halocycloalkyl, C-C alkenyl, are independently of each other hydrogen, methyl or methyl C-Chaloalkenyl, C-C alkynyl, C-C alkoxy, substituted by C-Calkoxy. US 8,530,667 B2 163 164 11. A compound according to claim 1, wherein R and R' together form a unit =O or —NR’, wherein R is C-Calkoxy. 12. A compound according to claim 1, wherein Het is a group of formula R. 5

(R2) 25 R X 10

A. Z wherein A designates the point of attachment to the ketoenol moiety, wherein X is S and Z is N and R and Rare as 15 defined in claim 1. 13. A compound according to claim 1, wherein Het is a group of formula R.

(R2) 2-R26 DC)-A Z 25 wherein A designates the point of attachment to the ketoenol moiety, X is S and Z is CR° and R, R and R are as defined in claim 1. 30