Pyrazole derivatives as herbicides

[0001] The present invention relates to novel, herbicidally active substituted pyridone derivatives, to a process for the preparation thereof, to compositions comprising those compounds, and to the use thereof in the control of weeds, especially in crops of useful plants, for example, cereals, maize, rice, cotton, soybean, rape, sorghum, sugar cane, sugar beet, sunflowers, vegetables, plantation crops and fodder plants, or in the inhibition of plant growth. Phenyl-pyrazole compounds having herbicidal activity are known and are described, for example, in EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728, WO 96/01254 and WO 97/00246.

[0002] Surprisingly, it has now been found that substituted pyridono-pyrazole derivatives have excellent herbicidal and growth-inhibiting properties.

[0003] The present invention accordingly relates to compounds of formula I

[0004] R1 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, cyano-C1-C4alkyl, C3- or C4-alkenyl, C3- or C4-haloalkenyl, C3- or C4-alkynyl or C3-C6cycloalkyl;

[0005] R2 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-C6alkynyl, C1-C4alkyl-S(O)2— or C1-C4haloalkyl-S(O)2—;

[0006] R3 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, halogen, cyano, NH2C(S)—, nitro or amino;

[0007] n1 is 0, 1 or 2;

[0008] R4 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-C6alkynyl or C3-C6cycloalkyl;

[0009] R5 is hydrogen, halogen, C1-C4alkyl, C1-C4haloalkyl, cyano, nitro, amino, NH2C(O)—, NH2C(S)—, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C4haloalkylcarbonyl, C2-C4alkenyl-carbonyl, C1-C3alkyl-CH(OH)—, OHC—, HOC(O)—, CIC(O)—, HON═CH—, C1-C4alkoxy-N═CH—, C2-C4haloalkenylcarbonyl or C2-C4alkynylcarbonyl;

[0010] R11 is hydrogen, fluorine, chlorine, bromine or methyl;

[0011] R12 is hydrogen, halogen, methyl, halomethyl, nitro, amino, hydroxy, OHC—, HOC(O)—, cyano, C1-C4alkoxycarbonyl or halomethoxy;

[0012] X1 is O, S, R20N═ or R25ON═;

[0013] R13 is hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6-haloalkenyloxy, C1-C6alkoxy-C1-C6alkyl, C3-C6alkenyloxy-C1-C6alkyl, C3-C6alkynyloxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, B1-C1-C6alkoxy, R21(R22)N—, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl, OHC—, C1-C6alkylcarbonyl, C1-C6alkylcarbonyloxy, C1-C6haloalkylcarbonyl, C2-C6alkenylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkyl-S(O)2—, C1-C6haloalkyl-S(O)2—, (C1-C6alkyl)2N—N═CH—,

[0014] B1-CH═N—, (CH3)2N—CH═N—, (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5haloalkyl)-CH2—, (hydroxy-C1-C5alkyl)-O— or (B1-C1-C5hydroxyalkyl)-O—;

[0015] B1 is cyano, OHC—, HOC(O)—, C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, benzyloxycarbonyl, benzyloxycarbonyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl, benzylthio-C(O)—, benzylthio-C(O)— mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl, C1-C6haloalkoxycarbonyl, C1-C6alkylthio-C(O)—, R26(R27)NC(O)—, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4haloalkyl, C1-C6-alkyl-S(O)2—, C1-C6alkyl-S(O)—, C1-C6alkylthio, C3-C6cycloalkyl, C1-C6alkoxy, C3-C6alkenylthio or C3-C6alkynylthio;

[0016] R20 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, cyano, R23(R24)N—, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, C2-C6haloalkoxycarbonyl, OHC—, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C6alkyl-S(O)2—, C1-C6haloalkyl-S(O)2—, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4haloalkyl, phenyl-C1-C6alkyl, or phenyl-C1-C6alkyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl;

[0017] R21 and R22 are each independently hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6-haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C1-C6alkoxy-C1-C6alkyl, OHC—, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C6alkyl-S(O)2— or C1-C6haloalkyl-S(O)2—;

[0018] R23 and R24 are each independently as defined for R21;

[0019] R25 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, C1-C6alkoxy-C1-C6alkyl, benzyl, C1-C6alkyl-S(O)2— or C1-C6haloalkyl-S(O)2—;

[0020] R26 and R27 are each independently hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4haloalkyl, benzyl, or benzyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl; or

[0021] X1 and R13 together form a group ═N—Y— wherein Y is bonded to the ring nitrogen atom;

[0022] Y is —C(R31)(R32)—CH2—, —C(R31)(R32)—O—, —C(R31)(R32)—CH2—CH2—, —C(R31)(R32)—CH2—O—, —O—CH2—, —O—CH2—CH2—, —O—CH═CH—, —N(R33)—CH2—, —N(R33)—CH2—CH2—, —N(R33)—CH═CH—, —N(R33)—C(X3)—CH2—, —C(X3)—CH2—, —C(X3)—CH2—CH2—, —C(X3)—CH2—O—, —C(X3)—O—, —C(R34)═CH—, —C(R31)(R32)—CH═CH—, —C(R34)═N—, —C(R31)(R32)—CH═N—, —C(R31)(R32)—N═CH—, —C(X3)—CH═CH—, —N═N—, —C(R31)(R32)—C(O)—, —C(R31)(R32)—C(S)—, —C(R31)(R32)—CH2—C(O)—, —C(R31)(R32)—CH2—C(S)—, —N(R33)—C(O)—, —N(R33)—C(S)—, —N(R33)—CH2—C(O)—, —N(R33)—CH2—C(S)—, —O—C(O)—, —O—C(S)—, —C(R34)═CH—C(O)— or —C(R34)═CH—C(S)—, the right-hand end of the bridge members in the above definitions of Y being bonded to the ring nitrogen atom;

[0023] R31 is hydrogen, C1-C6alkyl or C1-C6haloalkyl;

[0024] R32 is hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, cyano-C1-C6alkyl, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C3-C6alkenyloxy-C1-C6alkyl, C3-C6alkynyloxy-C1-C6alkyl, C1-C6alkylcarbonyloxy-C1-C6alkyl, C1-C6haloalkylcarbonyloxy-C1-C6alkyl, carboxyl, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, C1-C6haloalkoxycarbonyl, C3-C6cycloalkoxycarbonyl, C1-C4alkoxy-C1-C6alkoxycarbonyl, C1-C6alkyl-NHC(O)—, (C1-C6alkyl)2NC(O)—, C3-C6alkenyl-NHC(O)—, C1-C6alkyl-(C3-C6-alkenyl)NC(O)—, C3-C6alkynyl-NHC(O)—, aminocarbonyl, C1-C6alkylthio-C(O)—, C3-C6-alkenylthio-C(O)—, C3-C6alkynylthio-C(O)—, benzyloxycarbonyl, benzyloxycarbonyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl, phenoxycarbonyl, C1-C6alkyl-S(O)2NHC(O)—, C1-C6alkyl-S(O)2(C3-C6alkenyl)N—C(O)—, C1-C6haloalkyl-S(O)2NHC(O)—, HON═CH—, C1-C6alkoxy-N═CH—, C3-C6alkenyloxy-N═CH—, C3-C6alkynyloxy-N═CH—, HOC(O)—C1-C6alkyl, C1-C6alkoxycarbonyl-C1-C6alkyl, C3-C6alkenyloxycarbonyl-C1-C6alkyl, C3-C6alkynyloxycarbonyl-C1-C6alkyl, C1-C6alkylcarbonyl, CIC(O)—, H2NC(S)—, OHC—, cyano, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4-haloalkyl, phenyl-C1-C6alkyl, or phenyl-C1-C6alkyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl;

[0025] X3 is O, S, R20N═ or R25ON═;

[0026] R33 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C6alkyl-S(O)2— or B2-C1-C6-alkyl;

[0027] B2 is cyano, HOC(O)—, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1-C6alkoxy; and

[0028] R34 is as defined for R32 or is halogen, C1-C6alkoxy, C3-C6alkenyloxy, C1-C6haloalkoxy, C1-C6alkylthio, C1-C6alkyl-S(O)— or C1-C6alkyl-S(O)2—,

[0029] and also to the pyrazole N-oxides, agrochemically acceptable salts and stereoisomers of those compounds of formula I.

[0030] In the above definitions, halogen is to be understood as meaning iodine or, preferably, fluorine, chlorine or bromine.

[0031] The alkyl, alkenyl and alkynyl groups in the substituent definitions may be straight-chain or branched, this applying also to the alkyl, alkenyl and alkynyl moiety of the alkylcarbonyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkoxyalkoxyalkyl, alkylthio, alkylthio-C(O)—, alkylsulfonyl, alkylaminocarbonyl, dialkylaminocarbonyl, B1-alkyl and HOC(O)-alkyl groups. Alkyl groups are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl and the various isomers of pentyl and hexyl. Methyl, ethyl, n-propyl, isopropyl and n-butyl are preferred.

[0032] There may be mentioned as examples of alkenyl radicals vinyl, allyl, methallyl, 1-methylvinyl, but-2-en-1-yl, pentenyl and 2-hexenyl, with preference being given to alkenyl radicals having a chain length of from 3 to 5 carbon atoms.

[0033] There may be mentioned as examples of alkynyl radicals ethynyl, propargyl, 1-methylpropargyl, 3-butynyl, but-2-yn-1-yl, 2-methylbutyn-2-yl, but-3-yn-2-yl, 1-pentynyl, pent-4-yn-1-yl and 2-hexynyl, with preference being given to alkynyl radicals having a chain length of from 2 to 4 carbon atoms.

[0034] Suitable haloalkyl radicals are alkyl groups that are mono- or poly-substituted, especially mono- to tri-substituted, by halogen, halogen being in particular iodine or especially fluorine, chlorine or bromine, for example fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2-chloroethyl, 2,2-dichloroethyl, 2,2,2-trifluoroethyl and 2,2,2-trichloroethyl.

[0035] Suitable haloalkenyl radicals are alkenyl groups mono- or poly-substituted by halogen, halogen being in particular bromine, iodine or especially fluorine or chlorine, for example 2- or 3-fluoropropenyl, 2- or 3-chloropropenyl, 2- or 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl, 4,4,4-trifluorobut-2-en-1-yl and 4,4,4-trichlorobut-2-en-1-yl. Of the alkenyl radicals mono-, di- or tri-substituted by halogen, preference is given to those having a chain length of 3 or 4 carbon atoms. The alkenyl groups may be substituted by halogen at saturated or unsaturated carbon atoms.

[0036] Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl or an isomer of pentylsulfonyl or hexylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.

[0037] Haloalkylsulfonyl is, for example, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, chloromethylsulfonyl, trichloromethylsulfonyl, 2-fluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl or 2,2,2-trichloroethylsulfonyl.

[0038] Alkenylsulfonyl is, for example, allylsulfonyl, methallylsulfonyl, but-2-en-1-ylsulfonyl, pentenylsulfonyl or 2-hexenylsulfonyl.

[0039] Haloalkenylsulfonyl is, for example, 2- or 3-fluoropropenylsulfonyl, 2- or 3-chloropropenylsulfonyl, 2- or 3-bromopropenylsulfonyl, 2,3,3-trifluoropropenylsulfonyl, 2,3,3-trichloropropenylsulfonyl, 4,4,4-trifluorobut-2-en-1-ylsulfonyl or 4,4,4-trichlorobut-2-en-1-ylsulfonyl.

[0040] Cyanoalkyl is, for example, cyanomethyl, cyanoethyl, cyanoeth-1-yl or cyanopropyl.

[0041] Hydroxyalkyl is, for example, hydroxymethyl, 2-hydroxyethyl or 3-hydroxypropyl.

[0042] Alkylamino is, for example, methylamino, ethylamino or an isomer of propyl- or butyl-amino.

[0043] Dialkylamino is, for example, dimethylamino, diethylamino or an isomer of dipropyl- or dibutyl-amino.

[0044] Alkenylamino is, for example, allylamino, methallylamino or but-2-en-1-ylamino.

[0045] Alkynylamino is, for example, propargylamino or 1 -methylpropargylamino.

[0046] Haloalkylamino is, for example, chloroethylamino, trifluoroethylamino or 3-chloropropylamino.

[0047] Di(haloalkyl)amino is, for example, di(2-chloroethyl)amino.

[0048] Alkylcarbonyl is especially acetyl or propionyl.

[0049] Haloalkylcarbonyl is especially trifluoroacetyl, trichloroacetyl, 3,3,3-trifluoropropionyl or 3,3,3-trichloropropionyl.

[0050] Alkenylcarbonyl is especially vinylcarbonyl, allylcarbonyl, methallylcarbonyl, but-2-en-1-yl-carbonyl, pentenylcarbonyl or 2-hexenylcarbonyl.

[0051] Alkynylcarbonyl is especially acetylenecarbonyl, propargylcarbonyl, 1-methylpropargylcarbonyl, 3-butynylcarbonyl, but-2-yn-1-ylcarbonyl or pent-4-yn-1-ylcarbonyl.

[0052] Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy or an isomer of pentyloxy or hexyloxy.

[0053] Alkenyloxy is, for example, allyloxy, methallyloxy or but-2-en-1-yloxy.

[0054] Alkynyloxy is, for example, propargyloxy or 1-methylpropargyloxy.

[0055] Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.

[0056] Alkenyloxyalkyl is, for example, allyloxyalkyl, methallyloxyalkyl or but-2-en-1-yloxyalkyl.

[0057] Alkynyloxyalkyl is, for example, propargyloxyalkyl or 1-methylpropargyloxyalkyl.

[0058] Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl or n-butoxycarbonyl, preferably methoxycarbonyl or ethoxycarbonyl.

[0059] Alkenyloxycarbonyl is, for example, allyloxycarbonyl, methallyloxycarbonyl, but-2-en-1-yl-oxycarbonyl, pentenyloxycarbonyl or 2-hexenyloxycarbonyl.

[0060] Alkynyloxycarbonyl is, for example, propargyloxycarbonyl, 3-butynyloxycarbonyl, but-2-yn-1-yloxycarbonyl or 2-methylbutyn-2-yloxycarbonyl.

[0061] Alkoxyalkoxycarbonyl is, for example, methoxymethoxycarbonyl, ethoxymethoxycarbonyl, ethoxyethoxycarbonyl, propoxymethoxycarbonyl, propoxyethoxycarbonyl, propoxypropoxycarbonyl or butoxyethoxycarbonyl.

[0062] Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy or 2,2,2-trichloroethoxy.

[0063] Of the alkenyl radicals mono-, di- or tri-substituted by halogen, preference is given to those having a chain length of 3 or 4 carbon atoms. The alkenyloxy groups may be substituted by halogen at saturated or unsaturated carbon atoms.

[0064] Suitable haloalkenyloxy radicals are alkenyloxy groups mono- or poly-substituted by halogen, halogen being in particular bromine, iodine or especially fluorine or chlorine, for example 2- or 3-fluoropropenyloxy, 2- or 3-chloropropenyloxy, 2- or 3-bromopropenyloxy, 2,3,3-trifluoropropenyloxy, 2,3,3-trichloropropenyloxy, 4,4,4-trifluoro-but-2-en-1-yloxy and 4,4,4-trichlorobut-2-en-1-yloxy.

[0065] The cycloalkyl radicals suitable as substituents are, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0066] The cycloalkoxycarbonyl radicals suitable as substituents are, for example, cyclopropoxycarbonyl, cyclobutoxycarbonyl, cyclopentyloxycarbonyl and cyclohexyloxycarbonyl.

[0067] The halocycloalkyl radicals suitable as substituents are, for example, mono-, di- or up to per-halogenated cycloalkyl radicals, for example, fluorocyclopropyl, chlorocyclopropyl, bromocyclopropyl, 2,2-dichlorocyclopropyl, 2,2-difluorocyclopropyl, 2,2-dibromocyclopropyl, 2-fluoro-2-chlorocyclopropyl, 2-chloro-2-bromocyclopropyl, 2,2,3,3-tetrafluorocyclopropyl, 2,2,3,3-tetrachlorocyclopropyl, pentafluorocyclopropyl, fluorocyclobutyl, chlorocyclobutyl, 2,2-difluorocyclobutyl, 2,2,3,3-tetrafluorocyclobutyl, 2,2,3-trifluoro-3-chlorocyclobutyl, 2,2-dichloro-3,3-difluorocyclobutyl, fluorocyclopentyl, difluorocyclopentyl, chlorocyclopentyl, perfluorocyclopentyl, chlorocyclohexyl and pentachlorocyclohexyl.

[0068] Alkylthio is, for example, methylthio, ethylthio, propylthio or butylthio or a branched isomer thereof.

[0069] Phenyl or benzyl per se, or as part of a substituent, such as, for example, phenoxycarbonyl or benzyloxycarbonyl, may be unsubstituted or substituted, in which case the substituents may be in the ortho-, meta- or para-position. Substituents are, for example, C1-C4alkyl, C1-C4alkoxy, halogen or C1-C4haloalkyl.

[0070] Corresponding meanings may also be given to the substituents in combined definitions, such as, for example, in alkyl-S(O)—, alkoxy-N═CH—, (alkyl)2N—C(O)—, (alkyl)2N—N═CH—, alkenyl-NHC(O)—, alkyl(alkenyl)N—C(O)—, alkynyl-NHC(O)—, alkylcarbonyloxyalkyl, alkoxycarbonylalkyl, haloalkoxycarbonyl, haloalkylcarbonyloxyalkyl, haloalkenylcarbonyl, alkyl-S(O)2—NHC(O)—, haloalkyl-S(O)2NHC(O)—, B1-alkoxy and B2-alkyl.

[0071] In the definition of R13, (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2— and (B1-C1-C5-haloalkyl)-CH2— signify that only the C1-C5alkyl moiety is hydroxylated or halogenated, that is to say, the methylene group is not hydroxylated or halogenated.

[0072] In the definition of X1 and R13 together, a group ═N—Y— wherein Y is bonded to the ring nitrogen atom is to be understood as meaning one of the following bicyclic ring systems of formula I:

[0073] In the definition of Y, it is always the right-hand end of the bridge member that is bonded to the ring nitrogen atom, as is illustrated, for example where Y is —C(R31)(R32)—CH2—, —C(R31)(R32)—O— and —C(R34)═CH—, in the following bicyclic ring structures:

[0074] In the definitions of cyanoalkyl, alkylcarbonyl, alkenylcarbonyl, haloalkenylcarbonyl, alkynylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl and haloalkylcarbonyl, the upper and lower limits of the number of carbon atoms given in each case do not include the cyano or carbonyl carbon atom, as the case may be.

[0075] The compounds of formula I may, in respect of the group W (W1 to W3), be present in the form of mixtures consisting of the isomers substituted in the 3- and 5-positions of the pyrazole ring by the pyridone group (pyridone), for example in the form of regioisomers IW1a and IW1b

[0076] for the group W1. The ratio of isomers may vary as a function of the method of synthesis.

[0077] The invention relates also to the salts that the compounds of formula I having azide hydrogen, especially the derivatives having carboxylic acid groups and sulfonamide groups (for example carboxy-substituted alkyl, alkoxy and pyridone groups (R12) and alkyl-S(O)2NH— and haloalkyl-S(O)2NH-13 groups), are capable of forming with bases. Those salts are, for example, alkali metal salts, for example sodium and potassium salts; alkaline earth metal salts, for example calcium and magnesium salts; ammonium salts, that is to say unsubstituted ammonium salts and mono- or poly-substituted ammonium salts, for example triethylammonium and methylammonium salts; or salts with other organic bases.

[0078] Of the alkali metal and alkaline earth metal hydroxides as salt formers, attention is drawn, for example, to the hydroxides of lithium, sodium, potassium, magnesium and calcium, but especially to the hydroxides of sodium and potassium.

[0079] Examples of amines suitable for ammonium salt formation include ammonia as well as primary, secondary and tertiary C1-C18alkylamines, C1-C4hydroxyalkylamines and C2-C4-alkoxyalkylamines, for example methylamine, ethylamine, n-propylamine, isopropylamine, the four isomers of butylamine, n-amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, methylethylamine, methylisopropylamine, methylhexylamine, methylnonylamine, methylpentadecylamine, methyloctadecylamine, ethylbutylamine, ethylheptylamine, ethyloctylamine, hexylheptylamine, hexyloctylamine, dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-butylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, ethanolamine, n-propanolamine, isopropanolamine, N,N-diethanolamine, N-ethylpropanolamine, N-butylethanolamine, allylamine, n-butenyl-2-amine, n-pentenyl-2-amine, 2,3-dimethylbutenyl-2-amine, dibutenyl-2-amine, n-hexenyl-2-amine, propylenediamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, tri-sec-butylamine, tri-n-amylamine, methoxyethylamine and ethoxyethylamine; heterocyclic amines, for example pyridine, quinoline, isoquinoline, morpholine, thiomorpholine, piperidine, pyrrolidine, indoline, quinuclidine and azepine; primary arylamines, for example anilines, methoxyanilines, ethoxyanilines, o-, m- and p-toluidines, phenylenediamines, benzidines, naphthylamines and o-, m- and p-chloroanilines; especially triethylamine, isopropylamine and diisopropylamine.

[0080] The salts of compounds of formula I having basic groups, especially having basic pyrazolyl rings, or of derivatives having amino groups, for example alkylamino and dialkylamino groups, in the definition of R3, R5 or R13 are, for example, salts with inorganic or organic acids, for example hydrohalic acids, such as hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydriodic acid, and also sulfuric acid, phosphoric acid, nitric acid, and organic acids, such as acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, glycolic acid, thiocyanic acid, citric acid, benzoic acid, oxalic acid, formic acid, benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid.

[0081] The possible presence of at least one asymmetrical carbon atom in the compounds of formula 1, for example in the substituent R13, where R13 is a branched alkyl, alkenyl, haloalkyl or alkoxyalkyl group or where R13 is (B1-C1-C5hydroxyalkyl)-CH2— wherein, for example, B1 is C1-C6alkyl-S(O)—, means that the compounds may occur in the form of optically active single isomers or in the form of racemic mixtures. In the present invention, “compounds of formula I” is to be understood as including both the pure optical antipodes and the racemates or diastereoisomers. When an aliphatic C═C or C═N—O double bond (syn/anti) is present, geometric isomerism may occur. The invention relates to those isomers also.

[0082] Preferred compounds of formula I correspond to formula Ia

[0083] R1, R2, R3, R4, R5, R11, R12, R13, X1 and n1 are as defined for formula I. Of the compounds of formula Ia, preference is given to those wherein in the group Wa R3 is C1-C4alkyl or halogen; and R1 is methyl or ethyl.

[0084] Special preference is given to compounds of formula Ia wherein R3 is methyl, halomethyl, chlorine or bromine. Of those, the compounds wherein Wa is a group W1a or W2a are especially important.

[0085] Also especially important are compounds of formula Ia wherein Wa is the group W3a; and R5 is C1- or C2-halomethyl, cyano or H2NC(S)—.

[0086] Also particularly important are compounds of formula Ia wherein Wa is the group W1a; R1 is C1-C4alkyl; R2 is C1- or C2-haloalkyl; R3 is chlorine, bromine, methyl or halomethyl; R11 is fluorine, chlorine or bromine; and R12 is halogen, methyl or halomethyl. Of those, compounds in which R1 is methyl or ethyl; and R2 is difluoromethyl are more especially important.

[0087] Special preference is given also to compounds of formula Ia wherein Wa is the group W2a; R1 is C1-C4alkyl; R4 is methyl or ethyl; R3 is chlorine, bromine or methyl; R11 is fluorine, chlorine or bromine; and R12 is halogen, methyl or halomethyl. Of those compounds, those wherein R1 is methyl or ethyl; and R4 is methyl are more especially preferred.

[0088] Particularly important compounds of formula Ia are those wherein Wa is the group W3a; R1 is C1-C4alkyl; R5 is C1- or C2-haloalkyl, cyano, H2NC(S)— or CH3C(O)—; R3 is chlorine, bromine, methyl or halomethyl; R11 is fluorine, chlorine or bromine; and R12 is halogen, methyl or halomethyl. Of those, especially compounds wherein R1 is methyl or ethyl; and R5 is halomethyl or cyano are more especially important.

[0089] The process according to the invention for the preparation of a compound of formula I

[0090] wherein R11, R12 and W are as defined for formula I; X1 is O or S; R13 is C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl,

[0091] (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2— or (B1-C1-C5haloalkyl)-CH2—; and B1 is as defined for formula I, is carried out analogously to known processes and comprises oxidising a compound of formula III

[0092] for example with hydrogen peroxide-urea adduct in the presence of carboxylic acids and/or carboxylic acid anhydrides, organic peracids or persulfonic acid (Caro's acid) in a suitable solvent, to form a compound of formula V

[0093] and subsequently rearranging that compound in an inert solvent in the presence of an anhydride or in the presence of antimony pentachloride to yield, after aqueous working up, a compound of formula II

[0094] the radicals R11, R12 and W in the compounds of formulae II, III and V being as defined above, and then alkylating that compound in the presence of an inert solvent and a base with a compound of formula VI

R13—L (VI),

[0095] wherein R13 is as defined above and L is a leaving group, preferably chlorine, bromine, iodine, CH3SO2O— or

[0096] to form the isomeric compounds of formulae I and IV

[0097] wherein R11, R12, R13 and W are as defined above and X1 is O, and subsequently, where appropriate after separating off the compound of formula I, functionalising the pyridone group thereof according to the definition of X1 and R13, if desired, for example, converting it with the aid of a suitable sulfur reagent into the corresponding pyridinethione derivative (X1═S) (Reaction Scheme 1).

[0098] The process according to the invention for the preparation of a compound of formula I

[0099] wherein R11, R12 and W are as defined for formula I; X1 is S; R13 is hydroxy, C1-C6alkoxy, C3C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, B1-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylcarbonyloxy, C1-C6haloalkylcarbonyl, C2-C6alkenylcarbonyl or C1-C6alkoxycarbonyl; and B1 is as defined for formula I, is carried out analogously to known processes and comprises first of all oxidising a compound of formula III

[0100] to yield a compound of formula V

[0101] chlorinating or brominating that compound to form a compound of formula VIII

[0102] the radicals R11, R12 and W in the compounds of formulae III, V and VIII being as defined above and Hal in the compound of formula VIII being chlorine or bromine, subsequently converting the compound of formula VIII with a suitable sulfur reagent, for example thiourea, sodium hydrogen sulfide (NaSH) or phosphorus pentasulfide (P2S5), in the presence of a solvent into a compound of formula Ic

[0103] and reacting that compound in the presence of a solvent and a base with a compound of formula XI

R14—L (XI),

[0104] wherein R14 is C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, B1-C1-C6alkyl or C1-C6alkylcarbonyl; B1 is as defined above; and L is a leaving group (Reaction Scheme 2).

[0105] The process according to the invention for the preparation of a compound of formula I

[0106] wherein R11, R12, R13 and W are as defined for formula I and X1 is S is carried out analogously to known processes and comprises treating a compound of formula I

[0107] wherein R11, R12, R13 and W are as defined above and X1 is O, with a sulfur reagent in an inert solvent.

[0108] The preparation of compounds of formula I wherein X1 is O or S; and R13 is C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl,

[0109] (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2— or (B1-C1-C5haloalkyl)-CH2—; and B1 is as defined for formula I is illustrated in the following Reaction Scheme 1.

[0110] The pyridine N-oxides of formula V (Reaction Scheme 1) can be prepared according to known methods (e.g. Org. Synth. 4, 828 (1963); ibid. 3, 619 (1955); U.S. Pat. No. 3,047,579; and B. Iddon and H. Suschitzky in “Polychloroaromatic Compounds”, Editor H. Suschitzky, Plenum Press, London 1974, page 197), advantageously by reaction of a pyridine derivative of formula III with an oxidising agent, such as, for example, an organic peracid, for example m-chloroperbenzoic acid (MCPBA), peracetic acid or pertrifluoroacetic acid, or aqueous hydrogen peroxide solution or hydrogen peroxide-urea adduct together with a carboxylic acid and/or a carboxylic acid anhydride, or an inorganic peracid, for example pertungstic acid. Solvents suitable for that reaction are, for example, water, organic acids, for example acetic acid and trifluoroacetic acid, halogenated hydrocarbons, for example dichloromethane and 1,2-dichloroethane, esters, for example ethyl acetate, ethers, for example tetrahydrofuran and dioxane, or mixtures of those solvents. The reaction temperatures are generally in the range from −20° C. to 100° C., depending on the solvent or mixture of solvents used.

[0111] The 6-hydroxypyridine derivatives of formula II can be prepared according to known methods (e.g. Quart. Rev. 10, 395 (1956); J. Am. Chem. Soc. 85, 958 (1963); and J. Org. Chem. 26, 428 (1961)), advantageously by rearrangement of the pyridine N-oxides of formula V in the presence of an anhydride, for example acetic anhydride, trifluoroacetic anhydride or methanesulfonic anhydride, in a suitable inert solvent, such as, for example, a halogenated hydrocarbon, for example dichloromethane or 1,2-dichloroethane, an amide, for example N,N-dimethylformamide or 1-methyl-2-pyrrolidone (NMP), and, where appropriate, in the presence of sodium acetate. The reaction temperatures are generally in the range from −30° C. to 80° C.

[0112] The 6-O-acyl- or 6-O-sulfonyl-pyridines formed first can readily be hydrolysed, by aqueous working up of the reaction mixture, to form the desired 6-hydroxypyridines of formula II. Analogously to Tetrahedron 37, 187 (1981), as a further variant it is possible to use antimony pentachloride in the above rearrangement reaction.

[0113] The subsequent alkylation may be carried out according to known methods (e.g. Org. Prep. Proced. Int. 9, 5 (1977); J. Org. Chem. 35, 2517 (1970); ibid. 32, 4040 (1967); and Tetrahedron Lett. 36, 8917 (1995) as well as Preparation Examples P20 and P21), advantageously using an alkylation reagent of formula VI. The alkylation usually results in an isomeric mixture consisting of the compounds of formulae I (N-alkylation) and IV (O-alkylation).

[0114] Suitable solvents are, for example, alcohols, for example methanol, ethanol and isopropanol, amides, for example N,N-dimethylformamide (DMF) and 1-methyl-2-pyrrolidone (NMP), sulfoxides, for example dimethyl sulfoxide (DMSO), and sulfones, for example sulfolan, or mixtures of the above solvents with water, ethers, for example diethyl ether, tert-butyl methyl ether, dimethoxyethane (DME), dioxane and tetrahydrofuran (THF), esters, for example ethyl acetate, ketones, for example acetone and methyl ethyl ketone, and hydrocarbons, for example n-hexane, toluene and xylenes.

[0115] Suitable bases are organic and inorganic bases, for example alkali metal alcoholates, for example sodium methanolate, sodium ethanolate and potassium tert-butanolate, trialkylammonium hydroxides, trialkylammonium halides, for example triethylammonium iodide, alkali metal and alkaline earth metal hydrides, for example sodium hydride together with lithium bromide (2 equivalents), alkali metal carbonates, for example potassium carbonate, alkali metal hydroxides, for example sodium and potassium hydroxide, and also caesium fluoride.

[0116] The reaction temperatures for the alkylation are in the range from −20° C. to the reflux temperature of the solvent used, preferably from 0° C. to 50° C.

[0117] The isomers of formulae I and IV can readily be separated by means of silica gel chromatography or fractional crystallisation.

[0118] Optionally, the desired pyridone derivative of formula I separated from the secondary product of formula IV can readily be converted into the corresponding pyridinethione derivative (X1═S) according to known methods (e.g. Bull. Soc. Chim. Fr. 1953, 1001; and J. Am. Chem. Soc. 73, 3681 (1951)), for example with the aid of a suitable sulfur reagent, for example Lawesson's reagent or phosphorus pentasulfide in an inert solvent, such as, for example, a xylene, pyridine or sulfolan. The reaction temperatures are generally in the range from 20° C. to the boiling temperature of the solvent used.

[0119] The preparation of compounds of formula I wherein X1 is S; and R13 is hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, B1-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylcarbonyloxy, C1-C6haloalkylcarbonyl, C2-C6alkenylcarbonyl or C1-C6alkoxycarbonyl; and B1 is as defined for formula I is illustrated in the following Reaction Scheme 2.

[0120] The procedure for the preparation of pyridine N-oxides of formula V (Reaction Scheme 2) is analogous to that indicated under Reaction Scheme 1.

[0121] The pyridine N-oxides of formula V can be converted into the corresponding 6-chloro- or 6-bromo-pyridine derivatives of formula VIII analogously to known processes (e.g. Heterocycles 30, 875 (1990); Can. J. Chem. 31, 457 (1953); and J. Org. Chem. 19, 1633 (1954)), advantageously using a halogenating agent, for example phosphorus oxychloride, phosphorus oxybromide, sulfuryl chloride, thionyl chloride or phosphorus pentachioride in phosphorus oxychloride. The halogenation can generally be carried out at temperatures of from 20° C. to 100° C.

[0122] The reaction of the halopyridine N-oxides of formula VIII to form the compound of formula Ic can be effected analogously to known processes (e.g. U.S. Pat. Nos. 2,742,476, 2,809,971, J. Am. Chem. Soc. 72, 4362 (1950) and J. Chem. Soc. 1939, 1858), advantageously using a suitable sulfur reagent, such as, for example, hydrogen sulfide, sodium hydrogen sulfide or thiourea, in a solvent, such as, for example, water, an alcohol, for example ethanol, or a water/alcohol mixture, or an amide, for example N,N-dimethylformamide (DMF) or NMP. The reaction is generally carried out at temperatures of from −10° C. to 100° C.

[0123] The reaction of the compound of formula Ic with the reactive reagent of formula XI, wherein L is a leaving group, such as, for example, halogen, for example chlorine, bromine or iodine, CH3SO2O—,

[0124] or, in the case where R14 is C1-C6alkylcarbonyl and there is used as reactive reagent of formula XI the corresponding acid anhydride, C1-C6alkylcarbonyloxy, can be carried out analogously to known processes (e.g. Tetrahedron Lett. 31, 1965 (1990); Tetrahedron 1991, 7091; and J. Org. Chem. 54, 4330 (1989)). Advantageously, equimolar amounts of compound of formula Ic and reactive reagent of formula XI are reacted at temperatures of from 0° C. to 100° C. in the presence of a solvent and a base.

[0125] Suitable solvents include the familiar inert organic solvents, such as, for example, chlorinated hydrocarbons, for example dichloromethane, aromatic hydrocarbons, for example benzene, toluene and pyridine, ethers, for example dioxane and DME, amides, for example N,N-dimethylformamide and NMP, and sulfoxides, for example DMSO. Suitable bases include the known inorganic and organic bases, such as, for example, alkali metal and trialkylammonium hydroxides, for example sodium or potassium hydroxide and triethylammonium hydroxide, respectively, carbonates, for example sodium and potassium carbonate, and alcoholates, for example sodium ethanolate or potassium isopropanolate. The reaction may also, where appropriate, be carried out under phase transfer conditions. There may be used as phase transfer catalysts the customary quaternary ammonium salts, such as, for example tetraoctylammonium bromide and benzyltriethylammonium chloride. Under those conditions, a suitable organic solvent is any inert non-polar solvent, such as, for example, benzene or toluene.

[0126] The preparation of compounds of formula I wherein X1 is S; and R13 is C1-C6alkoxy-C1-C6-alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl,

[0127] (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2— or (B1-C1-C5haloalkyl)-CH2—; and B1 is as defined for formula I is illustrated in the following Reaction Scheme 3.

[0128] The conversion of the pyridone derivatives of formula I wherein R11, R12, R13 and W are as defined for formula I and X1 is O into the corresponding pyridinethione derivatives of formula I wherein X1 is S (Reaction Scheme 3) can be carried out analogously to known processes (e.g. J. Het. Chem. 25, 511 (1988); ibid. 22, 265 (1985); Bull. Soc. Chim. Fr. 1953, 1001; J. Prakt. Chem. 1988, 293; Chem. Ber. 62, 2732 (1929); Chem. Heterocycl. Compd. (Engl. Transl.) 1988, 658; Pharmazie 45, 731 (1990); and J. Prakt. Chem./Chem-Ztg 334, 119 (1992)), advantageously with the aid of a sulfur reagent such as, for example, P2S5 or Lawesson's reagent, in an organic solvent, such as, for example, an aromatic hydrocarbon, for example benzene, toluene, a xylene or pyridine, a halogenated aromatic hydrocarbon, for example dichlorobenzene, or an amide, for example DMF or NMP. The reaction temperatures are generally in the range from 20° C. to 200° C. depending on the solvent used.

[0129] The compounds lying within the scope of formula I wherein X1 and R13 together form a group ═N—Y— and Y is, for example, a bridge member —C(R31)(R32)—CH2— can be prepared analogously to known processes, as described, for example, in Sov. Prog. Chem. (Engl. Transl.) 42, 65 (1976); J. Chem. Soc., Perkin Trans 1 1976, 201; Justus Liebigs Ann. 1978, 1491; and Helv. Chim. Acta 73,1679 (1990).

[0130] The compounds lying within the scope of formula I wherein X1 and R13 together form a group ═N—Y— and Y is, for example, a bridge member —C(R34)═CH— can be prepared analogously to known processes, as described, for example, in Farmaco Ed. Sci. 37, 22 (1982); J. Chem. Res. (Miniprint) II, 3368 (1986); and J. Chem. Soc., Perkin Trans 1 1987, 1159.

[0131] Taking into consideration the chemical properties of the pyridyl or pyridonyl moiety, as the case may be, all other compounds within the scope of formula I can readily be prepared, in terms of the construction of the pyrazole rings, in a manner analogous to that described in Preparation Examples P1 to P21, or as described, for example, in “Methoden der Organ-ischen Chemie” (Houben-Weyl), Volume E 8b, Georg Thieme Verlag Stuttgart, 1994, page 399 ff.; or in “Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings”, Editor R. H. Wiley, Interscience Publishers, John Wiley & Sons, New York, 1967, page 1 ff.; or as described in the patent specifications WO 96/01254 and WO 97/00246.

[0132] A large number of known standard processes are available for the preparation of the pyridine derivatives of formula III, the choice of a suitable process being governed by the properties (reactivities) of the substituents in the respective intermediates. A number of specimen examples are also given in Preparation Examples P1 to P16. For example, a compound of formula III

[0133] wherein W is a group

[0134] (W1); R1, R2, R11 and R12 are as defined for formula I; and R3 is hydrogen, halogen, C1-C4alkyl or C1-C4haloalkyl, can be prepared starting from, for example, a compound of formula XII

[0135] wherein R11 and R12 are as defined above, which is reacted in an alcohol of formula XIII

R8—OH (XIII),

[0136] wherein R8 is C1-C4alkyl, in the presence of a suitable palladium or nickel catalyst, such as, for example, palladium bis(triphenylphosphine) dichloride (PdCl2(PPh3)2) and a base, such as, for example, triethylamine, under carbon monoxide excess pressure, to form a compound of formula XIV

[0137] wherein R8, R11 and R12 are as defined above, which is subjected to acid or basic hydrolysis to form the corresponding carboxylic acid of formula XV

[0138] and converted with a carboxylic acid halogenating reagent, such as, for example, thionyl chloride, phosphorus pentachloride or oxalyl chloride, into the corresponding carboxylic acid halide of formula XVI

[0139] wherein R11 and R12 are as defined above and X2 is halogen, preferably chlorine, and that compound is reacted in a solvent, such as, for example, acetonitrile in the presence of an alkaline earth metal salt, preferably magnesium chloride, and a base, such as, for example, triethylamine, with the malonic acid mono ester · salt of formula XVII

[0140] wherein R3 is hydrogen, C1-C4alkyl or C1-C4haloalkyl; M1+ is an alkali metal ion, preferably a potassium ion; and R7 is C1-C4alkoxy, to yield the keto ester of formula XIX

[0141] wherein R3, R7, R11 and R12 are as defined above, and that compound is cyclised in a solvent, such as, for example, glacial acetic acid, with a compound of formula XX

NH2NH—R1 (XX),

[0142] wherein R1 is as defined for formula I, to yield a compound of formula XXI

[0143] wherein R1, R3, R11 and R12 are as defined above, and subsequently in accordance with standard methods the hydroxyl group is functionalised, especially freonised (Example P13), according to the definition of R2, and the pyrazole ring is optionally halogenated (R3 is halogen; Example P14) or oxidised to the corresponding pyridine N-oxide (Example P17). The compounds of formula XXII

[0144] wherein R1, R3, R5, R11 and R12 are as defined for formula I, are important intermediates for the preparation of compounds of formula III, especially compounds of formula III wherein W is a group W3; R5 is haloalkyl (Example P11); and R1, R3, R11 and R12 are as defined for formula I.

[0145] The compounds of formula XXII are prepared according to EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.

[0146] The compounds of formula XIX

[0147] wherein R11 and R12 are as defined for formula I; R3 is hydrogen, C1-C4alkyl or C1-C4-haloalkyl; and R7 is C1-C4alkoxy, C1- or C2-haloalkyl or C1-C4alkoxycarbonyl, are important intermediates for the preparation of compounds of formula I, especially compounds of formula I wherein W is a group

[0148] (W1); R1, R2, R11 and R12 are as defined for formula I; and R3 is hydrogen, halogen, C1-C4alkyl or C1-C4haloalkyl. The compounds of formula XXIII

[0149] wherein R11 and R12 are as defined for formula I; and R3 is hydrogen, halogen, C1-C4alkyl or C1-C4haloalkyl, are important intermediates for the preparation of compounds of formula Ia wherein Wa is a group W3a; R5 is hydrogen; and R1, R3, R11 and R12 are as defined for formula I (Example 8).

[0150] The compounds of formula XXIII are prepared according to EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92106962, WO 95/33728 and WO 96/01254.

[0151] The compounds of formula XXIV

[0152] wherein R11 and R12 are as defined for formula I; and R3 is hydrogen, C1-C4alkyl or C1-C4-haloalkyl, are important intermediates for the preparation of compounds of formula I wherein W is a group W3

[0153] W3); R3 is hydrogen, C1-C4alkyl or C1-C4haloalkyl; R5 is amino; and R1, R11 and R12 are as defined for formula I.

[0154] The compounds of formula XXIV are prepared according to EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.

[0155] A large number of known standard processes are available for the preparation of the pyridonylpyrazoles of formula I substituted at the pyridone ring, the choice of a suitable preparation process being governed by the properties (reactivities) of the substituents in the respective intermediates.

[0156] A number of specimen examples are also given in Preparation Examples P19 to P24. The compound of formula XII, and the starting compounds 2,5dichloro-3-fluoropyridine, 2,3-dichloro-5-trifluoromethylpyridine and 3,5-dichloro-2-acetylpyridine used in Preparation Examples P1, P2 and P9, are either known or can be prepared analogously to published processes.

[0157] The reagents of formulae VI and XI used in the Reaction Schemes 1, 2 and 3 are either known or can be prepared analogously to published processes.

[0158] All other compounds within the scope of formula I can readily be prepared, taking into consideration the respective chemical reactivities, analogously to the processes according to Preparation Examples P1 to P25, or analogously to the methods described in “Methoden der Organischen Chemie” (Houben-Weyl), volume E 8b, Georg Thieme Verlag Stuttgart, 1994, page 399 ff.; ibid, volume E7B, Georg Thieme Verlag Stuttgart, 1992, page 286 ff.; in “Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings”, Editor R. H. Wiley, Interscience Publishers, John Wiley & Sons, New York, 1967, page 1 ff.; or in “Comprehensive Heterocyclic Chemistry”, Editors A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford, 1987, or by derivatisation according to known standard methods as described, for example, in “Advanced Organic Chemistry, Third Edition, Editor J. March, John Wiley & Sons, New York, 1985; in “Comprehensive Organic Transformations”, Editor R. C. Larock, VCH Publishers, Inc., New York, 1989; or in “Comprehensive Organic Functional Group Transformations”, Editors A. R. Katritzky, O. Meth-Cohn, C. W. Rees, Pergamon Press, Oxford, 1995, or as described in the Patent Specifications EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.

[0159] The end products of formula I can be isolated in conventional manner by concentration or evaporation of the solvent and purified by recrystallisation or trituration of the solid residue in solvents in which they are not readily soluble, such as ethers, aromatic hydrocarbons or chlorinated hydrocarbons, by distillation or by means of column chromatography and a suitable eluant. The sequence in which it is advantageous for certain reactions to be carried out so as to avoid possible secondary reactions will also be familiar to the person skilled in the art. Unless the synthesis is specifically aimed at the isolation of pure isomers, the product may be obtained in the form of a mixture of two or more isomers. The isomers can be separated according to methods known per se.

[0160] For the use according to the invention of the compounds of formula I or of compositions comprising them, there come into consideration all methods of application customary in agriculture, for example pre-emergence application, post-emergence application and seed dressing, and also various methods and techniques such as, for example, the controlled release of active ingredient. For that purpose a solution of the active ingredient is applied to mineral granule carriers or polymerised granules (urea/formaldehyde) and dried. If required, it is also possible to apply a coating (coated granules), which allows the active ingredient to be released in metered amounts over a specific period of time.

[0161] The compounds of formula I may be used in unmodified form, that is to say as obtained in the synthesising process, but they are preferably formulated in customary manner together with the adjuvants conventionally employed in formulation technology, for example into emulsifiable concentrates, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules or microcapsules. Such formulations are described, for example, in WO 97/34485, pages 9 to 13. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, wetting, scattering or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.

[0162] The formulations, that is to say the compositions, preparations or mixtures comprising the compound (active ingredient) of formula I or at least one compound of formula I and, usually, one or more solid or liquid formulation adjuvants, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients with the formulation adjuvants, for example solvents or solid carriers. Surface-active compounds (surfactants) may also be used in addition in the preparation of the formulations. Examples of solvents and solid carriers are given, for example, in WO 97/34485, page 6.

[0163] Depending on the nature of the compound of formula I to be formulated, suitable surface-active compounds are non-ionic, cationic and/or anionic surfactants and surfactant mixtures having good emulsifying, dispersing and wetting properties. Examples of suitable anionic, non-ionic and cationic surfactants are listed, for example, in WO 97/34485, pages 7 and 8.

[0164] In addition, the surfactants conventionally employed in formulation technology, which are described in, inter alia, “McCutcheon's Detergents and Emulsifiers Annual” MC Publishing Corp., Ridgewood N.J., 1981, Stache, H., “Tensid-Taschenbuch”, Carl Hanser Verlag, Munich/Vienna 1981, and M. and J. Ash, “Encyclopedia of Surfactants”, Vol. I-III, Chemical Publishing Co., New York, 1980-81, are also suitable for the preparation of the herbicidal compositions according to the invention.

[0165] The herbicidal formulations generally contain from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of herbicide, from 1 to 99.9% by weight, especially from 5 to 99.8% by weight, of a solid or liquid formulation adjuvant, and from 0 to 25% by weight, especially from 0.1 to 25% by weight, of a surfactant. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations. The compositions may also comprise further ingredients, such as stabilisers, for example vegetable oils or epoxidised vegetable oils (epoxidised coconut oil, rape oil or soybean oil), anti-foams, for example silicone oil, preservatives, viscosity regulators, binders, tackifiers, and also fertilisers or other active ingredients.

[0166] The compounds of formula I can be used successfully either in the form of a mixture comprising the isomers IW1a and IW1b or in the form of pure isomer IW1a or IW1b, generally on plants or the locus thereof, at rates of application of from 0.001 to 4 kg/ha, especially from 0.005 to 2 kg/ha. The concentration required to achieve the desired effect can be determined by experiment. It is dependent on the nature of the action, the stage of development of the cultivated plant and of the weed and on the application (place, time, method) and may vary within wide limits as a function of those parameters.

[0167] The compounds of formula I and, generally, the isomers of formula Ia especially, are distinguished by herbicidal and growth-inhibiting properties, allowing them to be used in crops of useful plants, especially cereals, cotton, soybeans, sugar beet, sugar cane, plantation crops, rape, maize and rice, and also for non-selective weed control.

[0168] “Crops” is to be understood as meaning also crops that have been made tolerant to herbicides or classes of herbicides as a result of conventional methods of breeding or genetic techniques. The weeds to be controlled may be either monocotyledonous or dicotyledonous weeds, such as, for example, Stellaria, Nasturtium, Agrostis, Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Phaseolus, Echinochloa, Scirpus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum halepense, Rottboellia, Cyperus, Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum, Galium, Viola and Veronica.

[0169] The following Examples further illustrate but do not limit the invention.

PREPARATION EXAMPLES

Example P1:3-Fluoro-5-chloro-2-pyridinecarboxylic acid ethyl ester

[0170]

[0171] An autoclave is charged with 31.4 g of 2,5-dichloro-3-fluoropyridine, 400 ml of dry ethanol, 27.8 ml of triethylamine and 3.5 g of palladium bis(triphenylphosphine) dichloride (PdCl2(PPh3)2) and then a pressure of 180 bars is applied with carbon monoxide. The mixture is maintained at 90° C. for 4 days. After cooling and releasing the pressure, a further 3.5 g of PdCl2(PPh3)2 are added, a pressure of 130 bars is applied with carbon monoxide, and the mixture is maintained at 90° C. for 3 days, after which it is cooled to 25° C., the pressure is released and the mixture is discharged. After concentration in vacuo, absorption from ethyl acetate onto silica gel is carried out. The silica gel is applied to a flash chromatography column (silica gel) and then eluted with n-hexane/ethyl acetate 3/1. 24.3 g of the desired target compound having a melting point of 48-50° C. are obtained.

Example P2: 3-Chloro-5-trifluoromethyl-2-pyridinecarboxylic acid ethyl ester

[0172]

[0173] An autoclave is charged with 200 g of 2,3-dichloro-5-trifluoromethylpyridine, 1.85 liters of ethanol, 260 ml of triethylamine and 6.5 g of palladium bis(triphenylphosphine) dichloride (PdCl2(PPh3)2). At 25° C. a pressure of 110 bars is then applied with carbon monoxide and the mixture is maintained at 110° C. for 24 hours. After cooling to 25° C., the crude mixture is concentrated to a thick slurry, which is then partitioned between dilute sodium chloride solution and ethyl acetate. After extraction by shaking, and separation of the phases, the ethyl acetate phase is washed with water, dried over sodium sulfate and concentrated to dryness. The crude product is distilled under a high vacuum of 0.035 mbar. 200 g of the desired product are obtained in the form of a yellow oil having a boiling point of 67-70° C./0.035 mbar (yield 85% of the theoretical yield).

Example P3: 3-Chloro-5-trifluoromethyl-2-pyridinecarboxylic acid

[0174]

[0175] 423 g of 3-chloro-5-trifluoromethyl-2-pyridinecarboxylic acid ethyl ester (Example P2) is placed in a mixture of 800 ml of water and 160 ml of ethanol. 800 ml of a 2N sodium hydroxide solution are added dropwise at below 35° C. After 3 hours, the mixture is washed twice with dichloromethane and then rendered acidic with excess concentrated hydrochloric acid while cooling with an ice-bath. The resulting slurry is filtered, washed with water and dried in vacuo. 318 g of the desired product are obtained in the form of a white solid having a melting point of 135° C. (decomposition).

Example P4: 3-Fluoro-5-chloropyridine-2-carboxylic acid

[0176]

[0177] 70 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid ethyl ester (Example P1) are placed in 105 ml of dimethyl sulfoxide (DMSO). 230 ml of a 2N sodium hydroxide solution are added dropwise at 40° C. over a period of 30 minutes. The resulting yellow suspension is introduced into a mixture of 2 liters of ice-water and 400 ml of 2N hydrochloric acid. After subsequently stirring for 20 minutes, the mixture is filtered and the filtration residue is washed twice with water. 56.4 g of the desired target compound are obtained in the form of a white solid.

[0178]

1
H-NMR (DMSO-D6): 13.79 ppm (broad signal, 1H); 8.60 ppm (d, 1H); 8.27 ppm (dxd, 1H).

Example P5: 3-Chloro-5-trifluoromethyl-2-pyridinecarboxylic acid chloride

[0179]

[0180] 89.3 g of 3-chloro-5-trifluoromethyl-2-pyridinecarboxylic acid (Example P3) are slowly heated to reflux with 60 ml of thionyl chloride and the mixture is then stirred at that temperature for 4 hours, after which it is cooled to 25° C. and concentrated to dryness in vacuo. Twice, toluene is added and the mixture is again concentrated to dryness. 94.0 g of the desired product are obtained in the form of a yellow residue.

[0181]

1
H-NMR (CDCl3): 8.91 ppm (d, 1H); 8.13 ppm (d, 1H).

Example P6: 3-Fluoro-5-chloro-2-pyridinecarboxylic acid chloride

[0182]

[0183] 71.38 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid (Example P4) are placed in a round-bottomed flask and heated to 90° C. 59 ml of thionyl chloride are added dropwise from a dropping funnel over a period of 30 minutes, and the gas formed is introduced into sodium hydroxide solution. Stirring is then carried out for 5 hours at 100° C., after which the thionyl chloride is distilled off at normal pressure. After the addition of 50 ml of dry toluene, 20 ml thereof are distilled off. The resulting solution is poured into 200 ml of n-hexane and stirred overnight. After cooling in an ice-bath, the mixture is filtered and the filtration residue is washed twice with n-hexane. 68.7 g of the desired compound are obtained in the form of a brown solid.

[0184]

1
H-NMR (CDCl3): 8.60 ppm (d, 1H); 7.69 ppm (dxd, 1H).

Example P7: 5-Chloro-3-fluoro-2-pyridinecarbaldehyde

[0185]

[0186] 110 g of 5-chloro-3-fluoro-2-pyridinecarboxylic acid ethyl ester (Example P1) are dissolved in 180 ml of tert-butanol. 27.4 g of sodium borohydride (NaBH4, 97%) are added to the slightly brown solution, in the course of which a weak exothermic reaction is observed. By cooling occasionally with an ice-bath, the internal temperature is maintained below 30° C. The exothermic reaction has subsided after 1½ hours. The reaction mixture is then stirred overnight at 22° C. and subsequently cold water is added slowly, while stirring well. Extraction is carried out with diethyl ether, and the combined ethereal phases are washed with dilute sodium hydrogen carbonate solution and brine, dried over sodium sulfate, filtered and concentrated in vacuo. 58 g of a tacky solid are isolated. After digestion with n-hexane/diethyl ether 50/1 and drying in vacuo, 48.6 g of a yellow solid are obtained having an Rf value on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) of 0.40.

[0187]

160
.7 g of active manganese(IV) oxide (90%) are added to 22.4 g of the alcohol obtained as intermediate in 300 ml of methylene chloride, and a slight exothermic reaction can be detected. After stirring for 3 hours, the mixture is filtered over Hyflo and the filtrate is concentrated in vacuo. The residue (20 g) is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)). In that manner 11.0 g of the desired target compound are obtained in the form of a white solid having a melting point of 70-72° C. The Rf value of the product on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 3/1 (v/v)) is 0.61.

Example P8: 3-Chloro-5-trifluoromethyl-2-acetylpyridine

[0188]

[0189] 55.3 ml of malonic acid dimethyl ester are stirred with 129 ml of triethylamine and 24.9 g of anhydrous magnesium chloride for 2 hours in 250 ml of dry toluene. With the exothermic reaction, the reaction temperature rises to 45° C. At 25° C. 94.0 g of 3-chloro-5-trifluoromethyl-2-pyridinecarboxylic acid chloride (Example P5) in 150 ml of toluene are added dropwise thereto and the reaction mixture is further stirred overnight. An excess of concentrated hydrochloric acid is then added dropwise, and the mixture is diluted with water and extracted with ethyl acetate. The organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to yield 142 g of a red oil which is slowly introduced into a mixture of 20 ml of water and 400 ml of dimethyl sulfoxide, which is under gentle reflux by means of an oil bath of a temperature of 150° C. When the evolution of gas can no longer be detected, water is added and extraction is carried out with ether. The combined ethereal phases are washed with water, dried over sodium sulfate, filtered and concentrated. The residue is purified by means of column chromatography (silica gel; eluant: n-hexane/ethyl acetate 15/1 (v/v)), yielding 61 g of the desired product in the form of a yellow oil (70% of the theoretical yield).

[0190]

1
H-NMR (CDCl3): 8.81 ppm (d, 1H); 8.05 ppm (d, 1H); 2.72 ppm (s, 3H).

Example P9: 1-(3-Chloro-5-trifluoromethyl-2-pyridyl)-3-dimethylamino-2-propen-1-one

[0191]

[0192] 5.0 g of 3-chloro-5-trifluoromethyl-2-acetylpyridine (Example P8) are introduced into 30 ml of toluene and 3.60 ml of N,N-dimethylformamide-dimethylacetal are added. The resulting yellow solution is stirred overnight at 100° C. After cooling to 25° C., the mixture is concentrated to dryness in vacuo, yielding 6.17 g of the desired target compound in the form of a dark-yellow oil which later solidifies.

[0193]

1
H-NMR (CDCl3): 8.74 ppm (d, 1H); 7.98 ppm (d, 1H); 7.92 ppm (broad signal, 1H); 5.54 ppm (broad d, 1H); 3.17 ppm (broad signal, 3H); 2.94 ppm (broad signal, 3H).

Example P10: 3-(3.5-Dichloro-2-pyridyl)-5-trifluoromethyl-[1H]-pyrazole

[0194]

[0195] 15.8 g of 3,5-dichloro-2-acetylpyridine are introduced together with 12.0 ml of trifluoroethyl acetate into 125 ml of absolute ether. With stirring, the mixture is cooled using an ice-bath and 46.6 ml of a 21% sodium ethanolate solution in ethanol are added dropwise. The ice-bath is then removed and the mixture is subsequently stirred overnight at 25° C. After cooling the reaction mixture in an ice-bath and adding dropwise 7.5 ml of glacial acetic acid, the mixture is concentrated in vacuo. 39.0 g of 1-(3,5-dichloro-2-pyridyl)-3-trifluoromethyl-propane-3-dione are obtained, which can be used directly for the following cyclisation step.

[0196] 39.0 g of 1-(3,5-dichloro-2-pyridyl)-3-trifluoromethylpropane-1,3-dione

[0197] are introduced into ethanol and 4.85 ml of hydrazine hydrate are slowly added. The reaction mixture is then heated at reflux with stirring. After one hour, the mixture is concentrated to dryness in vacuo and the residue is partitioned between dilute sodium hydrogen carbonate solution and ethyl acetate. After extraction by shaking, and separation of the phases, the organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. 22.25 g of a yellow oil are obtained, which is purified by means of flash chromatgraphy (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)) to yield 15.0 g of the desired product in the form of a yellow solid.

[0198]

1
H-NMR (DMSO-D6): 8.81 ppm (m, 1H); 8.64 ppm (m, 1H); 8.26 ppm (m, 1H); 7.45 ppm (broad signal, 1H).

Example P11: 3-(3,5-Dichloro-2-pyridyl)-5-trifluoromethyl-1-methyl-[1H]-pyrazole and 5-(3,5-dichloro-2-pyridyl)-3-trifluoromethyl-1-methyl-[1H]-pyrazole

[0199]

[0200] 8.88 g of 3-(3,5-dichloro-2-pyridyl)-5-trifluoromethyl-[1H]-pyrazole (Example P10) are introduced into 35 ml of N-methylpyrrolidone. After the addition of 13.0 g of potassium carbonate, the mixture is stirred and heated to 55° C. 2.36 ml of methyl iodide in 5.0 ml of N-methylpyrrolidone are then slowly added dropwise. After subsequently stirring for 2 hours, diethyl ether and water are added, the mixture is extracted by shaking and the organic phase is separated off. The separated ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product is purified by means of flash chromatography (silica gel; eluant: toluene/ethyl acetate 100/1). First of all 3.96 g of the 5-pyridylpyrazole isomer (yield 42%) are isolated in the form of a yellow oil and then 1.96 g of the 3-pyridylpyrazole (yield 21%) are isolated in the form of a yellow solid. The Rf values of the 3- and 5-pyridylpyrazole isomers on silica gel 60 F254 using toluene/ethyl acetate 30/1 as eluant (UV) are:

[0201] Rf value of 5-pyridylpyrazole: 0.50

[0202] Rf value of 3-pyridylpyrazole: 0.35

Example P12: 3-(3,5-Dichloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole

[0203]

[0204] 2.0 g of 3-(3,5-dichloro-2-pyridyl)-5-trifluoromethyl-1-methyl-[1H]-pyrazole (Example P11) are introduced into glacial acetic acid at 40° C. and, with stirring, chlorine gas is slowly passed over the solution. The reaction can be monitored analytically by means of thin-layer chromatography (silica gel 60 F254, eluant: n-hexane/ethyl acetate 4/1, UV). Once starting material can no longer be detected, glacial acetic acid is removed in vacuo and the residue is partitioned between dilute aqueous sodium hydroxide solution and ethyl acetate. After extraction by shaking, the separated organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated. The yellow oil is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 5/1). 1.6 g of of the desired compound are obtained in the form of a yellow oil (70% of the theoretical yield).

[0205]

1
H-NMR (DMSO-D6): 8.80 ppm (d, 1H); 8.48 ppm (d, 1H); 4.11 ppm (s, 3H).

[0206] The 5-pyridylpyrazole isomer is obtained in an analogous manner in a 90% yield (crude).

[0207]

1
H-NMR (CDCl3): 8.66 ppm (d, 1H); 7.95 ppm (d, 1H); 3.83 ppm (s, 3H).

Example P13: 3-(3-Fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole

[0208]

[0209] 110.6 g of malonic acid monomethyl ester · potassium salt are introduced into 500 ml of absolute acetonitrile. With stirring, the mixture is cooled in an ice-bath and 109 ml of triethylamine are added dropwise. 84.3 g of anhydrous magnesium chloride are then added. A slight exothermic reaction is observed. After removal of the icebath, the mixture is stirred for 2 hours at 25° C. After cooling again in an ice-bath, 68.7 g of 3-fluoro-5-chloro-2-pyridine-carboxylic acid chloride (Example P6) are added in several portions and 300 ml of absolute acetonitrile are added. A thick slurry gradually forms. The cooling bath is removed and the slurry is then stirred for 5 hours. The reaction mixture is subsequently poured into 3 liters of ice-water and 200 ml of concentrated hydrochloric acid, and then stirred for 15 minutes and extracted with ethyl acetate. The organic phase is washed with water and brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuo. 110 g of a brown oil are obtained, which is used directly for the next reaction step.

[0210] For that reaction step, the brown oil obtained above is introduced at 25° C. into a solution of 20.5 ml of methyl hydrazine in 300 ml of glacial acetic acid and then stirred for 2 hours at 85° C. After the resulting brown suspension has been cooled to 25° C. it is introduced in portions into 2.5 liters of ice-water, stirred for 1 hour, filtered and washed with water and n-hexane. After drying at 60° C. in vacuo, 65.8 g of the desired title compound having a melting point of 195-199° C. are obtained.

Example P14: 3-(3-Fluoro-5-chloro-2-pyridyl)-5-difluoromethoxy-1-methyl-[1H]-pyrazole

[0211]

[0212] 46.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) and 84 g of potassium carbonate are introduced into 250 ml of dry dimethylformamide and heated to 85° C. While stirring well, Freon 22 (chlorodifluoromethane) is then introduced for a period of 2 hours. TLC analysis of a worked-up sample (silica gel 60 F254; eluant: n-hexane/ethyl acetate/glacial acetic acid 20/20/1, UV) shows that there is no starting material present. The reaction mixture is partitioned between water and diethyl ether (foaming occurs on the addition of water). After extraction by shaking, and separation of the phases, the ethereal phase is washed twice with water and once with brine. After drying the organic phase over sodium sulfate and filtration, concentration in vacuo is carried out and the residue is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 22.0 g of the desired title compound are obtained in the form of a light-yellow solid.

[0213]

1
H-NMR (CDCl3): 8.51 ppm (broad signal, 1H); 7.56 ppm (dxd, 1H); 6.61 ppm (t, 1H); 6.53 ppm (d, 1H); 3.89 ppm (s, 3H).

Example P15: 3-(3-Fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole

[0214]

[0215] 17.92 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P14) are introduced into 60 ml of glacial acetic acid together with 10.6 g of sodium acetate. With stirring, the mixture is heated to 60° C. and a saturated solution of chlorine in glacial acetic acid is added until TLC analysis of a worked-up sample shows that the reaction is complete (silica gel 60 F254; eluant: n-hexane/ethyl acetate 2/1; UV; Rf value of the starting material 0.34; Rf value of the product 0.48). The mixture is then concentrated to dryness in vacuo and the residue obtained is partitioned between sodium hydrogen carbonate solution and ethyl acetate. The organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness by evaporation in vacuo. 19.8 g of the desired target compound (pure according to TLC) having a melting point of 95-96° C. are obtained.

Example P16: 3-(3-Fluoro-5-chloro-2-pyridyl)-4-formyl-5-difluoromethoxy-1-methyl-[1H]-pyrazole

[0216]

[0217] With cooling in an ice-bath, 2.41 ml of phosphorus oxychloride are introduced into 5 ml of N,N-dimethylformamide and the mixture is then stirred for 2 hours at 25° C. The mixture is then added dropwise at 80° C. to 5.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) in 15 ml of N,N-dimethylformamide over a period of 30 minutes. After subsequently stirring for 1.5 hours at 80° C., the mixture is cooled to 25° C. and ice and then water are added and extraction is carried out with diethyl ether. The organic phase is washed with water and dried over sodium sulfate to yield 1.1 g of a yellow solid as intermediate. The solid is introduced together with 1.72 g of pulverised anhydrous potassium carbonate into 10 ml of dry N,N-dimethylformamide. While stirring well, the mixture is heated to 75° C. and freon 22 (CHCIF2) is slowly introduced for a period of 7 hours. The mixture is then cooled to 25° C. and taken up in diethyl ether. The ethereal phase is washed with water and then with brine, dried over sodium sulfate, filtered and concentrated. 1.50 g of crude product are obtained in the form of a brown solid, which is purified using a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)). In that manner 0.14 g of the desired target compound is obtained in the form of a yellow solid having a melting point of 111-116° C.

Example P17: 3-(3-Fluoro-5-chloro-2-pyridyl)-4-difluoromethyl-5-difluoromethoxy-1-methyl-[1H]-pyrazole

[0218]

[0219] 0.13 g of 3-(3-fluoro-5-chloro-2-pyridyl)-4-formyl-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P16) is introduced into 3.0 ml of dry 1,2-dichlorethane. With stirring, 0.11 ml of diethylamino-sulfur trifluoride (DAST is added dropwise using a syringe, the reaction mixture taking on a dark colour. The mixture is then stirred for 1 hour at 50° C. The reaction solution is cooled to 25° C. and applied directly to a flash chromatography column (silica gel) and eluted with n-hexane/ethyl acetate 5/1 (v/v). 0.07 g of the desired compound is obtained in the form of a light-yellow oil having a melting point of 79-81° C.

Example P18: 3-(3-Fluoro-5-chloro-2-pyridyl)-5-bromo-1-methyl-[1H]-pyrazole

[0220]

[0221]

20
.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) are introduced into 80 ml of tetrachloroethane. A total of 25.2 g of phosphorus oxybromide (POBr3) is added in portions to the brown suspension. The mixture is then stirred for 2 hours at an internal temperature of 130° C., after which it is cooled and, with cooling with an ice-bath, 150 ml of a 2M sodium hydroxide solution are added dropwise. After the addition of diethyl ether and separation of the phases, the organic phase is washed in succession with water, dilute hydrochloric acid and brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuc. 19.94 g of a brown solid (crude product) are obtained, which is purified by means of digestion with 50 ml of n-hexane. 12.65 g of the desired compound are obtained in the form of a brown solid having a melting point of 110-111° C.

Example P19: 5-(5-Chloro-3-fluoro-2-pyridyl)-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester

[0222]

[0223] 5.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-bromo-1-methyl-[1H]-pyrazole (Example P18) are introduced into an autoclave together with 7.2 ml of triethylamine, 0.48 g of bis-triphenyl-phosphinepalladium dichloride (PdCl2(PPh3)2) and 70 ml of absolute ethanol. At 22° C. a pressure of 100 bar is applied with carbon monoxide and the reaction mixture is maintained at 100° C. for 48 hours. In the meantime a further 0.48 g of bis-triphenylphosphinepalladium dichloride is added, and the mixture is then cooled to 22° C. and the pressure is released. The reaction mixture is filtered over Hyflo and, after evaporating off the ethanol, taken up in ethyl acetate. The ethyl acetate phase is washed with dilute hydrochloric acid and then with brine, dried over sodium sulfate, filtered and finally concentrated to dryness in vacuc. 3.17 g of a brown solid are obtained, which is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 2.31 g of the desired title compound are obtained in the form of a light-yellow solid having a melting point of 117-118° C.

Example P20: 5-(5-Chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester

[0224]

[0225]

22
.9 g of 5-(5-chloro-3-fluoro-2-pyridyl)-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester (Example P19) are introduced together with 19.9 g of sodium acetate into 300 ml of glacial acetic acid at a temperature of 65° C. With stirring, 6.3 g of chlorine gas are passed over the solution at that temperature in the course of 1 hour. The reaction mixture is then poured into 2.5 liters of ice-water and subsequently stirred for 20 minutes. The resulting precipitate is filtered off, washed with ice-water and then dried in vacuo at 50° C. 24.4 g of the desired title compound are obtained in the form of a yellow solid having a melting point of 77-79° C.

Example P21: 5-(5-Chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid

[0226]

[0227] 11.0 g of 5(5-chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester (Example P20) are introduced into 60 ml of dimethyl sulfoxide at 22° C. With stirring, 25.9 ml of a 2N aqueous sodium hydroxide solution are added dropwise, in the course of which an exothermic reaction can be detected. After subsequently stirring for one hour, TLC analysis of a sample shows that all the starting material has reacted. The reaction mixture is introduced into 2 liters of ice-cold dilute hydrochloric acid, then stirred for 15 minutes and filtered over a paper filter. The filtration residue is washed with cold water and, after drying overnight at 60° C. in vacuo, 8.7 g of the desired title compound having a melting point of 230° C. (decomposition) are obtained.

[0228] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.75; and the Rf value of the desired title compound is 0.36.

Example P22: 3-(3-Fluoro-5-chloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[H]-pyrazole

[0229]

[0230] 8.63 g of 5-(5-chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid (Example P21) are introduced into a fluorination unit with 27 g of hydrogen fluoride (HF), 16.2 g of sulfur tetrafluoride (SF4) and 270 ml of methylene chloride. The mixture is maintained at 80° C. for 5 hours. It is then cooled to 22° C. and the SF4 is removed by way of a gas destroying unit (argon stream) and the HF is removed using a water-jet vacuum. After the addition of methylene chloride, the reaction mixture is extracted three times with ice-water, and the organic phase is dried over sodium sulfate and then concentrated to dryness in vacuo together with 40 g of silica gel. After applying the silica gel to a flash chromatography column, elution is carried out with an n-hexane/ethyl acetate 5/1 (v/v) mixture. 5.48 g of the desired title compound are obtained in the form of a beige solid having a melting point of 76-78° C.

Example P23: 3-(5,6-Dichloro-2-pyridyl)- and 3-(4,5-dichloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole (isomers A and B)

[0231]

[0232] 20 ml of phosphorus oxychloride are heated to 90° C. With stirring, 10.37 g of 3-(5-chloro-2-pyridyl-N-oxide)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole (Example P25) are introduced in several portions at that temperature and the mixture is then stirred for 1 hour at 90° C. The phosphorus oxychloride is then evaporated off in vacuo, the residue is taken up in diethyl ether and the ethereal phase is subsequently washed in succession with water, 0.5M sodium hydroxide solution and brine. After drying over sodium sulfate and filtering, concentration in vacuo is carried out and the residue obtained (8.93 g) is purified by column chromatography (silica gel; eluant: n-hexane/ethyl acetate 10/1). First 0.57 g of isomer B and then 5.11 g of isomer A are isolated in the form of a white solid.

[0233] On silica gel 60 F254 using the eluant n-hexane/ethyl acetate 4/1 (v/v), the Rf value of isomer A is 0.31 and the Rf value of isomer B is 0.41.

[0234] The treatment of 6.3 g of 3-(5-chloro-2-pyridyl-N-oxide)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole (Example P25) for 1 hour at 90° C. with 6.3 g of phosphorus pentachloride in 20 ml of phosphorus oxychloride yields, after working up as above, 4.36 g of isomer A and 1.01 g of isomer B.

Example P24: 3-(3-Fluoro-5.6-dichloro-2-pyridyl-N-oxide)4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole

[0235]

[0236] 1.5 g of 3-(3-fluoro-5,6-dichloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole are dissolved in 10 ml of 1,2-dichloroethane and 0.5 g of hydrogen peroxide/urea adduct is added. With cooling in an ice-bath, 0.66 ml of trifluoroacetic anhydride is then metered in using a syringe and the mixture is stirred at 22° C. for 3 hours. According to TLC analysis there is only partial reaction of the starting material. Consequently, 0.5 g of hydrogen peroxide/urea adduct and 0.66 ml of trifluoroacetic anhydride are added to the reaction mixture one after the other, in the manner described above, four times, followed each time by stirring for 3 hours at 22° C., in the course of which a yellow suspension is formed which is taken up in ethyl acetate. The organic phase is washed in succession with 1N sodium hydroxide solution, water and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product is purified by means of flash chromatography (silica gel; eluant: hexane/ethyl acetate 3/2). 0.25 g of the desired product is obtained in the form of yellow crystals having a melting point of 114-118° C.

Example P25: 3-(5-Chloro-2-pyridyl-N-oxide)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole

[0237]

[0238] 6.82 g of 3-(5-chloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole are introduced into 30 ml of methylene chloride at 250° C. With stirring, 7.23 g of m-chloroperbenzoic acid are added. After 48 hours a further 2.50 g of m-chloroperbenzoic acid are added. After a further 24 hours the reaction mixture is taken up in ethyl acetate and extracted twice with dilute sodium hydroxide solution, then washed with brine, dried over sodium sulfate and concentrated. Chromatography is then carried out (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 6.31 g of the desired compound are isolated in the form of a white solid.

[0239]

1
H-NMR (DMSO-D6): 8.75 ppm (d, 1H); 7.66 ppm (d, 1H); 7.59 ppm (dxd, 1H); 4.08 ppm (s, 3H).

[0240] Starting from the 5-(5-chloro-2-pyridyl)-4-chloro-3-trifluoromethyl-1-methyl-[1H]-pyrazole isomer, the 5-(5-chloro-2-pyridyl-N-oxide)-4-chloro-3-trifluoromethyl-1-methyl-[1H]-pyrazole isomer can be obtained in a yield of 70%.

Example P26: 3-(3-Fluoro-5-chloro-2-pyridyl-N-oxide)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole

[0241]

[0242] 0.57 g of 3-(3-fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P15) is introduced into 5 ml of methylene chloride and 0.63 g of a 55% m-chloroperbenzoic acid is added. After stirring for 4 days at 25° C., the crude mixture is taken up in ethyl acetate and washed in succession with sodium hydrogen carbonate solution, water and brine. After drying over sodium sulfate and filtering, concentration is carried out and the residue is purified by means of flash chromatography. 0.45 g of the desired target compound is obtained in the form of a white solid having a melting point of 115-120° C.

Example P27: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol

[0243]

[0244] 1.0 g of 3-(3-fluoro-5-chloro-2-pyridyl-N-oxide)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P26) is introduced into 12 ml of dry N,N-dimethylformamide. With stirring and cooling with an ice-bath, 4.2 ml of trifluoroacetic anhydride are added dropwise from a syringe and the mixture is subsequently stirred overnight at 25° C. The mixture is then concentrated by evaporation in vacuo and the residue is partitioned between diethyl ether and water. After extraction by shaking, and separation of the phases, the ethereal phase is washed with dilute aqueous sodium hydrogen carbonate soolution and brine, dried over sodium sulfate, filtered and concentrated. 1.23 g of a yellow oil are obtained, which is purified using a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 2/3 (v/v) and 1% glacial acetic acid). 0.59 g of the desired compound is obtained in the form of a yellow solid having a melting point of 126-128° C.

Example P28: 5-(5-Chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid

[0245]

[0246] 6.75 g of 5-(5-chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid ethyl ester are suspended in 40 ml of dimethyl sulfoxide. With occasional cooling in an ice-bath (internal temperature <30° C.), 14.3 ml of a 2N sodium hydroxide solution are added dropwise. The thick, yellowish-brown suspension is stirred at 22° C. for 2 hours. The suspension is then introduced into ice-water and adjusted to pH 1 with 2N hydrochloric acid. The resulting slurry is filtered, washed well with cold water and then dried in vacuo at 60° C. 5.97 g of the desired title compound are obtained in the form of a beige solid having a melting point of 194-196° C.

Example P29: 5-(5-Chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid amide

[0247]

[0248] 3.0 g of 5-(5chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid (Example P28) are introduced into 25 ml of 1,2-dichloroethane and, at 80° C., a total of 1.21 ml of thionyl chloride is added and the mixture is subsequently stirred for 5 hours at 80° C. The mixture is concentrated in vacuo, 20 ml of carbon tetrachloride are added three times and each time the mixture is concentrated to dryness by evaporation.

[0249] The resulting acid chloride is introduced into 35 ml of tetrahydrofuran. With cooling in an ice-bath, ammonia gas is introduced. A brown precipitate forms. Stirring is carried out overnight at 22° C. The resulting suspension is introduced into five times its volume of ice-water. After then stirring briefly, filtration is carried out and the filtration residue is subsequently washed with cold water and dried in vacuo at 60° C. 2.0 g of the desired title compound are obtained in the form of a brown solid having a melting point of 201-204° C.

Example P30: 5-(5-Chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carbonitrile

[0250]

[0251] 1.82 g of 5-(5-chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid amide (Example P29) are suspended in 20 ml of dioxane. With cooling with an ice-bath, first 1.65 ml of pyridine and then 1.44 ml of trifluoroacetic anhydride are added. After 5 minutes the cooling bath is removed and the mixture is subsequently stirred for 1 hour at 22° C. The brownish-red solution is diluted with diethyl ether and washed with 1N hydrochloric acid and then with brine. The mixture is dried over sodium sulfate and filtered and then directly concentrated with twice the amount of silica gel. After application of the silica gel to a flash chromatography column, elution is carried out with n-hexane/ethyl acetate 4/1 (v/v). 1.60 g of the desired title compound are obtained in the form of a beige solid having a melting point of 144-146° C.

Example P31: 3-(3-Fluoro-5-methyl-2-pyridyl)-4-chloro-5difluoromethoxy-1-methyl-[1H]-pyrazole

[0252]

[0253] 2.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P15) are introduced into 6 ml of absolute dioxane. In order to remove the oxygen, gentle evacuation is carried out three times (waterjet pump) and the mixture is gassed with argon. 6.4 ml of a 2M solution of trimethylaluminium in toluene and 0.10 g of tetrakis-triphenylphosphinepalladium (Pd(PPh3)4) are added thereto. The mixture is heated to 90° C., with stirring, in an argon atmosphere. The next day the mixture is cooled to 22° C., a further 0.10 g of Pd(PPh3)4 and 6.4 ml of a 2M solution of trimethylaluminium in toluene are added and the mixture is stirred at 110° C. After 4 hours, TLC analysis of a worked-up sample shows that all the starting material has reacted. The reaction mixture is introduced carefully into cold, dilute hydrochloric acid and is then extracted with ethyl acetate. The combined organic phases are washed with brine, dried over sodium sulfate, filtered and concentrated by evaporation in vacuo. The crude product obtained is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 1.36 g of the desired compound are obtained in the form of a yellow oil, which slowly crystallises; melting point 41-42° C.

[0254] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 2/1 (v/v)) is 0.37 and the Rf value of the title compound is 0.15.

Example P32: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-hydroxy-[1H]-pyridin-2-one

[0255]

[0256] 0.50 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) is introduced into 4 ml of 1,2-dichloroethane, and 0.15 g of hydrogen peroxide/urea adduct (30%) and 0.22 ml of trifluoroacetic anhydride are added. The mixture is stirred overnight at 22° C. and then a further 0.15 g of hydrogen peroxide/urea adduct is added together with 0.22 ml of trifluoroacetic anhydride. The mixture is subsequently stirred for 5 hours and then partitioned between ethyl acetate and dilute hydrochloric acid. The separated organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. 0.55 g of the desired compound is obtained in the form of a yellow resinous precipitate (crude product).

[0257]

1
H-NMR (CDCl3): 7.65 ppm (d, 1H); 6.74 ppm (t, 1H); 3.90 ppm (s, 3H).

Example P33: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methoxy-[1H]-pyridin-2-one

[0258]

[0259] 0.20 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-hydroxy-[1H]-pyridin-2-one (Example P32) is introduced into 2 ml of N-methylpyrrolidone (NMP) at 22° C. and 0.16 g of anhydrous potassium carbonate is added. With stirring, 0.10 g of methyl iodide in 0.5 ml of NMP is then added dropwise. The reaction mixture is stirred for 2 hours at 22° C. and then partitioned between 20 ml of water and diethyl ether. The separated ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness by evaporation in vacuo. 0.13 g of the desired crude product is obtained in the form of a yellow oil which, after purification by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)), yields 0.08 g of pure product in the form of a colourless oil.

[0260]

1
H-NMR (CDCl3): 7.62 ppm (d, 1H); 6.74 ppm (t, 1H); 4.00 ppm (s, 3H); 3.90 ppm (s, 3H).

Example P34: 3-(5-Chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid tert-butyl ester

[0261]

[0262] 32.3 g of diisopropylamine are introduced into 200 ml of tetrahydrofuran and, with cooling with a Co2/acetone cooling bath, 200 ml of a 1.6M solution of n-butyllithium in hexane are added dropwise. 49.2 ml of propionic acid tert-butyl ester are then added dropwise at approximately −75° C. and the mixture is stirred at that temperature for 45 minutes. At approximately −75° C. a solution of 32.6 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid ethyl ester (Example P1) in 40 ml of tetrahydrofuran (THF) is then added dropwise and the mixture is stirred at that temperature for 1 hour, after which it is diluted with 250 ml of tert-butyl methyl ether. A mixture of 100 ml of water and 200 ml of glacial acetic acid is added, the phases are separated, the aqueous phase is extracted again, and the combined organic phases are washed with water. After drying over magnesium sulfate, filtration and concentration to dryness in vacuo are carried out. 51 g of the desired compound are obtained in the form of an oil (crude product).

[0263] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 3/1 (v/v)) is 0.46, and the Rf value of the product is 0.63.

Example P35: 3-(5-Chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid

[0264]

[0265] 25.5 g of 3-(5-chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid tert-butyl ester (Example P34) are added dropwise to 30 ml of a 33% solution of hydrogen bromide (HBr) in glacial acetic acid to form a suspension. The mixture is subsequently stirred for 90 minutes and then introduced into 300 ml of ice-water. The resulting precipitate is filtered off, washed with water and dried. 15.9 g of the desired title compound are obtained in the form of a solid having a melting point of 101-102° C.

Example P36: 2-Chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one

[0266]

[0267] 20.8 g of 3-(5-chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid (Example P35) are introduced into 125 ml of glacial acetic acid. 6.3 g of chlorine gas are introduced into the solution in the course of 1 hour. The mixture is then poured into 700 ml of water and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water and dried over magnesium sulfate, filtered and concentrated by evaporation in vacuo. The crude product is dissolved in 180 ml of tert-butyl methyl ether, 45 g of silica gel are added and the mixture is stirred for 30 minutes, in the course of which the evolution of gas observed initially comes to a halt. The silica gel is then filtered off and subsequently washed and the combined ethereal phases are concentrated to dryness in vacuo. 20.1 g of an oily crude product are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)). 17.0 g of the desired title compound are obtained in the form of a solid having a melting point of 29-32° C.

Example P37: 5-(5-Chloro-3-fluoropyridin-2-yl)-3,6-dimethyl-3,6-dihydro-[1,3,4]-thiadiazine-2-thione

[0268]

[0269] 19.1 ml of a 4N sodium hydroxide solution and 3.5 g of methyl hydrazine are introduced into 76 ml of ethanol. At an internal temperature of <5° C., 4.5 ml of carbon disulfide are added dropwise with stirring, and the mixture is then stirred for 30 minutes. 17.0 g of 2-chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one (Example P36) are subsequently added in the course of 15 minutes at an internal temperature of <5° C. The temperature is then allowed to rise to 22° C. and the mixture is subsequently stirred for 30 minutes. TLC analysis (silica gel 60 F254; eluant: n-hexane/ethyl acetate, UV) of a worked-up sample shows that starting material is no longer present. 2.5 ml of a concentrated hydrochloric acid solution are then added dropwise to form a yellow precipitate. Stirring is carried out for 1 hour and the mixture is then poured into water and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. 20.3 g of the desired title compound are obtained in the form of a solid having a melting point of 107-112° C.

Example P38: 5-Chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine

[0270]

[0271] 21.6 g of crude 5-(5-chloro-3-fluoropyridin-2-yl)-3,6-dimethyl-3,6dihydro-[1.3.4]-thiadiazine-2-thione (Example P37) are introduced into 70 ml of tert-butanol, 19.1 g of triphenylphosphine are added and the mixture is stirred at an internal temperature of 65° C. for approximately 15 minutes, a clear solution forming. After cooling to 22° C., a suspension again forms, to which 8.2 g of potassium tert-butanolate are added in portions at an internal temperature of <40° C. (cooling with an ice-bath). The mixture is then stirred overnight, subsequently poured into 600 ml of water, stirred, filtered and washed, and the aqueous phase is extracted thoroughly with tert-butyl methyl ether. The aqueous phase is rendered strongly acidic with concentrated hydrochloric acid and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. 6.8 g of a crude intermediate are obtained.

[0272] 1.9 g of the intermediate are dissolved in 10 ml of dimethylformamide (DMF) and 2.2 g of potassium carbonate are added. 0.5 ml of methyl iodide in 2 ml of DMF is then added dropwise. The mixture is subsequently stirred at 22° C. for 5 hours, poured into 120 ml of ice-water, and extracted with diethyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. 1.8 g of an oil are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 1.3 g of the desired title compound are obtained in the form of a solid having a melting point of 61-64° C.

Example P39: 5-Chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine

[0273]

[0274] 2.1 g of 5-chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine (Example P38) are dissolved in 40 ml of methylene chloride, and 2.84 g of 70% meta-chloroperbenzoic acid are added in portions. The mixture is then stirred for 4 hours at 22° C. and subsequently stirred with 1N sodium hydrogen carbonate solution for 30 minutes. The organic phase is separated off, washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. 1.7 g of a solid are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 0.80 g of the desired sulfone having a melting point of 145-147° C. and 0.70 g of the sulfoxide having a melting point of 112-114° C. are obtained.

Example P40: 5-Chloro-3-fluoro-2-(5methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-pyridine-1-oxide

[0275]

[0276] 5.3 g of 5-chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine (Example P39) are dissolved in 50 ml of methylene chloride. With stirring, 19.2 g of 70% m-chloroperbenzoic acid (MCPBA) are introduced in portions at 22° C. with exothermic reaction. The mixture is then stirred overnight at 22° C. The next day, a further 4.9 g of MCPBA are added and the mixture is stirred overnight. The mixture is subsequently extracted with dilute sodium hydrogen carbonate solution and then with sodium thiosulfate solution. The extract is dried over magnesium sulfate and then filtered and concentrated to dryness in vacuo. The crude product (6 g) is purified over silica gel using ethyl acetate as eluant. 3.6 g of the desired title compound having a melting point of 174-176° C. are obtained.

Example P41: 3-Chloro-5-fluoro-6-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-[1H]-pyridin-2-one

[0277]

[0278] 2.6 g of 5-chloro-3-fluoro-2-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-pyridine-1-oxide (Example P40) are introduced into 35 ml of dry dimethylformamide. At a temperature of 10° C., 16.8 g of trifluoroacetic anhydride are added dropwise and the mixture is then stirred overnight at 22° C., subsequently poured into 2 liters of ice-water and extracted with tert-butyl methyl ether. After drying over magnesium sulfate, filtering and concentrating to dryness by evaporation in vacuo, 1.8 g of the desired compound are obtained as crude product, which can be used directly in the next step.

Example P42: 3-Chloro-5-fluoro-6-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-1-propyn-2-yl-[1H]-pyridin-2-one

[0279]

[0280] 1.8 g of 3-chloro-5-fluoro-6-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-[1H]-pyridin-2-one (Example P41) are dissolved in 10 ml of dimethyl sulfoxide and 3.0 ml of a 2N aqueous sodium hydroxide solution are added (slightly exothermic reaction). After subsequently stirring for 30 minutes at 22° C., 0.46 ml of propargyl bromide is added dropwise and the mixture is further stirred overnight at 22° C. The reaction mixture is then introduced into 120 ml of ice-water, filtered, and washed with water. It is taken up in ethyl acetate, dried over magnesium sulfate, filtered and concentrated to dryness by evaporation in vacuo. The crude product is purified by means of silica gel chromatography (eluant: n-hexane/ethyl acetate 1/1 (v/v)). 0.74 g of the desired title compound, which still contains 20% of the isomeric O-propargyl derivative, is obtained; m.p. 189-192° C.

[0281] The Rf value of the title compound on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.28, the Rf value of the O-propargyl isomer is 0.55, and the Rf value of the starting compound is 0.05.

Example P43: 5-(5-Chloro-3-fluoro-1-methyl-6-oxo-1,6-dihydropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carbonitrile

[0282]

[0283] 1.54 g of 3-chloro(1,4-dimethyl-5-cyano-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol are introduced into a mixture of 20 ml of absolute 1,2-dimethoxyethane and 5 ml of absolute dimethylformamide at 22° C. With stirring, first 1.20 g of lithium bromide are added and then, 10 minutes later, in portions, 0.28 g of a 60% sodium hydride dispersion in oil. After a further 10 minutes, 0.86 ml of methyl iodide is added, after which the mixture is stirred overnight at 90° C. The mixture is then cooled to 22° C., carefully poured into dilute hydrochloric acid, and extracted with diethyl ether. The combined ethereal phases are washed with brine, dried over sodium sulfate, filtered and concentrated in vacuc together with 4 g of silica gel. The silica gel is applied to a flash chromatography column and fractionated by means of gradient elution using n-hexane/ethyl acetate 3/1 to 1/1 (v/v). 0.68 g of the desired compound is obtained in the form of a white solid having a melting point of 190-191 ° C.

Example P44: 1-Allyl-3-chloro-6-(4-chloro-5-difuoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridin-2-one

[0284]

[0285] 1.50 g of 3-(3-fluoro-5-chloro-6-hydroxy-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P27) are suspended in a dry mixture of 16 ml of dimethoxyethane and 4 ml of N,N-dimethylformamide (DMF). With stirring, a total of 0.20 g of a 55% sodium hydride dispersion is added, in portions, at 250° C. The suspension is subsequently stirred for ten minutes, 0.79 g of anhydrous lithium bromide is then added and, after a further fifteen minutes' stirring, 0.77 ml of allyl bromide is added dropwise. The mixture is subsequently stirred overnight at 65° C. The next day, TLC analysis of a worked-up sample shows that starting material is no longer present. The reaction mixture is cooled to 25° C. and partitioned between dilute hydrochloric acid and tert-butyl methyl ether. After extraction by shaking, and separation of the phases, the ethereal phase is washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo together with 5 g of silica gel. The silica gel is applied to a flash chromatography column and chromatography is carried out (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 0.95 g of the target compound is obtained in the form of a slightly yellowish-brown-coloured oil, the Rf value of which on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.33.

Example P45: 1-Ethyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridin-2-one

[0286]

[0287] 1.5 g of 3-(3-fluoro-5-chloro-6-hydroxy-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P27) are introduced into 6 ml of dimethyl sulfoxide (DMSO). 2.5 ml of a 2N aqueous sodium hydroxide solution are added thereto. 0.78 g of ethyl iodide in 2 ml of DMSO is then added dropwise, with stirring, and the mixture is further stirred overnight at 70° C. The next day, the reaction mixture is partitioned between dilute hydrochloric acid and diethyl ether. After extraction by shaking, and separation of the phases, the ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. Finally, the residue is purified over a flash chromatography column (silica gel; elution gradient: n-hexane/ethyl acetate 4/1 to 1/1 (v/v)). 0.54 g of the desired target compound is obtained in the form of a yellow oil having an Rf value of 0.17 on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 2/1 (v/v)).

Example P46: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid benzyl ester

[0288]

[0289] 10.0 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) are introduced into a mixture of 100 ml of dimethoxyethane and 25 ml of dimethylformamide at 22° C. 1.22 g of sodium hydride (60%, moistened in oil) are then added in portions, evolution of gas being observed. After subsequently stirring for 15 minutes at 22° C., 5.3 g of dry lithium bromide are added (slightly exothermic reaction) and, after 10 minutes, 9.6 ml of bromoacetic acid benzyl ester are added. The mixture is then stirred for 5 hours at 75° C. After cooling to 22° C., the mixture is taken up in ethyl acetate, washed with dilute hydrochloric acid and then with brine, subsequently dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. 24.3 g of a yellow oil are obtained, which is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 7.67 g of the desired compound are obtained in the form of a yellow oil which crystallises on being left to stand; m.p. 83-85° C.

[0290] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate/glacial acetic acid 20/20/1 (v/v/v)) is 0.45, and the Rf value of the title compound is 0.60. The isomeric O-alkyl derivative is isolated as secondary product.

Example P47: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid

[0291]

[0292] 6.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid benzyl ester (Example P46) are hydrogenated at normal pressure and 22° C. with 0.35 g of 5% palladium-on-active carbon in 90 ml of tetrahydrofuran (THF). After 2.5 hours, the reaction mixture is filtered over Hyflo and washed with THF. 5.11 g of the desired title compound are obtained in the form of a colourless resin, which solidifies on being left to stand.

[0293]

1
H-NMR (CDCl3): 7.58 ppm (d, 1H); 6.66 ppm (t, 1H); 4.73 ppm (s, 2H); 3.77 ppm (s, 3H).

Example P48: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid imidazolide

[0294]

[0295] 2.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid (Example P47) are suspended in 20 ml of 1,2-dichloroethane. With stirring, 0.92 g of 1,1′-carbonyldiimidazole is added at 22° C. The mixture is stirred overnight and the resulting solution is concentrated to dryness by evaporation in vacuo. 2.40 g of the desired title compound are obtained in the form of a beige solid, which contains 20% by weight imidazole.

[0296]

1
H-NMR (DMSO-D6): 8.51 ppm (s, 1H); 8.41 ppm (d, 1H); 7.77 ppm (m, 1H); 7.33 ppm (t, 1H); 7.13 ppm (m, 1H); 5.46 ppm (s, 2H); 3.60 ppm (s, 3H).

Example P49: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid diethylamide

[0297]

[0298] 1.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid (Example P47) is introduced into 8 ml of 1,2-dichloroethane. 0.50 g of carbonyldiimidazole is added to the white suspension and the mixture is stirred for one hour at 22° C., in the course of which all undissolved components dissolve. 0.39 ml of diethylamine is then added and the mixture is stirred overnight at 22° C. The next day, the reaction mixture is taken up in ethyl acetate and washed in succession with dilute sodium hydrogen carbonate solution, dilute hydrochloric acid and brine. After drying over sodium sulfate, filtration is carried out and the residue is concentrated to dryness in vacuo. 1.20 g of a yellow oil is obtained which is purified over a flash chromatography column (silica gel; eluant: ethyl acetate). 1.27 g of the desired title compound are obtained in the form of a colourless resin.

[0299]

1
H-NMR (CDCl3): 7.61 ppm (d, 1H); 6.72 ppm (t, 1H); 4.99 ppm (s, 2H); 3.82 ppm (s, 3H); 3.27 ppm (m, 4H); 1.13 ppm (t, 3H); 1.04 ppm (t, 3H).

Example P50: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid allylamide

[0300]

[0301] 1.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl) -5-fluoro-2-oxo-[2H]-pyridin1-yl)-acetic acid imidazolide (crude product) (Example P48) is introduced into 6 ml of 1,2-dichloroethane at 22° C. After the addition of 0.21 ml of allylamine, the mixture is stirred overnight and then taken up in ethyl acetate and washed in succession with dilute sodium hydroxide solution, brine, dilute hydrochloric acid and brine. Drying over sodium sulfate, filtration and concentration by evaporation in vacuo yield 0.77 g of the desired compound in the form of a white solid having a melting point of 146-148° C.

Example P51: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfanylmethyl)-[1H]-pyridin-2-one

[0302]

[0303] 4.0 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) are introduced into a mixture of 40 ml of dry dimethoxyethane and 10 ml of dry dimethylformamide at 22° C., and 0.49 g of a 60% sodium hydride (NaH) dispersion in hexane is added. After 15 minutes' stirring, 2.12 g of lithium bromide are added and the mixture is subsequently stirred for 10 minutes. 2.0 ml of chlorodimethyl sulfide are then added and the mixture is further stirred overnight at 70° C. After cooling to 22° C., a sample is removed and analysed in a thin-layer chromatogram (TLC). Since starting material is still present, a further 0.30 g of sodium hydride dispersion (60%) and 0.60 ml of chlorodimethyl sulfide are added and the mixture is then again stirred overnight at 70° C. After cooling to 22° C., the mixture is taken up in ethyl acetate, and dilute hydrochloric acid is added carefully. After extraction by shaking, and separation of the phases, the ethyl acetate phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuo. The crude product is purified over silica gel (eluant: n-hexane/ethyl acetate 2/1 (v/v)). First 0.51 g of the O-alkyl isomer is eluted and then 3.04 g of the desired title compound in the form of a yellow oil, which slowly crystallises out.

[0304] The Rf value of the title compound on silica gel 60 F254 (eluant: n-hexane/ethyl acetate/glacial acetic acid 20/20/1 (v/v/v)) is 0.37, the Rf value of the O-alkyl isomer is 0.70 and the Rf value of the starting material is 0.31.

Example P52: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfonylmethyl)-[1H]-pyridin-2-one

[0305]

[0306] 1.97 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfanylmethyl)-[1H]-pyridin-2-one (Example P51) are introduced into 25 ml of dichloroethane at 22° C. 3.75 g of m-chloroperbenzoic acid (70%) are added to the yellow solution with a slight exothermic reaction. The mixture is stirred overnight at 22° C. The next day, the reaction mixture is taken up in ethyl acetate and washed with dilute sodium hydroxide solution and then with brine. After drying over sodium sulfate, filtration is carried out followed by concentration to dryness in vacuo. 2.05 g of the desired title compound are obtained in the form of a white solid having a melting point of 171-172° C.

Example P53: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5fluoro-1-methanesulfinylethyl)-[1H]-pyridin-2-one

[0307]

[0308] 1.18 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfanylethyl)-[1H]-pyridin-2-one are introduced into 7 ml of glacial acetic acid. After the addition of 0.27 g of hydrogen peroxide/urea adduct, the mixture is stirred overnight at 22° C. The next day, the reaction mixture is taken up in ethyl acetate and washed in succession with dilute sodium hydroxide solution, dilute hydrochloric acid and brine. After drying over sodium sulfate, the mixture is filtered and concentrated to dryness in vacuo. The residue (1.12 g of a yellow solid) is stirred with 10 ml of diethyl ether, and then filtered and washed with n-hexane. 1.05 g of the desired compound are obtained in the form of a white solid having a melting point of 143-145° C.

Example P54: 1-Benzyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridine-2-thione

[0309]

[0310] 0.50 g of 1-benzyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridin-2-one is introduced into 5 ml of toluene, 0.63 g of Lawesson's reagent is added and the resulting yellow suspension is stirred overnight at 120° C. The next day, the mixture is cooled to 22° C., diluted with methylene chloride and, after the addition of 3 g of silica gel, concentrated to dryness in vacuo. The silica gel is applied to a flash chromatography column and eluted first with toluene/ethyl acetate 30/1 (v/v) and then with n-hexane/ethyl acetate 2/1 (v/v). 0.32 g of the desired title compound is obtained in the form of a yellow solid having a melting point of 135-138° C.

[0311] The Rf value of the starting material on silica gel 60 F254 (eluant: toluene/ethyl acetate 30/1 (v/v)) is 0.02 and the Rf value of the title compound is 0.18.

Example P55: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-propionaldehyde

[0312]

100

[0313] 0.40 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-1-(2-[1.3]-dioxolan-2-ylethyl)-5-fluoro-[1H]-pyridin-2-one is stirred overnight at 22° C. in a mixture of 6 ml of 2N hydrochloric acid and 6 ml of diethyl ether. The next day, the same amount of the mixture together with 2 ml of tetrahydrofuran are added and the mixture is again stirred overnight. The mixture is subsequently diluted with diethyl ether and washed three times with brine, dried over sodium sulfate, filtered and concentrated to dryness in vacua. 0.23 g of the desired compound (crude) is obtained in the form of a yellow oil.

[0314]

1
H-NMR (CDCl3): 9.73 ppm (s, 1H); 7.61 ppm (d, 1H); 6.73 ppm (t, 1H); 4.15 ppm (broad signal, 2H); 3.85 ppm (s, 3H); 2.98 ppm (t, 2H).

Example P56: 2-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-yloxy)-acetamide

[0315]

101

[0316] 20.0 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) are placed together with 18.9 g of potassium carbonate and 6.4 g of chloroacetamide at 22° C. and the mixture is stirred overnight at 50° C. The next day, the mixture is cooled to 22° C. and then introduced into 2 liters of ice-water. After subsequently stirring for 10 minutes at 22° C., the resulting slurry is filtered. The filtration residue is washed with cold water and then dried in vacuo at 60° C. 20.2 g of the desired title compound are obtained in the form of a white solid having a melting point of 178-180° C.

Example P57: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ylamine

[0317]

102

[0318] 7.1 g of potassium carbonate are introduced into 200 ml of dry N-methylpyrrolidone (NMP) and the mixture is heated to a temperature of 150° C. With stirring, 19.6 g of 2-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-yloxy)-acetamide (Example P56) are introduced in portions in the course of 2 hours and then the mixture is stirred for 10 hours at 150° C., subsequently cooled to 22° C. and partitioned between diethyl ether and water. After extraction by shaking, and separation of the phases, the ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated together with twice the amount of silica gel. The silica gel is applied to a flash chromatography column and then elution is carried out with a n-hexane/ethyl acetate 1/1 (v/v) mixture. 9.3 g of the desired title compound having a melting point of 100-101° C. are obtained.

[0319] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.14 and the Rf value of the target compound is 0.43.

Example P58: 8-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester

[0320]

103

[0321] 1.96 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ylamine (Example P57) are placed together with 1.25 ml of bromopyruvic acid ethyl ester (90%) in 20 ml of absolute ethanol. The mixture is stirred for 6 hours at 90 ° C. and then cooled to 22° C. and concentrated to dryness in vacuo. The residue is crystallised by the addition of diethyl ether and stirred, and n-hexane is added until precipitation is complete. The crystal fraction is filtered off, washed with n-hexane and dried in vacuo. 2.52 g of a yellowish-brown solid are obtained, which is dissolved in ethyl acetate and washed with dilute sodium hydrogen carbonate solution and then with brine. The organic phase is dried over sodium sulfate and then filtered and concentrated to dryness in vacuo. The residue obtained is digested in n-hexane, filtered, washed and dried. 1.88 g of the title compound are obtained in the form of a beige solid having a melting point of 140-143° C.

Example P59: 8-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridine-2-carboxylic acid

[0322]

104

[0323] 0.51 g of 8-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (Example P58) is dissolved in 3 ml of dimethyl sulfoxide and, with cooling in an ice-bath, 0.63 ml of a 2N aqueous sodium hydroxide solution is added. The mixture is then stirred for 1 hour at 22° C. Because the TLC analysis of a worked-up sample indicates that starting material is still present, a further 0.1 ml of 2N sodium hydroxide solution is added. After subsequently stirring for 30 minutes, the mixture is rendered strongly acidic with dilute hydrochloric acid, the resulting slurry is filtered, and the filtration residue is subsequently washed with cold water and dried in vacuo at 50° C. 0.35 g of the desired title compound is obtained in the form of a white solid (crude product).

Example P60: 8-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridin-2-yl)methanol

[0324]

105

[0325] 0.56 g of 8-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (Example P58) is introduced at 22° C. into 5 ml of diethyl ether and then treated with a total of 0.18 g of lithium aluminium hydride in portions with stirring. The resulting reddish-brown suspension is subsequently stirred for 1 hour and then first an excess of ethyl acetate and then dilute hydrochloric acid are added dropwise. The separated organic phase is washed with brine, filtered and concentrated to dryness in vacuo. 0.14 g of a yellowish-brown oil is obtained, which is purified over silica gel using ethyl acetate as eluant. 0.40 g of the desired compound is obtained in the form of a beige solid having a melting point of 152-153° C.

[0326] The preferred compounds listed in the following Tables can also be prepared in an analogous manner, and according to methods such as are illustrated in the general Reaction Schemes 1-3 and in the references quoted.

1TABLE 1A preferred group of compounds of formula I corresponds to the general

106

formula (I1), in which the sets of correlated substituents R11, X1and R13 are given in Table A, thus disclosing 654 specific compounds offormula I1.

[0327]

2

TABLE 2

Another preferred group of compounds of formula I corresponds to the

general formula

107

(I2), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A,

thus disclosing 654 specific compounds of formula I2.

[0328]

3

TABLE 3

Another preferred group of compounds of formula I corresponds to the

general formula

108

(I3), in which the sets of correlated

substituents R11, X1 and R13 are given in Table A, thus disclosing 654

specific compounds of formula I3.

[0329]

4

TABLE 4

Another preferred group of compounds of formula I corresponds to the

general formula

109

(I4), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing

654 specific compounds of formula I4.

[0330]

5

TABLE 5

Another preferred group of compounds of formula I corresponds to the

general formula

110

(I5), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing

654 specific compounds of formula I5.

[0331]

6

TABLE 6

Another preferred group of compounds of formula I corresponds to the

general formula

111

(I6), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing

654 specific compounds of formula I6.

[0332]

7

TABLE 7

Another preferred group of compounds of formula I corresponds to the

general formula

112

(I7), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing

654 specific compounds of formula I7.

[0333]

8

TABLE 8

Another preferred group of compounds of formula I corresponds to the

general formula

113

(I8), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing

654 specific compounds of formula I8.

[0334]

9

TABLE 9

Another preferred group of forula I corresponds to the

general formula

114

(I9), in which the sets of correlated substituents, R11,

X1 and R13 are given in Table A, thus disclosing 654 specific

compounds of formula I9.

[0335]

10

TABLE 10

Another preferred group of compounds of formula I corresponds to the

general formula

115

(I10), in which the sets of correlated subtituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific

compounds of formula I10.

[0336]

11

TABLE 11

Another preferred group of compounds of formula I corresponds to the

general formula

116

(I11), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific compounds

of formula I11.

[0337]

12

TABLE 12

Another preferred group of compounds of formula I corresponds to the

general formula

117

(I12), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific compounds

of formula I12.

[0338]

13

TABLE 13

Another preferred group of compounds of formula I corresponds to the

general formula

118

(I13), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific compounds

of formula I13.

[0339]

14

TABLE 14

Another preferred group of compounds of formula I corresponds to the

general formula

119

(I14), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing 654 specific

compounds of formula I14.

[0340]

15

TABLE 15

Another preferred group of compounds of formula I corresponds to the

general formula

120

(I15), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific compounds

of formula I15.

[0341]

16

TABLE 16

Another preferred group of compounds of formula I corresponds to the

general formula

121

(I16), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific

compounds of formula I16.

[0342]

17

TABLE 17

Another preferred group of compounds of formula I corresponds to the

general formula

122

(I17), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing 654

specific compounds of formula I17.

[0343]

18

TABLE 18

Another preferred group of compounds of formula I corresponds to the

general formula

123

(I18), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific

compounds of formula I18.

[0344]

19

TABLE 19

Another preferred group of compounds of formula I corresponds to the

general formula

124

(I19), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing 654 specific

compounds of formula I19.

[0345]

20

TABLE 20

Another preferred group of compounds of formula I corresponds to the

general formula

125

(I20), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific compounds

of formula I20.

[0346]

21

TABLE 21

Another preferred group of compounds of formula I corresponds to the

general formula

126

(I21), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I21.

[0347]

22

TABLE 22

Another preferred group of compounds of formula I corresponds to the

general formula

127

(I22), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I22,

[0348]

23

TABLE 23

Another preferred group of compounds of formula I corresponds to the

general formula

128

(I23), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I23.

[0349]

24

TABLE 24

Another preferred group of compounds of formula I corresponds to the

general formula

129

(I24), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I24.

[0350]

25

TABLE 25

Another preferred group of compounds of formula I corresponds to the

general formula

130

(I25), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I25.

[0351]

26

TABLE 26

Another preferred group of compounds of formula I corresponds to the

general formula

131

(I26), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I26.

[0352]

27

TABLE 27

Another preferred group of compounds of formula I corresponds to the

general formula

132

(I27), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I27.

[0353]

28

TABLE 28

ANother preferred group of compounds of formula I corresponds to the

general formula

133

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I28.

[0354]

29

TABLE 29

Another preferred group of compounds of formula I corresponds to the

general formula

134

(I29), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I29.

[0355]

30

TABLE 30

Another preferred group of compounds of formula I correspons to the

general formula

135

(I30), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I30.

[0356]

31

TABLE 31

Another preferred group of compounds of formula I corresponds to the

general formula

136

(I31), in which the sets of correlated substituents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific compound of

formula I31.

[0357]

32

TABLE 32

Another preferred group of compounds of formula I corresponds to the

general formula

137

(I32), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I32.

[0358]

33

TABLE 33

Another preferred group of compounds of formula I corresponds to the

general formula

138

(I33), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I33.

[0359]

34

TABLE 34

Another preferred group of compounds of formula I corresponds to the

general formula

139

(I34), in which the sets of correlated substituents

R11, X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I34.

[0360]

35

TABLE 35

Another preferred group of compounds of formula I corresponds to the

general formula

140

(I35), in which the sets of correlated substitutents

R11, X1 and R13 are given in Table A, thus disclosing 654 specific com-

pounds of formula I35.

[0361]

36

TABLE 36

Another preferred group of compounds of formula I corresponds to the

general formula

141

(I36) in which the sets of correlated substitutents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific compounds

of formula I36.

[0362]

37

TABLE 37

Another preferred group of compounds of formula I corresponds to the

general formula

142

(I37), in which the sets of correlated substitutents R11,

X1 and R13 are given in Table A, thus disclosing 654 specific compounds

of formula I37.

[0363]

38

TABLE A

Compd.

No.
R11
X1
R13

.001
H
O
CH3

.002
F
O
CH3

.003
Cl
O
CH3

.004
F
O
CH2CH3

.005
Cl
O
CH2CH3

.006
H
O
CH2CH3

.007
F
O
CH2CH2CH3

.008
Cl
O
CH2CH2CH3

.009
H
O
CH2CH2CH3

.010
F
O
CH2CH2CH2CH3

.011
Cl
O
CH2CH2CH2CH3

.012
F
O
CH2CH2CH2CH2CH3

.013
Cl
O
CH2CH2CH2CH2CH3

.014
F
O
CH2CH2CH2CH2CH2CH3

.015
F
O
CH2CH2CH(CH3)2

.016
Cl
O
CH2CH2CH(CH3)2

.017
H
O
CH2CH2CH(CH3)2

.018
F
O
CH2CH(CH3)CH2CH3

.019
Cl
O
CH2CH(CH3)CH2CH3

.020
H
O
CH2CH(CH3)CH2CH3

.021
F
O
CH2CH(CH3)CH2CH2CH3

.022
F
O
CH2CH2CH(CH3)CH2CH3

.023
F
O
CH2CH2CH2CH(CH3)2

.024
F
O
CH(CH3)CH2CH2CH2CH3

.025
Cl
O
CH(CH3)CH2CH2CH2CH3

.026
H
O
CH(CH3)CH2CH2CH2CH3

.027
F
O
CH2C(CH3)3

.028
Cl
O
CH2C(CH3)3

.029
H
O
CH2CH(CH3)2

.030
Cl
O
CH2CH(CH3)2

.031
F
O
CH2CH(CH3)2

.032
F
O
CH2C(CH3)2CH2CH3

.033
Cl
O
CH2C(CH3)2CH2CH3

.034
H
O
CH2C(CH3)2CH2CH3

.035
F
O
CH2CH2C(CH3)3

.036
Cl
O
CH2CH2C(CH3)2

.037
F
O
CH2CH2CHCH2

.038
Cl
O
CH2CH2CHCH2

.039
H
O
CH2CH2CHCH2

.040
F
O
CH2CH2CH2CHCH2

.041
Cl
O
CH2CH2CH2CHCH2

.042
H
O
CH2CH2CH2CHCH2

.043
F
O
CH2CH2CH2CH3

.044
F
O
CH(CH3)2

.045
F
O
CH2CF3

.046
Cl
O
CH2CF3

.047
H
O
CH2CF3

.048
F
O
CH2CHF2

.049
Cl
O
CH2CHF2

.050
F
O
CH2CH2CF3

.051
Cl
O
CH2CH2CF3

.052
F
O
CH2CCl3

.053
F
O
CH2CH2CF3

.054
Cl
O
CH2CH2CF3

.055
F
O
CH2CH2CHF2

.056
Cl
O
CH2CH2CHF2

.057
H
O
CH2CH2CHF2

.058
F
O
CH2CH2CH(OH)CH3

.059
F
O
CH2CH(OH)CH2CH3

.060
Cl
O
CH2CH(OH)CH2CH3

.061
F
Cl
CH2CH(OH)CH3

.062
H
O
CH2CH2CHClCH3

.063
Cl
O
CH2CH2CHClCH3

.064
F
O
CH2CH2CHClCH3

.065
F
O
CH2CH2CHFCH3

.066
F
O
CH2CHFCH2CH3

.067
Cl
O
CH2CHFCH2CH3

.068
H
O
CH2CHFCH2CH3

.069
F
O
CH2CHClCH2CH3

.070
F
O
CH2CH2F

.071
Cl
O
CH2CH2F

.072
F
O
CH2CH2Cl

.073
F
O
CH2CH2Br

.074
Cl
O
CH2CH2Cl

.075
H
O
CH2CH2O

.076
F
O
CH2CHF2

.077
F
O
CH2CHBr2

.078
H
O
CH2CHCH2

.079
Cl
O
CH2CHCH2

.080
F
O
CH2CHCH2

.081
F
O
CH2CH(CH3)CH2

.082
F
O
CH2CHCH(CH3)

.083
F
O
CH2CHCH(Cl) (R-form)

.084
Cl
O
CH2CHCH(Cl) (E-form)

.085
H
O
CH2CHCH(Cl) (E-form)

.086
F
O
CH2CHCH(Cl) (Z-form)

.087
Cl
O
CH2CHCH(Cl) (Z-form)

.088
H
O
CH2CH2OH

.089
Cl
O
CH2CH2OH

.090
F
O
CH2CH2OH

.091
F
O
CH2CH2CH2OH

.092
Cl
O
CH2CH2CH2OH

.093
F
O
CH2CH(OH)CH3

.094
Cl
O
CH2CH(OH)CH3

.095
F
O
CH2CHCHCl

.096
Cl
O
CH2CHCHCl

.097
H
O
CH2CHCHCl

,098
H
O
CH2CCH

.099
Cl
O
CH2CCH

.100
F
O
CH2CCH

.101
F
O
CH2CH(CH3)CCH

.102
Cl
O
CH2CH2CCH

.103
F
O
CH2CH2CCH

.104
Cl
O
CH2CH2C6H5

.105
F
O
CH2CH2C6H5

.106
F
O
CH2CH2CH2C6H5

.107
F
O
CH2CH2CH(CH3)C6H5

.108
F
O
CH2CH2CH2CH2(p-F—C6H4)

.109
H
O
CH2C6H5

.110
Cl
O
CH2C6H5

.111
F
O
CH2C6H5

.112
F
O
CH2(o-F—C6H4)

.113
H
O
CH2(p-Cl—C6H4)

.114
F
O
CH2(m-CF3—C6H4)

.115
F
O
CH2(3,4-di-Cl—C6H3)

.116
F
O
CH2(3,5-di-CH3—C6H3)

.117
F
O
CH2CH2(2,6-di-F—C6H4)

.118
Cl
O
CH2CH2(2,6-di-F—C6H3)

.119
H
O
CH2CH2(2,6-di-F—C6H3)

.120
F
O
CH2CH2CH2(4-F—C6H4)

.121
Cl
O
CH2CH2CH2(4-F—C6H4)

.122
F
O
CH2CH2CH(CH3)(4-CH3—C6H4)

.123
Cl
O
CH2CH2CH(CH3)(4-CH3—C6H4)

.124
H
O
CH2CN

.125
Cl
O
CH2CN

.126
F
O
CH2CN

.127
F
O
CH2CHFCN

.128
F
O
cyclopropyl

.129
F
O
cyclopentyl

.130
F
O
CH2-cyclpentyl

.131
F
O
CH2-cyclopropyl

.132
F
O
CH2CH2Cl

.133
F
O
CH2CHCl2

.134
H
O
CH2OCH3

.135
Cl
O
CH2OCH3

.136
F
O
CH2OCH3

.137
F
O
CH2CH2OCH3

.138
Cl
O
CH2CH2OCH3

.139
H
O
CH2CH2OCH3

.140
F
O
CH2CH2OCH2CH3

.141
F
O
CH2CH(CH3)OCH3

.142
H
O
CH2CH2OCH2CH2OCH3

.143
Cl
O
CH2CH2OCH2CH2OCH3

.144
F
O
CH2CH2OCH2CH2OCH3

.145
H
O
CH2SCH3

.146
Cl
O
CH2SCH3

.147
F
O
CH2SCH3

.148
H
O
CH2S(O)CH3

.149
Cl
O
CH2S(O)CH3

.150
F
O
CH2S(O)CH3

.151
H
O
CH2S(O)2CH3

.152
Cl
O
CH2S(O)2CH3

.153
F
O
CH2S(O)2CH3

.154
F
O
CH2SCH2CH3

.155
F
O
CH2CH2SCH3

.156
F
O
CH2CH2SCH2CH3

.157
Cl
O
CH2CH2SCH2CH3

.158
H
O
CH2CH2SCH2CH3

.159
Cl
O
CH2CH2SCH3

.160
H
O
CH2CH2SCH3

.161
F
O
CH2CH2S(O)CH3

.162
F
O
CH2CH2S(O)2CH3

.163
Cl
O
CH2CH2S(O)CH3

.164
Cl
O
CH2CH2S(O)2CH3

.165
F
O
CH2CH2S(O)CH2CH3

.166
Cl
O
CH2CH2S(O)CH2CH3

.167
H
O
CH2CH2S(O)CH2CH3

.168
F
O
CH2CH2S(O)2CH2CH3

.169
Cl
O
CH2CH2S(O)2CH2CH3

.170
H
O
CH2CH2S(O)2CH2CH3

.171
F
O
CH2CH2CH2SCH3

.172
F
O
CH2CH2CH2S(O)CH3

.173
F
O
CH2CH2CH2S(O)2CH3

.174
F
O
CH2CH(CH3)SCH3

.175
H
O
CH2COOH

.176
Cl
O
CH2COOH

.177
F
O
CH2COOH

.178
F
O
CH2COOCH3

.179
H
O
CH2COOCH2CH3

.180
Cl
O
CH2COOCH2CH3

.181
F
O
CH2COOCH2CH3

.182
F
O
CH2COOCH(CH3)2

.183
Cl
O
CH2COOCH(CH3)2

.184
H
O
CH2COOCH(CH3)2

.185
F
O
CH2COOCH(CH2CH3)2

.186
Cl
O
CH2COOCH(CH3)CH2CH3

.187
F
O
CH2COOCH2CH2CH3

.188
F
O
CH2COOCH2CH2CH2CH3

.189
F
O
CH2COOCH2CH(CH3)2

.190
F
O
CH2COOC(CH3)2

.191
F
O
CH2COOCH2CHCH2

.192
F
O
CH2COOCH2CCH

.193
Cl
O
CH2COOCH2CCH

.194
H
O
CH2COOCH2CCH

.195
F
O
CH2COOCH2C6H5

.196
F
O
CH2COOCH2(o-F—C6H4)

.197
F
O
CH2COOCH2(p-Cl—C6H4)

.198
F
O
CH2COOCH2(m-CH3—C6H4)

.199
F
O
CH2COOCH2(2,4-di-CH3—C6H3)

.200
Cl
O
CH2COOCH2(2,4-di-CH3—C6H3)

.201
F
O
CH2CH2COOCH2(3,4-di-Cl—C6H3)

.202
F
O
CH2CH2CH2COOH

.203
Cl
O
CH2CH2CH2COOH

.204
F
O
CH2CH2CH2COOCH3

.205
F
O
CH2CH2CH2COOCH2CH3

.206
Cl
O
CH2CH2CH2COOCH2CH3

.207
F
O
CH2CH2CH2CH2COOH

.208
F
O
CH2CH2CH2CH2COOCH3

.209
Cl
O
CH2CH2CH2CH2COOCH3

.210
H
O
CH2CH2CH2CH2COOCH3

.211
H
O
CH2CHO

.212
Cl
O
CH2CHO

.213
F
O
CH2CHO

.214
H
O
CH2C(O)CH3

.215
Cl
O
CH2C(O)CH3

.216
F
O
CH2C(O)CH3

.217
F
O
CH2C(O)SCH3

.218
Cl
O
CH2C(O)CSCH3

.219
F
O
CH2C(O)SCH2CH2CH3

.220
Cl
O
CH2C(O)SCH2CH2CH3

.221
F
O
CH2C(O)SCH2CHCH2

.222
Cl
O
CH2C(O)SCH2CHCH2

.223
F
O
CH2COSCH2CH3

.224
H
O
CH2COSCH(CH3)2

.225
Cl
O
CH2COSCH(CH3)2

.226
F
O
CH2COSCH(CH3)2

.227
F
O
CH2COSCH2C6H5

.228
Cl
O
CH2COSCH2C6H5

.229
H
O
CH2COSCH2C6H5

.230
F
O
CH2CONH2

.231
F
O
CH2CONH(CH3)

.232
F
O
CH2CON(CH3)2

.233
Cl
O
CH2CON(CH3)2

.234
F
O
CH2CON(CH2CH3)2

.235
Cl
O
CH2CON(CH2CH3)2

.236
H
O
CH2CON(CH2CH3)2

.237
F
O
CH2CON(CH2CH3)(CH3)

.238
F
O
CH2CON(CH2CH2CH3)2

.239
Cl
O
CH2CON(CH2CH2CH3)2

.240
H
O
CH2CONH(CH2CH2CH3)

.241
F
O
CH2CONH(CH2CH2CH3)

.242
H
O
CH2CONHCH3CHCH2

.243
Cl
O
CH2CONHCH2CHCH2

.244
F
O
CH2CONHCH2CHCH2

.245
H
O
CH2CONHCH2CCH

.246
Cl
O
CH2CONHCH2CCH

.247
F
O
CH2CONHCH2CCH

.248
F
O
CH2CONHC6H5

.249
Cl
O
CH2CONHC6H5

.250
F
O
CH3CONH(3,4-di-Cl—C6H3)

.251
F
O
CH2CON(CH3)(C6H5)

.252
Cl
O
CH2CON(CH3)(C6H5)

.253
F
O
CH2CONH(o-F—C6H4)

.254
F
O
CH2CONHCH2(C6H5)

.255
Cl
O
CH2CONHCH2(C6H5)

.256
H
O
CH2CONHCH2(C6H5)

.257
F
O
CH2CON(CH3)CH2(C6H5)

.258
F
O
CH2CONH(3,4-di-Cl—C6H3)

.259
Cl
O
CH2CONH(3,4-di-Cl—C6H3)

.260
F
O
CH2CONHCH2(4-Cl—C6H4)

.261
Cl
O
CH2CONHCH2(4-Cl—C6H4)

.262
F
O
CH2CON(CH3)CH2(4-Cl—C6H4)

.263
F
O
CH2CON(CH2CH3)CH2(4-Cl—C6H4)

.264
Cl
O
CH2CON(CH2CH3)CH2(4-Cl—C6H4)

.265
F
O
CH2CON(CH2CHCH2)CH2(4-Cl—C6H4)

.266
Cl
O
CH2CON(CH2CHCH2)CH2(4-Cl—C6H4)

.267
H
O
CH2CH2COOH

.268
Cl
O
CH2CH2COOH

.269
F
O
CH2CH2COOH

.270
F
O
CH2CH2COOCH2CH3

.271
Cl
O
CH2CH2COOCH2CH3

.272
H
O
CH2CH2COOCH2CH3

.273
F
O
CH2CH2COOCH2CHCH2

.274
Cl
O
CH2CH2COOCH2CHCH2

.275
F
O
CH2CH2COOCH2(C6H5)

.276
F
O
CH2CH2COOCH(CH3)2

.277
Cl
O
CH2CH2COOCH(CH3)2

.278
H
O
CH2CH2CN

.279
Cl
O
CH2CH2CN

.280
F
O
CH2CH2CN

.281
F
O
CH2CH(CH3)CN

.282
Cl
O
CH2CH(CH3)CN

.283
H
O
CH2CH(CH3)CN

.284
F
O
CH2CH(Cl)CN

.285
Cl
O
CH2CH(Cl)CN

.286
F
O
CH2CH2CH2CN

.287
Cl
O
CH2CH2CH2CN

.288
F
O
CH2CH2CH(CH3)CN

.289
F
O
CH2CH(CH3)CH2CN

.290
Cl
O
CH2CH(CH3)CHO

.291
Cl
O
CH(CH3)CH2CN

.292
H
O
CH2CH2CHO

.293
Cl
O
CH2CH2CHO

.294
F
O
CH2CH2CHO

.295
F
O
CH2CH(Cl)CHO

.296
Cl
O
CH2CH(Cl)CHO

.297
F
O
CH2CH(CH3)CHO

.298
Cl
O
CH2CH(CH3)CHO

.299
H
O
CH2CH(CH3)CHO

.300
F
O
CH2CH2C(O)CH3

.301
Cl
O
CH2CH2C(O)CH3

.302
F
O
CH2COCH2CH3

.303
Cl
O
CH2COCH2CH3

.304
H
O
CH2COCH2CH3

.305
F
O
CH2COCH2CH2CH3

.306
F
O
CH2CH2COCH2CH3

.307
F
O
CH2CH2COCH2CH3

.308
F
O
CH2CH(CH3)COOH

.309
Cl
O
CH2CH(CH3)COOH

.310
H
O
CH2CH(CH3)COOH

.311
F
O
CH2CH(CH3)COOCH3

.312
F
O
CH2CH(CH3)COOCH2CH3

.313
Cl
O
CH2CH(CH3)COOCH2CH3

.314
F
O
CH2CH2CH2COOH

.315
Cl
O
CH2CH2CH2COOH

.316
Cl
O
CH2CH2CH2COOCH3

.317
F
O
CH2CH2CH2COOCH3

.318
F
O
CH2CH2CH2COSCH2CH3

.319
F
O
CH2CH2CH2CONHCH2CCH

.320
F
O
CH2CH2CH2CON(CH3)(CH2CCH)

.321
F
O
CH2CH2CH2CON(CH3)2

.322
F
O
CH2CH2CH(CH3)COOCH2CH3

.323
H
O
CH2CH(OH)COOH

.324
Cl
O
CH2CH(OH)COOH

.325
F
O
CH2CH(OH)COOH

.326
H
O
CH2CH(Cl)COOH

.327
Cl
O
CH2CH(Cl)COOH

.328
F
O
CH2CH(Cl)COOH

.329
Cl
O
CH2CH(Cl)COOCH2CH3

.330
F
O
CH2CH(Cl)COOCH2CH3

.331
F
O
CH2CH(Cl)COOCH2(4-Cl—C6H4)

.332
F
O
CH2CH(Cl)COOCH2CHCH2

.333
Cl
O
CH2CH(Cl)COOCH2CHCH2

.334
F
O
CH2CH(Cl)COOC(CH3)3

.335
Cl
O
CH2CH(Cl)COOCH(CH3)3

.336
F
O
CH2CH(Cl)COOCH2CH2CH3

.337
F
O
CH2C(CH3)(Cl)COOH

.338
Cl
O
CH2C(CH3)(Cl)COOH

.339
H
O
CH2C(CH3)(Cl)COOH

.340
F
O
CH2CH(Cl)COOCH2CHCH2

.341
Cl
O
CH2CH(Cl)COOCH2CHCH2

.342
H
O
CH2CH(Cl)COOCH2CHCH2

.343
F
O
CH2CH(Cl)COOCH2CCH

.344
F
O
CH2CH(Cl)COOCH2C6H5

.345
F
O
CH2CH(Br)COOH

.346
Cl
O
CH2CH(Br)COOH

.347
H
O
CH2CH(Br)COOH

.348
F
O
CH2CH(Br)COOCH3

.349
Cl
O
CH2CH(Br)COOCH3

.350
F
O
CH2CH(Br)COOCH2CH3

.351
F
O
CH2CH(Br)COOCH2CHCH2

.352
Cl
O
CH2CH(Br)COOCH2CHCH2

.353
F
O
CH2CH(Br)COOCH2CCH

.354
Cl
O
CH2CH(Br)COOCH2CCH

.355
F
O
CH2CHBrCOOC(CH3)3

.356
Cl
O
CH2CHBrCOOC(CH3)3

.357
F
O
CH2CH(Cl)C(O)SCH(CH3)2

.358
F
O
CH2CH(Cl)C(O)NH2

.359
Cl
O
CH2CH(Cl)C(O)NH2

.360
F
O
CH2CH(Cl)C(O)NH(CH2CCH)

.361
Cl
O
CH2CH(Cl)C(O)NH(CH2CCH)

.362
F
O
CH2CH(Cl)C(O)NH(CH2CHCH2)

.363
F
O
CH2CH(Cl)C(O)N(CH2CH3)(CH2CHCH2)

.364
Cl
O
CH2CH(Cl)C(O)N(CH2CH3)(CH2CHCH2)

.365
F
O
CH2CH(CH3)C(O)N(CH3)(CH2CHCH2)

.366
F
O
CH2COOCH2CH2Cl

.367
F
O
CH2COOCH2CF3

.368
Cl
O
CH2COOCH2CF3

.369
H
O
CH2COOCH2CF3

.370
F
O
CH2COOCH2CH2F

.371
Cl
O
CH2COOCH2CH2F

.372
F
O
CH2COOCH2CH2Cl

.373
Cl
O
CH2COOCH2CH2Cl

.374
F
O
CH2COOCH2CH2CH2Cl

.375
F
O
CH2COOCH2CH(Cl)CH3

.376
Cl
O
CH2COOCH2CH(Cl)CH3

.377
F
O
CH2COOCH2CH(F)CH3

.378
Cl
O
CH2COOCH2CH(F)CH3

.379
H
O

143

.380
H
O

144

.381
Cl
O

145

.382
Cl
O

146

.383
F
O

147

.384
F
O

148

.385
F
O
S(O)2CH3

.386
F
O
S(O)2CH2CH3

.387
Cl
O
S(O)2CF3

.388
Cl
O
S(O)2CH2CH3

.389
F
O
S(O)2CH(CH3)2

.390
H
O
C(O)CH3

.391
Cl
O
C(O)CH3

.392
F
O
C(O)CH3

.393
F
O
C(O)CF3

.394
F
O
C(O)CH2CH3

.395
H
O
OH

.396
Cl
O
OH

.397
F
O
OH

.398
H
O
OCH3

.399
Cl
O
OCH3

.400
F
O
OCH3

.401
H
O
OCH2CH3

.402
Cl
O
OCH2CH3

.403
F
O
OCH2CH3

.404
F
O
OCH2CH(CH3)2

.405
F
O
OCH2C(CH3)3

.406
F
O
OCF3

.407
F
O
OCHF2

.408
F
O
OCH2CHCH2

.409
F
O
OCH2C(CH3)CH2

.410
F
O
OCH2CHCHCl

.411
H
O
OCH2OCH3

.412
Cl
O
OCH2OCH3

.413
F
O
OCH2OCH3

.414
H
O
OCH2SCH3

.415
Cl
O
OCH2SCH3

.416
F
O
OCH2SCH3

.417
F
O
OCH2CCH

.418
H
O
OCH2COOH

.419
Cl
O
OCH2COOH

.420
F
O
OCH2COOH

.421
F
O
OCH2COOCH3

.422
F
O
OCH2COOCH2CH3

.423
F
O
OCH2COOCH(CH3)2

.424
H
O
OCH(CH3)COOH

.425
Cl
O
OCH(CH3)COOH

.426
F
O
OCH(CH3)COOH

.427
F
O
OCH(CH3)COOCH2CH3

.428
F
O
OCH(CH3)COOCH2CCH

.429
F
O
OCH(CH3)COOCH2CHCH2

.430
F
O
OCH2COSCH2CH3

.431
H
O
OCH2COSCH(CH3)2

.432
Cl
O
OCH2COSCH(CH3)2

.433
F
O
OCH2COSCH(CH3)2

.434
F
O
OCH2COSCH2C6H5

.435
F
O
OCH2CONH2

.436
F
O
OCH2CON(CH3)2

.437
H
O
OCH2CONHCH2CCH

.438
Cl
O
OCH2CONHCH2CCH

.439
F
O
OCH2CONHCH2CCH

.440
F
O
OCH2C6H5

.441
F
O
OCH2(p-CH3O—C6H4)

.442
F
O
OCH2(o-F—C6H4)

.443
Cl
O
OCH2(m-CF3—C6H4)

.444
F
O
OCH2CH2C6H5

.445
H
O
OCH2CN

.446
H
O
OCH2CH2Cl

.447
Cl
O
OCH2CN

.448
Cl
O
OCH2CH2Cl

.449
F
O
OCH2CN

.450
F
O
OCH2CH2Cl

.451
F
O
OCH2CH2CF3

.452
H
O
OCH2CH2OH

.453
Cl
O
OCH2CH2OH

.454
F
O
OCH2CH2OH

.455
H
O
OCH2CH2CN

.456
Cl
O
OCH2CH2CN

.457
F
O
OCH2CH2CN

.458
F
O
OCH2CH(OH)(C6H5)

.459
F
O
OCH2CH(OH)(CH3)

.460
Cl
O
OCH2CH(OCH3)(CH3)

.461
F
O
OCH2CH(OCH3)(CH3)

.462
H
O
OC(O)CH3

.463
Cl
O
OC(O)CH3

.464
F
O
OC(O)CH3

.465
H
S
CH3

.466
Cl
S
CH3

.467
F
S
CH3

.468
H
S
CH2CH3

.469
Cl
S
CH2CH3

.470
F
S
CH2CH3

.471
F
S
CH2CH2CH3

.472
F
S
CH2CH(CH3)2

.473
F
S
CH2CH2CF3

.474
F
S
CH(CH3)2

.475
F
S
CH2CH(CH3)2

.476
F
S
CH2CH(Cl)CH3

.477
F
S
CH2CH2CH(Cl)CH3

.478
F
S
CH2CH2CH(OH)CH3

.479
H
S
CH2CHCH2

.480
Cl
S
CH2CHCH2

.481
F
S
CH2CHCH2

.482
F
S
CH2C(CH3)CH2

.483
H
S
CH2CCH

.484
Cl
S
CH2CCH

.485
F
S
CH2CCH

.486
F
S
CH2CH2CCH

.487
F
S
CH(CH3)CCH

.488
H
S
CH2CH2OH

.489
Cl
S
CH2CH2OH

.490
F
S
CH2CH2OH

.491
F
S
CH2CH(OH)CH3

.492
H
S
CH2C6H5

.493
Cl
S
CH2C6H5

.494
F
S
CH2C6H5

.495
Cl
S
CH2(o-F—C6H4)

.496
F
S
CH2(o-F—C6H4)

.497
F
S
CH2(m-CF3—C6H4)

.498
F
S
CH2(p-CH3—C6H4)

.499
F
S
CH2(2,4-di-F—C6H3)

.500
F
S
CH2CH2CH(CH3)C6H5

.501
F
S
CH2CH2CH2CH2(p-F—C6H4)

.502
Cl
S
CH2CN

.503
F
S
CH2CN

.504
F
S
cyclopropyl

.505
Cl
S
CH2-cyclopropyl

.506
F
S
CH2-cyclopropyl

.507
F
S
CH2Cl

.508
H
S
CH2OCH3

.509
Cl
S
CH2OCH3

.510
F
S
CH2OCH3

.511
F
S
CH2OCH2CHCH2

.512
F
S
CH2CH2OCH3

.513
F
S
CH2CH(OCH3)CH3

.514
F
S
CH2CH(OCH2CCH)CH3

.515
H
S
CH2CH2OCH2CH2OCH3

.516
Cl
S
CH2CH2OCH2CH2OCH3

.517
F
S
CH2CH2OCH2CH2OCH3

.518
H
S
CH2SCH3

.519
Cl
S
CH2SCH3

.520
F
S
CH2SCH3

.521
F
S
CH2SCH2CHCH2

.522
F
S
CH2SCH2CCH

.523
F
S
CH2CH2SCH3

.524
F
S
CH2CH2S(O)CH3

.525
F
S
CH2CH2S(O)2CH3

.526
H
S
CH2COOH

.527
Cl
S
CH2COOH

.528
F
S
CH2COOH

.529
F
S
CH2COOCH3

.530
F
S
CH2COOCH2CH3

.531
F
S
CH2COOC(CH3)3

.532
F
S
CH2COOCH2C6H5

.533
F
S
CH2COOCH2(p-Cl—C6H4)

.534
F
S
CH2C(O)SCH3

.535
H
S
CH2C(O)SCH(CH3)2

.536
Cl
S
CH2C(O)SCH(CH3)2

.537
F
S
CH2C(O)SCH(CH3)2

.538
F
S
CH2C(O)SCH2C6H5

.539
F
S
CH2C(O)NH2

.540
F
S
CH2C(O)NH(CH3)

.541
F
S
CH2C(O)NH(CH2CCH)

.542
F
S
CH2C(O)NH(CH2CCH)

.543
F
S
CH2C(O)N(CH2CH3)2

.544
H
S
CH2CHO

.545
Cl
S
CH2CHO

.546
F
S
CH2CHO

.547
F
S
CH2C(O)CH3

.548
H
S
CH2CH2COOH

.549
Cl
S
CH2CH2COOH

.550
F
S
CH2CH2COOH

.551
H
S
CH2CH2CN

.552
Cl
S
CH2CH2CN

.553
F
S
CH2CH2CN

.554
F
S
CH2CH2COOCH3

.555
F
S
CH2CH2COOCH2C6H5

.556
Cl
S
CH2CH2C(O)SCH2CH3

.557
F
S
CH2CH2C(O)SCH2CH3

.558
H
S
CH2CH(OH)COOH

.559
Cl
S
CH2CH(OH)COOH

.560
F
S
CH2CH(OH)COOH

.561
H
S
CH2CH(Cl)COOH

.562
Cl
S
CH2CH(Cl)COOH

.563
F
S
CH2CH(Cl)COOH

.564
Cl
S
CH2CH(Cl)COOCH2CH3

.565
F
S
CH2CH(Cl)COOCH2CH3

.566
F
S
CH2CH(Cl)COOH

.567
F
S
CH2C(CH3)(Cl)COOH

.568
F
S
CH2CH(Cl)COOCH2CHCH2

.569
Cl
S
CH2CH(Cl)COOCH2CCH

.570
F
S
CH2CH(Cl)COOCH2CCH

.571
F
S
CH2CH(Cl)COOCH2C6H5

.572
Cl
S
CH2CH(Br)COOH

.573
F
S
CH2CH(Br)COOH

.574
Cl
S
CH2CH(Cl)C(O)SCH(CH3)2

.575
F
S
CH2CH(Cl)C(O)SCH(CH3)2

.576
F
S
CH2CH(Cl)C(O)NH(CH2CCH)

.577
F
S
CH2CH(CH3)C(O)N(CH3)(CH2CHCH2)

.578
F
S
CH2CH2C(O)NH(CH2CCH)

.579
H
S

149

.580
Cl
S

150

.581
F
S

151

.582
H
S

152

.583
Cl
S

153

.584
F
S

154

.585
H
S
OH

.586
Cl
S
OH

.587
F
S
OH

.588
H
S
OCH3

.589
Cl
S
OCH3

.590
F
S
OCH3

.591
F
S
OCH2CH3

.592
Cl
S
OCH2CH(CH3)2

.593
F
S
OCH2CH(CH3)2

.594
F
S
OCH(CH3)2

.595
F
S
OCF3

.596
H
S
OCH2OCH3

.597
Cl
S
OCH2OCH3

.598
F
S
OCH2OCH3

.599
H
S
OCH2SCH3

.600
Cl
S
OCH2SCH3

.601
F
S
OCH2SCH3

.602
Cl
S
OCH2CHCH2

.603
F
S
OCH2CHCH2

.604
H
S
OCH2CCH

.605
Cl
S
OCH2CCH

.606
F
S
OCH2CCH

.607
F
S
OCH(CH3)CHCH2

.608
F
S
OCH(CH3)CCH

.609
F
S
OCH2CH2Cl

.610
F
S
OCH2CH2CF3

.611
F
S
OCH2CHCH(Cl)

.612
H
S
OCH2CHO

.613
H
S
OCH2CHO

.614
H
S
OCH2CHO

.615
H
S
OCH2COOH

.616
Cl
S
OCH2COOH

.617
F
S
OCH2COOH

.618
H
S
OCH2COOCH2CH3

.619
Cl
S
OCH2COOCH2CH3

.620
F
S
OCH2COOCH2CH3

.621
F
S
OCH(CH3)COOH

.622
F
S
OCH(CH3)COOCH2CH3

.623
F
S
OCH(CH3)COOCH2CCH

.624
F
S
OCH2C(O)NH2

.625
F
S
OCH2C(O)NH(CH3)

.626
F
S
OCH2C(O)N(CH2CH3)2

.627
F
S
OCH2C(O)NH(CH2CCH)

.628
Cl
S
OCH2C(O)N(CH3)2

.629
F
S
OCH2C(O)N(CH3)2

.630
F
S
OCH2C(O)N(CH3)(CH2(o-F—C6H4))

.631
Cl
S
OCH2C(O)SCH3

.632
F
S
OCH2C(O)SCH3

.633
F
S
OCH2C(O)SCH2CH3

.634
H
S
OCH2C(O)SCH(CH3)2

.635
Cl
S
OCH2C(O)SCH(CH3)2

.636
F
S
OCH2C(O)SCH(CH3)2

.637
Cl
S
OCH2C(O)SCH2C6H5

.638
F
S
OCH(CH3)C(O)SCH2C6H5

.639
H
S
OCH2CH2OH

.640
Cl
S
OCH2CH2OH

.641
F
S
OCH2CH2OH

.642
H
S
OCH2CH(CH3)OH

.643
Cl
S
OCH2CH(CH3)OH

.644
F
S
OCH2CH(CH3)OH

.645
F
S
OCH2CH2Cl

.646
F
S
OCH2CF3

.647
Cl
S
OCH2CN

.648
F
S
OCH2CN

.649
H
S
OCH2CH2CM

.650
Cl
S
OCH2CH2CN

.651
F
S
OCH2CH2CN

.652
Cl
S
OCH2CH2CF3

.653
F
S
OCH2CH2CF3

.654
F
S
OCH2CH(OH)(C6H5)

[0364]

39

TABLE 38

A preferred group of compounds of formula I corresponds to the general

formula

155

(I38), in which the sets of correlated substituents R11, R12 and R32 are

given in Table B, thus disclosing 264 specific compounds of

formula I38.

[0365]

40

TABLE 39

Another preferred group of compounds of formula I corresponds to the

general formula

156

(I39), in which the sets of correlated substituents R11, R12 and R32 are

given in Table B, thus disclosing 264 specific compounds of

formula I39.

[0366]

41

TABLE 40

Another preferred group of compounds of formula I corresponds to the

general formula

157

(I40), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I40.

[0367]

42

TABLE 41

Another preferred group of compounds of formula I corresponds to the

general formula

158

(I41), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I41.

[0368]

43

TABLE 42

Another preferred group of compounds of formula I corresponds to the

general formula

159

(I42), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I42.

[0369]

44

TABLE 43

Another preferred group of compounds of formula I corresponds to the

general formula

160

(I43), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I43.

[0370]

45

TABLE 44

Another preferred group of compounds of formula I corresponds to the

general formula

161

(I44), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I44.

[0371]

46

TABLE 45

Another preferred group of compounds of formula I corresponds to the

general formula

162

(I45), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I45.

[0372]

47

TABLE 46

Another preferred group of compounds of formula I corresponds to the

general formula

163

(I46), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I46.

[0373]

48

TABLE 47

Another preferred group of compounds of formula I corresponds to the

general formula

164

(I47), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I47.

[0374]

49

TABLE 48

Another preferred group of compounds of formula I corresponds to the

general formula

165

(I48), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I48.

[0375]

50

TABLE 49

Another preferred group of compounds of formula I corresponds to the

general formula

166

(I49), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I49.

[0376]

51

TABLE 50

Another preferred group of compounds of formula I corresponds to the

general formula

167

(I50), in which the sets of correlated substituents R11,

R12 and R13 are given in Table B, thus disclosing 264 specific com-

pounds of formula I50.

[0377]

52

TABLE 51

Another preferred group of compounds of formula I corresponds to the

general formula

168

(I51), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I51.

[0378]

53

TABLE 52

Another preferred group of compounds of formula I corresponds to the

general formula

169

(I52), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I52.

[0379]

54

TABLE 53

Another preferred group of compounds of formula I corresponds to the

general formula

170

(I53), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I53.

[0380]

55

TABLE 54

Another preferred group of compounds of formula I corresponds to the

general formula

171

(I54), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I54.

[0381]

56

TABLE 55

Another preferred group of compounds of formula I corresponds to the

general formula

172

(I55), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I55.

[0382]

57

TABLE 56

Another preferred group of compounds of formula I corresponds to the

general formula

173

(I56), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I56.

[0383]

58

TABLE 57

Another preferred group of compounds of formula I corresponds to the

general formula

174

(I57), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula R57.

[0384]

59

TABLE 58

Another preferred group of compounds of formula I corresponds to the

general formula

175

(I58), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I58.

[0385]

60

TABLE 59

Another preferred group of compounds of formula I corresponds to the

general formula

176

(I59), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I59.

[0386]

61

TABLE 60

Another preferred group of compounds of formula I corresponds to the

general formula

177

(I60), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I50.

[0387]

62

TABLE 61

Another preferred group of compounds of formula I corresponds to the

general formula

178

(I61), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I61.

[0388]

63

TABLE 62

Another preferred group of compounds of formula I corresponds to the

general formula

179

(I62), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I62.

[0389]

64

TABLE 63

Another preferred group of compounds of formula I corresponds to the

general formula

180

(I63), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I63.

[0390]

65

TABLE 64

Another preferred group of compounds of formula I corresponds to the

general formula

181

(I64), in which the sets of correlated substitutents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I64.

[0391]

66

TABLE 65

Another preferred group of compounds of formula I corresponds to the

general formula

182

(I65), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I65.

[0392]

67

TABLE 66

Another preferred group of compounds of formula I corresponds to the

general formula

183

(I66), in which the sets of correlated substitutents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I66.

[0393]

68

TABLE 67

Another preferred group of compounds of formula I corresponds to the

general formula

184

(I67), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I67.

[0394]

69

TABLE 68

Another preferred group of compounds of formula I corresponds to the

general formula

185

(I68), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I68.

[0395]

70

TABLE 69

ANother preferred group of compounds of formula I corresponds to the

general formula

186

(I69), in which the sets of correlated substitutents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I69.

[0396]

71

TABLE 70

Another preferred group of compounds of formula I corresponds to the

general formula

187

(I70), in which the sets of forrelated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I70.

[0397]

72

TABLE 71

Another preferred group of compounds of formula I corresponds to the

general formula

188

(I71), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I71.

[0398]

73

TABLE 70

Another preferred group of compounds of formula I corresponds to the

general formula

189

(I72), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I72.

[0399]

74

TABLE 73

Another preferred group of compounds of formula I corresponds to the

general formula

190

(I73), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I73.

[0400]

75

TABLE 74

Another preferred group of compounds of formula I corresponds to the

general formula

191

(I74), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I74.

[0401]

76

TABLE 75

Another preferred group of compounds of formula I corresponds to the

general formula

192

(I75), in which the sets of correlated substituents

R11, R12 and R32 are given in table B, thus disclosing 264 specific com-

pounds of formula I75.

[0402]

77

TABLE 76

Another group of compounds of formula I corresponds to the

general formula

193

(I76), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I76.

[0403]

78

TABLE 77

Another preferred group of compounds of formula I corresponds to the

general formula

194

(I77), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I78.

[0404]

79

TABLE 78

Another preferred group of compounds of formula I corresponds to the

general formula

195

(I78), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I78.

[0405]

80

TABLE 79

Another preferred group of compounds of formula I corresponds to the

general formula

196

(I79), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I79.

[0406]

81

TABLE 80

Another preferred Group of compounds of formula I corresponds to the

general formula

197

(I80), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I80.

[0407]

82

TABLE 81

Another preferred group of compounds of formula I corresponds to the

general formula

198

(I81), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I81.

[0408]

83

TABLE 82

Another preferred group of compounds of formula I corresponds to the

genEral formula

199

(I82), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I82.

[0409]

84

TABLE 83

Another preferred group of compounds of formula I corresponds to the

general formula

200

(I83), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I83.

[0410]

85

TABLE 84

Another preferred group of compounds of formula I corresponds to the

general formula

201

(I84), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I84.

[0411]

86

TABLE 85

Another preferred group of compounds of formula I corresponds to the

general formula

202

(I85), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I85.

[0412]

87

TABLE 86

Another prefered group of compounds of formula I corresponds to the

general formula

203

(I86), in which the sets of correlated substituents

R11, R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I86.

[0413]

88

TABLE 87

Another preferred group of compounds of formula I corresponds to the

general formula

204

(I87) in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I87.

[0414]

89

TABLE 88

Another preferred group of compounds of formula I corresponds to the

general formula

205

(I88), in which the sets of correlated substituents R11,

R12 and R32 are given in Table B, thus disclosing 264 specific com-

pounds of formula I88.

[0415]

90

TABLE B

Compd.

No.
R11
R12
R32 or R34

.001
H
Cl
H

.002
Cl
Cl
H

.003
F
Cl
H

.004
H
Br
H

.005
Cl
Br
H

.006
F
Br
H

.007
Cl
CF3
H

.008
F
CF3
H

.009
F
CH3
H

.010
F
OCF3
H

.011
H
Cl
CH3

.012
Cl
Cl
CH3

.013
F
Cl
CH3

.014
H
Br
CH3

.015
Cl
Br
CH3

.016
F
Br
CH3

.017
Cl
CF3
CH3

.018
F
CF3
CH3

.019
F
CH3
CH3

.020
F
OCF3
CH3

.021
H
Cl
CH2CHCH2

.022
Cl
Cl
CH2CHCH2

.023
F
Cl
CH2CHCH2

.024
H
Br
CH2CHCH2

.025
Cl
Br
CH2CHCH2

.026
F
Br
CH2CHCH2

.027
Cl
CF3
CH2CHCH2

.028
F
CF3
CH2CHCH2

.029
F
CH3
CH2CHCH2

.030
F
OCF3
CH2CHCH2

.031
H
Cl
CH2CH(CH3)2

.032
Cl
Cl
CH2CH(CH3)2

.033
F
Cl
CH2CH(CH3)2

.034
H
Br
CH2CH(CH3)2

.035
Cl
Br
CH2CH(CH3)2

.036
F
Br
CH2CH(CH3)2

.037
Cl
CF3
CH2CH(CH3)2

.038
F
CF3
CH2CH(CH3)2

.039
F
CH3
CH2CH(CH3)2

.040
F
OCF3
CH2CH(CH3)2

.041
H
Cl
CH2CCH

.042
Cl
Cl
CH2CCH

.043
F
Cl
OH2CCH

.044
H
Br
CH2CCH

.045
Cl
Br
CH2CCH

.046
F
Br
CH2CCH

.047
Cl
CF3
CH2CCH

.048
F
CF3
CH2CCH

.049
F
CH3
CH2CCH

.050
F
OCF3
CH2CCH

.051
H
Cl
CF3

.052
Cl
Cl
CF3

.053
F
Cl
CF3

.054
H
Br
CF3

.055
Cl
Br
CF3

.056
F
Br
CF3

.057
Cl
CF3
CF3

.058
F
CF3
CF3

.059
F
CH3
CF3

.060
F
OCF3
CF3

.061
H
Cl
CH2Cl

.062
Cl
Cl
CH2Cl

.063
F
Cl
CH2Cl

.064
H
Br
CH2Cl

.065
Cl
Br
CH2Cl

.066
F
Br
CH2Cl

.067
Cl
CF3
CH2Cl

.068
F
CF3
CH2Cl

.069
F
CH3
CH2Cl

.070
F
OCF3
CH2Cl

.071
H
Cl
CH2CN

.072
Cl
Cl
CH2CN

.073
F
Cl
CH2CN

.074
H
Br
CH2CN

.075
Cl
Br
CH2CN

.076
F
Br
CH2CN

.077
Cl
CF3
CH2CN

.078
F
CF3
CH2CN

.079
F
CH3
CH2CN

.080
F
OCF3
CH2CN

.081
H
Cl
CH2OH

.082
Cl
Cl
CH2OH

.083
F
Cl
CH2OH

.084
H
Br
CH2OH

.085
Cl
Br
CH2OH

.086
F
Br
CH2OH

.087
Cl
CF3
CH2OH

.088
F
CF3
CH2OH

.089
F
CH3
CH2OH

.090
F
OCF3
CH2OH

.091
H
Cl
CH2OC(O)CH3

.092
Cl
Cl
CH2OC(O)CH3

.093
F
Cl
CH2OC(O)CH3

.094
H
Br
CH2OC(O)CH3

.095
Cl
Br
CH2OC(O)CH3

.096
F
Br
CH2OC(O)CH3

.097
Cl
CF3
CH2OC(O)CH3

.098
F
CF3
CH2OC(O)CH3

.099
F
CH3
CH2OC(O)CH3

.100
F
OCF3
CH2OC(O)CH3

.101
H
Cl
CH2OCH2CHCH2

.102
Cl
Cl
CH2OCH2CHCH2

.103
F
Cl
CH2OCH2CHCH2

.104
H
Br
CH2OCH2CHCH2

.105
Cl
Br
CH2OCH2CHCH2

.106
F
Br
CH2OCH2CHCH2

.107
Cl
CF3
CH2OCH2CHCH2

.108
F
CF3
CH2OCH2CHCH2

.109
F
CH3
CH2OCH2CHCH2

.110
F
OCF3
CH2OCH2CHCH2

.111
H
Cl
COOH

.112
Cl
Cl
COOH

.113
F
Cl
COOH

.114
H
Br
COOH

.115
Cl
Br
COOH

.116
F
Br
COOH

.117
Cl
CF3
COOH

.118
F
CF3
COOH

.119
F
CH3
COOH

.120
F
OCF3
COOH

.121
H
Cl
COOCH3

.122
Cl
Cl
COOCH3

.123
F
Cl
COOCH3

.124
H
Br
COOCH3

.125
Cl
Br
COOCH3

.126
F
Br
COOCH3

.127
Cl
CF3
COOCH3

.128
F
CF3
COOCH3

.129
F
CH3
COOCH3

.130
F
OCF3
COOCH3

.131
H
Cl
COOCH2CH3

.132
Cl
Cl
COOCH2CH3

.133
F
Cl
COOCH2CH3

.134
H
Br
COOCH2CH3

.135
Cl
Br
COOCH2CH3

.136
F
Br
COOCH2CH3

.137
Cl
CF3
COOCH2CH3

.138
F
CF3
COOCH2CH3

.139
F
CH3
COOCH2CH3

.140
F
OCF3
COOCH2CH3

.141
Cl
Cl
COOCH(CH3)2

.142
F
Cl
COOCH(CH3)2

.143
H
Br
COOCH(CH3)2

.144
Cl
Br
COOCH(CH3)2

.145
F
Br
COOCH(CH3)2

.146
Cl
CF3
COOCH(CH3)2

.147
F
CF3
COOCH(CH3)2

.148
F
CH3
COOCH(CH3)2

.149
F
OCF3
COOCH(CH3)2

.150
F
Cl
COOCH2CHCH2

.151
F
Cl
COOCH2CCH

.152
F
Cl
COOCH2(o-F—C6H5)

.153
H
Cl
COOCH2C6H5

.154
Cl
Cl
COOCH2C6H5

.155
F
Cl
COOCH2C6H5

.156
H
Br
COOCH2C6H5

.157
Cl
Br
COOCH2C6H5

.158
F
Br
COOCH2C6H5

.159
Cl
CF3
COOCH2C6H5

.160
F
CF3
COOCH2C6H5

.161
F
CH3
COOCH2C6H5

.162
F
OCF3
COOCH2C6H5

.163
F
Cl
COOCH2CH2Cl

.164
H
Cl
COSCH(CH3)2

.165
Cl
Cl
COSCH(CH3)2

.166
F
Cl
COSCH(CH3)2

.167
H
Br
COSCH(CH3)2

.168
Cl
Br
COSCH(CH3)2

.169
F
Br
COSCH(CH3)2

.170
Cl
CF3
COSCH(CH3)2

.171
F
CF3
COSCH(CH3)2

.172
F
CH3
COSCH(CH3)2

.173
F
OCF3
COSCH(CH3)2

.174
H
Cl
CONHCH2CCH

.175
Cl
Cl
CONHCH2CCH

.176
F
Cl
CONHCH2CCH

.177
H
Br
CONHCH2CCH

.178
Cl
Br
CONHCH2CCH

.179
F
Br
CONHCH2CCH

.180
Cl
CF3
CONHCH2CCH

.181
F
CF3
CONHCH2CCH

.182
F
CH3
CONHCH2CCH

.183
F
OCF3
CONHCH2CCH

.184
H
Cl
CON(CH2CH3)2

.185
Cl
Cl
CON(CH2CH3)2

.186
F
Cl
CON(CH2CH3)2

.187
H
Br
CON(CH2CH3)2

.188
Cl
Br
CON(CH2CH3)2

.189
F
Br
CON(CH2CH3)2

.190
Cl
CF3
CON(CH2CH3)2

.191
F
CF3
CON(CH2CH3)2

.192
F
CH3
CON(CH2CH3)2

.193
F
OCF3
CON(CH2CH3)2

.194
F
Cl
CON(CH2CHCH2)2

.195
F
Cl
CON(CH2CH3)CH2CHCH2

.196
F
Cl
CONHCH2CH(CH3)2

.197
F
Cl
CONH(SO2CH3)

.198
H
Cl
CHO

.199
Cl
Cl
CHO

.200
F
Cl
CHO

.201
H
Br
CHO

.202
Cl
Br
CHO

.203
F
Br
CHO

.204
Cl
CF3
CHO

.205
F
CF3
CHO

.206
F
CH3
CHO

.207
F
OCF3
CHO

.208
H
Cl
CHNOH

.209
Cl
Cl
CHNOH

.210
F
Cl
CHNOH

.211
H
Br
CHNOH

.212
Cl
Br
CHNOH

.213
F
Br
CHNOH

.214
Cl
CF3
CHNOH

.215
F
CF3
CHNOH

.216
F
CH3
CHNOH

.217
F
OCF3
CHNOH

.218
H
Cl
CHNOCH2CCH

.219
Cl
Cl
CHNOCH2CCH

.220
F
Cl
CHNOCH2CCH

.221
H
Br
CHNOCH2CCH

.222
Cl
Br
CHNOCH2CCH

.223
F
Br
CHNOCH2CCH

.224
Cl
CF3
CHNOCH2CCH

.225
F
CF3
CHNOCH2CCH

.226
F
CH3
CHNOCH2CCH

.227
F
OCF3
CHNOCH2CCH

.228
F
Cl
CHNOCH3

.229
F
Cl
CHNOCH2CHCH2

.230
H
Cl
CH2COOH

.231
Cl
Cl
CH2COOH

.232
F
Cl
CH2COOH

.233
H
Br
CH2COOH

.234
Cl
Br
CH2COOH

.235
F
Br
CH2COOH

.236
Cl
CF3
CH2COOH

.237
F
CF3
CH2COOH

.238
F
CH3
CH2COOH

.239
F
OCF3
CH2COOH

.240
F
Cl
CH2COOCH3

.241
F
Cl
CH2COOCH(CH3)2

.242
F
Cl
CH2COOCH2CHCH2

.243
H
Cl
CH2CH2COOH

.244
Cl
Cl
CH2CH2COOH

.245
F
Cl
CH2CH2COOH

.246
H
Br
CH2CH2COOH

.247
Cl
Br
CH2CH2COOH

.248
F
Br
CH2CH2COOH

.249
Cl
CF3
CH2CH2COOH

.250
F
CF3
CH2CH2COOH

.251
F
CH3
CH2CH2COOH

.252
F
OCF3
CH2CH2COOH

.253
F
Cl
CH2CH2COOCH2CH3

.254
F
Cl
CH2CH2COOCH(CH3)2

.255
F
Cl
CH2CH2COOCH2CHCH2

.256
F
Cl
CH2CH2COOCH2C(CH3)CH2

.257
F
Cl
CH2CH2COOCH2CCH

.258
F
Cl
CH2CH2COOCH(CH3)CCH

.259
F
Cl
CH(OH)CH3

.260
F
Cl
C(O)CH3

.261
F
Cl
CN

.262
Cl
CF3
CN

.263
F
Cl
C(S)NH2

.264
Cl
CF3
C(S)NH2

[0416]

91

TABLE 89

A preferred group of compounds of formula I corresponds to the

general formula

206

(I89), in which the sets of correlated substituents R11, R12 and

R13 are given in Table C, thus disclosing 627 specific compounds of

formula I89.

[0417]

92

TABLE 90

Another preferred group of compounds of formula I

corresponds to the general formula

207

(I90), in which the sets of correlated

substituents R11, R12 and R13

are given in Table C, thus disclosing 627 specific compounds of

formula I90.

[0418]

93

TABLE 91

Another preferred group of compounds of formula I

corresponds to the general formula

208

(I91), in which the sets of correlated substituents R11,

R12 and R13 are given in Table C,

thus disclosing 627 specific compounds of formula I91.

[0419]

94

TABLE 92

Another preferred group of compounds of formula I

corresponds to the general formula

209

(I92), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C,

thus disclosing 627 specific compounds

of formula I92.

[0420]

95

TABLE 93

Another preferred group of compounds of formula I

corresponds to the general formula

210

(I93), in which the sets of correlated substituents

R11, R12, and R13 are given in Table C,

thus disclosing 627 specific compounds of formula I93.

[0421]

96

TABLE 94

Another preferred group of compounds of formula I

corresponds to the general formula

211

(I94), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C,

thus disclosing 627 specifIc compounds of formula I94.

[0422]

97

TABLE 95

Another preferred group of compounds of formula I

corresponds to the general formula

212

(I95), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C,

thus disclosing 627 specific compounds of formula I95.

[0423]

98

TABLE 96

Another preferred group of compounds of formula I

corresponds to the general formula

213

(I96), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C,

thus disclosing 627 specific compounds of formula I96.

[0424]

99

TABLE 97

Another preferred group of compounds of formula I

corresponds to the general formula

214

(I97), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C,

thus disclosing 627 specific compounds of formula I97.

[0425]

100

TABLE 98

Another preferred group of compounds of formula I

corresponds to the general formula

215

(I98), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C,

thus disclosing 627 specific compounds of formula I98.

[0426]

101

TABLE 99

Another preferred group of compounds of formula I

corresponds to the general formula

216

(I99), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C,

thus disclosing 627 specific compounds of formula I99.

[0427]

102

TABLE 100

Another preferred group of compounds of formula I corresponds to the

general formula

217

(I100), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I100.

[0428]

103

TABLE 101

Another preferred group of compounds of formula I corresponds to the

general formula

218

(I101), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I101.

[0429]

104

TABLE 102

Another preferred group of compounds of formula I corresponds to the

general formula

219

(I102), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I102.

[0430]

105

TABLE 103

Another preferred group of compounds of formula I corresPonds to the

general formula

220

(I103), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I103.

[0431]

106

TABLE 104

Another preferred group of compounds of formula I corresponds to the

general formula

221

(I104), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific

compounds of formula I104.

[0432]

107

TABLE 105

Another preferred group of compounds of formula I corresponds to the

general formula

222

(I105), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific

compounds of formula (I105).

[0433]

108

TABLE 106

Another preferred group of compounds of formula I corresponds to the

general formula

223

(I106), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific

compounds of formula I106.

[0434]

109

TABLE 107

Another preferred group of compounds of formula I corresponds to the

general formula

224

(I107), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I107.

[0435]

110

TABLE 108

Another preferred group of compounds of formula I corresponds to the

general formula

225

(I108), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I108.

[0436]

111

TABLE 109

Another preferred group of compounds of formula I corresponds to the

general formula

226

(I109), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I109.

[0437]

112

TABLE 110

Another preferred group of compounds of formula I corresponds to the

general formula

227

(I110), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I110.

[0438]

113

TABLE 111

Another preferred group of compounds of formula I corresponds to the

general formula

228

(I111), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I111.

[0439]

114

TABLE 112

Another preferred group of compounds of formula I corresponds to the

general formula

229

(I112), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I112.

[0440]

115

TABLE 113

Another preferred group of compounds of formula I corresponds to the

general formula

230

(I113), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I113.

[0441]

116

TABLE 114

Another preferred group of compounds of formula I corresponds to the

general formula

231

(I114), in which the sets of correlated substituents

R11, R12 are R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I114.

[0442]

117

TABLE 115

Another preferred group of compounds of formula I corresponds to the

general formula

232

(I115), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I115.

[0443]

118

TABLE 116

Another preferred group of compounds of formula I corresponds to the

general formula

233

(I116), in which the sets of correlated

substituents R11, R12 and R13 are given in Table C, thus disclosing 627

specific compounds of formula I116.

[0444]

119

TABLE 117

Another preferred group of compounds of formula I corresponds to the

general formula

234

(I117), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I117.

[0445]

120

TABLE 118

Another preferred group of compounds of formula I corresponds to the

general formula

235

(I118), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I118.

[0446]

121

TABLE 119

Another preferred group of compounds of formula I corresponds to the

general formula

236

(I119), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I119.

[0447]

122

TABLE 120

Another preferred group of compounds of formula I corresponds to the

general formula

237

(I120), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I120.

[0448]

123

TABLE 121

Another preferred group of compounds of formula I corresponds to the

general formula

238

(I121), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I121.

[0449]

124

TABLE 122

Another preferred group of compounds of formula I corresponds to the

general formula

239

(I122), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I122.

[0450]

125

TABLE 123

Another preferred group of compounds of formula I corresponds to the

general formula

240

(I123), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I123.

[0451]

126

TABLE 124

Another preferred group of compounds of formula I corresponds to the

general formula

241

(I124), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I124.

[0452]

127

TABLE 125

Another preferred group of compounds of formula I corresponds to the

general formula

242

(I125), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I125.

[0453]

128

TABLE 126

Another preferred group of compounds of formula I corresponds to the

general formula

243

(I126), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I126.

[0454]

129

TABLE 127

Another preferred group of compounds of formula I corresponds to the

general formula

244

(I127), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I127.

[0455]

130

TABLE 128

Another preferred group of compounds of formula I corresponds to the

general formula

245

(I128), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I128.

[0456]

131

TABLE 129

Another preferred group of compounds of formula I corresponds to the

general formula

246

(I129), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I129.

[0457]

132

TABLE 130

Another preferred group of compounds of formula I corresponds to the

general formula

247

(I130), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I130.

[0458]

133

TABLE 131

Another preferred group of compounds of formula I corresponds to the

general formula

248

(I131), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I131.

[0459]

134

TABLE 132

Another preferred group of compounds of formula I corresponds to the

general formula

249

(I132), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I132.

[0460]

135

TABLE 133

Another preferred group of compounds of formula I corresponds to the

general formula

250

(I133), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I133.

[0461]

136

TABLE 134

Another preferred group of compounds of formula I corresponds to the

general formula

251

(I134), in which the sets of correlated substituents R11,

R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I134.

[0462]

137

TABLE 135

Another preferred group of compounds of formula I corresponds to the

general formula

252

(I135), in which the sets of correlated substituents R11,

R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I135.

[0463]

138

TABLE 136

Another preferred group of compounds of formula I corresponds to the

general formula

253

(I136), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I136.

[0464]

139

TABLE 137

Another preferred group of compounds of formula I corresponds to the

general formula

254

(I137), in which the sets of correlated substituents R11,

R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I137.

[0465]

140

TABLE 138

Another preferred group of compounds of formula I corresponds to the

general formula

255

(I138), in which the sets of correlated substituents R11,

R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I138.

[0466]

141

TABLE 139

Another preferred group of compounds of formula I corresponds to the

general formula

256

(I139), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I139.

[0467]

142

TABLE 140

Another preferred group of compounds of formula I corresponds to the

general formula

257

(I140), in which the sets of correlated substituents

R11, R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I140.

[0468]

143

TABLE 141

Another preferred group of compounds of formula I corresponds to the

general formula

258

(I141), in which the sets of correlated substituents R11,

R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I141.

[0469]

144

TABLE 142

Another preferred group of compounds of formula I corresponds to the

general formula

259

(I142), in which the sets of correlated substituents R11,

R12 and R13 are given in Table C, thus disclosing 627 specific com-

pounds of formula I142.

[0470]

145

TABLE C

Compd. No.
R11
R12
R13

.001
H
Cl
CH2CHCH2

.002
Cl
Cl
CH2CHCH2

.003
F
Cl
CH2CHCH2

.004
H
Br
CH2CHCH2

.005
Cl
Br
CH2CHCH2

.006
F
Br
CH2CHCH2

.007
H
I
CH2CHCH2

.008
Cl
I
CH2CHCH2

.009
F
I
CH2CHCH2

.010
H
CH3
CH2CHCH2

.011
Cl
CH3
CH2CHCH2

.012
F
CH3
CH2CHCH2

.013
H
OH
CH2CHCH2

.014
Cl
OH
CH2CHCH2

.015
F
OH
CH2CHCH2

.016
H
OCF3
CH2CHCH2

.017
Cl
OCF3
CH2CHCH2

.018
F
OCF3
CH2CHCH2

.019
H
CHO
CH2CHCH2

.020
Cl
CHO
CH2CHCH2

.021
F
CHO
CH2CHCH2

.022
H
CHF2
CH2CHCH2

.023
Cl
CHF2
CH2CHCH2

.024
F
CHF2
CH2CHCH2

.025
H
COOH
CH2CHCH2

.026
Cl
COOH
CH2CHCH2

.027
F
COOH
CH2CHCH2

.028
H
COOCH2CH3
CH2CHCH2

.029
CL
COOCH2CH3
CH2CHCH2

.030
F
COOCH2CH3
CH2CHCH2

.031
H
CN
CH2CHCH2

.032
Cl
CN
CH2CHCH2

.033
F
CN
CH2CHCH2

.034
H
Cl
CH2C6H5

.035
Cl
Cl
CH2C6H5

.036
F
Cl
CH2C6H5

.037
H
Br
CH2C6H5

.038
Cl
Br
CH2C6H5

.039
F
Br
CH2C6H5

.040
H
I
CH2C6H5

.041
Cl
I
CH2C6H5

.042
F
I
CH2C6H5

.043
H
CH3
CH2C6H5

.044
Cl
CH3
CH2C6H5

.045
F
CH3
CH2C6H5

.046
H
OH
CH2C6H5

.047
Cl
OH
CH2C6H5

.048
F
OH
CH2C6H5

.049
H
OCF3
CH2C6H5

.050
Cl
OCF3
CH2C6H5

.051
F
OCF3
CH2C6H5

.052
H
CHO
CH2C6H5

.053
Cl
CHO
CH2C6H5

.054
F
CHO
CH2C6H5

.055
H
CHF2
CH2C6H5

.056
Cl
CHF2
CH2C6H5

.057
F
CHF2
CH2C6H5

.058
H
COOH
CH2C6H5

.059
Cl
COOH
CH2C6H5

.060
F
COOH
CH2C6H5

.061
H
COOCH2CH3
CH2C6H5

.062
Cl
COOCH2CH3
CH2C6H5

.063
F
COOCH2CH3
CH2C6H5

.064
H
CN
CH2C6H5

.065
Cl
CN
CH2C6H5

.066
F
CN
CH2C6H5

.067
H
Cl
CH2CCH

.068
Cl
Cl
CH2CCH

.069
F
Cl
CH2CCH

.070
H
Br
CH2CCH

.071
Cl
Br
CH2CCH

.072
F
Br
CH2CCH

.073
H
I
CH2CCH

.074
Cl
I
CH2CCH

.075
F
I
CH2CCH

.076
H
CH3
CH2CCH

.077
Cl
CH3
CH2CCH

.078
F
CH3
CH2CCH

.079
H
OH
CH2CCH

.080
Cl
OH
CH2CCH

.081
F
OH
CH2CCH

.082
H
OCF3
CH2CCH

.083
Cl
OCF3
CH2CCH

.084
F
OCF3
CH2CCH

.085
H
CHO
CH2CCH

.086
Cl
CHO
CH2CCH

.087
F
CHO
CH2CCH

.088
H
CHF2
CH2CCH

.089
Cl
CHF2
CH2CCH

.090
F
CHF2
CH2CCH

.091
H
COOH
CH2CCH

.092
Cl
COOH
CH2CCH

.093
F
COOH
CH2CCH

.094
H
COOCH2CH3
CH2CCH

.095
Cl
COOCH2CH3
CH2CCH

.096
F
COOCH2CH3
CH2CCH

.097
H
CN
CH2CCH

.098
Cl
CN
CH2CCH

.099
F
CN
CH2CCH

.100
H
Cl
CH2COOH

.101
Cl
Cl
CH2COOH

.102
F
Cl
CH2COOH

.103
H
Br
CH2COOH

.104
Cl
Br
CH2COOH

.105
F
Br
CH2COOH

.106
H
I
CH2COOH

.107
Cl
I
CH2COOH

.108
F
I
CH2COOH

.109
H
CH3
CH2COOH

.110
Cl
CH3
CH2COOH

.111
F
CH3
CH2COOH

.112
H
OH
CH2COOH

.113
Cl
OH
CH2COOH

.114
F
OH
CH2COOH

.115
H
OCF3
CH2COOH

.116
Cl
OCF3
CH2COOH

.117
F
OCF3
CH2COOH

.118
H
CHO
CH2COOH

.119
Cl
CHO
CH2COOH

.120
F
CHO
CH2COOH

.121
H
CHF2
CH2COOH

.122
Cl
CHF2
CH2COOH

.123
F
CHF2
CH2COOH

.124
H
COOH
CH2COOH

.125
Cl
COOH
CH2COOH

.126
F
COOH
CH2COOH

.127
H
COOCH2CH3
CH2COOH

.128
Cl
COOCH2CH3
CH2COOH

.129
F
COOCH2CH3
CH2COOH

.130
H
CN
CH2COOH

.131
Cl
CN
CH2COOH

.132
F
CN
CH2COOH

.133
H
Cl
CH2COOCH3

.134
Cl
Cl
CH2COOCH3

.135
F
Cl
CH2COOCH3

.136
H
Br
CH2COOCH3

.137
Cl
Br
CH2COOCH3

.138
F
Br
CH2COOCH3

.139
H
I
CH2COOCH3

.140
Cl
I
CH2COOCH3

.141
F
I
CH2COOCH3

.142
H
CH3
CH2COOCH3

.143
Cl
CH3
CH2COOCH3

.144
F
CH3
CH2COOCH3

.145
H
OH
CH2COOCH3

.146
Cl
OH
CH2COOCH3

.147
F
OH
CH2COOCH3

.148
H
OCF3
CH2COOCH3

.149
Cl
OCF3
CH2COOCH3

.150
F
OCF3
CH2COOCH3

.151
H
CHO
CH2COOCH3

.152
Cl
CHO
CH2COOCH3

.153
F
CHO
CH2COOCH3

.154
H
CHF2
CH2COOCH3

.155
Cl
CHF2
CH2COOCH3

.156
F
CHF2
CH2COOCH3

.157
H
COOH
CH2COOCH3

.158
Cl
COOH
CH2COOCH3

.159
F
COOH
CH2COOCH3

.160
H
COOCH2CH3
CH2COOCH3

.161
Cl
COOCH2CH3
CH2COOCH3

.162
F
COOCH2CH3
CH2COOCH3

.163
H
CN
CH2COOCH3

.164
Cl
CN
CH2COOCH3

.165
F
CN
CH2COOCH3

.166
H
Cl
OH

.167
Cl
Cl
OH

.168
F
Cl
OH

.169
H
Br
OH

.170
Cl
Br
OH

.171
F
Br
OH

.172
H
I
OH

.173
Cl
I
OH

.174
F
I
OH

.175
H
CH3
OH

.176
Cl
CH3
OH

.177
F
CH3
OH

.178
H
OH
OH

.179
Cl
OH
OH

.180
F
OH
OH

.181
H
OCF3
OH

.182
Cl
OCF3
OH

.183
F
OCF3
OH

.184
H
CHO
OH

.185
Cl
CHO
OH

.186
F
CHO
OH

.187
H
CHF2
OH

.188
Cl
CHF2
OH

.189
F
CHF2
OH

.190
H
COOH
OH

.191
Cl
COOH
OH

.192
F
COOH
OH

.193
H
COOCH2CH3
OH

.194
Cl
COOCH2CH3
OH

.195
F
COOCH2CH3
OH

.196
H
CN
OH

.197
Cl
CN
OH

.198
F
CN
OH

.199
H
Cl
OCH2CHCH2

.200
Cl
Cl
OCH2CHCH2

.201
F
Cl
OCH2CHCH2

.202
H
Br
OCH2CHCH2

.203
Cl
Br
OCH2CHCH2

.204
F
Br
OCH2CHCH2

.205
H
I
OCH2CHCH2

.206
Cl
I
OCH2CHCH2

.207
F
I
OCH2CHCH2

.208
H
CH3
OCH2CHCH2

.209
Cl
CH3
OCH2CHCH2

.210
F
CH3
OCH2CHCH2

.211
H
OH
OCH2CHCH2

.212
Cl
OH
OCH2CHCH2

.213
F
OH
OCH2CHCH2

.214
H
OCF3
OCH2CHCH2

.215
Cl
OCF3
OCH2CHCH2

.216
F
OCF3
OCH2CHCH2

.217
H
CHO
OCH2CHCH2

.218
Cl
CHO
OCH2CHCH2

.219
F
CHO
OCH2CHCH2

.220
H
CHF2
OCH2CHCH2

.221
Cl
CHF2
OCH2CHCH2

.222
F
CHF2
OCH2CHCH2

.223
H
COOH
OCH2CHCH2

.224
Cl
COOH
OCH2CHCH2

.225
F
COOH
OCH2CHCH2

.226
H
COOCH2CH3
OCH2CHCH2

.227
Cl
COOCH2CH3
OCH2CHCH2

.228
F
COOCH2CH3
OCH2CHCH2

.229
H
CN
OCH2CHCH2

.230
Cl
CN
OCH2CHCH2

.231
F
CN
OCH2CHCH2

.232
H
Cl
OCH2C6H5

.233
Cl
Cl
OCH2C6H5

.234
F
Cl
OCH2C6H5

.235
H
Br
OCH2C6H5

.236
Cl
Br
OCH2C6H5

.237
F
Br
OCH2C6H5

.238
H
I
OCH2C6H5

.239
Cl
I
OCH2C6H5

.240
F
I
OCH2C6H5

.241
H
CH3
OCH2C6H5

.242
Cl
CH3
OCH2C6H5

.243
F
CH3
OCH2C6H5

.244
H
OH
OCH2C6H5

.245
Cl
OH
OCH2C6H5

.246
F
OH
OCH2C6H5

.247
H
OCF3
OCH2C6H5

.248
Cl
OCF3
OCH2C6H5

.249
F
OCF3
OCH2C6H5

.250
H
CHO
OCH2C6H5

.251
Cl
CHO
OCH2C6H5

.252
F
CHO
OCH2C6H5

.253
H
CHF2
OCH2C6H5

.254
Cl
CHF2
OCH2C6H5

.255
F
CHF2
OCH2C6H5

.256
H
COOH
OCH2C6H5

.257
Cl
COOH
OCH2C6H5

.258
F
COOH
OCH2C6H5

.259
H
COOCH2CH3
OCH2C6H5

.260
Cl
COOCH2CH3
OCH2C6H5

.261
F
COOCH2CH3
OCH2C6H5

.262
H
CN
OCH2C6H5

.263
Cl
CN
OCH2C6H5

.264
F
CN
OCH2C6H5

.265
H
Cl
OCH2COOH

.266
Cl
Cl
OCH2COOH

.267
F
Cl
OCH2COOH

.268
H
Br
OCH2COOH

.269
Cl
Br
OCH2COOH

.270
F
Br
OCH2COOH

.271
H
I
OCH2COOH

.272
Cl
I
OCH2COOH

.273
F
I
OCH2COOH

.274
H
CH3
OCH2COOH

.275
Cl
CH3
OCH2COOH

.276
F
CH3
OCH2COOH

.277
H
OH
OCH2COOH

.278
Cl
OH
OCH2COOH

.279
F
OH
OCH2COOH

.280
H
OCF3
OCH2COOH

.281
Cl
OCF3
OCH2COOH

.282
F
OCF3
OCH2COOH

.283
H
CHO
OCH2COOH

.284
Cl
CHO
OCH2COOH

.285
F
CHO
OCH2COOH

.286
H
CHF2
OCH2COOH

.287
Cl
CHF2
OCH2COOH

.288
F
CHF2
OCH2COOH

.289
H
COOH
OCH2COOH

.290
Cl
COOH
OCH2COOH

.291
F
COOH
OCH2COOH

.292
H
COOCH2CH3
OCH2COOH

.293
Cl
COOCH2CH3
OCH2COOH

.294
F
COOCH2CH3
OCH2COOH

.295
H
CN
OCH2COOH

.296
Cl
CN
OCH2COOH

.297
F
CN
OCH2COOH

.298
H
Cl
OCH2COOCH3

.299
Cl
Cl
OCH2COOCH3

.300
F
Cl
OCH2COOCH3

.301
H
Br
OCH2COOCH3

.302
Cl
Br
OCH2COOCH3

.303
F
Br
OCH2COOCH3

.304
H
I
OCH2COOCH3

.305
Cl
I
OCH2COOCH3

.306
F
I
OCH2COOCH3

.307
H
CH3
OCH2COOCH3

.308
Cl
CH3
OCH2COOCH3

.309
F
CH3
OCH2COOCH3

.310
H
OH
OCH2COOCH3

.311
Cl
OH
OCH2COOCH3

.312
F
OH
OCH2COOCH3

.313
H
OCF3
OCH2COOCH3

.314
Cl
OCF3
OCH2COOCH3

.315
F
OCF3
OCH2COOCH3

.316
H
CHO
OCH2COOCH3

.317
Cl
CHO
OCH2COOCH3

.318
F
CHO
OCH2COOCH3

.319
H
CHF2
OCH2COOCH3

.320
Cl
CHF2
OCH2COOCH3

.321
F
CHF2
OCH2COOCH3

.322
H
COOH
OCH2COOCH3

.323
Cl
COOH
OCH2COOCH3

.324
F
COOH
OCH2COOCH3

.325
H
COOCH2CH3
OCH2COOCH3

.326
Cl
COOCH2CH3
OCH2COOCH3

.327
F
COOCH2CH3
OCH2COOCH3

.328
H
CN
OCH2COOCH3

.329
Cl
CN
OCH2COOCH3

.330
F
CN
OCH2COOCH3

.331
H
Cl
CH2CHO

.332
Cl
Cl
CH2CHO

.333
F
Cl
CH2CHO

.334
H
Br
CH2CHO

.335
Cl
Br
CH2CHO

.336
F
Br
CH2CHO

.337
H
I
CH2CHO

.338
Cl
I
CH2CHO

.339
F
I
CH2CHO

.340
H
CH3
CH2CHO

.341
Cl
CH3
CH2CHO

.342
F
CH3
CH2CHO

.343
H
OH
CH2CHO

.344
Cl
OH
CH2CHO

.345
F
OH
CH2CHO

.346
H
OCF3
CH2CHO

.347
Cl
OCF3
CH2CHO

.348
F
OCF3
CH2CHO

.349
H
CHO
CH2CHO

.350
Cl
CHO
CH2CHO

.351
F
CHO
CH2CHO

.352
H
CHF2
CH2CHO

.353
Cl
CHF2
CH2CHO

.354
F
CHF2
CH2CHO

.355
H
COOH
CH2CHO

.356
Cl
COOH
CH2CHO

.357
F
COOH
CH2CHO

.358
H
COOCH2CH3
CH2CHO

.359
Cl
COOCH2CH3
CH2CHO

.360
F
COOCH2CH3
CH2CHO

.361
H
CN
CH2CHO

.362
Cl
CN
CH2CHO

.363
F
CN
CH2CHO

.364
H
Cl
OCH2CHO

.365
Cl
Cl
OCH2CHO

.366
F
Cl
OCH2CHO

.367
H
Br
OCH2CHO

.368
Cl
Br
OCH2CHO

.369
F
Br
OCH2CHO

.370
H
I
OCH2CHO

.371
Cl
I
OCH2CHO

.372
F
I
OCH2CHO

.373
H
CH3
OCH2CHO

.374
Cl
CH3
OCH2CHO

.375
F
CH3
OCH2CHO

.376
H
OH
OCH2CHO

.377
Cl
OH
OCH2CHO

.378
F
OH
OCH2CHO

.379
H
OCF3
OCH2CHO

.380
Cl
OCF3
OCH2CHO

.381
F
OCF3
OCH2CHO

.382
H
CHO
OCH2CHO

.383
Cl
CHO
OCH2CHO

.384
F
CHO
OCH2CHO

.385
H
CHF2
OCH2CHO

.386
Cl
CHF2
OCH2CHO

.387
F
CHF2
OCH2CHO

.388
H
COOH
OCH2CHO

.389
Cl
COOH
OCH2CHO

.390
F
COOH
OCH2CHO

.391
H
COOCH2CH3
OCH2CHO

.392
Cl
COOCH2CH3
OCH2CHO

.393
F
COOCH2CH3
OCH2CHO

.394
H
CN
OCH2CHO

.395
Cl
CN
OCH2CHO

.396
F
CN
OCH2CHO

.397
H
Cl
OCH3

.398
Cl
Cl
OCH3

.399
F
Cl
OCH3

.400
H
Br
OCH3

.401
Cl
Br
OCH3

.402
F
Br
OCH3

.403
H
I
OCH3

.404
Cl
I
OCH3

.405
F
I
OCH3

.406
H
CH3
OCH3

.407
Cl
CH3
OCH3

.408
F
CH3
OCH3

.409
H
OH
OCH3

.410
Cl
OH
OCH3

.411
F
OH
OCH3

.412
H
OCF3
OCH3

.413
Cl
OCF3
OCH3

.414
F
OCF3
OCH3

.415
H
CHO
OCH3

.416
Cl
CHO
OCH3

.417
F
CHO
OCH3

.418
H
CHF2
OCH3

.419
Cl
CHF2
OCH3

.420
F
CHF2
OCH3

.421
H
COOH
OCH3

.422
Cl
COOH
OCH3

.423
F
COOH
OCH3

.424
H
COOCH2CH3
OCH3

.425
Cl
COOCH2CH3
OCH3

.426
F
COOCH2CH3
OCH3

.427
H
CN
OCH3

.428
Cl
CN
OCH3

.429
F
CN
OCH3

.430
H
Cl
CH2OCH3

.431
Cl
Cl
CH2OCH3

.432
F
Cl
CH2OCH3

.433
H
Br
CH2OCH3

.434
Cl
Br
CH2OCH3

.435
F
Br
CH2OCH3

.436
H
I
CH2OCH3

.437
Cl
I
CH2OCH3

.438
F
I
CH2OCH3

.439
H
CH3
CH2OCH3

.440
Cl
CH3
CH2OCH3

.441
F
CH3
CH2OCH3

.442
H
OH
CH2OCH3

.443
Cl
OH
CH2OCH3

.444
F
OH
CH2OCH3

.445
H
OCF3
CH2OCH3

.446
Cl
OCF3
CH2OCH3

.447
F
OCF3
CH2OCH3

.448
H
CHO
CH2OCH3

.449
Cl
CHO
CH2OCH3

.450
F
CHO
CH2OCH3

.451
H
CHF2
CH2OCH3

.452
Cl
CHF2
CH2OCH3

.453
F
CHF2
CH2OCH3

.454
H
COOH
CH2OCH3

.455
Cl
COOH
CH2OCH3

.456
F
COOH
CH2OCH3

.457
H
COOCH2CH3
CH2OCH3

.458
Cl
COOCH2CH3
CH2OCH3

.459
F
COOCH2CH3
CH2OCH3

.460
H
CN
CH2OCH3

.461
Cl
CN
CH2OCH3

.462
F
CN
CH2OCH3

.463
H
Cl
CH2SCH3

.464
Cl
Cl
CH2SCH3

.465
F
Cl
CH2SCH3

.466
H
Br
CH2SCH3

.467
Cl
Br
CH2SCH3

.468
F
Br
CH2SCH3

.469
H
I
CH2SCH3

.470
Cl
I
CH2SCH3

.471
F
I
CH2SCH3

.472
H
CH3
CH2SCH3

.473
Cl
CH3
CH2SCH3

.474
F
CH3
CH2SCH3

.475
H
OH
CH2SCH3

.476
Cl
OH
CH2SCH3

.477
F
OH
CH2SCH3

.478
H
OCF3
CH2SCH3

.479
Cl
OCF3
CH2SCH3

.480
F
OCF3
CH2SCH3

.481
H
CHO
CH2SCH3

.482
Cl
CHO
CH2SCH3

.483
F
CHO
CH2SCH3

.484
H
CHF2
CH2SCH3

.485
Cl
CHF2
CH2SCH3

.486
F
CHF2
CH2SCH3

.487
H
COOH
CH2SCH3

.488
Cl
COOH
CH2SCH3

.489
F
COOH
CH2SCH3

.490
H
COOCH2CH3
CH2SCH3

.491
Cl
COOCH2CH3
CH2SCH3

.492
F
COOCH2CH3
CH2SCH3

.493
H
CN
CH2SCH3

.494
Cl
CN
CH2SCH3

.495
F
CN
CH2SCH3

.496
H
Cl
OCH2OCH3

.497
Cl
Cl
OCH2OCH3

.498
F
Cl
OCH2OCH3

.499
H
Br
OCH2OCH3

.500
Cl
Br
OCH2OCH3

.501
F
Br
OCH2OCH3

.502
H
I
OCH2OCH3

.503
Cl
I
OCH2OCH3

.504
F
I
OCH2OCH3

.505
H
CH3
OCH2OCH3

.506
Cl
CH3
OCH2OCH3

.507
F
CH3
OCH2OCH3

.508
H
OH
OCH2OCH3

.509
Cl
OH
OCH2OCH3

.510
F
OH
OCH2OCH3

.511
H
OCF3
OCH2OCH3

.512
Cl
OCF3
OCH2OCH3

.513
F
OCF3
OCH2OCH3

.514
H
CHO
OCH2OCH3

.515
Cl
CHO
OCH2OCH3

.516
F
CHO
OCH2OCH3

.517
H
CHF2
OCH2OCH3

.518
Cl
CHF2
OCH2OCH3

.519
F
CHF2
OCH2OCH3

.520
H
COOH
OCH2OCH3

.521
Cl
COOH
OCH2OCH3

.522
F
COOH
OCH2OCH3

.523
H
COOCH2CH3
OCH2OCH3

.524
Cl
COOCH2CH3
OCH2OCH3

.525
F
COOCH2CH3
OCH2OCH3

.526
H
CN
OCH2OCH3

.527
Cl
CN
OCH2OCH3

.528
F
CN
OCH2OCH3

.529
H
Cl
OCH2SCH3

.530
Cl
Cl
OCH2SCH3

.531
F
Cl
OCH2SCH3

.532
H
Br
OCH2SCH3

.533
Cl
Br
OCH2SCH3

.534
F
Br
OCH2SCH3

.535
H
I
OCH2SCH3

.536
Cl
I
OCH2SCH3

.537
F
I
OCH2SCH3

.538
H
CH3
OCH2SCH3

.539
Cl
CH3
OCH2SCH3

.540
F
CH3
OCH2SCH3

.541
H
OH
OCH2SCH3

.542
Cl
OH
OCH2SCH3

.543
F
OH
OCH2SCH3

.544
H
OCF3
OCH2SCH3

.545
Cl
OCF3
OCH2SCH3

.546
F
OCF3
OCH2SCH3

.547
H
CHO
OCH2SCH3

.548
Cl
CHO
OCH2SCH3

.549
F
CHO
OCH2SCH3

.550
H
CHF2
OCH2SCH3

.551
Cl
CHF2
OCH2SCH3

.552
F
CHF2
OCH2SCH3

.553
H
COOH
OCH2SCH3

.554
Cl
COOH
OCH2SCH3

.555
F
COOH
OCH2SCH3

.556
H
COOCH2CH3
OCH2SCH3

.557
Cl
COOCH2CH3
OCH2SCH3

.558
F
COOCH2CH3
OCH2SCH3

.559
H
CN
OCH2SCH3

.560
Cl
CN
OCH2SCH3

.561
F
CN
OCH2SCH3

.562
H
Cl
OCH2CH2CN

.563
Cl
Cl
OCH2CH2CN

.564
F
Cl
OCH2CH2CN

.565
H
Br
OCH2CH2CN

.566
Cl
Br
OCH2CH2CN

.567
F
Br
OCH2CH2CN

.568
H
I
OCH2CH2CN

.569
Cl
I
OCH2CH2CN

.570
F
I
OCH2CH2CN

.571
H
CH3
OCH2CH2CN

.572
Cl
CH3
OCH2CH2CN

.573
F
CH3
OCH2CH2CN

.574
H
OH
OCH2CH2CN

.575
Cl
OH
OCH2CH2CN

.576
F
OH
OCH2CH2CN

.577
H
OCF3
OCH2CH2CN

.578
Cl
OCF3
OCH2CH2CN

.579
F
OCF3
OCH2CH2CN

.580
H
CHO
OCH2CH2CN

.581
Cl
CHO
OCH2CH2CN

.582
F
CHO
OCH2CH2CN

.583
H
CHF2
OCH2CH2CN

.584
Cl
CHF2
OCH2CH2CN

.585
F
CHF2
OCH2CH2CN

.586
H
COOH
OCH2CH2CN

.587
Cl
COOH
OCH2CH2CN

.588
F
COOH
OCH2CH2CN

.589
H
COOCH2CH3
OCH2CH2CN

.590
Cl
COOCH2CH3
OCH2CH2CN

.591
F
COOCH2CH3
OCH2CH2CN

.592
H
CN
OCH2CH2CN

.593
Cl
CN
OCH2CH2CN

.594
F
CN
OCH2CH2CN

.595
H
Cl
CH2CH2CN

.596
Cl
Cl
CH2CH2CN

.597
F
Cl
CH2CH2CN

.598
H
Br
CH2CH2CN

.599
Cl
Br
CH2CH2CN

.600
F
Br
CH2CH2CN

.601
H
I
CH2CH2CN

.602
Cl
I
CH2CH2CN

.603
F
I
CH2CH2CN

.604
H
CH3
CH2CH2CN

.605
Cl
CH3
CH2CH2CN

.606
F
CH3
CH2CH2CN

.607
H
OH
CH2CH2CN

.608
Cl
OH
CH2CH2CN

.609
F
OH
CH2CH2CN

.610
H
OCF3
CH2CH2CN

.611
Cl
OCF3
CH2CH2CN

.612
F
OCF3
CH2CH2CN

.613
H
CHO
CH2CH2CN

.614
Cl
CHO
CH2CH2CN

.615
F
CHO
CH2CH2CN

.616
H
CHF2
CH2CH2CN

.617
Cl
CHF2
CH2CH2CN

.618
F
CHF2
CH2CH2CN

.619
H
COOH
CH2CH2CN

.620
Cl
COOH
CH2CH2CN

.621
F
COOH
CH2CH2CN

.622
H
COOCH2CH3
CH2CH2CN

.623
Cl
COOCH2CH3
CH2CH2CN

.624
F
COOCH2CH3
CH2CH2CN

.625
H
CN
CH2CH2CN

.626
Cl
CN
CH2CH2CN

.627
F
CN
CH2CH2CN

[0471]

146

TABLE 143

A preferred group of compounds of formula I corresponds to the

general formula

260

(I143), in which the sets of correlated substituents R11, R12

and R13 are given in Table D, thus disclosing 627 specific compounds of

formula I143.

[0472]

147

TABLE 144

Another preferred group of compounds of formula I corresponds to the

general formula

261

(I144), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I444.

[0473]

148

TABLE 145

Another preferred group of compounds of formula I corresponds to the

general formula

262

(I145), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific com-

pounds of formula I145.

[0474]

149

TABLE 146

Another preferred group of compounds of formula I corresponds to the

general formula

263

(I146), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I146.

[0475]

150

TABLE 147

Another preferred group of compounds of formula I corresponds to the

general formula

264

(I147), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific com-

pounds of formula I147.

[0476]

151

TABLE 148

Another preferred group of compounds of formula I corresponds to the

general formula

265

(I148), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific com-

pounds of formula I148.

[0477]

152

TABLE 149

Another preferred group of compounds of formula I corresponds to the

general formula

266

(I149), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific com-

pounds of formula I149.

[0478]

153

TABLE 150

Another preferred group of compounds of formula I corresponds to the

general formula

267

(I150), in which the sets of correlaqted substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I150.

[0479]

154

TABLE 151

Another preferred group of compounds of formula I corresponds to the

general formula

268

(I151), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I151.

[0480]

155

TABLE 152

Another preferred group of compounds of formula I corresponds to the

general formula

269

(I152), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I152.

[0481]

156

TABLE 153

Another preferred group of compounds of formula I corresponds to the

general formula

270

(I153), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I153.

[0482]

157

TABLE 154

Another preferred group of compounds of formula I corresponds to the

general formula

271

(I154), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I154.

[0483]

158

TABLE 155

Another preferred group of compounds of formula I corresponds to the

general formula

272

(I155), in which the sets of correlated

substituents R11 , R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I155.

[0484]

159

TABLE 156

Another preferred froup of compounds of formula I corresponds to the

general formula

273

(I156), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I156.

[0485]

160

TABLE 157

Another preferred group of compounds of formula I corresponds to the

general formula

274

(I157), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I157.

[0486]

161

TABLE 158

Another preferred group of compounds of formula I corresponds to the

general formula

275

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I158.

[0487]

162

TABLE 159

Another preferred group of compounds of formula I corresponds to the

general formula

276

(I159, in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I159.

[0488]

163

TABLE 160

Another preferred group of compounds of formula I corresponds to the

general formula

277

(I160), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I160.

[0489]

164

TABLE 161

Another preferred group of compounds of formula I corresponds to the

general formula

278

(I161), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I161.

[0490]

165

TABLE 162

Another preferred group of compounds of formula I corresponds to the

general formula

279

(I162), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I162.

[0491]

166

TABLE 163

Another preferred group of compounds of formula I corresponds to the

general formula

280

(I163), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I163.

[0492]

167

TABLE 164

Another preferred group of compounds of formula I corresponds to the

general formula

281

(I164), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I164.

[0493]

168

TABLE 165

Another preferred group of compounds of formula I corresponds to the

general formula

282

(I165), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I165.

[0494]

169

TABLE 166

Another preferred group of compounds of formula I corresponds to the

general formula

283

(I166), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I166.

[0495]

170

TABLE 167

Another preferred group of compounds of formula I corresponds to the

general formula

284

(I167), in which the sets of correlated cubstituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I167.

[0496]

171

TABLE 168

Another preferred group of compounds of formula I corresponds to the

general formula

285

(I168), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I168.

[0497]

172

TABLE 169

Another preferred group of compounds of formula I corresponds to the

general formula

286

(I169), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I169.

[0498]

173

TABLE 170

Another preferred group of compounds of formula I corresponds to the

general formula

287

(I170), in which the sets of correlated

substituents R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I170.

[0499]

174

TABLE 171

Another preffered group of compounds of formula I corresponds to the

general formula

288

(I171), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I171.

[0500]

175

TABLE 172

Another preferred froup of compounds of formula I corresponds to the

general formula

289

(I172), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I172.

[0501]

176

TABLE 173

Another preferred group of compounds of formula I corresponds to the

general formula

290

(I173), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I173.

[0502]

177

TABLE 174

Another preferred group of compounds of formula I corresponds to the

general formula

291

(I174), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I174.

[0503]

178

TABLE 175

Another preferred group of compounds of formula I corresponds to the

general formula

292

(I175), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I175.

[0504]

179

TABLE 176

Another preferred group of compounds of formula I corresponds to the

general formula

293

(I176), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I176.

[0505]

180

TABLE 177

Another preferred group of compounds of formula I corresponds to the

general formula

294

(I177), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I177.

[0506]

181

TABLE 178

Another preferred group of compounds of formula I corresponds to the

general formula

295

(I178), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I178.

[0507]

182

TABLE 179

Another preferred group of compounds of formula I corresponds to the

general formula

296

(I179), in whichy the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I179.

[0508]

183

TABLE 180

Another preferred group of compounds of formula I corresponds to the

general formula

297

(I180), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I180.

[0509]

184

TABLE 181

Another preferred group of compounds of formula I corresponds to the

general formula

298

(I181), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I181.

[0510]

185

TABLE 182

Another preferred group of compounds of formula I corresponds to the

general formula

299

(I182), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I182.

[0511]

186

TABLE 183

Another preferred group of compounds of formula I corresponds to the

general formula

300

(I183), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I183.

[0512]

187

TABLE 184

Another preferred group of compounds of formula I corresponds to the

general formula

301

(I184), in which the sets of compounds substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I184.

[0513]

188

TABLE 185

Another preferred group of compounds of formula I corresponds to the

general formula

302

(I185), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I185.

[0514]

189

TABLE 186

Another preferred group of compounds of formula I corresponds to the

general formula

303

(I186), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I186.

[0515]

190

TABLE 187

Another preferred group of compounds of formula I corresponds to the

general formula

304

(I187), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I187.

[0516]

191

TABLE 188

Another preferred group of compounds of formula I corresponds to the

general formula

305

(I186), in which the sets of correlatred substituents R11,

R12 and R13 are given in Table D, thus disclosing 627 specific compounds

of formula I188.

[0517]

192

TABLE 189

Another pre ferred group of compounds of formula I corresponds to the

general formula

306

(I189), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I189.

[0518]

193

TABLE 190

Another preferred group of compounds of formula I corresponds to the

general formula

307

(I190), in which the sets of correlated substituents R11,

R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I190.

[0519]

194

TABLE 191

Another preferred group of compounds of formula I corresponds to the

general formula

308

(I191), in which the sets of correlated substituents R11,

R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I191.

[0520]

195

TABLE 192

Another preferred group of compounds of formula I corresponds to the

general formula

309

(I192), in which the sets of correlated substituents R11,

R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I192.

[0521]

196

TABLE 193

Another preferred group of compounds of formula I corresponds to the

general formula

310

(I193), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627

specific compounds of formula I193.

[0522]

197

TABLE 194

Another preferred group of compounds of formula I corresponds to the

general formula

311

(I194), in which the sets of correlated substituents

R11, R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I194.

[0523]

198

TABLE 195

Another preferred group of compounds of formula I corresponds to the

general formula

312

(I195), in which the sets of correlated substituents R11,

R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I195.

[0524]

199

TABLE 196

Another preferred group of compounds of formula I corresponds to the

general formula

313

(I196), in which the sets of correlated substituents R11,

R12 and R13 are given in Table D, thus disclosing 627 specific

compounds of formula I196.

[0525]

200

TABLE D

Compd. No.
R11
R12
R13

.001
H
Cl
CH2CHCH2

.002
Cl
Cl
CH2CHCH2

.003
F
Cl
CH2CHCH2

.004
H
Br
CH2CHCH2

.005
Cl
Br
CH2CHCH2

.006
F
Br
CH2CHCH2

.007
H
I
CH2CHCH2

.008
Cl
I
CH2CHCH2

.009
F
I
CH2CHCH2

.010
H
CH3
CH2CHCH2

.011
Cl
CH3
CH2CHCH2

.012
F
CH3
CH2CHCH2

.013
H
OH
CH2CHCH2

.014
Cl
OH
CH2CHCH2

.015
F
OH
CH2CHCH2

.016
H
OCF3
CH2CHCH2

.017
Cl
OCF3
CH2CHCH2

.018
F
OCF3
CH2CHCH2

.019
H
CHO
CH2CHCH2

.020
Cl
CHO
CH2CHCH2

.021
F
CHO
CH2CHCH2

.022
H
CHF2
CH2CHCH2

.023
Cl
CHF2
CH2CHCH2

.024
F
CHF2
CH2CHCH2

.025
H
COOH
CH2CHCH2

.026
Cl
COOH
CH2CHCH2

.027
F
COOH
CH2CHCH2

.028
H
COOCH2CH3
CH2CHCH2

.029
Cl
COOCH2CH3
CH2CHCH2

.030
F
COOCH2CH3
CH2CHCH2

.031
H
CN
CH2CHCH2

.032
Cl
CN
CH2CHCH2

.033
F
CN
CH2CHCH2

.034
H
Cl
CH2C6H5

.035
Cl
Cl
CH2C6H5

.036
F
Cl
CH2C6H5

.037
H
Br
CH2C6H5

.038
Cl
Br
CH2C6H5

.039
F
Br
CH2C6H5

.040
H
I
CH2C6H5

.041
Cl
I
CH2C6H5

.042
F
I
CH2C6H5

.043
H
CH3
CH2C6H5

.044
Cl
CH3
CH2C6H5

.045
F
CH3
CH2C6H5

.046
H
OH
CH2C6H5

.047
Cl
OH
CH2C6H5

.048
F
OH
CH2C6H5

.049
H
OCF3
CH2C6H5

.050
Cl
OCF3
CH2C6H5

.051
F
OCF3
CH2C6H5

.052
H
CHO
CH2C6H5

.053
Cl
CHO
CH2C6H5

.054
F
CHO
CH2C6H5

.055
H
CHF2
CH2C6H5

.056
Cl
CHF2
CH2C6H5

.057
F
CHF2
CH2C6H5

.058
H
COOH
CH2C6H5

.059
Cl
COOH
CH2C6H5

.060
F
COOH
CH2C6H5

.061
H
COOCH2CH3
CH2C6H5

.062
Cl
COOCH2CH3
CH2C6H5

.063
F
COOCH2CH3
CH2C6H5

.064
H
CN
CH2C6H5

.065
Cl
CN
CH2C6H5

.066
F
CN
CH2C6H5

.067
H
Cl
CH2CCH

.068
Cl
Cl
CH2CCH

.069
F
Cl
CH2CCH

.070
H
Br
CH2CCH

.071
Cl
Br
CH2CCH

.072
F
Br
CH2CCH

.073
H
I
CH2CCH

.074
Cl
I
CH2CCH

.075
F
I
CH2CCH

.076
H
CH3
CH2CCH

.077
Cl
CH3
CH2CCH

.078
F
CH3
CH2CCH

.079
H
OH
CH2CCH

.080
Cl
OH
CH2CCH

.081
F
OH
CH2CCH

.082
H
OCF3
CH2CCH

.083
Cl
OCF3
CH2CCH

.084
F
OCF3
CH2CCH

.085
H
CHO
CH2CCH

.086
Cl
CHO
CH2CCH

.087
F
CHO
CH2CCH

.088
H
CHF2
CH2CCH

.089
Cl
CHF2
CH2CCH

.090
F
CHF2
CH2CCH

.091
H
COOH
CH2CCH

.092
Cl
COOH
CH2CCH

.093
F
COOH
CH2CCH

.094
H
COOCH2CH3
CH2CCH

.095
Cl
COOCH2CH3
CH2CCH

.096
F
COOCH2CH3
CH2CCH

.097
H
CN
CH2CCH

.098
Cl
CN
CH2CCH

.099
F
CN
CH2CCH

.100
H
Cl
CH2COOH

.101
Cl
Cl
CH2COOH

.102
F
Cl
CH2COOH

.103
H
Br
CH2COOH

.104
Cl
Br
CH2COOH

.105
F
Br
CH2COOH

.106
H
I
CH2COOH

.107
Cl
I
CH2COOH

.108
F
I
CH2COOH

.109
H
CH3
CH2COOH

.110
Cl
CH3
CH2COOH

.111
F
CH3
CH2COOH

.112
H
OH
CH2COOH

.113
Cl
OH
CH2COOH

.114
F
OH
CH2COOH

.115
H
OCF3
CH2COOH

.116
Cl
OCF3
CH2COOH

.117
F
OCF3
CH2COOH

.118
H
CHO
CH2COOH

.119
Cl
CHO
CH2COOH

.120
F
CHO
CH2COOH

.121
H
CHF2
CH2COOH

.122
Cl
CHF2
CH2COOH

.123
F
CHF2
CH2COOH

.124
H
COOH
CH2COOH

.125
Cl
COOH
CH2COOH

.126
F
COOH
CH2COOH

.127
H
COOCH2CH3
CH2COOH

.128
Cl
COOCH2CH3
CH2COOH

.129
F
COOCH2CH3
CH2COOH

.130
H
CN
CH2COOH

.131
Cl
CN
CH2COOH

.132
F
CN
CH2COOH

.133
H
Cl
CH2COOCH3

.134
Cl
Cl
CH2COOCH3

.135
F
Cl
CH2COOCH3

.136
H
Br
CH2COOCH3

.137
Cl
Br
CH2COOCH3

.138
F
Br
CH2COOCH3

.139
H
I
CH2COOCH3

.140
Cl
I
CH2COOCH3

.141
F
I
CH2COOCH3

.142
H
CH3
CH2COOCH3

.143
Cl
CH3
CH2COOCH3

.144
F
CH3
CH2COOCH3

.145
H
OH
CH2COOCH3

.146
Cl
OH
CH2COOCH3

.147
F
OH
CH2COOCH3

.148
H
OCF3
CH2COOCH3

.149
Cl
OCF3
CH2COOCH3

.150
F
OCF3
CH2COOCH3

.151
H
CHO
CH2COOCH3

.152
Cl
CHO
CH2COOCH3

.153
F
CHO
CH2COOCH3

.154
H
CHF2
CH2COOCH3

.155
Cl
CHF2
CH2COOCH3

.156
F
CHF2
CH2COOCH3

.157
H
COOH
CH2COOCH3

.158
Cl
COOH
CH2COOCH3

.159
F
COOH
CH2COOCH3

.160
H
COOCH2CH3
CH2COOCH3

.161
Cl
COOCH2CH3
CH2COOCH3

.162
F
COOCH2CH3
CH2COOCH3

.163
H
CN
CH2COOCH3

.164
Cl
CN
CH2COOCH3

.165
F
CN
CH2COOCH3

.166
H
Cl
OH

.167
Cl
Cl
OH

.168
F
Cl
OH

.169
H
Br
OH

.170
Cl
Br
OH

.171
F
Br
OH

.172
H
I
OH

.173
Cl
I
OH

.174
F
I
OH

.175
H
CH3
OH

.176
Cl
CH3
OH

.177
F
CH3
OH

.178
H
OH
OH

.179
Cl
OH
OH

.180
F
OH
OH

.181
H
OCF3
OH

.182
Cl
OCF3
OH

.183
F
OCF3
OH

.184
H
CHO
OH

.185
Cl
CHO
OH

.186
F
CHO
OH

.187
H
CHF2
OH

.188
Cl
CHF2
OH

.189
F
CHF2
OH

.190
H
COOH
OH

.191
Cl
COOH
OH

.192
F
COOH
OH

.193
H
COOCH2CH3
OH

.194
Cl
COOCH2CH3
OH

.195
F
COOCH2CH3
OH

.196
H
CN
OH

.197
Cl
CN
OH

.198
F
CN
OH

.199
H
Cl
OCH2CHCH2

.200
Cl
Cl
OCH2CHCH2

.201
F
Cl
OCH2CHCH2

.202
H
Br
OCH2CHCH2

.203
Cl
Br
OCH2CHCH2

.204
F
Br
OCH2CHCH2

.205
H
I
OCH2CHCH2

.206
Cl
I
OCH2CHCH2

.207
F
I
OCH2CHCH2

.208
H
CH3
OCH2CHCH2

.209
Cl
CH3
OCH2CHCH2

.210
F
CH3
OCH2CHCH2

.211
H
OH
OCH2CHCH2

.212
Cl
OH
OCH2CHCH2

.213
F
OH
OCH2CHCH2

.214
H
OCF3
OCH2CHCH2

.215
Cl
OCF3
OCH2CHCH2

.216
F
OCF3
OCH2CHCH2

.217
H
CHO
OCH2CHCH2

.218
Cl
CHO
OCH2CHCH2

.219
F
CHO
OCH2CHCH2

.220
H
CHF2
OCH2CHCH2

.221
Cl
CHF2
OCH2CHCH2

.222
F
CHF2
OCH2CHCH2

.223
H
COOH
OCH2CHCH2

.224
Cl
COOH
OCH2CHCH2

.225
F
COOH
OCH2CHCH2

.226
H
COOCH2CH3
OCH2CHCH2

.227
Cl
COOCH2CH3
OCH2CHCH2

.228
F
COOCH2CH3
OCH2CHCH2

.229
H
CN
OCH2CHCH2

.230
Cl
CN
OCH2CHCH2

.231
F
CN
OCH2CHCH2

.232
H
Cl
OCH2C6H5

.233
Cl
Cl
OCH2C6H5

.234
F
Cl
OCH2C6H5

.235
H
Br
OCH2C6H5

.236
Cl
Br
OCH2C6H5

.237
F
Br
OCH2C6H5

.238
H
I
OCH2C6H5

.239
Cl
I
OCH2C6H5

.240
F
I
OCH2C6H5

.241
H
CH3
OCH2C6H5

.242
Cl
CH3
OCH2C6H5

.243
F
CH3
OCH2C6H5

.244
H
OH
OCH2C6H5

.245
Cl
OH
OCH2C6H6

.246
F
OH
OCH2C6H5

.247
H
OCF3
OCH2C6H5

.248
Cl
OCF3
OCH2C6H5

.249
F
OCF3
OCH2C6H5

.250
H
CHO
OCH2C6H5

.251
Cl
CHO
OCH2C6H5

.252
F
CHO
OCH2C6H5

.253
H
CHF2
OCH2C6H5

.254
Cl
CHF2
OCH2C6H5

.255
F
CHF2
OCH2C6H5

.256
H
COOH
OCH2C6H5

.257
Cl
COOH
OCH2C6H5

.258
F
COOH
OCH2C6H5

.259
H
COOCH2CH3
OCH2C6H5

.260
Cl
COOCH2CH3
OCH2C6H5

.261
F
COOCH2CH3
OCH2C6H5

.262
H
CN
OCH2C6H5

.263
Cl
CN
OCH2C6H5

.264
F
CN
OCH2C6H5

.265
H
Cl
OCH2COOH

.266
Cl
Cl
OCH2COOH

.267
F
Cl
OCH2COOH

.268
H
Br
OCH2COOH

.269
Cl
Br
OCH2COOH

.270
F
Br
OCH2COOH

.271
H
I
OCH2COOH

.272
Cl
I
OCH2COOH

.273
F
I
OCH2COOH

.274
H
CH3
OCH2COOH

.275
Cl
CH3
OCH2COOH

.276
F
CH3
OCH2COOH

.277
H
OH
OCH2COOH

.278
Cl
OH
OCH2COOH

.279
F
OH
OCH2COOH

.280
H
OCF3
OCH2COOH

.281
Cl
OCF3
OCH2COOH

.282
F
OCF3
OCH2COOH

.283
H
CHO
OCH2COOH

.284
Cl
CHO
OCH2COOH

.285
F
CHO
OCH2COOH

.286
H
CHF2
OCH2COOH

.287
Cl
CHF2
OCH2COOH

.288
F
CHF2
OCH2COOH

.289
H
COOH
OCH2COOH

.290
Cl
COOH
OCH2COOH

.291
F
COOH
OCH2COOH

.292
H
COOCH2CH3
OCH2COOH

.293
Cl
COOCH2CH3
OCH2COOH

.294
F
COOCH2CH3
OCH2COOH

.295
H
CN
OCH2COOH

.296
Cl
CN
OCH2COOH

.297
F
CN
OCH2COOH

.298
H
Cl
OCH2COOCH3

.299
Cl
Cl
OCH2COOCH3

.300
F
Cl
OCH2COOCH3

.301
H
Br
OCH2COOCH3

.302
Cl
Br
OCH2COOCH3

.303
F
Br
OCH2COOCH3

.304
H
I
OCH2COOCH3

.305
Cl
I
OCH2COOCH3

.306
F
I
OCH2COOCH3

.307
H
CH3
OCH2COOCH3

.308
Cl
CH3
OCH2COOCH3

.309
F
CH3
OCH2COOCH3

.310
H
OH
OCH2COOCH3

.311
Cl
OH
OCH2COOCH3

.312
F
OH
OCH2COOCH3

.313
H
OCF3
OCH2COOCH3

.314
Cl
OCF3
OCH2COOCH3

.315
F
OCF3
OCH2COOCH3

.316
H
CHO
OCH2COOCH3

.317
Cl
CHO
OCH2COOCH3

.318
F
CHO
OCH2COOCH3

.319
H
CHF2
OCH2COOCH3

.320
Cl
CHF2
OCH2COOCH3

.321
F
CHF2
OCH2COOCH3

.322
H
COOH
OCH2COOCH3

.323
Cl
COOH
OCH2COOCH3

.324
F
COOH
OCH2COOCH3

.325
H
COOCH2CH3
OCH2COOCH3

.326
Cl
COOCH2CH3
OCH2COOCH3

.327
F
COOCH2CH3
OCH2COOCH3

.328
H
CN
OCH2COOCH3

.329
Cl
CN
OCH2COOCH3

.330
F
CN
OCH2COOCH3

.331
H
Cl
CH2CHO

.332
Cl
Cl
CH2CHO

.333
F
Cl
CH2CHO

.334
H
Br
CH2CHO

.335
Cl
Br
CH2CHO

.336
F
Br
CH2CHO

.337
H
I
CH2CHO

.338
Cl
I
CH2CHO

.339
F
I
CH2CHO

.340
H
CH3
CH2CHO

.341
Cl
CH3
CH2CHO

.342
F
CH3
CH2CHO

.343
H
OH
CH2CHO

.344
Cl
OH
CH2CHO

.345
F
OH
CH2CHO

.346
H
OCF3
CH2CHO

.347
Cl
OCF3
CH2CHO

.348
F
OCF3
CH2CHO

.349
H
CHO
CH2CHO

.350
Cl
CHO
CH2CHO

.351
F
CHO
CH2CHO

.352
H
CHF2
CH2CHO

.353
Cl
CHF2
CH2CHO

.354
F
CHF2
CH2CHO

.355
H
COOH
CH2CHO

.356
Cl
COOH
CH2CHO

.357
F
COOH
CH2CHO

.358
H
COOCH2CH3
CH2CHO

.359
Cl
COOCH2CH3
CH2CHO

.360
F
COOCH2CH3
CH2CHO

.361
H
CN
CH2CHO

.362
Cl
CN
CH2CHO

.363
F
CN
CH2CHO

.364
H
Cl
OCH2CHO

.365
Cl
Cl
OCH2CHO

.366
F
Cl
OCH2CHO

.367
H
Br
OCH2CHO

.368
Cl
Br
OCH2CHO

.369
F
Br
OCH2CHO

.370
H
I
OCH2CHO

.371
Cl
I
OCH2CHO

.372
F
I
OCH2CHO

.373
H
CH3
OCH2CHO

.374
Cl
CH3
OCH2CHO

.375
F
CH3
OCH2CHO

.376
H
OH
OCH2CHO

.377
Cl
OH
OCH2CHO

.378
F
OH
OCH2CHO

.379
H
OCF3
OCH2CHO

.380
Cl
OCF3
OCH2CHO

.381
F
OCF3
OCH2CHO

.382
H
CHO
OCH2CHO

.383
Cl
CHO
OCH2CHO

.384
F
CHO
OCH2CHO

.385
H
CHF2
OCH2CHO

.386
Cl
CHF2
OCH2CHO

.387
F
CHF2
OCH2CHO

.388
H
COOH
OCH2CHO

.389
Cl
COOH
OCH2CHO

.390
F
COOH
OCH2CHO

.391
H
COOCH2CH3
OCH2CHO

.392
Cl
COOCH2CH3
OCH2CHO

.393
F
COOCH2CH3
OCH2CHO

.394
H
CN
OCH2CHO

.395
Cl
CN
OCH2CHO

.396
F
CN
OCH2CHO

.397
H
Cl
OCH3

.398
Cl
Cl
OCH3

.399
F
Cl
OCH3

.400
H
Br
OCH3

.401
Cl
Br
OCH3

.402
F
Br
OCH3

.403
H
I
OCH3

.404
Cl
I
OCH3

.405
F
I
OCH3

.406
H
CH3
OCH3

.407
Cl
CH3
OCH3

.408
F
CH3
OCH3

.409
H
OH
OCH3

.410
Cl
OH
OCH3

.411
F
OH
OCH3

.412
H
OCF3
OCH3

.413
Cl
OCF3
OCH3

.414
F
OCF3
OCH3

.415
H
CHO
OCH3

.416
Cl
CHO
OCH3

.417
F
CHO
OCH3

.418
H
CHF2
OCH3

.419
Cl
CHF2
OCH3

.420
F
CHF2
OCH3

.421
H
COOH
OCH3

.422
Cl
COOH
OCH3

.423
F
COOH
OCH3

.424
H
COOCH2CH3
OCH3

.425
Cl
COOCH2CH3
OCH3

.426
F
COOCH2CH3
OCH3

.427
H
CN
OCH3

.428
Cl
CN
OCH3

.429
F
CN
OCH3

.430
H
Cl
CH2OCH3

.431
Cl
Cl
CH2OCH3

.432
F
Cl
CH2OCH3

.433
H
Br
CH2OCH3

.434
Cl
Br
CH2OCH3

.435
F
Br
CH2OCH3

.436
H
I
CH2OCH3

.437
Cl
I
CH2OCH3

.438
F
I
CH2OCH3

.439
H
CH3
CH2OCH3

.440
Cl
CH3
CH2OCH3

.441
F
CH3
CH2OCH3

.442
H
OH
CH2OCH3

.443
Cl
OH
CH2OCH3

.444
F
OH
CH2OCH3

.445
H
OCF3
CH2OCH3

.446
Cl
OCF3
CH2OCH3

.447
F
OCF3
CH2OCH3

.448
H
CHO
CH2OCH3

.449
Cl
CHO
CH2OCH3

.450
F
CHO
CH2OCH3

.451
H
CHF2
CH2OCH3

.452
Cl
CHF2
CH2OCH3

.453
F
CHF2
CH2OCH3

.454
H
COOH
CH2OCH3

.455
Cl
COOH
CH2OCH3

.456
F
COOH
CH2OCH3

.457
H
COOCH2CH3
CH2OCH3

.458
Cl
COOCH2CH3
CH2OCH3

.459
F
COOCH2CH3
CH2OCH3

.460
H
CN
CH2OCH3

.461
Cl
CN
CH2OCH3

.462
F
CN
CH2OCH3

.463
H
Cl
CH2SCH3

.464
Cl
Cl
CH2SCH3

.465
F
Cl
CH2SCH3

.466
H
Br
CH2SCH3

.467
Cl
Br
CH2SCH3

.468
F
Br
CH2SCH3

.469
H
I
CH2SCH3

.470
Cl
I
CH2SCH3

.471
F
I
CH2SCH3

.472
H
CH3
CH2SCH3

.473
Cl
CH3
CH2SCH3

.474
F
CH3
CH2SCH3

.475
H
OH
CH2SCH3

.476
Cl
OH
CH2SCH3

.477
F
OH
CH2SCH3

.478
H
OCF3
CH2SCH3

.479
Cl
OCF3
CH2SCH3

.480
F
OCF3
CH2SCH3

.481
H
CHO
CH2SCH3

.482
Cl
CHO
CH2SCH3

.483
F
CHO
CH2SCH3

.484
H
CHF2
CH2SCH3

.485
Cl
CHF2
CH2SCH3

.486
F
CHF2
CH2SCH3

.487
H
COOH
CH2SCH3

.488
Cl
COOH
CH2SCH3

.489
F
COOH
CH2SCH3

.490
H
COOCH2CH3
CH2SCH3

.491
Cl
COOCH2CH3
CH2SCH3

.492
F
COOCH2CH3
CH2SCH3

.493
H
CN
CH2SCH3

.494
Cl
CN
CH2SCH3

.495
F
CN
CH2SCH3

.496
H
Cl
OCH2OCH3

.497
Cl
Cl
OCH2OCH3

.498
F
Cl
OCH2OCH3

.499
H
Br
OCH2OCH3

.500
Cl
Br
OCH2OCH3

.501
F
Br
OCH2OCH3

.502
H
I
OCH2OCH3

.503
Cl
I
OCH2OCH3

.504
F
I
OCH2OCH3

.505
H
CH3
OCH2OCH3

.506
Cl
CH3
OCH2OCH3

.507
F
CH3
OCH2OCH3

.508
H
OH
OCH2OCH3

.509
Cl
OH
OCH2OCH3

.510
F
OH
OCH2OCH3

.511
H
OCF3
OCH2OCH3

.512
Cl
OCF3
OCH2OCH3

.513
F
OCF3
OCH2OCH3

.514
H
CHO
OCH2OCH3

.515
Cl
CHO
OCH2OCH3

.516
F
CHO
OCH2OCH3

.517
H
CHF2
OCH2OCH3

.518
Cl
CHF2
OCH2OCH3

.519
F
CHF2
OCH2OCH3

.520
H
COOH
OCH2OCH3

.521
Cl
COOH
OCH2OCH3

.522
F
COOH
OCH2OCH3

.523
H
COOCH2CH3
OCH2OCH3

.524
Cl
COOCH2CH3
OCH2OCH3

.525
F
COOCH2CH3
OCH2OCH3

.526
H
CN
OCH2OCH3

.527
Cl
CN
OCH2OCH3

.528
F
CN
OCH2OCH3

.529
H
Cl
OCH2SCH3

.530
Cl
Cl
OCH2SCH3

.531
F
Cl
OCH2SCH3

.532
H
Br
OCH2SCH3

.533
Cl
Br
OCH2SCH3

.534
F
Br
OCH2SCH3

.535
H
I
OCH2SCH3

.536
Cl
I
OCH2SCH3

.537
F
I
OCH2SCH3

.538
H
CH3
OCH2SCH3

.539
Cl
CH3
OCH2SCH3

.540
F
CH3
OCH2SCH3

.541
H
OH
OCH2SCH3

.542
Cl
OH
OCH2SCH3

.543
F
OH
OCH2SCH3

.544
H
OCF3
OCH2SCH3

.545
Cl
OCF3
OCH2SCH3

.546
F
OCF3
OCH2SCH3

.547
H
CHO
OCH2SCH3

.548
Cl
CHO
OCH2SCH3

.549
F
CHO
OCH2SCH3

.550
H
CHF2
OCH2SCH3

.551
Cl
CHF2
OCH2SCH3

.552
F
CHF2
OCH2SCH3

.553
H
COOH
OCH2SCH3

.554
Cl
COOH
OCH2SCH3

.555
F
COOH
OCH2SCH3

.556
H
COOCH2CH3
OCH2SCH3

.557
Cl
COOCH2CH3
OCH2SCH3

.558
F
COOCH2CH3
OCH2SCH3

.559
H
CN
OCH2SCH3

.560
Cl
CN
OCH2SCH3

.561
F
CN
OCH2SCH3

.562
H
Cl
OCH2CH2CN

.563
Cl
Cl
OCH2CH2CN

.564
F
Cl
OCH2CH2CN

.565
H
Br
OCH2CH2CN

.566
Cl
Br
OCH2CH2CN

.567
F
Br
OCH2CH2CN

.568
H
I
OCH2CH2CN

.569
Cl
I
OCH2CH2CN

.570
F
I
OCH2CH2CN

.571
H
CH3
OCH2CH2CN

.572
Cl
CH3
OCH2CH2CN

.573
F
CH3
OCH2CH2CN

.574
H
OH
OCH2CH2CN

.575
Cl
OH
OCH2CH2CN

.576
F
OH
OCH2CH2CN

.577
H
OCF3
OCH2CH2CN

.578
Cl
OCF3
OCH2CH2CN

.579
F
OCF3
OCH2CH2CN

.580
H
CHO
OCH2CH2CN

.581
Cl
CHO
OCH2CH2CN

.582
F
CHO
OCH2CH2CN

.583
H
CHF2
OCH2CH2CN

.584
Cl
CHF2
OCH2CH2CN

.585
F
CHF2
OCH2CH2CN

.586
H
COOH
OCH2CH2CN

.587
Cl
COoH
OCH2CH2CN

.588
F
COOH
OCH2CH2CN

.589
H
COOCH2CH3
OCH2CH2CN

.590
Cl
COOCH2CH3
OCH2CH2CN

.591
F
COOCH2CH3
OCH2CH2CN

.592
H
CN
OCH2CH2CN

.593
Cl
CN
OCH2CH2CN

.594
F
CN
OCH2CH2CN

.595
H
Cl
CH2CH2CN

.596
Cl
Cl
CH2CH2CN

.597
F
Cl
CH2CH2CN

.598
H
Br
CH2CH2CN

.599
Cl
Br
CH2CH2CN

.600
F
Br
CH2CH2CN

.601
H
I
CH2CH2CN

.602
Cl
I
CH2CH2CN

.603
F
I
CH2CH2CN

.604
H
CH3
CH2CH2CN

.605
Cl
CH3
CH2CH2CN

.606
F
CH3
CH2CH2CN

.607
H
OH
CH2CH2CN

.608
Cl
OH
CH2CH2CN

.609
F
OH
CH2CH2CN

.610
H
OCF3
CH2CH2CN

.611
Cl
OCF3
CH2CH2CN

.612
F
OCF3
CH2CH2CN

.613
H
CHO
CH2CH2CN

.614
Cl
CHO
CH2CH2CN

.615
F
CHO
CH2CH2CN

.616
H
CHF2
CH2CH2CN

.617
Cl
CHF2
CH2CH2CN

.618
F
CHF2
CH2CH2CN

.619
H
COOH
CH2CH2CN

.620
Cl
COOH
CH2CH2CN

.621
F
COOH
CH2CH2CN

.622
H
COOCH2CH3
CH2CH2CN

.623
Cl
COOCH2CH3
CH2CH2CN

.624
F
COOCH2CH3
CH2CH2CN

.625
H
CN
CH2CH2CN

.626
Cl
CN
CH2CH2CN

.627
F
CN
CH2CH2CN

[0526]

201

TABLE E

Prepared compounds from the above Tables with physicochemical data.

The numbers in front of the point designates the number of the Table e.g.

1.150 signifies in Table 1 the compound No. 150 of Table A and 72.133

signifies in Table 72 the compound No. 133 of Table B.

Compd. No.
Physicochemical data

1.001
m.p. 137-139° C.

1.002
m.p. 142-146° C.

1.003
m.p. 122-124° C.

1.004
amorphous (Example P45)

1.007
solid

1.010
resin

1.015
m.p. 76-78° C.

1.031
m.p. 88-90° C.

1.045
m.p. 85-86° C.

1.080
resin (Example P44)

1.100
m.p. 104-105° C.

1.105
m.p. 105-107° C.

1.106
resin

1.111
m.p. 93-94° C.

1.126
m.p. 104-106° C.

1.137
m.p. 89-93° C.

1.147
resin (Example P51)

1.150
m.p. 137-138° C.

1.152
m.p. 167-168° C.

1.153
m.p. 171-172° C. (Example P52)

1.155
m.p. 102-104° C.

1.156
m.p. 113-114° C.

1.161
m.p. 143-145° C. (Example P53)

1.162
m.p. 180-182° C.

1.168
m.p. 122-124° C.

1.177
solid (Example P47)

1.181
amorphous

1.182
m.p. 98-100° C.

1.190
oil

1.195
m.p. 83-85° C. (Example P46)

1.205
resin

1.216
m.p. 80-86° C.

1.234
amorphous (Example P49)

1.244
m.p. 146-148° C. (Example P50)

1.294
oil (Example P55)

1.302
m.p. 102-104° C.

1.397
resin (Example P32)

1.400
resin (Example P33)

1.422
m.p. 100-101° C.

1.494
m.p. 135-138° C. (Example P54)

7.100
m.p. 111-113° C.

9.002
resin

9.100
m.p. 110-112° C.

10.100
m.p. 126-127° C.

22.002
m.p. 131-133° C.

22.100
m.p. 190-191° C. (Example P43)

28.100
m.p. 189-192° C. (Example P42)

72.083
m.p. 152-153° C. (Example P60)

72.113
m.p. 250° C. (decomposition) (Example P59)

72.133
m.p. 140-143° C. (Example P58)

[0527] Examples of specific formulations of the compounds of formula 1, such as emulsifiable concentrates, solutions, wettable powders, coated granules, extruder granules, dusts and suspension concentrates, are described in WO 97/34485, pages 9 to 13.

BIOLOGICAL EXAMPLES

Example B1: Herbicidal action prior to emergence of the plants (pre-emergence action)

[0528] Monocotyledonous and dicotyledonous test plants are sown in standard soil in plastics pots. Immediately after sowing, the test compounds, each in the form of an aqueous suspension or emulsion prepared from a 25% emulsifiable concentrate (Example F1, c) in WO 97/34485, pages 9 and 10), are applied by spraying at a rate of application of 2000 g of active ingredient/ha (500 liters water/ha). The test plants are then grown in a greenhouse under optimum conditions. After 3 weeks' test duration, the test is evaluated in accordance with a scale of nine ratings (1=total damage, 9=no action). Ratings of from 1 to 4 (especially from 1 to 3) indicate good to very good herbicidal action.

[0529] Test plants: Avena, Setaria, Sinapis, Stellaria

[0530] The compounds according to the invention exhibit a good herbicidal action.

[0531] Examples of the good herbicidal activity of the compounds of formula I are given in Table B1.

202TABLE B1Pre-emergence action:Test plantConcentrationCompd. No.AvenaSetariaSinapisStellaria[g a.i./ha]1.001111120001.002111120001.003111120001.004111120001.010111120001.080111120001.100111120001.105111120001.106211120001.111211120001.126111120001.147111120001.150111120001.152111120001.153111120001.156111120001.168111120001.181111120001.190211120001.195311120001.205111120001.302111120001.400111120007.100111120009.002131120009.1001111200010.1001111200028.10011112000

[0532] The same results are obtained when compounds of formula I are formulated according to Examples F2 to F8 in WO 97/34485, pages 10 to 12.

Example B2: Post-emergence herbicidal action

[0533] Monocotyledonous and dicotyledonous test plants are grown in a greenhouse in plastics pots containing standard soil and at the 4- to 6-leaf stage are sprayed with an aqueous suspension or emulsion of the test substances of formula I, prepared from a 25% emulsifiable concentrate (Example F1, c) in WO 97/34485, pages 9 and 10), at a rate of application corresponding to 2000 g of active ingredient/ha (500 liters water/ha). The test plants are then grown on in the greenhouse under optimum conditions. After approximately 18 days' test duration, the test is evaluated in accordance with a scale of nine ratings (1=total damage, 9=no action). Ratings of from 1 to 4 (especially from 1 to 3) indicate good to very good herbicidal action.

[0534] Test plants: Avena, Setaria, Sinapis, Stellaria

[0535] In this test, too, the compounds of formula I exhibit a strong herbicidal action.

[0536] Examples of the good herbicidal activity of the compounds of formula I are given in Table B2

203TABLE B2Post-emergence action:Test plantConcentrationCompd. No.AvenaSetariaSinapisStellaria[g a.i./ha]1.001111120001.002111120001.003111120001.004121120001.010111120001.080111120001.100111120001.105121120001.106331120001.111211220001.126111120001.147111120001.150111120001.152111120001.153111120001.156111120001.168111120001.181111120001.190111120001.195111120001.205111120001.302111120001.400121120007.100111120009.002131120009.1002211200010.1001211200028.10011112000

[0537] The same results are obtained when the compounds of formula I are formulated according to examples F2 to F8 in WO 97/34485, pages 10 to 12.

	Number	Date	Country
Parent	09380678	Sep 1999	US
Child	09881160	Jun 2001	US

Pyrazole derivatives as herbicides

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CPC

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International Classifications

Abstract

Description

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Priority Claims (1)

Divisions (1)