WO2008031548A1 - Process for the preparation of anthranilamide derivatives - Google Patents

Process for the preparation of anthranilamide derivatives Download PDF

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Publication number
WO2008031548A1
WO2008031548A1 PCT/EP2007/007871 EP2007007871W WO2008031548A1 WO 2008031548 A1 WO2008031548 A1 WO 2008031548A1 EP 2007007871 W EP2007007871 W EP 2007007871W WO 2008031548 A1 WO2008031548 A1 WO 2008031548A1
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alkyl
alkoxy
haloalkyl
cycloalkyl
alkylthio
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PCT/EP2007/007871
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French (fr)
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Thomas Vettiger
André Stoller
David Anthony Jackson
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Syngenta Participations Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to a novel process for the preparation of insecticidally active anthranilamide derivatives.
  • Rx, Ry and Rz are organic substituents, may be made from the ring opening of a benzoxazinone of formula B
  • Benzoxazinones of formula B may be made from amino acids of formula C,
  • benzoxazinones of formula B may be obtained by the treatment of amino acids of formula C with an acid chloride of formula Ry-COCI under basic conditions (for example in pyridine), followed if necessary by a second cyclisation step.
  • the present invention accordingly relates to a process for the preparation of compounds of formula I
  • Ai, A 2 , A 3 and A 4 are each independently of the others hydrogen, halogen, nitro, cyano, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, C 2 - C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl, d-C 4 alkoxy, d-C ⁇ aloalkoxy, d- C 4 alkylthio, d-Cihaloalkylthio, d-C ⁇ aloalkylsulfinyl, Ci-C 4 haloalkylsulfonyl, C 1 - C 4 alkylsulfinyl, Ci-C 4 alkylsulfonyl, Ci-C 4 alkylamino
  • a 2 and A 3 together or A 3 and A 4 together are a bivalent group -J 1 -J 2 -J 3 -J 4 -;
  • J 1 , J 2 , J 3 and J 4 form together with the two carbon atoms to which J 1 and J 4 are attached, an aromatic ring system;
  • J 1 is nitrogen, sulfur, oxygen, a direct bond or C-R 53 ;
  • J 2 is nitrogen, sulfur, oxygen, a direct bond or C-R 5b ;
  • J 3 is nitrogen, sulfur, oxygen, a direct bond or C-R 5c ;
  • J 4 is nitrogen, sulfur, oxygen, a direct bond or C-R 5d ; with the provisos that a) not more than 1 substituent selected from J 1 , J 2 , J 3 and J 4 can at the same time form a direct bond, b) not more than 2 substituents selected from J 1 , J 2 , J 3 and J 4 can be oxygen or sulfur, and c) 2 substituents selected from J 1 , J 2 , J 3 and J 4 as oxygen and/or sulfur are separated by at least one carbon atom; each of R 53 , Rs b , R 50 and R 5d which may be the same or different, represents hydrogen, halogen, nitro, cyano, hydroxy, CHO, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl,
  • C 1 -C 6 haloalkyl C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl, d-C 4 alkoxy, C 1 - C 4 alkoxy-d-C 4 alkoxy-d-C 4 alkyl, d-C 4 haloalkoxy, C r C 4 alkylthio, d-C 4 haloalkylthio, C 1 - C 4 haloalkylsulfinyl, d-C 4 haloalkylsulfonyl, d-C 4 alkylsulfinyl, d-C 4 alkylsulfonyl, C 1 - C 4 alkylsulfonyl-C 1 -C 4 alkyl, d-dalkylsulfoximino-d-dalkyl, d-C 4 alkylamino, C
  • a 5 is a group -A-(X)p-(Y)q-B, wherein
  • A is a chemical bond, or is C 1 -C 6 alkylene, C 2 -C 6 alkenylene, C 2 -C 6 alkynylene, or is a bivalent three- to ten-membered monocyclic or fused bicyclic ring system which can be partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms; and it being possible for the three- to ten-membered ring system itself and also for the C 1 - C 6 alkylene, C 2 -C 6 alkenylene and C 2 -C 6 alkynylene groups to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkyny
  • Y is C 1 -C 6 alkylene, C 2 -C 6 alkenylene, C 2 -C 6 alkynylene, or a bivalent three- to ten-membered monocyclic or fused bicyclic ring system which can be partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms; and it being possible for the three- to ten-membered ring system itself and also for the C 1 - C 6 alkylene, C 2 -C 6 alkenylene and C 2 -C 6 alkynylene groups to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C
  • B is a three- to four-membered ring system which is fully or partially saturated and can contain a hetero atom selected from the group consisting of nitrogen, oxygen and sulfur, and it being possible for the three- to four-membered ring system itself to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 5 - dcycloalkenyl, C 5 -C 8 cycloalkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 - C 6 halocycloalkyl, C 5 -dhalocycloalkenyl, C 5 -C 8 halo
  • G 6 is oxygen, N(-Z 7 ) or sulfur
  • G 7 is oxygen, N(-Z 8 ) or sulfur
  • Gio is oxygen, N(-Zn) or sulfur
  • G 11 is oxygen, N(-Zi 2 ) or sulfur
  • R 20 and R 21 independently of one another are halogen, nitro, cyano, hydroxy, C 1 -C 6 alkyl,
  • C 1 -C 6 haloalkyl C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylthio,
  • Yib is a direct bond or is a C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 3 -C 6 alkynylene chain which may be mono-, di- or trisubstituted by R 22 , where the unsaturated bonds of the chain are not attached directly to the sulfur atom; or is C 3 -C 6 cycloalkylene, which may be mono-, di- or trisubstituted by R 23 , or is 1 ,2-, 1 ,3- or 1 ,4-phenylene;
  • R 22 and R 23 independently of one another are halogen, nitro, cyano, hydroxy, C 1 -C 6 alkyl,
  • C 1 -C 6 haloalkyl C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylthio,
  • Y 2 is a C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 3 -C 6 alkynylene chain which may be mono-, di- or trisubstituted by R 24 , where the unsaturated bonds of the chain are not attached directly to the sulfur atom; or is C 3 -C 6 cycloalkylene, which may be mono-, di- or trisubstituted by R 25 ;
  • R 24 and R 25 independently of one another are halogen, nitro, cyano, hydroxy, C 1 -C 6 alkyl,
  • C 1 -C 6 haloalkyl C r C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C r C 6 alkylsulfonyl, C 1 -C 6 haloalkylthio,
  • Y 3 is hydrogen, halogen, C 1 -C 6 haloalkyl or C 1 -C 6 alkyl;
  • Gi is a direct bond, oxygen, N(-Z 2 ) or sulfur
  • G 2 is oxygen, N(-Z 3 ) or sulfur
  • G 3 is a direct bond, oxygen, N(-Z 4 ) or sulfur;
  • Z, Z 1 , Z 2 , Z 3 and Z 4 independently of one another are hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl,
  • R 34 is C 1 -C 6 alkyl, C r C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkylthio,
  • R 2 9 > R3Q, R31.
  • R33, R35 and R 36 independently of one another are C 1 -C 6 alkyl,
  • C 1 -C 6 haloalkyl C 3 -C 6 cycloalkyl or C 3 -C 6 halocycloalkyl; or C 1 -C 6 alkyl, C 1 -C 6 haloalkyl,
  • a 5 is a group
  • R 37 and R 38 which may be the same or different, represents hydrogen, COOH, halogen, nitro, cyano, hydroxy, C 1 -C 6 alkyl, d-C ⁇ haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 2 - C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, CrC 6 haloalkylthio, C 1 -C 6 haloalkylsulfinyl, CrC 6 haloalkylsulfonyl, C 1 -C 6 alkoxycarbonyl, CrC 6 alkylcarbonyl, QrCealkylaminocarbonyl, Cs-Cedialkylaminocarbonyl,
  • R 39 is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, CrC 6 haloalkyl, CrC 6 alkoxy, hydroxy, C 1 -C 6 cycloalkyl, C 1 -C 6 cycloalkyl-C 1 -C 6 alkyl, benzyl or phenyl; where phenyl and benzyl for their part may be mono- di- or trisubstituted by C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano or nitro; or R 33 is O Na + , O Li + or O K + ;
  • R 40 is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 - C 6 haloalkynyl, C 1 -C 6 alkoxy-C 1 -C 6 alkyl, C 1 -C 6 haloalkoxy-C 1 -C 6 alkyl or benzyl; R is hydrogen, CrC 6 alkyl, CrC 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl,
  • R is cyano, nitro, -C(O)R 41 , -C(O)OR 42 , -CONR 43 R 44 , -SO 2 R 45 or - P(O)(OR 46 )(OR 47 );
  • R 0 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl,
  • R 0 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, Cs-Cehalocycloalkyl, C 1 -C 6 alkylthio,
  • R 0 is cyano, nitro, -C(O)R 04I , -C(O)OR 042 , -CONR 043 R 044 , -SO 2 R 045 or -P(O)(ORo 46 (OR 047 ); each of R 41 and R 04 i, which may be the same or different, represents hydrogen, C 1 -C 6 alkyl,
  • each of R 42 , R 43 , R 44 , R 45 , R 4 e, R 4 /, Ro4i, Ro 4 2, Ro 4 3, Ro 44 , Ro 4 S Ro 4 e and R 047 which may be the same or different, represents C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 cycloalkyl or
  • C 1 -C 6 halocycloalkyl or C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 cycloalkyl or C 1 -C 6 halocycloalkyl substituted by C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 cycloalkyl, C 1 -C 6 halocycloalkyl, C r C 6 alkoxy or C 1 -C 6 haloalkoxy;
  • a 6 is hydrogen, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, cyano, C 1 -CaIkOXy, C 1 -
  • a 7 is C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, halogen, cyano, d-C 4 alkoxy, C 1 -
  • a 1 , A 2 , A 3 , A 4 and A 5 are as defined under formula I above and R 1 is CrC ⁇ alkyl, in the presence of a base to form a compound of formula IV
  • a 1 , A 2 , A 3 , A 4 , A 5 A 6 and A 7 are as defined under formula I above and b) converting said compound of formula IV in the presence of an acid or a base to the compound of formula I.
  • alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso- butyl, tert-butyl, pentyl and hexyl and their branched isomers.
  • Alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned.
  • the alkenyl and alkynyl groups can be mono- or polyunsaturated.
  • Halogen is generally fluorine, chlorine, bromine or iodine. This also applies, correspondingly, to halogen in combination with other meanings, such as haloalkyl or halophenyl.
  • Haloalkyl groups preferably have a chain length of from 1 to 6 carbon atoms.
  • Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1 ,1-difluoro- 2,2,2-trichloroethyl, 2,2,3, 3-tetrafluoroethyl and 2,2,2-trichloroethyl; preferably trichloro- methyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.
  • Suitable haloalkenyl groups are alkenyl groups which are mono- or polysubstituted by halogen, halogen being fluorine, chlorine, bromine and iodine and in particular fluorine and chlorine, for example 2,2-difluoro-1 -methylvinyl, 3-fluoropropenyl, 3-chloropropenyl, 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl and 4,4,4-trifluorobut-2-en- 1-yl.
  • halogen being fluorine, chlorine, bromine and iodine and in particular fluorine and chlorine, for example 2,2-difluoro-1 -methylvinyl, 3-fluoropropenyl, 3-chloropropenyl, 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl and 4,4,4-trifluorobut
  • Suitable haloalkynyl groups are, for example, alkynyl groups which are mono- or polysubstituted by halogen, halogen being bromine, iodine and in particular fluorine and chlorine, for example 3-fluoropropynyl, 3-chloropropynyl, 3-bromopropynyl, 3,3,3-trifluoro- propynyl and 4,4,4-trifluorobut-2-yn-1 -yl.
  • alkynyl groups which are mono- or polysubstituted by halogen preference is given to those having a chain length of from 3 to 5 carbon atoms.
  • Alkoxy groups preferably have a preferred chain length of from 1 to 6 carbon atoms.
  • Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy and also the isomeric pentyloxy and hexyloxy radicals; preferably methoxy and ethoxy.
  • Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert- butoxycarbonyl; preferably methoxycarbonyl or ethoxycarbonyl.
  • Haloalkoxy groups preferably have a chain length of from 1 to 6 carbon atoms.
  • Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2- tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2- trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.
  • Alkylthio groups preferably have a chain length of from 1 to 6 carbon atoms.
  • Alkylthio is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert- butylthio, preferably methylthio and ethylthio.
  • Alkylsulfinyl is, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl; preferably methylsulfinyl and ethylsulfinyl.
  • Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.
  • Alkylamino is, for example, methylamino, ethylamino, n-propylamino, isopropylamino or the isomeric butylamines.
  • Dialkylamino is, for example, dimethylamino, methylethylamino, diethylamino, n-propylmethylamino, dibutylamino and diisopropylamino.
  • Preference is given to alkylamino groups having a chain length of from 1 to 4 carbon atoms.
  • Alkoxyalkyl groups preferably have a chain length of 1 to 6 carbon atoms.
  • Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n- propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.
  • Alkylthioalkyl groups preferably have from 1 to 6 carbon atoms.
  • Alkylthioalkyl is, for example, methylthiomethyl, methylthioethyl, ethylthiomethyl, ethylthioethyl, n-propylthiomethyl, n- propylthioethyl, isopropylthiomethyl, isopropylthioethyl, butylthiomethyl, butylthioethyl or butylthiobutyl.
  • the cycloalkyl groups preferably have from 3 to 6 ring carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • Phenyl also as part of a substituent such as phenoxy, benzyl, benzyloxy, benzoyl, phenylthio, phenylalkyl, phenoxyalkyl, may be substituted.
  • the substituents can be in ortho, meta and/or para position.
  • the preferred substituent positions are the ortho and para positions to the ring attachment point.
  • a three- to ten-membered, monocyclic or fused bicyclic ring system which may be partially saturated or fully saturated is, depending of the number of ring members, for example, selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, where said cycloalkylgroups for their part may be preferably unsubstituted or substituted by C 1 -C 6 alkyl or halogen, and
  • each R 26 is methyl
  • each R 27 and each R 28 are independently hydrogen, d-C 3 alkyl, Ci-C 3 alkoxy, d-C 3 alkylthio or trifluoromethyl
  • the second valence for the bivalent ring system of substituent A or Y can be located at any suitable position of the ring.
  • a three- to ten-membered monocyclic or fused bicyclic ring system which may be aromatic, partially saturated or fully saturated is, depending of the number of ring members, for example, selected from the group consisting of
  • each R 26 is methyl
  • each R 2 7 and each R 2 s are independently hydrogen, d-C 3 alkyl, CrCaalkoxy, d-C 3 alkylthio or trifluoromethyl
  • X 4 is oxygen or sulfur and r is 1 , 2, 3 or 4.
  • B as a optionally substituted three- to four-membered ring system which is fully or partially saturated and can contain a hetero atom selected from the group consisting of nitrogen, oxygen and sulfur, are cyclopropyl, methyl-cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, - ⁇ J° , or - ⁇ !
  • a 1 is C 1 -C 4 alkyl, halogen, especially methyl
  • a 2 is hydrogen
  • a 3 is cyano, d-C 4 alkyl or halogen, especially methyl or chloro;
  • a 4 is hydrogen
  • a 5 is a group -A-(X)p-(Y)q-B, wherein
  • A is a chemical bond or is C 1 -C 6 alkylene which may be substituted by C 3 -C 6 cycloalkyl, C 2 -
  • A is Ca-C ⁇ cycloalkylene.
  • A is C 1 -C 6 alkylene or cyclopropylene, most preferably methylene or cyclopropylene.
  • X is preferably oxygen, NH; NMe or NEt.
  • Y is preferably d-C 4 alkylene, C 2 -C 6 alkenylene or C 3 -C 6 alkinylene or, d-C 4 alkylene, C 2 -
  • B is C 1 -C 6 alkyl, cyclopropyl or cyclobutyl, preferably cyclopropyl or methyl.
  • a 6 is d-C 4 halogenalkyl, especially trifluoromethyl
  • a 7 is chloro.
  • a 1 is hydrogen or d-C 4 alkyl, especially hydrogen or methyl
  • a 2 is hydrogen
  • a 3 is hydrogen
  • a 4 is hydrogen
  • a 5 is d-dalkyl or is C 3 -C 4 cycloalkyl which can be substituted by C 3 -C 4 cycloalkyl, especially
  • a 5 is methyl or cyclopropyl substituted by cyclopropyl;
  • a 6 is C 1 -C 4 halogenalkyl, especially trifluoromethyl; and
  • a 7 is chloro.
  • Me means the methyl group.
  • Et means the ethyl group.
  • tBu is tert.- butyl. If no definition for substituent X is given, then p is O, if X is a substituent, then p is 1. If no definition for substituent Y is given, then q is 0, if Y is a substituent, then q is 1.
  • Table P3 Compounds of formula Ic: The following compounds can also be advantageously prepared according to the process of the present invention:
  • Me means the methyl group.
  • Et means the ethyl group. If no definition for substituent X is given, then p is 0, if X is a substituent, then p is 1. If no definition for substituent A is given, then q is 0, if A is a substituent, then q is 1.
  • the group C(CH 2 CH 2 ) for the substituent Y means cyclopropyl with two free valences:
  • Preferred bases for the treatment of a compound of formula Il with a compound of formula are selected from alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamines, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines.
  • Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N- dimethylamine, N.N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N- methylmorpholine, benzyltrimethylammonium hydroxide, 1. ⁇ -diazabicycloI ⁇ AOlundec ⁇ -ene (DBU) and 1 ,5-diazabicyclo[4.3.0]non-5-ene (DBN).
  • DBU 1. ⁇ -diazabic
  • Especially preferred bases are selected from n-Butyl-Li, sec-Butyl-Li, tert-Butyl-Li, LiN(Si(CH 3 )3) 2l KN(Si(CH 3 ) 3 ) 2 , NaN(Si(CH 3 ) 3 )2, NaH 1 KH 1 tert-Butyl-ONa, tert-ButylOK, 1 ,8- diazabicyclo[5.4.0]undec-7-ene (DBU) and 1 ,5-diazabicyclo[4.3.0]non-5-ene (DBN).
  • DBU diazabicyclo[5.4.0]undec-7-ene
  • DBN 1,5-diazabicyclo[4.3.0]non-5-ene
  • Preferred acids for the conversion of the formula IV to the formula I are mineral acids, especially preferred are HCI, H 2 SO 4 , HNO 3 , CF 3 COOH or CF 2 HCOOH.
  • Preferred bases are selected from alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamines, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines.
  • Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide, 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1 ,5- diazabicyclo[4.3.0]non-5-ene (DBN).
  • reaction steps a) and b) are preferably carried out in the presence of a solvent such as a hydrocarbon, ether or dipolar aprotic solvent.
  • a solvent such as a hydrocarbon, ether or dipolar aprotic solvent.
  • Preferred solvents are tetrahydrofurane, toluene, dioxane, diethylether, diisopropylether or methyltertbutylether and mixtures thereof.
  • the reaction is preferably carried out at a temperature of from -10O 0 C to +100 0 C, especially at from -78 0 C to 0 0 C (step a), and at a temerature of from 0 0 C to +100 0 C, especially from +60°C to +100°C.
  • the reaction steps a) and b) are carried out without isolation of intermediates, that is to say the compound of formula Vl obtained according to Reaction Step a) is converted in situ with acid to the compound of formula I.
  • the possibility of carrying out the process according to the invention in a one-pot reaction constitutes a considerable advantage especially for large-scale application.
  • hal is halogen and R 1 is CrC 6 alkyl in the presence of a base.
  • Suitable bases for the reaction are N(C 2 H 5 ) 3 , 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or 1 ,5- diazabicyclo[4.3.0]non-5-ene (DBN) or imidazole.
  • DBU 1 ,8-diazabicyclo[5.4.0]undec-7-ene
  • DBN 1 ,5- diazabicyclo[4.3.0]non-5-ene
  • imidazole imidazole.
  • the reaction is carried out at temperatures of from 0°C to 100 0 C, preferably at +15°C to +30 0 C in particular at ambient temperature.
  • the compounds of formula V can be prepared by reacting a compound of formula VII with a compound of formula VIII in the presence of a base and an inert solvent:
  • Suitable bases are for example N(C 2 H 5 ) 3 , DBU, DBN or imidazole.
  • Preferred solvents are tetrahydrofurane, dioxane, glyme, ethyl acetate or toluene.
  • the reaction is carried out at temperatures of from 0 0 C to 100 0 C, preferably at +15 0 C to +3O 0 C in particular at ambient temperature.
  • a further process for the preparation of compounds of formula V is described in WO2006/1 11341.
  • Bicyclopropyl-1 -ylamine hydrochloride (0.632 g, 4.64 mmole) was suspended in 4 ml of dichloromethane. Triethylamine (1.5 ml) was added, followed by a solution of 3-methyl-2- sulfinylaminobenzoyl chloride (1.000 g, 4.64 mmole) in dichloromethane (6 ml). The reaction mixture was stirred at 20 0 C for an hour, and then treated 0.5 ml of HCI 2N for another hour.
  • reaction was treated with ca. 23ml of 2N HCI.
  • reaction mixture was diluted with
  • Example P6 Preparation of methyl anthranilamide of formula Vc: lsatoic anhydride methylamine methyl anthranilamide
  • Step i Step 2
  • N ⁇ S-Chloro-pyridin ⁇ -yO-N'- ⁇ -trifluoro-i -methyl-ethylideneJ-hydrazine (0.5 g) was added to THF (5mls) and cooled to -70 0 C (dry ice/acetone bath) to this was added lithium diisopropylamide (LDA) (2M solution in THF) (5.3ml, 10.5mmol). Stirred at -7O 0 C for 40mins forming the anion.
  • a solution of N-(2-methylcarbamoyl-phenyl)-oxalamic acid ethyl ester (0.525 g, 2.1 mmol) in THF (5ml) was then added over 20mins.
  • Example P1 1 Preparation of 2-(3-Chloro-pyridinyl)-5-trifluoromethyl-2H-pyrazole-3- carboxylic acid (2-bicvclopropyl-i yl-carbamoyl-phenyl)-amide of formula Ih:
  • N-(3-Chloro-pyridin-2-yl)-N'-[2,2,2-trifluoro-1 -methyl-ethylidene]-hydrazine (0.5 g) in THF (5mls) was cooled to -7O 0 C (dry ice/acetone bath) and lithium diisopropylamide (LDA) (in THF) (12.7ml, 10.5mmol) was added. The mixture was stirred at -70 0 C for 40min to form the anion.
  • LDA lithium diisopropylamide
  • the crude product was then purified by column chromatography (silica gel, eluent: ethyl acetate/lso-Hexane 50:50) to afford the hydroxy intermediate 0.19 g.
  • the hydroxy intermediate (0.05 g) was suspended in chlorobenzene (2mls) and trifluoroacetic acid added (0.01 g) to give a purple/red solution. This was heated to 8O 0 C for 20mins using a microwave reactor. The chlorobenzene was removed by evaporation, redissolved in ethyl acetate and washed with 5% sodium carbonate solution.

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Abstract

The present invention relates to a process for the preparation of a compound of formula (I), by a) treating a compound of formula (Il), with a compound of formula (III), in the presence of a base to form a compound of formula (IV), and b) converting said compound of formula (IV) in the presence of an acid or base to the compound of formula (I).

Description

Process for the preparation of anthranilamide derivatives
The present invention relates to a novel process for the preparation of insecticidally active anthranilamide derivatives.
Processes for the preparation of anthranilamide derivatives are described, for example, in WO 03/015519, WO2005/085234 and WO2006/040113.
According to WO 03/015519, WO2006/0401 13 and WO2005/085234, anthranilamide derivatives of formula A,
Figure imgf000002_0001
wherein Rx, Ry and Rz are organic substituents, may be made from the ring opening of a benzoxazinone of formula B
Figure imgf000002_0002
with an amine of formula NHRxRx.
WO2005/085234 describes that Benzoxazinones of formula B may be made from amino acids of formula C,
(C)
Figure imgf000002_0003
by treatment with a carboxylic acid of formula Ry-COOH and a dehydrating reagent such as methanesulfonyl chloride (optionally in the presence of a base such as pyridine or triethylamine). Alternatively benzoxazinones of formula B may be obtained by the treatment of amino acids of formula C with an acid chloride of formula Ry-COCI under basic conditions (for example in pyridine), followed if necessary by a second cyclisation step.
However, such processes have the disadvantage that the compound Ry-COOH has to be prepared independently, using technically difficult steps such as metallation at very low temperature with strong bases, or using protecting groups such as esters.
The present invention accordingly relates to a process for the preparation of compounds of formula I
Figure imgf000003_0001
wherein
Ai, A2, A3 and A4 are each independently of the others hydrogen, halogen, nitro, cyano, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6haloalkyl, C2- C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, d-C4alkoxy, d-C^aloalkoxy, d- C4alkylthio, d-Cihaloalkylthio, d-C^aloalkylsulfinyl, Ci-C4haloalkylsulfonyl, C1- C4alkylsulfinyl, Ci-C4alkylsulfonyl, Ci-C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino,
C1-C6alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2-C6alkoxycarbonyl, C2- C6alkylaminocarbonyl, C3-C6dialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, C2- C6alkylaminocarbonyloxy, C3-C6dialkylaminocarbonyloxy or C3-C6trialkylsilyl, phenyl, benzyl or phenoxy; or phenyl, benzyl or phenoxy mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, halogen, C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-
C6haloalkynyl, C3-C6halocycloalkyl, d-C4alkoxy, d-C4haloalkoxy, Ci-C4alkylthio, C1-
C4haloalkylthio, d-C4alkylsulfinyl, d-C4alkylsulfonyl, d-C4alkylamino, C2-C4dialkylamino,
C3-C6cycloalkylamino, C1-C6alkyl-Cs-CeCycloalkylamino, C2-C4alkylcarbonyl, C2-
C6alkoxycarbonyl, C1-C6alkylaminocarbonyl, Cs-Cedialkylaminocarbonyl, C2-
C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy, Cs-Cedialkylaminocarbonyloxy and C3-
Cβtrialkylsilyl; or
A2 and A3 together or A3 and A4 together are a bivalent group -J1-J2-J3-J4-; wherein
J1, J2, J3 and J4 form together with the two carbon atoms to which J1 and J4 are attached, an aromatic ring system; wherein
J1 is nitrogen, sulfur, oxygen, a direct bond or C-R53;
J2 is nitrogen, sulfur, oxygen, a direct bond or C-R5b;
J3 is nitrogen, sulfur, oxygen, a direct bond or C-R5c;
J4 is nitrogen, sulfur, oxygen, a direct bond or C-R5d; with the provisos that a) not more than 1 substituent selected from J1, J2, J3 and J4 can at the same time form a direct bond, b) not more than 2 substituents selected from J1, J2, J3 and J4 can be oxygen or sulfur, and c) 2 substituents selected from J1, J2, J3 and J4 as oxygen and/or sulfur are separated by at least one carbon atom; each of R53, Rsb, R50 and R5d which may be the same or different, represents hydrogen, halogen, nitro, cyano, hydroxy, CHO, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl,
C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, d-C4alkoxy, C1- C4alkoxy-d-C4alkoxy-d-C4alkyl, d-C4haloalkoxy, CrC4alkylthio, d-C4haloalkylthio, C1- C4haloalkylsulfinyl, d-C4haloalkylsulfonyl, d-C4alkylsulfinyl, d-C4alkylsulfonyl, C1- C4alkylsulfonyl-C1-C4alkyl, d-dalkylsulfoximino-d-dalkyl, d-C4alkylamino, C2- C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-Cs-Cβcycloalkylamino, C2-C4alkylcarbonyl, C2-C6alkoxycarbonyl, C1-C6alkylaminocarbonyl, Cs-Cedialkylaminocarbonyl, C2- C6alkoxycarbonyloxy, CrCβalkylaminocarbonyloxy, Cs-Cedialkylaminocarbonyloxy, C1- C4alkoxyimino-d-C4alkyl, C3-C6trialkylsilyl, phenyl, benzyl or phenoxy; or phenyl, benzyl or phenoxy mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C6cycloalkyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, C1- C4alkoxy, CrC4haloalkoxy, d-C4alkylthio, d-C4haloalkylthio, d-C4alkylsulfinyl, C1- - A -
C4alkylsulfonyl, Ci-Cvjalkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3- C6cycloalkylamino, C2-C4alkylcarbonyl, C2-C6alkoxycarbonyl, CrCβalkylaminocarbonyl, C3- Cβdialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, CrCealkylaminocarbonyloxy, C3- C6dialkylaminocarbonyloxy and C3-C6trialkylsilyl; A5 is a group -A-(X)p-(Y)q-B, wherein
A is a chemical bond, or is C1-C6alkylene, C2-C6alkenylene, C2-C6alkynylene, or is a bivalent three- to ten-membered monocyclic or fused bicyclic ring system which can be partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms; and it being possible for the three- to ten-membered ring system itself and also for the C1- C6alkylene, C2-C6alkenylene and C2-C6alkynylene groups to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5-C7cycloalkenyl, C5- C8cycloalkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, C5- C7halocycloalkenyl, C5-C8halocycloalkynyl, CrC4alkoxy, d-C4haloalkoxy, d-C4alkylthio, d- C4haloalkylthio, CrC4alkylsulfinyl, d-C4alkylsulfonyl, d-C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2- C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, drCedialkylaminocarbonyl, C2- C6alkoxycarbonyloxy, CrCβalkylaminocarbonyloxy, Cs-Cedialkylaminocarbonyloxy, C3- C6trialkylsilyl, and a three- to ten-membered monocyclic or fused bicyclic ring system which can be aromatic, partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms, and it being possible for the three- to ten-membered ring system itself to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5-C7cycloalkenyl, C5- C8cycloalkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, C5- C7halocycloalkenyl, C5-C8halocycloalkynyl, d-C4alkoxy, Ci-C4haloalkoxy, d-C4alkylthio, d- C4haloalkylthio, d-C4alkylsulfinyl, d-C4alkylsulfonyl, d-C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2- C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, Cr-Cedialkylaminocarbonyl, C2- C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy, Cs-Cedialkylaminocarbonyloxy, C3- C6trialkylsilyl and phenyl, it being possible for the phenyl group in turn to be substituted by substituents independently selected from the group consisting of hydroxy, C1-C6alkyl, C1- C6haloalkyl, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3- C6alkynylthio, Ci-C3alkoxy-Ci-C3alkylthio, Qrdalkylcarbonyl-d-Csalkylthio, C2- C4alkoxycarbonyl-C1-C3alkylthio, cyano-d-C3alkylthio, C1-C6alkylsulfinyl, C1-C6halo- alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, d-C2alkylamino- sulfonyl, N,N-di(Ci-C2alkyl)aminosulfonyl, di(CrC4alkyl)amino, halogen, cyano and nitro; and substituents at nitrogen atoms in the ring systems being other than halogen; X is oxygen, -N(H)- or -N(CrC4alkyl)-;
Y is C1-C6alkylene, C2-C6alkenylene, C2-C6alkynylene, or a bivalent three- to ten-membered monocyclic or fused bicyclic ring system which can be partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms; and it being possible for the three- to ten-membered ring system itself and also for the C1- C6alkylene, C2-C6alkenylene and C2-C6alkynylene groups to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5-C7cycloalkenyl, C5- C8cycloalkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, C5- dhalocycloalkenyl, C5-C8halocycloalkynyl, d-C4alkoxy, d-C4haloalkoxy, Ci-C4alkylthio, C1- C4haloalkylthio, d-C4alkylsulfinyl, Ci-C4alkylsulfonyl, d-C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2- C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, Cs-Cβdialkylaminocarbonyl, C2- C6alkoxycarbonyloxy, C1-C6alkylaminocarbonyloxy, Cs-Cedialkylaminocarbonyloxy, C3- C6trialkylsilyl and a three- to ten-membered monocyclic or fused bicyclic ring system which can be aromatic, partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms, and it being possible for the three- to ten-membered ring system itself to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5- C7cycloalkenyl, C5-C8cycloalkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, C5-C7halocycloalkenyl, C5-C8halocycloalkynyl, d-C4alkoxy, C1- C4haloalkoxy, d-C4alkylthio, C1-C4haloalkylthio, C1-C4alkylsulfinyl, d-C4alkylsulfonyl, C1- C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2- C4alkylcarbonyl, C2-C6alkoxycarbonyl, C2-C6alkylanninocarbonyl, Cs-Cedialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy, Cs-Cedialkylaminocarbonyloxy, C3- C6trialkylsilyl and phenyl, it being possible for the phenyl group in turn to be substituted by substituents independently selected from the group consisting of hydroxy, C1-C6alkyl, C1- Cβhaloalkyl, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3- C6alkynylthio, d-C3alkoxy-d-C3alkylthio, C2-C4alkylcarbonyl-C1-C3alkylthio, C2- C4alkoxycarbonyl-d-C3alkylthio, cyano-d-Csalkylthio, C1-C6alkylsulfinyl, C1-C6halo- alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, d-C2alkylamino- sulfonyl, N.N-dKd-dalkyOaminosulfonyl, di(d-C4alkyl)amino, halogen, cyano and nitro; and substituents at nitrogen atoms in the ring systems being other than halogen; p is 0 or 1 ; q is 0 or 1 ;
B is a three- to four-membered ring system which is fully or partially saturated and can contain a hetero atom selected from the group consisting of nitrogen, oxygen and sulfur, and it being possible for the three- to four-membered ring system itself to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5- dcycloalkenyl, C5-C8cycloalkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, C5-dhalocycloalkenyl, C5-C8halocycloalkynyl, d-C4alkoxy, C1- C4haloalkoxy, d-C4alkylthio, d-C4haloalkylthio, d-C4alkylsulfinyl, d-C4alkylsulfonyl, C1- C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2- C4alkylcarbonyl, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, drCedialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy, Cs-Cβdialkylaminocarbonyloxy, C3- C6trialkylsilyl and a three- to ten-membered monocyclic or fused bicyclic ring system which can be aromatic, partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms, and it being possible for the three- to ten-membered ring system itself to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5- Cycycloalkenyl, C5-C8cycloalkynyl, C1- C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, Cs-Cyhalocycloalkenyl, C5-C8halocycloalkynyl, d-C4alkoxy, C1- C4haloalkoxy, CrC4alkylthio, CrC4haloalkylthio, d-C4alkylsulfinyl, d-C4alkylsulfonyl, C1- C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2- C4alkylcarbonyl, C2-C6alkoxycarbonyl, Ca-Cealkylaminocarbonyl, Cs-Cβdialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy, Ca-Cβdialkylaminocarbonyloxy, C3- Cβtrialkylsilyl and phenyl, it being possible for the phenyl group in turn to be substituted by substituents independently selected from the group consisting of hydroxy, C1-C6alkyl, C1- C6haloalkyl,C1-C6alkylthio, CrC6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3- C6alkynylthio, Ci-C3alkoxy-Ci-C3alkylthio, C2-C4alkylcarbonyl-CrC3alkylthio, C2- C4alkoxycarbonyl-Ci-C3alkylthio, cyano-d-C3alkylthio, C1-C6alkylsulfinyl, C1-C6halo- alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, Ci-C2alkylamino- sulfonyl, N,N-di(C1-C2alkyl)aminosulfonyl, di(d-C4alkyl)amino, halogen, cyano and nitro; and substituents at nitrogen atoms in the ring systems being other than halogen; or B is hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl or C5-C6cycloalkyl; or is C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl and C5-C6cycloalkyl substituted with one, two or three substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1- C4alkyl, d-C4alkoxy, d-C4haloalkoxy, CrC4alkylthio, C1-C4alkylsulfinyl, d-C4alkylsulfonyl, CrC4alkylsulfoximino, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyl, C2-C6trialkylsilyl, benzyl, phenoxy and a three- to ten-membered, monocyclic or fused bicyclic ring system which may be aromatic, partially saturated or fully saturated, wherein the six-membered aromatic ring system contains at least one heteroatom selected from the group consisting of oxygen, nitro and sulfur; it being possible for said benzyl, phenoxy and three- to ten-membered, monocyclic or fused bicyclic ring system in turn to be substituted by one to three substituents independently selected from the group consisting of d-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C3-C6cycloalkyl, CrC4haloalkyl, C2-C4haloalkenyl, C2-C4haloalkynyl, C3-C6halocycloalkyl, halogen, cyano, nitro, d-C4alkoxy, CrC4haloalkoxy, CrC4alkylthio, d-C4alkylsulfinyl, C1- C4alkylsulfonyl, Ci-C4alkylsulfoximino, d-C4alkylamino, C2-C6dialkylamino, C3- C6cycloalkylamino, d-C4alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2- C6alkoxycarbonyl, C1-C6alkylaminocarbonyl, C2-C8 dialkylaminocarbonyl and C2-C6 trialkylsilyl; it being possible for said three- to ten-membered, monocyclic or fused bicyclic ring system to be spiro-bonded to the C3-C6cycloalkyl group; or B is d-C4alkoxy, d-C4alkylamino, C2-C8dialkylamino, C3-C6cycloalkylamino, C2- C6alkoxycarbonyl or C2-C6alkylcarbonyl; or A5 is a group
Figure imgf000009_0001
n
Y1a is a C1-C6alkylene, C2-C6alkenylene or C3-C6alkynylene chain which may be mono-, di- or trisubstituted by R2o, where the unsaturated bonds of the chain are not attached directly to the sulfur atom; or is C3-C6cycloalkylene, which may be mono-, di- or trisubstituted by R2i; or Y1a and Y2 form together with the chain -G-Y1b-S(=O=N-Z)- a ring system of at least 3 members; wherein Yia and Y2 together represent the group
-CH2-; -CH2-CH2-; -CH2-CH2-CH2; -CH2-CH=CH-; -CH=CH-CH2-; -CH2-G6-CH2-;
-CH2-CH2-G10-CH2-; -CH2-G7-CH2-CH2- or -CH2-CH2-G11-CH2-CH2-;
G6 is oxygen, N(-Z7) or sulfur;
G7 is oxygen, N(-Z8) or sulfur;
Gio is oxygen, N(-Zn) or sulfur;
G11 is oxygen, N(-Zi2) or sulfur;
R20 and R21 independently of one another are halogen, nitro, cyano, hydroxy, C1-C6alkyl,
C1-C6haloalkyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylthio,
C1-C6haloalkylsulfinyl, C1-C6haloalkylsulfonyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl,
C1-C6alkoxy- C1-C6alkyl, C1-C6alkoxy- C1-C6alkyl, C1-C6alkoxy, d-C6halo-alkoxy, benzyl or phenyl, where phenyl and benzyl for their part may be mono-, di- or trisubstituted by substituents independently selected from the group consisting of C1-C6alkyl, C1-C6haloalkyl,
C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxyl and nitro;
Yib is a direct bond or is a C1-C6alkylene, C2-C6alkenylene or C3-C6alkynylene chain which may be mono-, di- or trisubstituted by R22, where the unsaturated bonds of the chain are not attached directly to the sulfur atom; or is C3-C6cycloalkylene, which may be mono-, di- or trisubstituted by R23, or is 1 ,2-, 1 ,3- or 1 ,4-phenylene;
R22 and R23 independently of one another are halogen, nitro, cyano, hydroxy, C1-C6alkyl,
C1-C6haloalkyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylthio,
C1-C6haloalkylsulfinyl, C1-C6haloalkylsulfonyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl,
C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy, C1-C6halo-alkoxy, benzyl or phenyl, where phenyl and benzyl for their part may be mono-, di- or trisubstituted by substituents independently selected from the group consisting of C1-C6alkyl, C1-C6haloalkyl,
C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxyl and nitro; Y2 is a C1-C6alkylene, C2-C6alkenylene or C3-C6alkynylene chain which may be mono-, di- or trisubstituted by R24, where the unsaturated bonds of the chain are not attached directly to the sulfur atom; or is C3-C6cycloalkylene, which may be mono-, di- or trisubstituted by R25;
R24 and R25 independently of one another are halogen, nitro, cyano, hydroxy, C1-C6alkyl,
C1-C6haloalkyl, CrC6alkylthio, C1-C6alkylsulfinyl, CrC6alkylsulfonyl, C1-C6haloalkylthio,
C1-C6haloalkylsulfinyl, C1-C6haloalkylsulfonyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl,
C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy, CrC6halo-alkoxy, benzyl or phenyl, where phenyl and benzyl for their part may be mono-, di- or trisubstituted by substituents independently selected from the group consisting of C1-C6alkyl, C1-C6haloalkyl,
C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxyl and nitro;
Y3 is hydrogen, halogen, C1-C6haloalkyl or C1-C6alkyl;
G is a direct bond, oxygen, N^Z1), sulfur or the group GrC(=G2)-G3;
Gi is a direct bond, oxygen, N(-Z2) or sulfur;
G2 is oxygen, N(-Z3) or sulfur;
G3 is a direct bond, oxygen, N(-Z4) or sulfur;
Z, Z1, Z2, Z3 and Z4 independently of one another are hydrogen, C1-C6alkyl, C1-C6haloalkyl,
C1-C6cycloalkyl, C1-C6halocycloalkyl, C1-C6alkylthio, C1-C6haloalkylthio or
C1-C6alkoxy-C1-C6alkyl; or C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl,
CrC6alkylthio, C1-C6haloalkylthio or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkyl,
C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkoxy, cyano, nitro or d-C6haloalkoxy; or Z, Zi, Z2, Z3 and Z4 independently of one another are -C(O)R34, -C(O)O-R35, -CONR36R29,
-SO2R30 or -P(O)(OR31 )(OR32)-OR33;
R34 is C1-C6alkyl, CrC6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkylthio,
C1-C6haloalkylthio, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1-C6alkoxy-C1-C6alkyl; or
C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkylthio,
C1-C6haloalkylthio, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1-C6alkoxy-C1-C6alkyl substituted by substituents independently selected from the group consisting of C1-C6alkyl,
C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkoxy and C1-C6haloalkoxy; and
R29> R3Q, R31. R32. R33, R35 and R36 independently of one another are C1-C6alkyl,
C1-C6haloalkyl, C3-C6cycloalkyl or C3-C6halocycloalkyl; or C1-C6alkyl, C1-C6haloalkyl,
C3-C6cycloalkyl or C3-C6halocycloalkyl substituted by C1-C6alkyl, C1-C6haloalkyl,
C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkoxy, C1-C6haloalkoxy; or A5 is a group
Figure imgf000011_0001
R37 and R38, which may be the same or different, represents hydrogen, COOH, halogen, nitro, cyano, hydroxy, C1-C6alkyl, d-Cεhaloalkyl, C2-C6alkenyl, C2-C6alkynyl, C2- C6haloalkenyl, C2-C6haloalkynyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, CrC6haloalkylthio, C1-C6haloalkylsulfinyl, CrC6haloalkylsulfonyl, C1-C6alkoxycarbonyl, CrC6alkylcarbonyl, QrCealkylaminocarbonyl, Cs-Cedialkylaminocarbonyl,
C1-C6alkoxy-C1-C6alkyl, C1-C6haloalkoxy-C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkoxy, Cr C6alkylamino, C2-C6dialkylamino, C3-C6trialkylsilyl, benzyl or phenyl; where phenyl and benzyl for their part may be mono- di- or trisubstituted by C1-C6alkyl, C1-C6haloalkyl,
C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxyl or nitro; k is O, 1 , 2, 3 or 4;
A8 is oxygen, sulfur, SO, SO2, S(O)U=N-R, C=N-OR40, N-R0, C=O or P(X)1-R39; R39 is hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, CrC6haloalkyl, CrC6alkoxy, hydroxy, C1-C6cycloalkyl, C1-C6cycloalkyl-C1-C6alkyl, benzyl or phenyl; where phenyl and benzyl for their part may be mono- di- or trisubstituted by C1-C6alkyl, C1-C6haloalkyl, halogen, cyano or nitro; or R33 is O Na+, O Li+ or O K+;
R40 is hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2- C6haloalkynyl, C1-C6alkoxy-C1-C6alkyl, C1-C6haloalkoxy-C1-C6alkyl or benzyl; R is hydrogen, CrC6alkyl, CrC6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl,
C1-C6alkylthio, C1-C6haloalkylthio, C1-C6alkoxy-C1-C6alkyl or C1-C6haloalkoxy-C1-C6alkyl; or R is C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkylthio,
C1-C6haloalkylthio, C1-C6alkoxy-C1-C6alkyl or C1-C6haloalkoxy-C1-C6alkyl substituted by
C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkoxy, or
C1-C6haloalkoxy; or R is cyano, nitro, -C(O)R41, -C(O)OR42, -CONR43R44, -SO2R45 or - P(O)(OR46)(OR47);
R0 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl,
C1-C6alkylthio, C1-C6haloalkylthio, C1-C6alkoxy-C1-C6alkyl or C1-C6haloalkoxy-C1-C6alkyl; or R0 is C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, Cs-Cehalocycloalkyl, C1-C6alkylthio,
C1-C6haloalkylthio, C1-C6alkoxy-C1-C6alkyl or C1-C6haloalkoxy-C1-C6alkyl substituted by
C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkoxy, or
C1-C6haloalkoxy; or R0 is cyano, nitro, -C(O)R04I, -C(O)OR042, -CONR043R044, -SO2R045 or -P(O)(ORo46(OR047); each of R41 and R04i, which may be the same or different, represents hydrogen, C1-C6alkyl,
CrC6haloalkyl, C1-C6cycloalkyl, CrC6halocycloalkyl, C1-C6alkylthio, C1-C6haloalkylthio,
C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1-C6alkoxy-C1-C6alkyl; or C1-C6alkyl,
C1-C6haloalkyl, CrC6cycloalkyl, C1-C6halocycloalkyl, C1-C6alkylthio, C1-C6haloalkylthio,
C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkyl,
C1-C6haloalkyl, C1-C6cycloalkyl, CrC6halocycloalkyl, C1-C6alkoxy, or C1-C6haloalkoxy; each of R42, R43, R44, R45, R4e, R4/, Ro4i, Ro42, Ro43, Ro44, Ro4S Ro4e and R047 which may be the same or different, represents C1-C6alkyl, C1-C6haloalkyl, C1-C6cycloalkyl or
C1-C6halocycloalkyl; or C1-C6alkyl, C1-C6haloalkyl, C1-C6cycloalkyl or C1-C6halocycloalkyl substituted by C1-C6alkyl, C1-C6haloalkyl, C1-C6cycloalkyl, C1-C6halocycloalkyl, CrC6alkoxy or C1-C6haloalkoxy;
X is oxygen or sulfur; u is 0 or 1 ; and t is O or 1 ;
A6 is hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C1-C6haloalkyl, cyano, C1-CaIkOXy, C1-
C4haloalkoxy, d-C4alkylthio, d-C4haloalkylthio, d-C4alkylsulfinyl, d-C4alkylsulfonyl, C1-
C4haloalkylsulfinyl or d-C4haloalkylsulfonyl; and
A7 is C1-C6alkyl, C3-C6cycloalkyl, C1-C6haloalkyl, halogen, cyano, d-C4alkoxy, C1-
C4haloalkoxy, d-C4alkylthio, d-C4haloalkylthio, CrC4alkylsulfinyl, CrC4alkylsulfonyl, C1-
C4haloalkylsulfinyl or d-C4haloalkylsulfonyl; which process comprises a) treating a compound of formula Il
Figure imgf000012_0001
wherein A6 and A7 are as defined under formula I above, with a compound of formula
Figure imgf000013_0001
wherein A1, A2, A3, A4 and A5 are as defined under formula I above and R1 is CrCβalkyl, in the presence of a base to form a compound of formula IV
Figure imgf000013_0002
wherein A1, A2, A3, A4, A5 A6 and A7 are as defined under formula I above and b) converting said compound of formula IV in the presence of an acid or a base to the compound of formula I.
The alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso- butyl, tert-butyl, pentyl and hexyl and their branched isomers. Alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned. The alkenyl and alkynyl groups can be mono- or polyunsaturated.
Halogen is generally fluorine, chlorine, bromine or iodine. This also applies, correspondingly, to halogen in combination with other meanings, such as haloalkyl or halophenyl.
Haloalkyl groups preferably have a chain length of from 1 to 6 carbon atoms. Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1 ,1-difluoro- 2,2,2-trichloroethyl, 2,2,3, 3-tetrafluoroethyl and 2,2,2-trichloroethyl; preferably trichloro- methyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.
Suitable haloalkenyl groups are alkenyl groups which are mono- or polysubstituted by halogen, halogen being fluorine, chlorine, bromine and iodine and in particular fluorine and chlorine, for example 2,2-difluoro-1 -methylvinyl, 3-fluoropropenyl, 3-chloropropenyl, 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl and 4,4,4-trifluorobut-2-en- 1-yl. Among the C3-C2oalkenyl groups which are mono-, di- or trisubstituted by halogen, preference is given to those having a chain length of from 3 to 5 carbon atoms.
Suitable haloalkynyl groups are, for example, alkynyl groups which are mono- or polysubstituted by halogen, halogen being bromine, iodine and in particular fluorine and chlorine, for example 3-fluoropropynyl, 3-chloropropynyl, 3-bromopropynyl, 3,3,3-trifluoro- propynyl and 4,4,4-trifluorobut-2-yn-1 -yl. Among the alkynyl groups which are mono- or polysubstituted by halogen, preference is given to those having a chain length of from 3 to 5 carbon atoms.
Alkoxy groups preferably have a preferred chain length of from 1 to 6 carbon atoms. Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy and also the isomeric pentyloxy and hexyloxy radicals; preferably methoxy and ethoxy.
Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert- butoxycarbonyl; preferably methoxycarbonyl or ethoxycarbonyl. Haloalkoxy groups preferably have a chain length of from 1 to 6 carbon atoms. Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2- tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2- trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy. Alkylthio groups preferably have a chain length of from 1 to 6 carbon atoms. Alkylthio is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert- butylthio, preferably methylthio and ethylthio. Alkylsulfinyl is, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl; preferably methylsulfinyl and ethylsulfinyl.
Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.
Alkylamino is, for example, methylamino, ethylamino, n-propylamino, isopropylamino or the isomeric butylamines. Dialkylamino is, for example, dimethylamino, methylethylamino, diethylamino, n-propylmethylamino, dibutylamino and diisopropylamino. Preference is given to alkylamino groups having a chain length of from 1 to 4 carbon atoms.
Alkoxyalkyl groups preferably have a chain length of 1 to 6 carbon atoms.
Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n- propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.
Alkylthioalkyl groups preferably have from 1 to 6 carbon atoms. Alkylthioalkyl is, for example, methylthiomethyl, methylthioethyl, ethylthiomethyl, ethylthioethyl, n-propylthiomethyl, n- propylthioethyl, isopropylthiomethyl, isopropylthioethyl, butylthiomethyl, butylthioethyl or butylthiobutyl.
The cycloalkyl groups preferably have from 3 to 6 ring carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Phenyl, also as part of a substituent such as phenoxy, benzyl, benzyloxy, benzoyl, phenylthio, phenylalkyl, phenoxyalkyl, may be substituted. In this case, the substituents can be in ortho, meta and/or para position. The preferred substituent positions are the ortho and para positions to the ring attachment point.
According to the present invention, a three- to ten-membered, monocyclic or fused bicyclic ring system which may be partially saturated or fully saturated is, depending of the number of ring members, for example, selected from the group consisting of
Figure imgf000016_0001
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, where said cycloalkylgroups for their part may be preferably unsubstituted or substituted by C1-C6alkyl or halogen, and
Figure imgf000016_0002
Figure imgf000017_0001
wherein each R26 is methyl, each R27 and each R28 are independently hydrogen, d-C3alkyl, Ci-C3alkoxy, d-C3alkylthio or trifluoromethyl, X4 is oxygen or sulfur and r = 1 , 2, 3 or 4.
CH
Where no free valency is indicated in those definitions, for example as in ° , the linkage
site is located at the carbon atom labelled "CH" or in a case such as, for example,
Figure imgf000017_0002
at the bonding site indicated at the bottom left. The second valence for the bivalent ring system of substituent A or Y can be located at any suitable position of the ring.
According to the present invention, a three- to ten-membered monocyclic or fused bicyclic ring system which may be aromatic, partially saturated or fully saturated is, depending of the number of ring members, for example, selected from the group consisting of
Figure imgf000017_0003
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, where said cycloalkylgroups for their part may be preferably unsubstituted or substituted by C1-C6alkyl or halogen, or is naphthyl or the following heterocyclic groups: pyrrolyl; pyridyl; pyrazolyl; pyrimidyl; pyrazinyl; imidazolyl; thiadiazolyl; quinazolinyl; furyl; oxadiazolyl; indolizinyl; pyranyl; isobenzofuranyl; thienyl; naphthyridinyl; (1 -methyl-1 H-pyrazol-3-yl)-; (1 -ethyl-1 H-pyrazol-3-yl)-; (1 -propyl-1 H-pyrazol- 3-yl)-; (1 H-pyrazol-3-yl)-; (1 ,5-dimethyl-1 H-pyrazol-3-yl)-; (4-chloro-1 -methyl-1 H-pyrazol-3- yl)-; (1 H-pyrazol-1-yl)-; (3-methyl-1 H-pyrazol-1 -yl)-; (3,5-dimethyl-1 H-pyrazol-1 -yl)-; (3- isoxazolyl)-; (5-methyl-3-isoxazolyl)-; (3-methyl-5-isoxazolyl)-; (5-isoxazolyl)-; (1 H-pyrrol-2- yl)-; (1-methyl-1 H-pyrrol-2-yl)-; (1 H-pyrrol-1-yl)-; (1 -methyl-1 H-pyrrol-3-yl)-; (2-furanyl)-; (5- methyl-2-furanyl)-; (3-furanyl)-; (5-methyl-2-thienyl)-; (2-thienyl)-; (3-thienyl)-; (1 -methyl-1 H- imidazol-2-yl)-; (1 H-imidazol-2-yl)-; (1 -methyl-1 H- imidazol-4-yl)-; (1 - methyl-1 H-imidazol-5- yl)-; (4-methyl-2-oxazolyl)-; (5-methyl-2-oxazolyl)-; (2-oxazolyl)-; (2-methyl-5-oxazolyl)-; (2- methyl-4-oxazolyl)-; (4-methyl-2-thiazolyl)-; (5-methyl-2-thiazolyl)-; (2-thiazolyl)-; (2-methyl-5- thiazolyl)-; (2-methyl-4-thiazolyl)-; (3-methyl-4-isothiazolyl)-; (3-methyl-5-isothiazolyl)-; (5- methyl-3-isothiazolyl)-; (1 -methyl-1 H-1 ,2,3-triazol-4-yl)-; (2-methyl-2H-1 ,2,3-triazol-4-yl)-; (4- methyl-2H-1 ,2,3-triazol-2-yl)-; (1 -methyl-1 H-1 ,2,4-triazol-3-yl)-; (1 ,5-dimethyl-1 H-1 ,2,4-triazol- 3-yl)-; (3-methyl-1 H-1 ,2,4-triazol-1 -yl)-; (5-methyl-1 H-1 ,2,4-triazol-1 -yl)-; (4,5-dimethyl-4H- 1 ,2,4-triazol-3-yl)-; (4-methyl-4H-1 ,2,4-triazol-3-yl)-; (4H-1 ,2,4-triazol-4-yl)-; (5-methyl-1 ,2,3- oxadiazol-4-yl)-; (1 ,2,3-oxadiazol-4-yl)-; (3-methyl-1 ,2,4-oxadiazol-5-yl)-; (5-methyl-1 ,2,4- oxadiazol-3-yl)-; (4-methyl-3-furazanyl)-; (3-furazanyl)-; (5-methyl-1 ,2,4-oxadiazol-2-yl)-; (5- methyl-1 ,2,3-thiadiazol-4-yl)-; (1 ,2,3-thiadiazol-4-yl)-; (3-methyl-1 ,2,4-thiadiazol-5-yl)-; (5- methyl-1 ,2,4-thiadiazol-3-yl)-; (4-methyl-1 ,2,5-thiadiazol-3-yl)-; (5-methyl-1 ,3,4-thiadiazol-2- yl)-; (1 -methyl-1 H-tetrazol-5-yl)-; (1 H-tetrazol-5-yl)-; (5-methyl-1 H-tetrazol-1 -yl)-; (2-methyl- 2H-tetrazol-5-yl)-; (2-ethyl-2H-tetrazol-5-yl)-; (5-methyl-2H-tetrazol-2-yl)-; (2H-tetrazol-2-yl)-; (2-pyridyl)-; (6-methyl-2-pyridyl)-; (4-pyridyl)-; (3-pyridyl)-; (6-methyl-3-pyridazinyl)-; (5- methyl-3-pyridazinyl)-; (3-pyridazinyl)-; (4,6-dimethyl-2-pyrimidinyl)-; (4-methyl-2-pyrimidinyl)- ; (2-pyrimidinyl)-; (2-methyl-4-pyrimidinyl)-; (2-chloro-4-pyrimidinyl)-; (2,6-dimethyl-4- pyrimidinyl)-; (4-pyrimidinyl)-; (2-methyl-5-pyrimidinyl)-; (6-methyl-2-pyrazinyl)-; (2-pyrazinyl)-; (4,6-dimethyl-1 ,3,5-triazin-2-yl)-; (4,6-dichloro-1 ,3,5-triazin-2-yl)-; (1 ,3,5-triazin-2-yl)-; (4- methyl-1 ,3,5-triazin-2-yl)-; (3-methyl-1 ,2,4-triazin-5-yl)-; (3-methyl-1 ,2,4-triazin-6-yl)-;
Figure imgf000018_0001
Figure imgf000019_0001
and wherein each R26 is methyl, each R27 and each R2s are independently hydrogen, d-C3alkyl, CrCaalkoxy, d-C3alkylthio or trifluoromethyl, X4 is oxygen or sulfur and r is 1 , 2, 3 or 4.
Examples for a three- to ten-membered, monocyclic or fused bicyclic ring system which is
Figure imgf000019_0002
spiro-bonded to the C3-C6cycloalkyl group of the substituent R20 are
Figure imgf000019_0003
Where no free valency is indicated in those definitions, for example as in ° , the linkage
site is located at the carbon atom labelled "CH" or in a case such as, for example,
Figure imgf000019_0004
at the bonding site indicated at the bottom left. Examples for B as a optionally substituted three- to four-membered ring system which is fully or partially saturated and can contain a hetero atom selected from the group consisting of nitrogen, oxygen and sulfur, are cyclopropyl, methyl-cyclopropyl, cyclopropenyl, cyclobutyl,
Figure imgf000020_0001
cyclobutenyl, -<J° , or -<!
Compounds of formula I that are highly suitable for preparation using the process according to the invention are those wherein
A1 is C1-C4alkyl, halogen, especially methyl;
A2 is hydrogen;
A3 is cyano, d-C4alkyl or halogen, especially methyl or chloro;
A4 is hydrogen;
A5 is a group -A-(X)p-(Y)q-B, wherein
A is a chemical bond or is C1-C6alkylene which may be substituted by C3-C6cycloalkyl, C2-
C6alkenyl, cyano, d-C4alkylthio, d-C4alkylsulfonyl, d-dalkoxy, halogen or C1-C6haloalkyl; or A is Ca-Cβcycloalkylene. Preferably A is C1-C6alkylene or cyclopropylene, most preferably methylene or cyclopropylene. p and/or q is 0;
X is preferably oxygen, NH; NMe or NEt.
Y is preferably d-C4alkylene, C2-C6alkenylene or C3-C6alkinylene or, d-C4alkylene, C2-
C6alkenylene or C3-C6alkinylene substituted by halogen, C3-C6cycloalkyl, d-C4alkylsulfonyl or d-C4alkoxy.
B is C1-C6alkyl, cyclopropyl or cyclobutyl, preferably cyclopropyl or methyl.
A6 is d-C4halogenalkyl, especially trifluoromethyl; and
A7 is chloro.
Further compounds of formula I that are highly suitable for preparation using the process according to the invention are those wherein
A1 is hydrogen or d-C4alkyl, especially hydrogen or methyl;
A2 is hydrogen;
A3 is hydrogen;
A4 is hydrogen;
A5 is d-dalkyl or is C3-C4cycloalkyl which can be substituted by C3-C4cycloalkyl, especially
A5 is methyl or cyclopropyl substituted by cyclopropyl; A6 is C1-C4halogenalkyl, especially trifluoromethyl; and A7 is chloro.
Using the process according to the invention it is possible, especially advantageously, to prepare the bisamide derivatives described in tables P1 , P2 and tables 1 to 91 of WO2005/085234 (provided that the substituent which corresponds to A6 of formula I of the invention is not halogen) and further the anthranilamides described in the table P and the tables 1 to 57 of WO2006/061200 (provided that the substituent which corresponds to A6 of formula I of the invention is not halogen) and further the anthranilamide derivatives described in the following tables:
Table P1 : Compounds of formula Ia:
Figure imgf000022_0001
Figure imgf000022_0002
Figure imgf000023_0001
Figure imgf000024_0001
Figure imgf000025_0001
Table P2: Compounds of formula Ib:
Figure imgf000026_0001
Figure imgf000026_0002
In the following tables, Me means the methyl group. Et means the ethyl group. tBu is tert.- butyl. If no definition for substituent X is given, then p is O, if X is a substituent, then p is 1. If no definition for substituent Y is given, then q is 0, if Y is a substituent, then q is 1. Table P3: Compounds of formula Ic:
Figure imgf000027_0001
Figure imgf000027_0002
Figure imgf000028_0001
Figure imgf000029_0001
Figure imgf000030_0001
Figure imgf000031_0001
Figure imgf000032_0001
Figure imgf000033_0001
Figure imgf000034_0001
Figure imgf000035_0001
Figure imgf000036_0001
Figure imgf000037_0001
Figure imgf000038_0001
Figure imgf000039_0001
Figure imgf000040_0001
Figure imgf000041_0001
Figure imgf000042_0001
Figure imgf000043_0001
Figure imgf000044_0001
Figure imgf000045_0001
Figure imgf000046_0001
Figure imgf000047_0001
Figure imgf000048_0001
Figure imgf000049_0001
Figure imgf000050_0001
Figure imgf000051_0001
Figure imgf000052_0001
Figure imgf000053_0001
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000061_0001
Figure imgf000062_0001
Figure imgf000063_0001
Figure imgf000064_0001
Figure imgf000065_0001
Figure imgf000066_0001
The following compounds can also be advantageously prepared according to the process of the present invention:
Me means the methyl group. Et means the ethyl group. If no definition for substituent X is given, then p is 0, if X is a substituent, then p is 1. If no definition for substituent A is given, then q is 0, if A is a substituent, then q is 1. The group C(CH2CH2) for the substituent Y means cyclopropyl with two free valences:
Figure imgf000067_0001
Table P4: Compounds of formula Id:
Figure imgf000067_0002
Figure imgf000067_0003
Figure imgf000068_0001
Figure imgf000069_0001
Figure imgf000070_0001
Figure imgf000071_0001
Figure imgf000072_0001
Figure imgf000073_0002
Table P5: Compounds of formula Ie:
Figure imgf000073_0001
Figure imgf000073_0003
Figure imgf000074_0001
Preferred bases for the treatment of a compound of formula Il with a compound of formula are selected from alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamines, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N- dimethylamine, N.N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N- methylmorpholine, benzyltrimethylammonium hydroxide, 1.δ-diazabicycloIδAOlundec^-ene (DBU) and 1 ,5-diazabicyclo[4.3.0]non-5-ene (DBN).
Especially preferred bases are selected from n-Butyl-Li, sec-Butyl-Li, tert-Butyl-Li, LiN(Si(CH3)3)2l KN(Si(CH3)3)2, NaN(Si(CH3)3)2, NaH1 KH1 tert-Butyl-ONa, tert-ButylOK, 1 ,8- diazabicyclo[5.4.0]undec-7-ene (DBU) and 1 ,5-diazabicyclo[4.3.0]non-5-ene (DBN).
Preferred acids for the conversion of the formula IV to the formula I are mineral acids, especially preferred are HCI, H2SO4, HNO3, CF3COOH or CF2HCOOH. Preferred bases are selected from alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamines, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide, 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1 ,5- diazabicyclo[4.3.0]non-5-ene (DBN).
The reaction steps a) and b) are preferably carried out in the presence of a solvent such as a hydrocarbon, ether or dipolar aprotic solvent. Preferred solvents are tetrahydrofurane, toluene, dioxane, diethylether, diisopropylether or methyltertbutylether and mixtures thereof.
The reaction is preferably carried out at a temperature of from -10O0C to +1000C, especially at from -780C to 00C (step a), and at a temerature of from 00C to +1000C, especially from +60°C to +100°C. In an especially preferred embodiment of the process according to the invention, the reaction steps a) and b) are carried out without isolation of intermediates, that is to say the compound of formula Vl obtained according to Reaction Step a) is converted in situ with acid to the compound of formula I. The possibility of carrying out the process according to the invention in a one-pot reaction constitutes a considerable advantage especially for large-scale application.
Compounds of formula Il are known or can be prepared according to known methods. A process for the preparation of compounds of formula Il is described, for example, in WO03/016282.
Compounds of formula III can be prepared by reacting a compound of formula V
Figure imgf000076_0001
wherein A1, A2, A3, A4 and A5 are as defined under formula I above, with a compound of formula Vl
Figure imgf000076_0002
wherein hal is halogen and R1 is CrC6alkyl in the presence of a base. Suitable bases for the reaction are N(C2H5)3, 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or 1 ,5- diazabicyclo[4.3.0]non-5-ene (DBN) or imidazole. The reaction is carried out at temperatures of from 0°C to 1000C, preferably at +15°C to +300C in particular at ambient temperature.
Compounds of formula V are described, for example, in WO2006/0401 13 or WO2006/111341.
The compounds of formula V can be prepared by reacting a compound of formula VII with a compound of formula VIII in the presence of a base and an inert solvent:
Figure imgf000077_0001
Suitable bases are for example N(C2H5)3, DBU, DBN or imidazole. Preferred solvents are tetrahydrofurane, dioxane, glyme, ethyl acetate or toluene. The reaction is carried out at temperatures of from 00C to 1000C, preferably at +150C to +3O0C in particular at ambient temperature. A further process for the preparation of compounds of formula V is described in WO2006/1 11341.
Compounds of formula VII are known for example from WO2006/0401 13 or WO2006/061200 or can be prepared according to known methods.
Compounds of formula VIII and their preparation are described in Tetrahedron Letters, 1991 , 32, 3263.
The process according to the invention is explained in greater detail by the following Examples.
Example P1 : Preparation of a compound of formula Villa:
Figure imgf000077_0002
Villa
In a flask equipped with a magnetic stirring bar, a reflux condenser and a nitrogen inlet with a bubbler outlet, 2-amino-3-methylbenzoic acid (18.56 g, 0.122 mole) was suspended in 160 ml toluene. Thionyl chloride (35.7 ml, 0.49 mole) was added and the mixture was heated at 800C and stirred at that temperature until the rapid gas evolution slowed down. The resulting solution was then gradually heated to reflux temperature for an hour. The solvent was then distilled off at the rotary evaporator. After the residual solvent was removed under high vacuum, the residue was distilled under high vacuum and the 3-methyl-2- sulfinylaminobenzoyl chloride (Eb: 125°C/ 3. 10'2 torr) was isolated as a bright yellow oil that crystallized on standing.
Example P2: Preparation of a compound of formula Va:
Figure imgf000078_0001
Bicyclopropyl-1 -ylamine hydrochloride (0.632 g, 4.64 mmole) was suspended in 4 ml of dichloromethane. Triethylamine (1.5 ml) was added, followed by a solution of 3-methyl-2- sulfinylaminobenzoyl chloride (1.000 g, 4.64 mmole) in dichloromethane (6 ml). The reaction mixture was stirred at 200C for an hour, and then treated 0.5 ml of HCI 2N for another hour. After neutralization and extraction with dichloromethane, the crude amide was purified by column chromatography on silica gel, using a gradient of ethyl acetate / cyc/o-hexane (20%- 80% to 40%-60%). The 2-amino-3-methyl-N-(bicyclopropyl-1 -yl)-benzamide was obtained as colorless crystals with a melting point of 145-148°C.
Example P3: Preparation of a compound of formula Vb:
Figure imgf000078_0002
Vb
5.0 gr (1.0 eq) 2-amino-3-methylbenzoic acid were suspended in 45g toluene under argon. At 75°C, 6g (1.5 eq) of thionylchloride were carefully added during 15 minutes. Gas evolution was observed. The suspension was held at 75°C for an additional hour. Another portion of 6g (1.5 eq) of thionylchloride was added. After one hour, the mixture was cooled to room temperature and was added carefully during 20 minutes to a solution of 31 g (4 eq) of a methylamine solution (33% in ethanol). The reaction temperature was held between 20° and 300C with sporadic cooling using an ice bath. After the addition was complete, the suspension was held for 30 minutes at room temperature. Workup with ethylacetate (5Og) and water ( 24g) gave after phase separation and evaporation of the organic solvent 6g of crude product (LC: 65%). Recrystallisation from toluene (10g) and washing with hexanes (5g) gave 2.8g 2-amino-3,N-dimethyl benzamide. MS M++1 =165
1H-NMR (CDCI3): 2.15 (s, 3H, Ar-CH3), 2.98 (d, 3H1 NCH3), 2.55 (s, br, 2H1 NH2) 6.05 (s, 1 H, NH), 6.55 (1 H, t), 7.12(d, 1 H), 7.2 (d, 1 H)
Example P4. Preparation of a compound of formula MIa:
Figure imgf000079_0001
MIa
3.7g 2-amino-3,N-dimethyl benzamide were dissolved in 45g tetrahydrofurane at room temperature. 3.5g (1.5 eq) triethylamine were added during 10 minutes. With cooling, 3.5g (1 eq) of ethyloxalylchloride were added carefully, so that the reaction temperature did not exceed 300C. After one hour at room temperature another 0.35g (0.1 eq) of triethylamine and 0.35g (0.1 eq) of ethyloxalylchloride were added during 5 minutes. The reaction mixture was diluted with 100 ml ethylacetate and 45g water. Phase separation, drying of the organic phase with Na2SO4 and evaporation gave 5.9g N-(2-methyl-6- methylcarbamoyl-phenyl)-oxalamic acid ethyl ester. MS MVl =265
1H-NMR (CDCI3): 1.48 (t, 3H), 2.28 (s,3H), 2.87 (d, 3H), 4.45 (q,2H) 6.48 (d, br, 1 H), 7.15 (t, 1 H), 7.2-7.35 (d,d, 2 H), 10.5 (s, 1 H) Example P5: Preparation of a compound of formula If:
Figure imgf000080_0001
A solution of 0.9g (1.0 eq) N-(3-chloro-pyridin-2-yl)-N'-[2,2,2-trifluoro-1 -methyl-ethylidene]- hydrazine in 8.1 g tetrahydrofurane was cooled to -700C under argon. A solution of lithiumdiisopropylamine (2 M in THF) was added carefully during 15 minutes. The mixture was stirred at this temperature for 40 minutes.
A solution of 1.0 g (1.0 eq) N-(2-methyl-6-methylcarbamoyl-phenyl)-oxalamic acid ethyl ester in 10ml tetrahydrofurane was added slowly during 30 minutes. The mixture was stirred at -
700C for an hour, then allowed to warm to room temperature.
The reaction was treated with ca. 23ml of 2N HCI. The reaction mixture was diluted with
50ml ethylacetate, washed with water, dried with Na2SO4 and evaporated to give 1 .7g crude intermedate. Stirring with 14g toluene at room temperature, filtration and drying gave 0.2 g of an intermediate which was suspended in 10ml of chlorobenzene and heated with 0.3g of trifluoroacetic acide at 600C for ohe hour. Evaporation of the solvent, redissolving in ethylacetate and washing with 5ml of a 5% of a NaHCO3 solution, drying and evaporation gave 2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (2-methyl-6- methylcarbamoyl-phenyl)-amide .
MS: M++1= 438
1H-NMR(CDCI3): 2.21 (s, 3H), 2.97 (s,3H), 6.17 (s,br, 1 H), 7.15 (dd,J=7.6 Hz, J=7.6 Hz, 1 H),
7.24-7.29 (m, 2H), 7.33 (s, 1 H), 7.41 (dd, J=8.1 , J= 4.7), 7.88 (dd, J=8.1 , J=1.8, 1 H), 8.48
(dd, J = 4.8, J=0.5), 10.34 (s, br, 1 H).
Example P6: Preparation of methyl anthranilamide of formula Vc:
Figure imgf000081_0001
lsatoic anhydride methylamine methyl anthranilamide
To lsatoic anhydride (6.6 g) was added 40% Methylamine in water (16.4 g) over 30mins. After stirring for 1 hour the reaction mixture was neutralised with 2M Hydrochloric acid (1OmIs). The mixture was stirred for a further 2 hour and the pmflyct precipitated. Filtration then gave 3.8 g of methyl anthranilamide solid.
1H NMR CDCI3 D 7.23 (d, 1 H), 7.13 (m, 1 H), 6.61 (d, 1 H), 6.56 (m, 1 H), 6.10 (s, br, 1 H), 2.85 (d, 3H). GCMS m+ 150
Example P7: Preparation of N-(2-methylcarbamoyl-phenyl)-oxalamic acid ethyl ester of formula IMb:
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To N-methyl anthranilamide (5 g) in THF (60 g) was added triethylamine (7 g). An ice bath was then used to cool the reaction to below 250C and maintain this temperature while ethyloxalychloride (5mls) was added slowly. The mixture was stirred for 20 hours at room temperature. The product was then extracted into ethyl acetate and water washed at pH5. The washing was repeated 4 times to ensure complete removal of residual triethylamine. After separation, the solvent was removed by evaporation in vacuo to afford 4.9g of N-(2- methylcarbamoyl-phenyl)-oxalamic acid ethyl ester.
1H NMR CDCI3 D 12.6 (s, br, 1 H1 NH), 8.5 (d, 1 H)1 7.5 (d, 1 H), 7.4 (m, 1 H), 7.05 (m, 1 H), 6.8 (s, br, 1 H), 4.3 (q, 2H), 2.9 (s, 3H, NCH3), 1.3 (t, 3H). GCMS m+ 250.
Example P8: Preparation of 2-(3-Chloro-pyridinyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (2-methyl carbamoyl-phenvD-amide of formula Ig:
Figure imgf000082_0001
Step i. Step 2
N^S-Chloro-pyridin^-yO-N'-^^^-trifluoro-i -methyl-ethylideneJ-hydrazine (0.5 g) was added to THF (5mls) and cooled to -700C (dry ice/acetone bath) to this was added lithium diisopropylamide (LDA) (2M solution in THF) (5.3ml, 10.5mmol). Stirred at -7O0C for 40mins forming the anion. A solution of N-(2-methylcarbamoyl-phenyl)-oxalamic acid ethyl ester (0.525 g, 2.1 mmol) in THF (5ml) was then added over 20mins. Stirred for 1 hour at this temp, before allowing to warm to room temperature. To the reaction mass was added 2M Hydrochloric acid (13ml) to neutralise. The reaction mass was extracted into ethyl acetate, water washed then dried over magnesium sulphate and the solvent removed in vacuo 0.547 g recovered. The product was then purified by column chromatography (silica gel, eluent: ethyl acetate/iso-hexane 50:50) to afford purified hydroxy intermediate (0.33 g). The hydroxy intermediate was then suspended in chlorobenzene (2mls) with trifluoroacetic acid added (0.01 g) to give a purple/red solution. This was heated to 8O0C for 20mins using a microwave reactor. The chlorobenzene was removed by evaporation, redissolved in ethyl acetate and washed with 5% sodium carbonate solution. Drying and evaporation of solvent gave 0.09 g of 2-(3-Chloro-pyridinyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (2- methyl carbamoyl-phenyl)-amide.
1H NMR d6 DMSO. D 12.85 (s, 1 H), 8.93 (d, br, NHCH3), 8.60 (dd, 1 H)1 8.30 (dd, 1 H), 8.2 (d, 1 H), 7.8 (d, 1 H), 7.70 (dd, 1 H), 7.55 (s, 1 H), 7.50 (m, 1 H), 7.20 (m, 1 H), 2.83 (d, 3H, NHCH3).
(Vd) Example P9: Preparation of 2-amino-N-(bicvclopropyl-1 -yl)-benzamide of formula Vd:
Error! Objects cannot be created from editing field codes. lsatoic anhydride To bicyclopropylamine hydrochloride (2 g) was added dichloromethane (16ml) and triethylamine (3g). To this was then added isatoic anhydride (2.22 g) in dichloromethane (20ml). The mixture was stirred for 2.5 hours at 2O0C and then the solvent removed in vacuo to leave a waxy solid. The solid was redissolved in ethyl acetate and washed with water at pH7. The solvent layer was separated and dried over magnesium solvent. Filtration and evaporation of the solvent afforded the 2-amino-N-(bicyclopropyl-1 -yl)-benzamide product 1.49g.
1H NMR (CDCI3) □ 7.2 (d, 1 H), 7.1 (dd, 1 H), 6.65 (d, 1 H), 6.55 (dd, 1 H), 6.45 (s, 1 H, NH), 5.8 (s, 2H, NH2), 1.45 (m, 1 H), 0.7 (m, 2H), 0.6 (m, 2H), 0.35 (m, 2H), 0.1 (m, 2H) and GC/MS m+ 216.
Example P10: Preparation of N-(2-bicvclopropyl-1 yl-carbamov,l-Phenyl)-oxalamic acid ethyl
(TTfC) ester of formula IMc:
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To 2-amino-N-(bicyclopropyl-1-yl)-benzamide (1.25 g) in tetrahydrofuran (21 ml) was added triethylamine (1.25 g). The mixture was cooled to 00C and ethyloxalylchloride (0.8 g) was added dropwise. The mixture was stirred at 00C for 1 hour. A further amount of ethyloxalylchloride (0.26 g) was then added to complete the reaction. Ethyl acetate was added and the mixture was washed with water (pH5) 3 times. The organic layer was separated and dried over magnesium sulphate, filtered and the solvent evaporated in vacuo to yield 1.68g of N-(2-bicyclopropyl-1yl-carbamoyl-phenyl)-oxalamic acid ethyl ester. The crude product was then passed through a short silica gel column (eluent: ethyl acetate/iso- hexane 70:30) to give the purified product as a cream solid (1.4g).
1H NMR CDCI3 Q12.6 (s, 1 H, NH), 8.5 (d, 1 H), 7.45 (d, 1 H), 7.32 (m, 1 H), 7.11 (s, or, 1 H), 6.98 (m, 1 H), 4.3 (q, 2H), 1.5 (m, 1 H), 1.35 (t, 3H)1 0.73 (m, 2H), 0.6 (m, 2H), 0.34 (m, 2H), 0.12 (m, 2H).
Example P1 1 : Preparation of 2-(3-Chloro-pyridinyl)-5-trifluoromethyl-2H-pyrazole-3- carboxylic acid (2-bicvclopropyl-i yl-carbamoyl-phenyl)-amide of formula Ih:
Figure imgf000084_0001
N-(3-Chloro-pyridin-2-yl)-N'-[2,2,2-trifluoro-1 -methyl-ethylidene]-hydrazine (0.5 g) in THF (5mls) was cooled to -7O0C (dry ice/acetone bath) and lithium diisopropylamide (LDA) (in THF) (12.7ml, 10.5mmol) was added. The mixture was stirred at -700C for 40min to form the anion. A solution of N-(2-bicyclopropyl-1yl-carbamoyl-phenyl)-oxalamic acid ethyl ester (0.66g, 2.1 mmol) in THF (5ml) was then added over 20mins. The mixture was stirred at - 7O0C for 1 hour before allowing to warm to room temperature. To the reaction mass was added 2M Hydrochloric acid (8 g) to neutralise. The reaction mass was extracted into ethyl acetate, water washed then dried over magnesium sulphate and solvent evaporated to afford the crude product 0.8 g. The crude product was then purified by column chromatography (silica gel, eluent: ethyl acetate/lso-Hexane 50:50) to afford the hydroxy intermediate 0.19 g. The hydroxy intermediate (0.05 g) was suspended in chlorobenzene (2mls) and trifluoroacetic acid added (0.01 g) to give a purple/red solution. This was heated to 8O0C for 20mins using a microwave reactor. The chlorobenzene was removed by evaporation, redissolved in ethyl acetate and washed with 5% sodium carbonate solution. Drying and evaporation of solvent gave 0.05g of 2-(3-Chloro-pyridinyl)-5-trifluoromethyl-2H-pyrazole-3- carboxylic acid) 2-bicyclopropyl-1yl-carbamoyl-phenyl)-amide.
1H NMR d6 DMSO D 12.50 (s, 1 H), 8.58 (dd, 1 H), 8.29 (dd, 1 H), 8.09 (d, 1 H), 7.78 (d, 1 H), 7.73 (dd, 1 H), 7.56 (s, 1 H), 7.47 (m, 1 H), 7.22 (m, 1 H), 1.44 (m, 1 H), 0.71 (m, 2H), 0.60 (m, 2H), 0.36 (m, 2H), 0.20 (m, 2H).

Claims

What is claimed is:
1. A process for the preparation of a compound of formula I
Figure imgf000085_0001
wherein
Ai, A2, A3 and A4 are each independently of the others hydrogen, halogen, nitro, cyano, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C2- C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, d-C4alkoxy, Ci-C4haloalkoxy, C1- C4alkylthio, d-C4haloalkylthio, d-C4haloalkylsulfinyl, Ci-C4haloalkylsulfonyl, C1- dalkylsulfinyl, d-C4alkylsulfonyl, d-C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino,
C1-C6alkyl-Cs-Cecycloalkylamino, C2-C4alkylcarbonyl, C2-C6alkoxycarbonyl, C2- C6alkylaminocarbonyl, Cs-Cβdialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, C2- C6alkylaminocarbonyloxy, Cs-Cβdialkylaminocarbonyloxy or C3-C6trialkylsilyl, phenyl, benzyl or phenoxy; or phenyl, benzyl or phenoxy mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, halogen, C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, CrC6haloalkyl, C2-C6haloalkenyl, C2- C6haloalkynyl, C3-C6halocycloalkyl, d-C4alkoxy, Ci-dhaloalkoxy, Ci-C4alkylthio, C1- dhaloalkylthio, d-C4alkylsulfinyl, d-C4alkylsulfonyl, d-dalkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2- C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, Cs-Cβdialkylaminocarbonyl, C2- C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy, C1-C6dialkylaminocarbonyloxy and C3- C6trialkylsilyl; or
A2 and A3 together or A3 and A4 together are a bivalent group -J1-J2-J3-J4-; wherein J1, J2, J3 and J4 form together with the two carbon atoms to which J1 and J4 are attached, an aromatic ring system; wherein
J1 is nitrogen, sulfur, oxygen, a direct bond or C-R53;
J2 is nitrogen, sulfur, oxygen, a direct bond or C-R5b;
J3 is nitrogen, sulfur, oxygen, a direct bond or C-R5c;
J4 is nitrogen, sulfur, oxygen, a direct bond or C-R5d; with the provisos that a) not more than 1 substituent selected from J1, J2, J3 and J4 can at the same time form a direct bond, b) not more than 2 substituents selected from J1, J2, J3 and J4 can be oxygen or sulfur, and c) 2 substituents selected from J1, J2, J3 and J4 as oxygen and/or sulfur are separated by at least one carbon atom; each of R5a, R5b, R5c> and R5d which may be the same or different, represents hydrogen, halogen, nitro, cyano, hydroxy, CHO, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl,
C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, d-dalkoxy, C1- C4alkoxy-C! -CUaIkOXy-C1 -C4alkyl, C1-C4haloalkoxy, CrC4alkylthio, d-C4haloalkylthio, C1- C4haloalkylsulfinyl, d-C4haloalkylsulfonyl, d-dalkylsulfinyl, d-dalkylsulfonyl, C1- C4alkylsulfonyl-C1-C4alkyl, C1-C4alkylsulfoximino-C1-C4alkyl, Ci-C4alkylamino, C2- C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2-C6alkoxycarbonyl, CVCβalkylaminocarbonyl, Cs-Cβdialkylaminocarbonyl, C2- C6alkoxycarbonyloxy,
Figure imgf000086_0001
CVCβdialkylaminocarbonyloxy, C1- C4alkoxyimino-d-C4alkyl, C3-C6trialkylsilyl, phenyl, benzyl or phenoxy; or phenyl, benzyl or phenoxy mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C6cycloalkyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, C1- C4alkoxy, d-C4haloalkoxy, CrC4alkylthio, CrC4haloalkylthio, d-C4alkylsulfinyl, C1- C4alkylsulfonyl, d-C4alkylamino, C2-ddialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3- C6cycloalkylamino, C2-C4alkylcarbonyl, C2-C6alkoxycarbonyl, (VCβalkylaminocarbonyl, C3- C6dialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, C1-C6alkylaminocarbonyloxy, C3- C6dialkylaminocarbonyloxy and C3-C6trialkylsilyl; A5 is a group -A-(X)p-(Y)q-B, wherein
A is a chemical bond, or is C1-C6alkylene, C2-C6alkenylene, C2-C6alkynylene, or is a bivalent three- to ten-membered monocyclic or fused bicyclic ring system which can be partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms; and it being possible for the three- to ten-membered ring system itself and also for the C1- C6alkylene, C2-C6alkenylene and C2-C6alkynylene groups to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5-C7cycloalkenyl, C5- C8cycloalkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3-C6halocycloalkyl, C5- Cyhalocycloalkenyl, C5-C8halocycloalkynyl, Ci-C4alkoxy, d-C4haloalkoxy, Ci-C4alkylthio, C1- C4haloalkylthio, d-C4alkylsulfinyl, d-C4alkylsulfonyl, Ci-C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2- C6alkoxycarbonyl,
Figure imgf000087_0001
Cs-Cβdialkylaminocarbonyl, C2- C6alkoxycarbonyloxy, C1-C6alkylaminocarbonyloxy, Cs-Cβdialkylaminocarbonyloxy, C3- C6trialkylsilyl, and a three- to ten-membered monocyclic or fused bicyclic ring system which can be aromatic, partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms, and it being possible for the three- to ten-membered ring system itself to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5-C7cycloalkenyl, C5- Cfjcycloalkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, QrCehalocycloalkyl, C5- Cyhalocycloalkenyl, C5-C8halocycloalkynyl, Ci-C4alkoxy, Ci-C4haloalkoxy, d-C4alkylthio, C1- dhaloalkylthio, C1-C4alkylsulfinyl, d-C4alkylsulfonyl, d-C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-Cs-Cecycloalkylamino, C2-C4alkylcarbonyl, C2- C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, Cs-Cβdialkylaminocarbonyl, C2- C6alkoxycarbonyloxy, C2-C6alkylaminocarbonyloxy, QrCedialkylaminocarbonyloxy, C3- C6trialkylsilyl and phenyl, it being possible for the phenyl group in turn to be substituted by substituents independently selected from the group consisting of hydroxy, C1-C6alkyl, C1- C6haloalkyl, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3- C6alkynylthio, d-Csalkoxy-d-Csalkylthio, Ca-Czialkylcarbonyl-d-Csalkylthio, C2- C4alkoxycarbonyl-d-C3alkylthio, cyano-d-C3alkylthio, C1-C6alkylsulfinyl, C1-C6halo- alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, CrC^lkylamino- sulfonyl, N,N-di(d-C2alkyl)aminosulfonyl, di(d-C4alkyl)amino, halogen, cyano and nitro; and substituents at nitrogen atoms in the ring systems being other than halogen; X is oxygen, -N(H)- or -N(d-C4alkyl)-;
Y is C1-C6alkylene, C2-C6alkenylene, C2-C6alkynylene, or a bivalent three- to ten-membered monocyclic or fused bicyclic ring system which can be partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms; and it being possible for the three- to ten-membered ring system itself and also for the d- C6alkylene, C2-C6alkenylene and C2-C6alkynylene groups to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5-C7cycloalkenyl, C5- C8cycloalkynyl, CrC6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C-s-Cehalocycloalkyl, C5- Cyhalocycloalkenyl, C5-C8halocycloalkynyl, d-C4alkoxy, d-C4haloalkoxy, Ci-C4alkylthio, CV C4haloalkylthio, Ci-C4alkylsulfinyl, C1-C4alkylsulfonyl, Ci-C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2- C6alkoxycarbonyl, CVCβalkylaminocarbonyl, CVCβdialkylaminocarbonyl, C2- C6alkoxycarbonyloxy, CVCβalkylaminocarbonyloxy, CVCedialkylaminocarbonyloxy, C3- C6trialkylsilyl and a three- to ten-membered monocyclic or fused bicyclic ring system which can be aromatic, partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms, and it being possible for the three- to ten-membered ring system itself to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5- C7cycloalkenyl, C5-C8cycloalkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, C5-C7halocycloalkenyl, C5-C8halocycloalkynyl, d-C4alkoxy, C1- C4haloalkoxy, CrC4alkylthio, CrC4haloalkylthio, Ci-C4alkylsulfinyl, Ci-C4alkylsulfonyl, C1- C4alkylamino, C2-C4dialkylamino, CVCeCycloalkylamino, C1-C6alkyl-C3-C-6cycloalkylamino, C2- C4alkylcarbonyl, C2-C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, Cs-Cedialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, CVCealkylaminocarbonyloxy, CVCedialkylaminocarbonyloxy, C3- C6trialkylsilyl and phenyl, it being possible for the phenyl group in turn to be substituted by substituents independently selected from the group consisting of hydroxy, C1-C6alkyl, C1- C6haloalkyl, C1-C6alkylthio, C1-C6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3- C6alkynylthio, CrCsalkoxy-d-Csalkylthio, Ca-C^lkylcarbonyl-CrCsalkylthio, C2- dalkoxycarbonyl-CrCsalkylthio, cyano-d-C3alkylthio, C1-C6alkylsulfinyl, C1-C6halo- alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, C1-C2alkylamino- sulfonyl, N>N-di(C1-C2alkyl)aminosulfonyl, di(Ci-C4alkyl)amino, halogen, cyano and nitro; and substituents at nitrogen atoms in the ring systems being other than halogen; p is 0 or 1 ; q is O or 1 ;
B is a three- to four-membered ring system which is fully or partially saturated and can contain a hetero atom selected from the group consisting of nitrogen, oxygen and sulfur, and it being possible for the three- to four-membered ring system itself to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5- Cycycloalkenyl, C5-C8cycloalkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, C5-C7halocycloalkenyl, C5-C8halocycloalkynyl, d-C4alkoxy, d- C4haloalkoxy, d-C4alkylthio, d-C4haloalkylthio, CrC4alkylsulfinyl, d-C4alkylsulfonyl, C1- C4alkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2- dalkylcarbonyl, C2-C6alkoxycarbonyl, CVCβalkylaminocarbonyl, Cs-Cβdialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, (VCεalkylaminocarbonyloxy, Cs-Cedialkylaminocarbonyloxy, C3- C6trialkylsilyl and a three- to ten-membered monocyclic or fused bicyclic ring system which can be aromatic, partially saturated or fully saturated and can contain 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms, and it being possible for the three- to ten-membered ring system itself to be mono-, di- or trisubstituted by substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C5- dcycloalkenyl, C5-C8cycloalkynyl, C1- C6haloalkyl, C2-C6haloalkenyl, C2-C6haloalkynyl, C3- C6halocycloalkyl, C5-C7halocycloalkenyl, C5-C8halocycloalkynyl, d-C4alkoxy, d- C4haloalkoxy, d-C4alkylthio, d-C4haloalkylthio, d-C4alkylsulfinyl, d-C4alkylsulfonyl, C1- dalkylamino, C2-C4dialkylamino, C3-C6cycloalkylamino, C1-C6alkyl-C3-C6cycloalkylamino, C2- dalkylcarbonyl, C2-C6alkoxycarbonyl, Ca-Cβalkylaminocarbonyl, Ca-Cβdialkylaminocarbonyl, C2-C6alkoxycarbonyloxy, C1-C6alkylaminocarbonyloxy, Cs-Cedialkylaminocarbonyloxy, C3- C6trialkylsilyl and phenyl, it being possible for the phenyl group in turn to be substituted by substituents independently selected from the group consisting of hydroxy, C1-C6alkyl, C1- C6haloalkyl,C1-C6alkylthio, C1-C6haloalkylthio, C3-C6alkenylthio, C3-C6haloalkenylthio, C3- C6alkynylthio, d-C3alkoxy-d-C3alkylthio, Ca-Cialkylcarbonyl-d-Csalkylthio, C2- C4alkoxycarbonyl-d-C3alkylthio, cyano-d-C3alkylthio, C1-C6alkylsulfinyl, C1-C6halo- alkylsulfinyl, CrC6alkylsulfonyl, C1-C6haloalkylsulfonyl, aminosulfonyl, d-C2alkylamino- sulfonyl, N,N-di(C1-C2alkyl)aminosulfonyl, di(Ci-C4alkyl)amino, halogen, cyano and nitro; and substituents at nitrogen atoms in the ring systems being other than halogen; or B is hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl or C5-C6cycloalkyl; or is C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl and C5-C6cycloalkyl substituted with one, two or three substituents independently selected from the group consisting of halogen, cyano, nitro, hydroxy, d- C4alkyl, d-C4alkoxy, d-C4haloalkoxy, d-dalkylthio, Ci -C4a I ky lsulf i ny I , C1-C4alkylsulfonyl, d-dalkylsulfoximino, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyl, C2-C6trialkylsilyl, benzyl, phenoxy and a three- to ten-membered, monocyclic or fused bicyclic ring system which may be aromatic, partially saturated or fully saturated, wherein the six-membered aromatic ring system contains at least one heteroatom selected from the group consisting of oxygen, nitro and sulfur; it being possible for said benzyl, phenoxy and three- to ten-membered, monocyclic or fused bicyclic ring system in turn to be substituted by one to three substituents independently selected from the group consisting of d-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C3-C6cycloalkyl, d-C4haloalkyl, C2-C4haloalkenyl, C2-C4haloalkynyl, C3-C6halocycloalkyl, halogen, cyano, nitro, d-C4alkoxy, d-C4haloalkoxy, d-C4alkylthio, d-C4alkylsulfinyl, d- dalkylsulfonyl, d-C4alkylsulfoximino, d-C4alkylamino, C2-C6dialkylamino, C3- C6cycloalkylamino, d-C4alkyl-C3-C6cycloalkylamino, C2-C4alkylcarbonyl, C2- C6alkoxycarbonyl, C2-C6alkylaminocarbonyl, C2-C8 dialkylaminocarbonyl and C2-C6 trialkylsilyl; it being possible for said three- to ten-membered, monocyclic or fused bicyclic ring system to be spiro-bonded to the C3-C6cycloalkyl group; or B is d-C4alkoxy, d-C4alkylamino, C2-C8dialkylamino, C3-C6cycloalkylamino, C2- C6alkoxycarbonyl or C2-C6alkylcarbonyl; or A5 is a group
Figure imgf000090_0001
Y^ is a C1-C6alkylene, C2-C6alkenylene or C3-C6alkynylene chain which may be mono-, di- or trisubstituted by R20, where the unsaturated bonds of the chain are not attached directly to the sulfur atom; or is C3-C6cycloalkylene, which may be mono-, di- or trisubstituted by R21; or Y,a and Y2 form together with the chain -G-Y1b-S(=O=N-Z)- a ring system of at least 3 members; wherein Y1S and Y2 together represent the group -CH2-; -Cn2-CH2-; -CH2-CH2-CH2; -CH2-CH=CH-; -CH=CH-CH2-; -CH2-G6-CH2-; -CH2-CH2-G10-CH2-; -CH2-G7-CH2-CH2- or -CH2-CH2-G11-CH2-CH2-; G6 is oxygen, N(-Z7) or sulfur; G7 is oxygen, N(-Z8) or sulfur; G10 is oxygen, N (-Z1 ^ or sulfur; Gn is oxygen, N(-Z12) or sulfur;
R20 and R21 independently of one another are halogen, nitro, cyano, hydroxy, C1-C6alkyl,
C1-C6haloalkyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylthio,
C1-C6haloalkylsulfinyl, C1-C6haloalkylsulfonyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl,
C1-C6alkoxy-CrCβalkyl, C1 -C6alkoxy-d -C6alkyl, C1-C6alkoxy, C1-C6halo-alkoxy, benzyl or phenyl, where phenyl and benzyl for their part may be mono-, di- or trisubstituted by substituents independently selected from the group consisting of C1-C6alkyl, C1-C6haloalkyl,
C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxyl and nitro;
Y^ is a direct bond or is a C1-C6alkylene, C2-C6alkenylene or C3-C6alkynylene chain which may be mono-, di- or trisubstituted by R22, where the unsaturated bonds of the chain are not attached directly to the sulfur atom; or is C3-C6cycloalkylene, which may be mono-, di- or trisubstituted by R23, or is 1 ,2-, 1 ,3- or 1 ,4-phenylene;
R22 and R23 independently of one another are halogen, nitro, cyano, hydroxy, C1-C6alkyl,
C1-C6haloalkyl, CrC6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylthio,
C1-C6haloalkylsulfinyl, C1-C6haloalkylsulfonyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl,
C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy, C1-C6halo-alkoxy, benzyl or phenyl, where phenyl and benzyl for their part may be mono-, di- or trisubstituted by substituents independently selected from the group consisting of C1-C6alkyl, C1-C6haloalkyl,
C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxyl and nitro;
Y2 is a C1-C6alkylene, C2-C6alkenylene or C3-C6alkynylene chain which may be mono-, di- or trisubstituted by R24, where the unsaturated bonds of the chain are not attached directly to the sulfur atom; or is C3-C6cycloalkylene, which may be mono-, di- or trisubstituted by R25 ; R24 and R25 independently of one another are halogen, nitro, cyano, hydroxy, C1-C6alkyl,
C1-C6haloalkyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, C1-C6haloalkylthio,
C1-C6haloalkylsulfinyl, C1-C6haloalkylsulfonyl, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl,
C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy, CrC6halo-alkoxy, benzyl or phenyl, where phenyl and benzyl for their part may be mono-, di- or trisubstituted by substituents independently selected from the group consisting of C1-C6alkyl, C1-C6haloalkyl,
C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxyl and nitro; Y3 is hydrogen, halogen, CrC6haloalkyl or C1-C6alkyl; G is a direct bond, oxygen, NC-Z1), sulfur or the group G1-C(=G2)-G3;
Gi is a direct bond, oxygen, N(-Z2) or sulfur;
G2 is oxygen, N(-Z3) or sulfur;
G3 is a direct bond, oxygen, N(-Z4) or sulfur;
Z, Z1, Z2, Z3 and Z4 independently of one another are hydrogen, CrC6alkyl, CrC6haloalkyl,
C1-C6Cycloalkyl, CrC6halocycloalkyl, C1-C6alkylthio, C1-C6haloalkylthio or
C1-C6alkoxy-C1-C6alkyl; or C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl,
C1-C6alkylthio, C1-C6haloalkylthio or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkyl,
C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkoxy, cyano, nitro or
C1-C6haloalkoxy; or Z, Z1, Z2, Z3 and Z4 independently of one another are -C(O)R34, -C(O)O-R35, -CONR36R29, -SO2R30 or -P(O)(OR31 )(OR32)-OR33;
R34 is C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkylthio,
C1-C6haloalkylthio, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1-C6alkoxy-C1-C6alkyl; or
C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, Ca-Cβhalocycloalkyl, C1-C6alkylthio,
C1-C6haloalkylthio, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1 -C6BIkOXy-C1 -C6alkyl substituted by substituents independently selected from the group consisting of C1-C6alkyl,
C1-C6haloalkyl, C3-C6cycloalkyl, Cs-Cehalocycloalkyl, C1-C6alkoxy and C1-C6haloalkoxy; and R29, R30, R31, R32, R33, R35 and R36 independently of one another are C1-C6alkyl,
C1-C6haloalkyl, C3-C6cycloalkyl or C3-C6halocycloalkyl; or C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl or C3-C6halocycloalkyl substituted by C1-C6alkyl, CrC6haloalkyl, C3-C6cycloalkyl, Cs-Cεhalocycloalkyl, CrC6alkoxy, C1-C6haloalkoxy;
or A5 is a group
Figure imgf000092_0001
; wherein
R37 and R38, which may be the same or different, represents hydrogen, COOH, halogen, nitro, cyano, hydroxy, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C2- C6haloalkenyl, C2-C6haloalkynyl, C1-C6alkylthio, CrC6alkylsulfinyl, CrC6alkylsulfonyl,
C1-C6haloalkylthio, C1-C6haloalkylsulfinyl, C1-C6haloalkylsulfonyl, C1-C6alkoxycarbonyl, CrC6alkylcarbonyl, Cs-Cealkylaminocarbonyl, Cs-Cβdialkylaminocarbonyl,
C1-C6alkoxy-C1-C6alkyl, C1-C6haloalkoxy-C1-C6alkyl, CrC6alkoxy, C1-C6haloalkoxy, C1- C6alkylamino, C2-C6dialkylamino, C3-C6trialkylsilyl, benzyl or phenyl; where phenyl and benzyl for their part may be mono- di- or trisubstituted by C1-C6alkyl, C1-C6haloalkyl,
C1-C6alkoxy, C1-C6haloalkoxy, halogen, cyano, hydroxyl or nitro; k is O, 1 , 2, 3 or 4;
A8 is oxygen, sulfur, SO, SO2, S(O)11=N-R, C=N-OR40, N-R0, C=O or P(X)1-R39;
R39 is hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C1-C6alkoxy, hydroxy, C1-C6cycloalkyl, C1-C6Cycloalkyl-C1-C6alkyl, benzyl or phenyl; where phenyl and benzyl for their part may be mono- di- or trisubstituted by C1-C6alkyl, C1-C6haloalkyl, halogen, cyano or nitro; or R33 is O Na+, O Li+ or O K+;
R40 is hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, C2-
C6haloalkynyl, C1-C6alkoxy-C1-C6alkyl, C1-C6haloalkoxy-C1-C6alkyl or benzyl;
R is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl,
C1-C6alkylthio, C1-C6haloalkylthio, C1-C6alkoxy-C1-C6alkyl or C1-C6haloalkoxy-C1-C6alkyl; or
R is C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkylthio,
C1-C6haloalkylthio, C1-C6alkoxy-C1-C6alkyl or C1-C6haloalkoxy-C1-C6alkyl substituted by
C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, Ca-Cehalocycloalkyl, C1-C6alkoxy, or
C1-C6haloalkoxy; or R is cyano, nitro, -C(O)R4I, -C(O)OR42, -CONR43R44, -SO2R45 or -
P(O)(OR46)(OR47);
R0 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl,
C1-C6alkylthio, C1-C6haloalkylthio, C1 -C6BIkOXy-C1 -C6alkyl or C1-C6haloalkoxy-C1-C6alkyl; or
R0 is C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, C1-C6alkylthio,
C1-C6haloalkylthio, C1 -C6BIkOXy-C1 -C6alkyl or C1-C6haloalkoxy-C1-C6alkyl substituted by
C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, Cs-Cehalocycloalkyl, C1-C6alkoxy, or
C1-C6haloalkoxy; or R0 is cyano, nitro, -C(O)R041, -C(O)OR042, -CONR043R044, -SO2R045 or
-P(O)(OR046(OR047); each of R41 and R041, which may be the same or different, represents hydrogen, C1-C6alkyl,
C1-C6haloalkyl, C1-C6cycloalkyl, C1-C6halocycloalkyl, C1-C6alkylthio, C1-C6haloalkylthio,
C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or d-Cεalkoxy-C1-C6alkyl; or C1-C6alkyl,
C1-C6haloalkyl, C1-C6cycloalkyl, C1-C6halocycloalkyl, C1-C6alkylthio, C1-C6haloalkylthio,
C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1-C6alkoxy-C1-C6alkyl substituted by C1-C6alkyl,
C1-C6haloalkyl, C1-C6cycloalkyl, C1-C6halocycloalkyl, C1-C6alkoxy, or C1-C6haloalkoxy; each of R42, R43, R44, R45, R46, R47, R041, R042, R043, R044, R045 R046 and R047 which may be the same or different, represents C1-C6alkyl, C1-C6haloalkyl, C1-C6cycloalkyl or
C1-C6halocycloalkyl; or CrC6alkyl, C1-C6haloalkyl, C1-C6cycloalkyl or C1-C6halocycloalkyl substituted by C1-C6alkyl, C1-C6haloalkyl, C1-C6cycloalkyl, C1-C6halocycloalkyl, C1-C6alkoxy or C1-C6haloalkoxy;
X is oxygen or sulfur; u is 0 or 1 ; and t is O or 1 ;
A6 is hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C1-C6haloalkyl, cyano, d-C4alkoxy, d-
C4haloalkoxy, d-C4alkylthio, d-dhaloalkylthio, C1-C4alkylsulfinyl, Ci-C4alkylsulfonyl, d- dhaloalkylsulfinyl or d-C4haloalkylsulfonyl; and
A7 is C1-C6alkyl, C3-C6cycloalkyl, C1-C6haloalkyl, halogen, cyano, d-C4alkoxy, d-
C4haloalkoxy, d-C4alkylthio, d-C4haloalkylthio, d-C4alkylsulfinyl, d-C4alkylsulfonyl, d-
C4haloalkylsulfinyl or d-dhaloalkylsulfonyl; which process comprises a) treating a compound of formula Il
Figure imgf000094_0001
wherein A6 and A7 are as defined under formula I above, with a compound of formula
Figure imgf000094_0002
wherein A1, A2, A3, A4 and A5 are as defined under formula I above and R1 is C1-C6alkyl, in the presence of a base to form a compound of formula IV
Figure imgf000095_0001
wherein A1, A2, A3, A4, A5 A6 and A7 are as defined under formula I above and b) converting said compound of formula IV in the presence of an acid or a base to the compound of formula I.
PCT/EP2007/007871 2006-09-11 2007-09-10 Process for the preparation of anthranilamide derivatives WO2008031548A1 (en)

Applications Claiming Priority (2)

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EP06018929.7 2006-09-11
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CN106588870A (en) * 2015-10-19 2017-04-26 海利尔药业集团股份有限公司 Substituted salicylamide compound and application thereof
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