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WO2016087593A1 - Novel fungicidal quinolinylamidines - Google Patents

Novel fungicidal quinolinylamidines Download PDF

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Publication number
WO2016087593A1
WO2016087593A1 PCT/EP2015/078542 EP2015078542W WO2016087593A1 WO 2016087593 A1 WO2016087593 A1 WO 2016087593A1 EP 2015078542 W EP2015078542 W EP 2015078542W WO 2016087593 A1 WO2016087593 A1 WO 2016087593A1
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Prior art keywords
methyl
alkyl
ethyl
butyl
phenyl
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PCT/EP2015/078542
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French (fr)
Inventor
Olivier Jacob
Sarah Sulzer-Mosse
Fredrik Emil Malcolm Cederbaum
Thomas James Hoffman
Werner Zambach
Matthias Weiss
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Syngenta Participations Ag
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Publication of WO2016087593A1 publication Critical patent/WO2016087593A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to novel microbiocidal, in particular fungicidal, quinolinylamidine compounds.
  • compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.
  • the present invention relates to compounds of formula (I)
  • R and R 2 independently of each other represent hydrogen, Ci-C 4 alkyl, Ci-C 4 fluoroalkyl or C 3 - C 6 cycloalkyl; or
  • R and R 2 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom;
  • R 3 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C 4 alkyl, C 2 - C 5 alkenyl, C 2 -C 5 alkynl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy or C 3 -C 6 cycloalkyl;
  • R 4 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynl, d-C 6 haloalkyl, d-C 6 alkoxy or C 3 -C 6 cycloalkyl;
  • R 5 represents R 9 -(Z) m -;
  • R 6 , R 7 ,R 8 independently of each other represent hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C 4 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy or d- C 4 haloalkoxy;
  • n 0, 1 or 2;
  • Z represents Ci-C 4 alkyl, wherein the alkyl is optionally substituted by one or more groups independently selected from halogen, CN, OH, Ci-C 4 alkylcarbonyl, Ci-C 4 alkoxycarbonyl, d- C 4 -haloalkyl, CN, Ci-C 4 -alkoxy and Ci-C 4 -haloalkoxy;
  • R 9 represents hydrogen, d-C 8 alkyl, C 3 -C 8 alkenyl or C 3 -C 8 alkynyl, wherein the alkyl, alkenyl, alkynyl and cycloalkoxyare optionally substituted by one or more groups independently selected from halogen, hydroxyl, cyano, N0 2 , OH, SH, d-C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynl, d-C 6 haloalkyl, d-C 6 alkoxy, C 3 -C 8 cycloalkyl C 3 -C 8 cycloalkoxy, formyl, C 2 -C 6 alkylcarbonyl, Ci-C 6 alkylthio, Ci-C 6 alkylsulfinyl and Ci-C 6 alkylsulfonyl; or
  • R 9 represents D-A-Ci-C 6 alkyl-, D-A-Ci-C 6 alkyl-, D-A-C C 6 alkyl-, D-A-Ci-C 6 alkyl-, D-A-d- C 6 alkyl-, D-A-Ci-C 6 alkyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl- , D-A-C 2 -C 6 alkenyl- , D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkynyl-, D-A-C 2
  • R 9 represents NHR 4 ;
  • D represents d-dalkyl, d-dalkenyl, d-dalkynyl, d-dcycloalkyl, benzyl, phenyl each of which are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, mercapto, d-dhaloalkyl, d-dalkoxy, formyl, C 2 -C 5 alkylcarbonyl, d-dalkoxycarbonyl, d- dalkylthio, d-dhaloalkylthio, d-dalkylsulfinyl and d-dalkylsulfonyl;
  • each R 2 and R 3 independently of each other represents hydrogen, formyl, d-dalkyl, d- dhaloalkyl, d-dalkylcarbonyl, d-dalkoxycarbonyl, benzyl or phenyl; or
  • R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom;
  • R 4 represents phenyl optionally substituted by fluoro, CN , OH, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 and OCF 3 ;
  • each R 5 independently represents hydrogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 3 -C 5 alkenyl, C 3 - C 5 haloalkenyl, C 3 -C 5 alkynyl, C 3 -C 6 cycloalkyl, benzyl or phenyl wherein the alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, cycloalkyl, benzyl and phenyl are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy and d- C 4 haloalkoxy;
  • Substituents at a nitrogen atom are always different from halogen.
  • a hydroxy, mercapto or amino substituent is not to be placed on an ocarbon relative to a heteroatom of a core fragment.
  • Halogen either as a lone substituent or in combination with another substituent (e.g. haloalkyl) is generally fluorine, chlorine, bromine or iodine, and usually fluorine, chlorine or bromine.
  • Each alkyl moiety (including the alkyl moiety of alkoxy, alkylthio, etc.) is a straight or branched chain and, depending on the number of carbon atoms it contains, is, for example, methyl, ethyl, n- propyl, n-butyl, n-pentyl, n-hexyl, / ' so-propyl, sec-butyl, / ' so-butyl, ieri-butyl, neo-pentyl, n-heptyl or 1 ,3- dimethylbutyl, and usually methyl or ethyl.
  • alkenyl and alkynyl groups can be mono- or di-unsatu rated and examples thereof are derived from the above mentioned alkyl groups.
  • the alkenyl group is an unsaturated straight or branched chain having a carbon-carbon double bond and, depending on the number of carbon atoms it contains, is, for example ethenyl, 1 -propenyl, 2-propenyl, 1 -methyl-ethenyl, 1 -butenyl, 2-butenyl, 3-butenyl, 1 -methyl-1 -propenyl, 2-methyl-1 - propenyl, 2-methyl-2-propenyl, 1 -pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1 -methyl-1 -butenyl, 2- methyl-1 -butenyl, 3-methyl-1 -butenyl, 1 -methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1 -methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1 , 1 -dimethyl-2-
  • the alkynyl group is an unsaturated straight or branched chain having a carbon-carbon triple bond and, depending on the number of carbon atoms it contains, is, for example ethynyl, 1 -propynyl, 2-propynyl, 1 -butynyl, 2-butynyl, 3-butynyl, 1 -methyl-2-propynyl, 1 -pentynyl, 2-pentynyl, 3-pentynyl, 4- pentynyl, 3-methyl-1 -butynyl, 1 -methyl-2-butynyl, 1 -methyl-3-butynyl, 2-methyl-3-butynyl, 1 , 1 -dimethyl- 2-propynyl, 1 -ethyl-2-propynyl, 1 -hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexyny
  • Haloalkyl moieties are alkyl moieties which are substituted by one or more of the same or different halogen atoms and are, for example, monofluoromethyl, difluoromethyl, trifluoromethyl, monochloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2,2-difluoroethyl, 2-fluoroethyl, 1 , 1-difluoroethyl, 1-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1 , 1-difluoro-2,2,2-trichloroethyl, 2,2,3,3- tetrafluoroethyl and 2,2,2-trichloroethyl, and typically trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.
  • Alkoxy is, for example, methoxy, ethoxy, propoxy, / ' so-propoxy, n-butoxy, / ' so-butoxy, sec-butoxy and ieri-butoxy, and usually methoxy or ethoxy.
  • 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, and usually difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.
  • Alkylthio is, for example, methylthio, ethylthio, propylthio, / ' so-propylthio, n-butylthio, iso- butylthio, sec-butylthio or ieri-butylthio, and usually methylthio or ethylthio.
  • Alkylsulphonyl is, for example, methylsulphonyl, ethylsulphonyl, propylsulphonyl, iso- propylsulphonyl, n-butylsulphonyl, / ' so-butylsulphonyl, sec-butylsulphonyl or ieri-butylsulphonyl, and usually methylsulphonyl or ethylsulphonyl.
  • Alkylsulphinyl is, for example, methylsulphinyl, ethylsulphinyl, propylsulphinyl, iso- propylsulphinyl, n-butylsulphinyl, / ' so-butylsulphinyl, sec-butylsulphinyl or ieri-butylsulphinyl, and usually methylsulphinyl or ethylsulphinyl.
  • Cycloalkyl may be saturated or partially unsaturated, preferably fully saturated, and is, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
  • Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n- propoxymethyl, n-propoxyethyl, /so-propoxymethyl or / ' so-propoxyethyl.
  • Aryl includes phenyl, naphthyl, anthracyl, fluorenyl and indanyl, but is usually phenyl.
  • Carbocycle includes cycloalkyl groups and aryl groups.
  • Heterocycloalkyl is a non-aromatic ring that may be saturated or partially unsaturated, preferably fully saturated, containing carbon atoms as ring members and at least one heteroatom selected from O, S and N as ring members.
  • Examples include oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, 1 ,3-dioxolanyl, 1 ,4-dioxanyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, oxazinanyl, morpholinyl, thiomorpholinyl, imidazolidinyl, pyrazolidinyl and piperazinyl, preferably morpholinyl, pyrrolidinyl, piperdinyl and piperazinyl, more preferably morpholinyl and pyrollidinyl.
  • Heteroaryl is, for example, a monovalent monocyclic or bicyclic aromatic hydrocarbon radical.
  • monocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, and thiadiazolyl.
  • bicyclic groups include quinolinyl, cinnolinyl, quinoxalinyl, benzimidazolyl, benzothiophenyl, and benzothiadiazolyl.
  • Monocyclic heteroaryl groups are preferred, preferably pyridyl, pyrrolyl, imidazolyl and triazolyl, e.g. 1 ,2,4 triazolyl, pyridyl and imidazolyl being most preferred.
  • heterocycle and “heterocyclic ring” are used interchangeably and are defined to include heterocycloalkyl and heteroaryl groups. Any reference herein to a heterocycle or heterocyclic ring preferably refers to the specific examples given under the definition of heteroaryl and
  • heterocycloalkyl above, and are preferably morpholinyl, pyrrolidinyl, piperdinyl, piperazinyl pyridyl, pyrrolyl, imidazolyl and triazolyl, e.g. 1 ,2,4 triazolyl, more preferably morpholinyl, pyrollidinyl, pyridyl and imidazolyl.
  • No heterocycle contains adjacent oxygen atoms, adjacent sulphur atoms, or adjacent oxygen and sulphur atoms.
  • a moiety is indicated as being (optionally) substituted, e.g. alkyl, this includes those moieties where they are part of a larger group, e.g. the alkyl in the alkylthio group. The same applies, e.g. to the phenyl moiety in phenylthio etc.
  • a moiety is indicated as being optionally substituted by one or more other groups, preferably there are one to five optional substituents, more preferably one to three optional substituents.
  • a moiety is substituted by a cyclic group, e.g. aryl, heteroaryl, cycloalkyl, preferably there are no more than two such substituents, more preferably no more than one such substituent.
  • R and R 2 independently of each other represent hydrogen, Ci-C 4 alkyl, Ci-C 4 fluoroalkyl or C 3 - C 6 cycloalkyl; or
  • R and R 2 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom.
  • R and R 2 independently of each other represent hydrogen, Ci-C 4 alkyl or cyclopropyl.
  • R and R 2 independently of each other represent hydrogen, methyl, ethyl, isopropyl, n-propyl or cyclopropyl.
  • R and R 2 independently of each other represent methyl or ethyl.
  • R represents methyl and R 2 represents ethyl.
  • R represents methyl and R 2 is as defined above.
  • R 3 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, C 1 -C4 alkyl, C 2 - C 5 alkenyl, C 2 -C 5 alkynl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy or C 3 -C 6 cycloalkyl.
  • R 3 represents hydrogen, chloro, methyl or ethyl.
  • R 3 represents methyl.
  • R 4 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynl, d-C 6 haloalkyl, d-C 6 alkoxy or C 3 -C 6 cycloalkyl.
  • R 4 represents hydrogen, halogen, cyano, hydroxy, Ci-C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynl, d-C 6 haloalkyl or d-C 6 alkoxy.
  • R 4 represents hydrogen, halogen, cyano, hydroxy, d-d alkyl or d-C 6 haloalkyl.
  • R 4 represents hydrogen
  • R 5 represents R 9 -(Z) m -.
  • n 0, 1 or 2.
  • m represents 0 or 1 .
  • Z represents methylene or ethylene, each of which is optionally substituted by one or more methyl groups.
  • Z represents Ci-C 4 alkyl, wherein the alkyl is optionally substituted by one or more groups independently selected from halogen, CN, OH, Ci-C 4 alkylcarbonyl, Ci-C 4 alkoxycarbonyl, d- C 4 -haloalkyl, CN , Ci-C 4 -alkoxy and Ci-C 4 -haloalkoxy.
  • Z represents methlyene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from fluorine, CN, OH, methyl, ethyl, propyl, iso-propyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , CN, OMe, OEt, COMe, COEt, COiPr, COtBu, C0 2 Me, C0 2 Et, C0 2 iPr, and C0 2 tBu.
  • R 9 represents d-C 8 alkyl, C 3 -C 8 alkenyl or C 3 -C 8 alkynyl, wherein the alkyl, alkenyl, alkynyl and cycloalkoxyare optionally substituted by one or more groups independently selected from halogen, hydroxyl, cyano, N0 2 , OH, SH, Ci-C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynl, Ci-C 6 haloalkyl, Ci-C 6 alkoxy, C 3 -C 8 cycloalkyl C 3 -C 8 cycloalkoxy, formyl, C 2 -C 6 alkylcarbonyl, d-C 6 alkylthio, d-C 6 alkylsulfinyl and d-C 6 alkylsulfonyl; or
  • R 9 represents D-A-d-C 6 alkyl-, D-A-d-C 6 alkyl-, D-A-C C 6 alkyl-, D-A-d-C 6 alkyl-, D-A-C C 6 alkyl-, D-A-d-C 6 alkyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl- , D-A-C 2 -C 6 alkenyl- , D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkenyl-, D-A-C 2 -C 6 alkynyl-, D-A-C 2 -C 6 alkynyl-, D-A-C 2 -C 6 al
  • R 9 represents NHR 4 .
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or d-C 6 alkynyl wherein the alkyl, alkenyl and alkynyl are optionally be optionally substituted by one or more groups independently selected from halogen, CN, OH, d-C 4 alkyl, C 2 -C 4 alkenyl, d-C 4 fluoroalkyl, d-C 4 alkoxy, and C 2 - C 5 alkylcarbonyl; or
  • R 9 represents a five- or six-membered saturated or partially saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R 11 ), O and S, optionally substituted by one or more groups independently selected from the group consisting of halogen, CN, N0 2 , OH, SH, CHO, d-C 4 alkyl, d-C 4 haloalkyl, C 3 -C 6 cycloalkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 2 - C 5 haloalkynyl, Ci-C 4 alkoxy, Ci-C 4 haloalkoxy, C 3 -C 5 alkynyloxy, Ci-C 4 alkylcarbonyl and Ci-C 4 alkoxycarbonyl; or
  • R 9 represents a C 3 -C 8 carbocyclic system, which may be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from halogen, CN, N0 2 , OH, SH, CHO, COOH, d-C 4 alkyl, d-C 4 alkoxy, d-C 4 haloalkyl, d-C 4 haloalkoxy, C 3 -C 6 cycloalkyl and d-C 4 alkylcarbonyl; or
  • R 9 represents NHR 14 ;
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or d-C 6 alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 , and OCF 3 ; or
  • R 9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R 11 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, CHO, Ci-C 4 alkyl, Ci-C 4 fluoroalkyl, d-C 4 alkoxy, Ci-C 4 fluoroalkoxy, Ci-C 4 alkylcarbonyl and Ci-C 4 alkoxycarbonyl; or
  • R 9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R 16 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, CHO, Ci-C 4 alkyl, Ci-C 4 fluoroalkyl, Ci-C 4 alkoxy, Ci-C 4 fluoroalkoxy, Ci-C 4 alkylcarbonyl, and Ci-C 4 alkoxycarbonyl; or
  • R 9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, Ci-C 4 alkyl, Ci-C 4 alkoxy, Ci-C 4 fluoroalkyl and Ci-C 4 fluoroalkoxy; or R 9 represents NHR 4 .
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or d-C 6 alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from fluoro, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF- CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr; or
  • R 9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R 11 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH , SH , methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 - CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OnPr, OCHF 2 and OCF 3 ; or
  • R 9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R 16 ), O and S, optionally substituted by one or more groups independently selected from fluoro, CN, N0 2 , OH, SH, CHO, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 , OCF 3 , SCHF 2 , SCF 3 , COMe, COEt, COiPr, COtBu, C0 2 Me, C0 2 Et, C0 2 iPr, and C0 2 t
  • R 9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from fluoro, CN, N0 2 , OH, SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 and OCF 3 ; or
  • R 9 represents NHR 4 .
  • R 0 represents hydrogen, formyl, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 3 -C 5 alkenyl or C 2 -C 5 alkylcarbonyl.
  • Each R independently represents hydrogen, formyl, d-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy,
  • Each R 2 and R 3 independently of each other represents hydrogen, formyl, Ci-C 4 alkyl, d- C 4 haloalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 alkoxycarbonyl, benzyl or phenyl; or
  • R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom.
  • each R 2 and R 3 independently of each other represents hydrogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, benzyl or phenyl; or
  • R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom.
  • R 4 represents phenyl optionally substituted by fluoro, CN, OH, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 - CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 and OCF 3 .
  • Each R 5 independently represents hydrogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 3 -C 5 alkenyl, C 3 -
  • Each R 7 and R 8 independently of each other represents hydrogen, Ci-C 4 alkyl, d- C 4 fluoroalkyl, benzyl or phenyl; or
  • R 7 and R 8 together with the nitrogen atom to which they are attached form aziridine, azetidine, pyrolidine, piperidine, morpholine, and thiomorpholine.
  • each R 7 and R 8 independently of each other represents hydrogen, methyl, ethyl, propyl, isopropyl, CHF 2 , CF 3 , benzyl or phenyl.
  • each R 7 and R 8 independently of each other represents hydrogen, methyl, ethyl, propyl or isopropyl.
  • D represents Ci-C 4 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 3 -C 6 cycloalkyl, benzyl, phenyl each of which are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, mercapto, Ci-C 4 haloalkyl, Ci-C 4 alkoxy, formyl, C 2 -C 5 alkylcarbonyl, Ci-C 4 alkoxycarbonyl, d- C 4 alkylthio, Ci-C 4 haloalkylthio, C 1 -C 4 alkylsulfinyl and Ci-C 4 alkylsulfonyl.
  • Z represents methlyene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from fluorine, CN, OH, methyl, ethyl, propyl, iso-propyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , CN, OMe, OEt, COMe, COEt, COiPr, COtBu, C0 2 Me, C0 2 Et, C0 2 iPr, and C0 2 tBu;
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or CrC 6 alkynyl wherein the alkyl, alkenyl and alkynyl are optionally be optionally substituted by one or more groups independently selected from halogen, CN, OH, Ci-C 4 alkyl, C 2 -C 4 alkenyl, Ci-C 4 fluoroalkyl, Ci-C 4 alkoxy, and C 2 -C 5 alkylcarbonyl; or R 9 represents a five- or six-membered saturated or partially saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R 11 ), O and S, optionally substituted by one or more groups independently selected from the group consisting of halogen, CN, N0 2 , OH, SH, CHO, d-C 4 alkyl, d-C 4 haloalkyl, C 3 -C 6 cycloalkyl, C 2 -C 5 alkeny
  • R 9 represents a C 3 -C 8 carbocyclic system, which may be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from halogen, CN, N0 2 , OH, SH, CHO, COOH, d-d alkyl, d-d alkoxy, d-d haloalkyl, d-d haloalkoxy, C 3 -C 6 cycloalkyl and Ci-C 4 alkylcarbonyl; or
  • R 9 represents NHR 4 ;
  • each R independently represents hydrogen, formyl, Ci-C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 alkoxy,
  • each R 2 and R 3 independently of each other represents hydrogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, benzyl or phenyl; or
  • R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom;
  • R 7 and R 8 together with the nitrogen atom to which they are attached form aziridine, azetidine, pyrolidine, piperidine, morpholine, and thiomorpholine.
  • m represents 0 or 1 ;
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or d-C 6 alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 , and OCF 3 ;
  • R 9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R 11 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, CHO, Ci-C 4 alkyl, Ci-C 4 fluoroalkyl, d-C 4 alkoxy, Ci-C 4 fluoroalkoxy, Ci-C 4 alkylcarbonyl and Ci-C 4 alkoxycarbonyl; or
  • R 9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R 16 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, CHO, Ci-C 4 alkyl, Ci-C 4 fluoroalkyl, Ci-C 4 alkoxy, Ci-C 4 fluoroalkoxy, Ci-C 4 alkylcarbonyl, and Ci-C 4 alkoxycarbonyl; or
  • R 9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, Ci-C 4 alkyl, Ci-C 4 alkoxy, Ci-C 4 fluoroalkyl and Ci-C 4 fluoroalkoxy; or
  • R 9 represents NHR 4 ;
  • R 0 represents hydrogen or methyl
  • each R 7 and R 8 independently of each other represents hydrogen, methyl, ethyl, propyl, isopropyl, CHF 2 , CF 3 , benzyl or phenyl.
  • m represents 0 or 1 ;
  • Z represents methylene or ethylene, each of which is optionally substituted by one or more methyl groups
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or d-C 6 alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from fluoro, CN , OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 - CH 3 , CF 2 -CF 3 OMe, OEt, OiPr, OPr; or
  • R 9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R 11 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH , SH , methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 - CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OnPr, OCHF 2 and OCF 3 ; or
  • R 9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R 16 ), O and S, optionally substituted by one or more groups independently selected from fluoro, CN, N0 2 , OH, SH, CHO, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 , OCF 3 , SCHF 2 , SCF 3 , COMe, COEt, COiPr, COtBu, C0 2 Me, C0 2 Et, C0 2 iPr, and C0 2 tBu
  • R 9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from fluoro, CN, N0 2 , OH, SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 and OCF 3 ; or
  • R 9 represents NHR 4 ;
  • each R 7 and R 8 independently of each other, represents hydrogen, methyl, ethyl, propyl or isopropyl.
  • R 9 represents hydrogen, d-C 8 alkyl, C 3 -C 8 alkenyl or C 3 -C 8 alkynyl, wherein the alkyl, alkenyl, alkynyl and cycloalkoxyare optionally substituted by one or more groups independently selected from halogen, hydroxyl, cyano, N0 2 , OH, SH, d-C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynl, d-C 6 haloalkyl, d-C 6 alkoxy, C 3 -C 8 cycloalkyl C 3 -C 8 cycloalkoxy, formyl, C 2 - C 6 alkylcarbonyl, d-C 6 alkylthio, d-C 6 alkylsulfinyl and d-C 6 alkylsulfonyl.
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or d- C 6 alkynyl wherein the alkyl, alkenyl and alkynyl are optionally be optionally substituted by one or more groups independently selected from halogen, CN, OH, d-C 4 alkyl, C 2 -C 4 alkenyl, d-C 4 fluoroalkyl, d- dalkoxy, and C 2 -C 5 alkylcarbonyl.
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or d-C 6 alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso- butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 , and OCF 3 .
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or d-C 6 alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from fluoro, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3, OMe, OEt, OiPr, OPr.
  • R 9 represents hydrogen, d-C 6 alkyl, d-C 6 alkenyl or Ci-C 6 alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from fluoro, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3
  • R represents D-A-Ci-C 6 alkyl-, D-A-Ci-C 6 alkyl-, D-A-d-C 6 alkyl-, D-A-Ci-C 6 alkyl-, D-A-Ci-C 6
  • R 9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N , N(R ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, CHO, d-C 4 alkyl, d-C 4 fluoroalkyl, d-C 4 alkoxy, d-C 4 fluoroalkoxy, d-C 4 alkylcarbonyl and Ci-C 4 alkoxycarbonyl.
  • R 9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N , N(R ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH , SH , methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert- butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OnPr, OCHF 2 and OCF 3 .
  • R represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R 16 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, CHO, d-C 4 alkyl, Ci-C 4 fluoroalkyl, d-C 4 alkoxy, d-C 4 fluoroalkoxy, Ci-C 4 alkylcarbonyl, and Ci-C 4 alkoxycarbonyl.
  • R 9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R 16 ), O and S, optionally substituted by one or more groups independently selected from fluoro, CN, N0 2 , OH, SH, CHO, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 , OCF 3 , SCHF 2 , SCF 3 , COMe, COEt, COiPr, COtBu, C0 2 Me, C0 2 Et, C0 2 iP
  • groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, CHO, COOH, d- C 4 alkyl, Ci-C 4 alkoxy, Ci-C 4 fluoroalkyl, C 3 -C 6 cycloalkyl, C 2 -C 4 alkenyl, Ci-C 4 flu
  • R 9 represents a C 3 -C 8 carbocyclic system, which may be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from halogen, CN, N0 2 , OH, SH, CHO, COOH, d-C 4 alkyl, d-C 4 alkoxy, d- C 4 haloalkyl, Ci-C 4 haloalkoxy, C 3 -C 6 cycloalkyl and Ci-C 4 alkylcarbonyl.
  • R 9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N0 2 , OH, SH, Ci-C 4 alkyl, Ci-C 4 alkoxy, d- dfluoroalkyl and Ci-C 4 fluoroalkoxy.
  • R 9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from fluoro, CN, N0 2 , OH, SH, methyl, ethyl, n-propyl, iso-propyl, n- butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 and OCF 3.
  • groups independently selected from fluoro, CN, N0 2 , OH, SH, methyl, ethyl, n-propyl, iso-propyl, n- butyl, iso-butyl, sec-butyl, tert-butyl, CH
  • R 9 represents NHR 4 , wherein R 4 is as described above.
  • Z represents methylene or ethylene each of which is optionally substituted by one or more substituents independently selected from methyl, ethyl, OH, CN, CF 3 , OMe, OEt, C0 2 Me, C0 2 Et and C0 2 iPr;
  • n 0 or 1
  • R 9 represents H, NHR 4 , Ci-C 6 alkyl, Ci-C 6 alkenyl, Ci-C 6 alkoxy, Ci-C 6 alkenoxy, C 3 -
  • C 6 cycloalkylmethoxy, phenyl, benzyl or a five- or six-membered saturated or aromatic monocyclic system which contains one or two members selected from the group consisting of N and O, each of which are optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 , OCF 3 ;
  • R 4 represents phenyl optionally substituted by fluoro, CN, OH, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 - CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 and OCF 3 .
  • Z represents methylene or ethylene each of which is optionally substituted by one or more substituents independently selected from methyl, ethyl, OH, CN, CF 3 , OMe, OEt, C0 2 Me, C0 2 Et and C0 2 iPr;
  • n 0 or 1
  • R 9 represents NHR 14 , d-C 6 alkyl, Ci-C 6 alkenyl, d-C 6 alkoxy, d-C 6 alkenoxy, C 3 - C 6 cycloalkylmethoxy, phenyl, benzyl or a five- or six-membered saturated or aromatic monocyclic system which contains one or two members selected from the group consisting of N and O, each of which are optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr,
  • R 4 represents phenyl optionally substituted by fluoro, CN, OH, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 -CH 3 , CF 2 -CH 3 , CF 2 - CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 and OCF 3 .
  • Z represents methylene or ethylene each of which is optionally substituted by one or more substituents independently selected from methyl, ethyl, OH, CN, CF 3 , OMe, OEt, C0 2 Me, C0 2 Et and C0 2 iPr;
  • n 0 or 1
  • R 9 represents d-C 6 alkyl, d-C 6 alkenyl, d-C 6 alkoxy, d-C 6 alkenoxy, C 3 -C 6 cycloalkylmethoxy, phenyl, benzyl or a five- or six-membered saturated or aromatic monocyclic system which contains one or two members selected from the group consisting of N and O, each of which are optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH 2 F, CHF 2 , CF 3 , CHF-CH 3 , CF 2 - CH 3 , CF 2 -CH 3 , CF 2 -CF 3 , OMe, OEt, OiPr, OPr, OCHF 2 and
  • R and R 2 independently of each other represent hydrogen, d-C 4 alkyl or cyclopropyl;
  • R 4 represents hydrogen;
  • R 6 , R 7 and R 9 independently of each other represent hydrogen, halogen, CN, d-C 4 alkyl, d- C 4 alkoxy, Ci-C 4 haloalkyl or C1-C4 haloalkoxy.
  • R and R 2 independently of each other represent hydrogen, methyl, ethyl, isopropyl, n-propyl or cyclopropyl;
  • R 3 represents hydrogen, chloro, methyl or ethyl
  • R 4 represents hydrogen
  • R 6 , R 7 and R 8 independently of each other represent hydrogen, fluoro, chloro, bromo, CN, methyl, ethyl, propyl, OMe, OEt, CHF 2 , CF 3 or OCHF 2 .
  • R represents methyl
  • R 2 represents ethyl
  • R 3 represents methyl
  • R 4 , R 6 , R 7 and R 8 represent hydrogen.
  • the present invention further provides novel intermediate compounds of the formula (XIX).
  • R 3 , R 4 , R 6 , R 7 and R 8 are as defined herein for a compound of formula (I) and R is defined as hydrogen or C0 2 tBu;
  • X is CI, Br, I, boronic ester, boronic acid, tri-alkylstannane, CN, CH 2 OH, CH(Me)OH, CHO, C(0)Me, C0 2 Me, and C0 2 Et.
  • X is CI, Br, I, CN, CH 2 OH, CH(Me)OH, CHO, C(0)Me, C0 2 Me, C0 2 Et, B(OH) 2 , B(OMe) 2 , B[0 2 C 2 (Me) 4 ], SnMe 3 , or SnBu 3 .
  • X is CI, Br, I, B(OH) 2 , B(OMe) 2 ,
  • X is CI, Br or I.
  • X is bromine
  • R is hydrogen
  • the invention is further illustrated by making available the following individual compounds of formula (I) listed below in Tables 1 to 16.
  • Tables 1 to 16 which follow Table A below, make available 552 compounds of the formula (I) in which R , R 2 and R 5 are the substituents defined in Table A and the remaining substituents are defined in each of Tables 1 to 16 respectively.
  • Table 1 individualises 552 compounds of formula (I) wherein R , R 2 and R 5 are as defined in each respective row of Table A, and the remaining substituents are as defined in Table 1.
  • Table 2 individualises 552 compounds of formula (I) wherein R , R 2 and R 5 are as defined in each respective row of Table A, and the remaining substituents are as defined in Table 2; and so on for Tables 3 to 16.
  • Table A discloses 552 sets of meanings of the variables R , R 2 and R 5 in a compound of formula (IA), as follows:
  • A.221 H isopropyl 3-(difluoromethoxy)propyl
  • A.229 H isopropyl (4-difluoromethyl)cyclohexylmethyl
  • A.269 H isopropyl tert-bu tyl 4-m ethylpi perid i ne- 1 -carboxylate
  • A.405 H isopropyl [4-(difluoromethyl)phenyl]ethyl
  • A.429 H isopropyl [4-(difluoromethyl)phenyl]methyl
  • A.501 H isopropyl [3-(difluoromethyl)phenoxy]methyl
  • Table 1 discloses 552 compounds of formula (I) wherein each of R 3 , R 4 , R 6 , R 7 and R ! are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • compound 1.1 has the following structure:
  • Table 2 discloses 552 compounds of formula (I) wherein R 3 is methyl, each of R 4 , R 6 , R 7 and R 8 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 3 discloses 552 compounds of formula (I) wherein R 3 is ethyl, each of R 4 , R 6 , R 7 and R 8 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 4 discloses 552 compounds of formula (I) wherein R 3 is cycloproply, each of R 4 , R 6 , R 7 and R 8 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 5 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 8 is chloro, each of R 4 , R 6 and R 7 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 6 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 8 is methyl, each of R 4 , R 6 and R 7 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 7 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 8 is methoxy, each of R 4 , R 6 and R 7 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 8 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 8 is cyano, each of R 4 , R 6 and R 7 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 9 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 7 is chloro, each of R 4 , R 6 and R 8 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 10 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 7 is methyl, each of R 4 , R 6 and R 8 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 1 1 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 8 is methoxy, each of R 4 , R 6 and R 7 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 12 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 8 is cyano, each of R 4 , R 6 and R 7 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 13 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 6 is chloro, each of R 4 , R 7 and R 8 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 14 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 6 is methyl, each of R 4 , R 7 and R 8 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 15 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 6 is methoxy, each of R 4 , R 7 and R 8 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • Table 16 discloses 552 compounds of formula (I) wherein R 3 is methyl, R 6 is cyano, each of R 4 , R 7 and R 8 are hydrogen and each of the variables R , R 2 and R 5 has the specific meaning given in the corresponding row of Table A.
  • the compounds of formula (I) according to the invention have, for practical purposes, a very advantageous spectrum of activities for protecting useful plants against diseases that are caused by phytopathogenic microorganisms, such as fungi, bacteria or viruses, in particular against diseases that are caused by fungi.
  • Compounds of formula I and fungicidal compositions containing them may be used to control plant diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete,
  • the invention therefore also relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula (I) is applied as active ingredient to the plants, to parts thereof or the locus thereof.
  • plants refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
  • locus means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.
  • the compounds of formula I can be used in the agricultural sector and related fields of use e.g. as active ingredients for controlling plant pests or on non-living materials for control of spoilage microorganisms or organisms potentially harmful to man.
  • the compounds of formula (I) according to the invention are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous useful plants.
  • the compounds of formula (I) can be used to inhibit or destroy the diseases that occur on plants or parts of plants of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later from phytopathogenic micro-organisms.
  • fungicide as used herein means a compound that controls, modifies, or prevents the growth of fungi.
  • fungicidally effective amount means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all deviation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.
  • a preferred method of applying a compound of formula (I) is foliar application.
  • the frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen.
  • the compounds of formula (I) may also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
  • compounds of formula (I) as dressing agents for the treatment of plant propagation material, in particular of seeds and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.
  • the propagation material can be treated with a composition comprising a compound of formula I before planting: seed, for example, can be dressed before being sown.
  • the active ingredients according to the invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation.
  • the composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing.
  • the invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.
  • plant propagation material denotes all generative parts of a plant, for example seeds or vegetative parts of plants such as cuttings and tubers. It includes seeds in the strict sense, as well as roots, fruits, tubers, bulbs, rhizomes, and parts of plants.
  • the compounds of formula (I) according to the invention may be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene management.
  • the invention could be used to protect non-living materials from fungal attack, e.g. lumber, wall boards and paint.
  • the compounds of formula I are for example, effective against Fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses.
  • pathogens may include:
  • Oomycetes including Phytophthora diseases such as those caused by Phytophthora capsici, Phytophthora infestans, Phytophthora sojae, Phytophthora fragariae, Phytophthora nicotianae, Phytophthora cinnamomi, Phytophthora citricola, Phytophthora citrophthora and Phytophthora erythroseptica; Pythium diseases such as those caused by Pythium aphanidermatum, Pythium arrhenomanes, Pythium graminicola, Pythium irregulare and Pythium ultimum; diseases caused by Peronosporales such as Peronospora destructor, Peronospora parasitica, Plasmopara viticola, Plasmopara halstedii, Pseudoperonospora cubensis, Albugo Candida, Sclerophthora macrospora and Br
  • Ascomycetes including blotch, spot, blast or blight diseases and/or rots for example those caused by Pleosporales such as Stemphylium solani, Stagonospora tainanensis, Spilocaea oleaginea, Setosphaeria turcica, Pyrenochaeta lycoperisici, Pleospora herbarum, Phoma destructiva,
  • Pleosporales such as Stemphylium solani, Stagonospora tainanensis, Spilocaea oleaginea, Setosphaeria turcica, Pyrenochaeta lycoperisici, Pleospora herbarum, Phoma destructiva,
  • Ophiobolus graminis Leptosphaeria maculans, Hendersonia creberrima, Helminthosporium triticirepentis, Setosphaeria turcica, Drechslera glycines, Didymella bryoniae, Cycloconium
  • Mycosphaerella fijiensis Mycosphaerella graminicola, Mycovellosiella koepkeii, Phaeoisariopsis bataticola, Pseudocercospora vitis, Pseudocercosporella herpotrichoides, Ramularia beticola, Ramularia collo-cygni, Magnaporthales such as Gaeumannomyces graminis, Magnaporthe grisea, Pyricularia oryzae, Diaporthales such as Anisogramma anomala, Apiognomonia errabunda, Cytospora platani, Diaporthe phaseolorum, Discula destructiva, Gnomonia fructicola, Greeneria uvicola, Melanconium juglandinum, Phomopsis viticola, Sirococcus clavigignenti-juglandacearum, Tubakia dryina, Dicarpella spp.
  • Valsa ceratosperma and others such as Actinothyrium graminis, Ascochyta pisi, Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Asperisporium caricae, Blumeriella jaapii, Candida spp.
  • Phialophora gregata Phyllachora pomigena, Phymatotrichum omnivora, Physalospora abdita, Plectosporium tabacinum, Polyscytalum pustulans, Pseudopeziza medicaginis, Pyrenopeziza brassicae, Ramulispora sorghi, Rhabdocline pseudotsugae, Rhynchosporium secalis, Sacrocladium oryzae, Scedosporium spp., Schizothyrium pomi, Sclerotinia sclerotiorum, Sclerotinia minor,
  • Sclerotium spp. Typhula ishikariensis, Seimatosporium mariae, Lepteutypa cupressi, Septocyta ruborum, Sphaceloma perseae, Sporonema phacidioides, Stigmina palmivora, Tapesia yallundae, Taphrina bullata, Thielviopsis basicola, Trichoseptoria fructigena, Zygophiala jamaicensis; powdery mildew diseases for example those caused by Erysiphales such as Blumeria graminis, Erysiphe polygoni, Uncinula necator, Sphaerotheca fuligena, Podosphaera leucotricha, Podospaera macularis Golovinomyces cichoracearum, Leveillula taurica, Microsphaera diffusa, Oidiopsis gossypii,
  • Phyllactinia guttata and Oidium arachidis molds for example those caused by Botryosphaeriales such as Dothiorella aromatica, Diplodia seriata, Guignardia bidwellii, Botrytis cinerea, Botryotinia allii, Botryotinia fabae, Fusicoccum amygdali, Lasiodiplodia theobromae, Macrophoma theicola,
  • Macrophomina phaseolina Phyllosticta cucurbitacearum
  • anthracnoses for example those caused by Glommerelales such as Colletotrichum gloeosporioides, Colletotrichum lagenarium, Colletotrichum gossypii, Glomerella cingulata, and Colletotrichum graminicola
  • wilts or blights for example those caused by Hypocreales such as Acremonium strictum, Claviceps purpurea, Fusarium culmorum, Fusarium graminearum, Fusarium virguliforme, Fusarium oxysporum, Fusarium subglutinans, Fusarium oxysporum f.sp. cubense, Gerlachia nivale, Gibberella fujikuroi, Gibberella zeae,
  • Gliocladium spp. Myrothecium verrucaria, Nectria ramulariae, Trichoderma viride, Trichothecium roseum, and Verticillium theobromae.
  • Basidiomycetes including smuts for example those caused by Ustilaginales such as
  • Ustilaginoidea virens Ustilago nuda, Ustilago tritici, Ustilago zeae, rusts for example those caused by Pucciniales such as Cerotelium fici, Chrysomyxa arctostaphyli, Coleosporium ipomoeae, Hemileia vastatrix, Puccinia arachidis, Puccinia cacabata, Puccinia graminis, Puccinia recondita, Puccinia sorghi, Puccinia hordei, Puccinia striiformis f.sp. Hordei, Puccinia striiformis f.sp. Secalis,
  • Pucciniastrum coryli or Uredinales such as Cronartium ribicola, Gymnosporangium juniper!- viginianae, Melampsora medusae, Phakopsora pachyrhizi, Phragmidium mucronatum, Physopella ampelosidis, Tranzschelia discolor and Uromyces viciae-fabae; and other rots and diseases such as those caused by Cryptococcus spp., Exobasidium vexans, Marasmiellus inoderma, Mycena spp., Sphacelotheca reiliana, Typhula ishikariensis, Urocystis agropyri, Itersonilia perplexans, Corticium invisum, Laetisaria fuciformis, Waitea circinata, Rhizoctonia solani, Thanetephorus cucurmeris, Entyloma dahliae,
  • Blastocladiomycetes such as Physoderma maydis.
  • Mucoromycetes such as Choanephora cucurbitarum.; Mucor spp.; Rhizopus arrhizus, As well as diseases caused by other species and genera closely related to those listed above.
  • the compounds and compositions comprising them may also have activity against bacteria such as Erwinia amylovora, Erwinia caratovora, Xanthomonas campestris, Pseudomonas syringae, Strptomyces scabies and other related species as well as certain protozoa.
  • Crops of useful plants in which the composition according to the invention can be used include perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass, St.
  • perennial and annual crops such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries
  • cereals for example barley, maize (corn), mille
  • Augustine grass and Zoysia grass herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme; legumes for example beans, lentils, peas and soya beans; nuts for example almond, cashew, ground nut, hazelnut, peanut, pecan, pistachio and walnut; palms for example oil palm; ornamentals for example flowers, shrubs and trees; other trees, for example cacao, coconut, olive and rubber; vegetables for example asparagus, aubergine, broccoli, cabbage, carrot, cucumber, garlic, lettuce, marrow, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach and tomato; and vines for example grapes.
  • herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme
  • legumes for example beans, lentils, peas and soya beans
  • Crops are to be understood as being those which are naturally occurring, obtained by conventional methods of breeding, or obtained by genetic engineering. They include crops which contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
  • output traits e.g. improved storage stability, higher nutritional value and improved flavour.
  • Crops are to be understood as also including those crops which have been rendered tolerant to herbicides like bromoxynil or classes of herbicides such as ALS-, EPSPS-, GS-, HPPD- and PPO- inhibitors.
  • herbicides like bromoxynil or classes of herbicides such as ALS-, EPSPS-, GS-, HPPD- and PPO- inhibitors.
  • An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer canola.
  • crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.
  • Crops are also to be understood as being those which naturally are or have been rendered resistant to harmful insects. This includes plants transformed by the use of recombinant DNA techniques, for example, to be capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria. Examples of toxins which can be expressed include ⁇ -endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonising nematodes, and toxins produced by scorpions, arachnids, wasps and fungi.
  • Vip vegetative insecticidal proteins
  • insecticidal proteins of bacteria colonising nematodes and toxins produced by scorpions, arachnids, wasps and fungi.
  • An example of a crop that has been modified to express the Bacillus thuringiensis toxin is the Bt maize KnockOut® (Syngenta Seeds).
  • An example of a crop comprising more than one gene that codes for insecticidal resistance and thus expresses more than one toxin is VipCot® (Syngenta Seeds).
  • Crops or seed material thereof can also be resistant to multiple types of pests (so-called stacked transgenic events when created by genetic modification).
  • a plant can have the ability to express an insecticidal protein while at the same time being herbicide tolerant, for example Herculex I® (Dow AgroSciences, Pioneer Hi-Bred International).
  • the compounds of formula (I) can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation.
  • the invention also relates to compositions for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula (I) and an inert carrier, and to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a composition, comprising a compound of formula (I) as active ingredient and an inert carrier, is applied to the plants, to parts thereof or the locus thereof.
  • compounds of formula (I) and inert carriers are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances.
  • the methods of application such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.
  • the compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
  • Suitable carriers and adjuvants can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.
  • a formulation i.e. a composition comprising the compound of formula (I) and, if desired, a solid or liquid adjuvant, is prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface-active compounds (surfactants).
  • extenders for example solvents, solid carriers and, optionally, surface-active compounds (surfactants).
  • the agrochemical formulations will usually contain from 0.1 to 99% by weight, preferably from
  • the end user will normally use dilute formulations.
  • Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 20g to 600g a.i./ha.
  • convenient rates of application are from 10mg to 1g of active substance per kg of seeds.
  • the rate of application for the desired action can be determined by experiments. It depends for example on the type of action, the developmental stage of the useful plant, and on the application (location, timing, application method) and can, owing to these parameters, vary within wide limits.
  • agronomic chemicals include insecticides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection, as well as plant nutrients and plant fertilizers.
  • the present invention provides a composition
  • a composition comprising a compound of formula (I) according to the present invention together with one or more pesticides, plant nutrients or plant fertilizers.
  • the combination may also encompass specific plant traits incorporated into the plant using any means, for example conventional breeding or genetic modification.
  • Such compositions may also contain one or more inert carriers as described above.
  • the invention also provides for the use of provides a composition comprising a compound of formula (I) according to the present invention together with one or more pesticides, plant nutrients, plant fertilizers, synergists, herbicides or plant growth regulators, where appropriate.
  • the combination may also encompass specific plant traits incorporated into the plant using any means, for example conventional breeding or genetic modification.
  • Suitable examples of plant nutrients or plant fertilizers are calcium sulfate (CaS0 4 ), calcium nitrate (Ca(N0 3 )2.4H 2 0), calcium carbonate (CaC0 3 ), potassium nitrate (KN0 3 ), magnesium sulfate (MgS0 4 ), potassium hydrogen phosphate (KH 2 P0 4 ), manganese sulfate (MnS0 4 ), copper sulfate (CuS0 4 ), zinc sulfate (ZnS0 4 ), nickel chloride (NiCI 2 ), cobalt sulfate (CoS0 4 ), potassium hydroxide (KOH), sodium chloride (NaCI), boric acid (H 3 B0 3 ) and metal salts thereof (Na 2 Mo0 4 ).
  • CaS0 4 calcium sulfate
  • Ca(N0 3 )2.4H 2 0 calcium carbonate
  • CaC0 3 calcium carbonate
  • KN0 3 potassium nitrate
  • the nutrients may be present in an amount of 5% to 50% by weight, preferably of 10% to 25% by weight or of 15% to 20% by weight each.
  • Preferred additional nutrients are urea ((NH 2 ) 2 CO), melamine (C 3 H 6 N 6 ), potassium oxide (K 2 0), and inorganic nitrates.
  • the most preferred additional plant nutrient is potassium oxide. Where the preferred additional nutrient is urea, it is present in an amount of generally 1 % to 20% by weight, preferably 2% to 10% by weight or of 3% to 7% by weight.
  • Suitable additional active ingredients include the following acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, anilide fungicides, antibiotic fungicides, aromatic fungicides, arsenical fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged diphenyl fungicides, carbamate fungicides, carbanilate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, , dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine
  • triazolopyrimidine fungicides triazolopyrimidine fungicides, urea fungicides, valinamide fungicides, and zinc fungicides.
  • suitable additional active ingredients also include the following: 3-difluoromethyl-1- methyl-1 H-pyrazole-4-carboxylic acid (9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano- naphthalen-5-yl)-amide , 3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid methoxy-[1-methyl- 2-(2,4,6-trichlorophenyl)-ethyl]-amide , 1-methyl-3-difluoromethyl-1 H-pyrazole-4-carboxylic acid (2- dichloromethylene-3-ethyl-1-methyl-indan-4-yl)-amide (1072957-71-1 ), 1-methyl-3-difluoromethyl-1 H- pyrazole-4-carboxylic acid (4'-methylsulfanyl-biphenyl-2-yl)-amide, 1-methyl-3-difluoromethyl-4H- pyrazo
  • phenol derivatives such as tribromophenol, tetrachlorophenol, 3-methyl-4-chlorophenol, 3,5-dimethyl- 4-chlorophenol, phenoxyethanol, dichlorophene, o-phenylphenol, m-phenylphenol, p-phenylphenol, 2- benzyl-4-chlorophenol, 5-hydroxy-2(5H)-furanone; 4,5-dichlorodithiazolinone, 4,5-benzodithiazolinone, 4,5-trimethylenedithiazolinone, 4,5-dichloro-(3H)-1 ,2-dithiol-3-one, 3,5-dimethyl-tetrahydro-1 ,3,5- thiadiazine-2-thione, N-(2-p-chlorobenzoylethyl)-hexaminium chloride, acibenzolar, acypetacs, alanycarb, albendazole, aldimorph, allicin, allyl
  • imibenconazole iminoctadine, iminoctadine triacetate, inezin, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isopropanyl butyl carbamate, isoprothiolane, isopyrazam, isotianil, isovaledione, izopamfos, kasugamycin, kresoxim-methyl, LY186054, LY21 1795, LY248908, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid, mefenoxam, mepanipyrim, mepronil, mercuric chloride, mercurous chloride, meptyldinocap, metalaxyl, metalaxyl-M, metam, metazoxolon, metconazole, methasulfocarb, methfuroxam, methyl
  • the compounds of the invention may also be used in combination with anthelmintic agents.
  • anthelmintic agents include, compounds selected from the macrocyclic lactone class of compounds such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin derivatives as described in EP- 357460, EP- 444964 and EP-594291.
  • Additional anthelmintic agents include semisynthetic and biosynthetic avermectin/milbemycin derivatives such as those described in US-5015630, WO-9415944 and WO- 9522552. Additional anthelmintic agents include the benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of the class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxantel or morantel.
  • Additional anthelmintic agents include flukicides, such as triclabendazole and clorsulon and the cestocides, such as praziquantel and epsiprantel.
  • the compounds of the invention may be used in combination with derivatives and analogues of the paraherquamide/marcfortine class of anthelmintic agents, as well as the antiparasitic oxazolines such as those disclosed in US-5478855, US- 4639771 and DE-19520936.
  • the compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO-9615121 and also with anthelmintic active cyclic depsipeptides such as those described in WO-961 1945, WO-9319053, WO- 9325543, EP-626375, EP-382173, WO-9419334, EP-382173, and EP-503538.
  • the compounds of the invention may be used in combination with other ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron;
  • ectoparasiticides for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron;
  • ecdysone agonists such as tebufenozide and the like; neonicotinoids such as imidacloprid and the like.
  • the compounds of the invention may be used in combination with terpene alkaloids, for example those described in International Patent Application Publication Numbers W095/19363 or WO04/72086, particularly the compounds disclosed therein.
  • Organophosphates acephate, azamethiphos, azinphos-ethyl, azinphos- methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl, demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos, fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate, isoxathion, malathion, me
  • Carbamates alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb, fenoxycarb, fenthiocarb, furathiocarb, HCN-801 , isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m-cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, UC-51717.
  • Arthropod growth regulators a) chitin synthesis inhibitors: benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, diofenolan, hexythiazox, etoxazole, chlorfentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide, tebufenozide; c) juvenoids: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.
  • antiparasitics acequinocyl, amitraz, AKD-1022, ANS-1 18, azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl, bromopropylate, BTG-504, BTG-505, camphechlor, cartap, chlorobenzilate, chlordimeform, chlorfenapyr, chromafenozide, clothianidine, cyromazine, diacloden, diafenthiuron, DBI-3204, dinactin, dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan, ethiprole, ethofenprox, fenazaquin, flumite, MTI- 800, fenpyroximate, fluacrypyrim, flubenzimine, flubrocythrinate, flufenzine, flufenprox, fluproxyfen, halofenprox, hydra
  • Biological agents Bacillus thuringiensis ssp aizawai, kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, virus and fungi.
  • Bactericides chlortetracycline, oxytetracycline, streptomycin.
  • Another aspect of invention is related to the use of a compound of formula I or of a preferred individual compound as above-defined, of a composition comprising at least one compound of formula I or at least one preferred individual compound as above-defined, or of a fungicidal or insecticidal mixture comprising at least one compound of formula I or at least one preferred individual compound as above-defined, in admixture with other fungicides or insecticides as described above, for controlling or preventing infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non-living materials by insects or by phytopathogenic microorganisms, preferably fungal organisms.
  • useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non-living materials by insects or by phytopathogenic microorganisms, preferably fungal organisms.
  • a further aspect of invention is related to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or of non-living materials by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, which comprises the application of a compound of formula I or of a preferred individual compound as above- defined as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the non-living materials.
  • Controlling or preventing means reducing infestation by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated.
  • a preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, or insects which comprises the application of a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application.
  • the frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen or insect.
  • the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
  • the compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
  • a formulation e.g. a composition containing the compound of formula I, and, if desired, a solid or liquid adjuvant or monomers for encapsulating the compound of formula I, may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface active compounds (surfactants).
  • extenders for example solvents, solid carriers and, optionally, surface active compounds (surfactants).
  • Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 20g to 600g a.i./ha.
  • convenient dosages are from 10mg to 1g of active substance per kg of seeds.
  • rates of 0.001 to 50 g of a compound of formula I per kg of seed preferably from 0.01 to 10g per kg of seed are generally sufficient.
  • compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK
  • compositions may be produced in conventional manner, e.g. by mixing the active ingredients with appropriate formulation inerts (diluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects).
  • appropriate formulation inerts diiluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects.
  • conventional slow release formulations may be employed where long lasting efficacy is intended.
  • Particularly formulations to be applied in spraying forms such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain surfactants such as wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g.
  • a seed dressing formulation is applied in a manner known per se to the seeds employing the combination of the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds.
  • suitable seed dressing formulation form e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds.
  • seed dressing formulations are known in the art.
  • Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g. as slow release capsules or microcapsules.
  • the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula I together with component (B) and (C), and optionally other active agents, particularly microbiocides or conservatives or the like.
  • Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent.
  • Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent.
  • commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations.
  • an activating reagent such as POCI 3 , PCI 3 , COCI 2 , PhS0 2 CI, Me 2 NS0 2 CI, (CF 3 CO) 2 0 or (MeO)
  • Scheme 1 b Compounds of formula (I) can be prepared by known methods from reacting an amino derivative of formula (IV), wherein R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined for a compound of formula (I) and R' is defined as hydrogen or C0 2 tBu, with an orthoamide HC(OR z ) 2 -N(R )(R 2 ) of formula (V), wherein R-i and R 2 are as defined for a compound of formula (I) and R z is alkyl, in the presence of an acid.
  • a metal or metalloid group
  • a metal e.g. palladium
  • alkyllithium or alkymagnesium so as to perform a metal halogen exchange or trans-metalation followed by the introduction of an electrophile of formula (XI), wherein R 5d is as defined for a compound of formula (I) and T is an aldehyde or activated carboxylic acid derivative (i.e. acyl chloride, ester, acid anhydride or carboxamide).
  • R 5d is as defined for a compound of formula (I) and T is an aldehyde or activated carboxylic acid derivative (i.e. acyl chloride, ester, acid anhydride or carboxamide).
  • a compound of formula (le), wherein R , R 2 , R 3 , R 4 , R 6 , R 7 and R 8 are as defined for a compound of formula (I) and R 5ea is selected from aryl, heteroaryl, carbocyclic, heterocylic or alkyl groups and R 5eb is selected from hydrogen or alkyl, can be obtained from a compound of formula (VI), wherein R , R 2 , R 3 , R 4 , R 6 , R 7 and R 8 are as defined herein for a compound of formula (I) and X" is a halogen (e.g.
  • a compound of formula (IV), that is a compound of formula (IV) wherein R'is Hydrogen or Ac, can be prepared from a compound of formula (XVI), wherein R 5 , R 6 , R 7 , and R 8 are as defined for a compound of formula (IV), and an N-acyl amino ketone of formula (XVII), wherein R 3 is as defined herein for a compound of formula (I), via heating in the presence of base in aquous media followed by acidification and additional heating.
  • Compounds of formula (XVI) are known to be commercially available or can be made by known methods from known compounds. For examples, see: Wang, S. H. et al Med. Chem. Res. (2014), 23, 2161-2168
  • Compounds of formula (XVIII) are known or are commercially available.
  • Scheme 12 A compound of formula ( ⁇ '), wherein R 3 , R 4 , R 6 , R 7 and R 8 are as defined for a compound of formula (I), R is defined as hydrogen or C0 2 tBu and X'" is CN, CH 2 OH, CHO, C(0)Me, C0 2 Me, C0 2 Et, or a metal or metalloid (i.e.
  • boronic ester, boronic acid, tri-alkylstannane can be prepared from a compound of formula (XIX), wherein R 3 , R 4 , R 6 , R 7 and R 8 are as defined for a compound of formula (I), and X' is selected from CI, Br, or I, via treatment with an organometallic reagent (e.g. alkyllithium or alkymagnesium) followed by the introduction of an electrophile, such as an aldehyde, or an activated carboxylic acid derivative (i.e. acyl chloride, ester, acid anhydride or carboxamide), or via introduction of a Pd catalyst and a organometal or organometaloid (i.e. boronic ester, tri-alkylstannane chloride, or CuCN).
  • organometallic reagent e.g. alkyllithium or alkymagnesium
  • an electrophile such as an aldehyde, or an activated carboxylic
  • a compound of formula (XX) can be prepared from an amino compound of formula (XIX"), wherein R 3 , R 4 , R 6 , R 7 and R 8 are as defined for a compound of formula (I), X" is CI, Br, I, CN, CH 2 OH, CHO, C(0)Me, C0 2 Me, C0 2 Et, or a metal or metalloid (i.e.
  • an activating reagent such as POCI 3 , PCI 3 , COCI 2 , PhS0 2 CI, Me 2 NS0 2 CI, (CF 3 CO) 2 0 or (MeO) 2 S0 2 and then introducing a compound of formula (XIX").
  • a compound of formula (XX) can be prepared from an amino compound of formula (XIX"), wherein R 3 , R 4 , R 6 , R 7 and R 8 are as defined for a compound of formula (I), X" is CI, Br, I, CN, CH 2 OH, CHO, C(0)Me, C0 2 Me, C0 2 Et, or a metal or metalloid (i.e.
  • boronic ester, boronic acid, tri-alkylstannane) and R is defined as hydrogen or C0 2 tBu via a reaction with an orthoamide HC(OR z ) 2 -N(R )(R 2 ) of formula (V), wherein R-i and R 2 are as defined for a compound of formula (I) and R z is alkyl, in the presence of an acid.
  • a compound of formula (XIX) is selected from a compound of formula (XIX) or compound of formula ( ⁇ ').
  • Wettable powders a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % sodium lignosulfonate 5 % 5 %
  • the active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
  • Powders for drv seed treatment a) b) c) active ingredient [compound of formula (1)] 25 % 50 % 75 % light mineral oil 5 % 5 % 5 % highly dispersed silicic acid 5 % 5 % -
  • the active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
  • Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water. Dusts a) b) c)
  • Active ingredient [compound of formula (I)] 5 % 6 % 4 % talcum 95 %
  • Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.
  • the active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water.
  • the mixture is extruded and then dried in a stream of air.
  • polyethylene glycol (mol. wt. 200) 3 %
  • the finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner. Suspension concentrate
  • nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 %
  • silicone oil (in the form of a 75 % emulsion in water) 1 %
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • Silicone oil (in the form of a 75 % emulsion in water) 0.2 %
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • 28 parts of a combination of the compound of formula I are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8: 1 ).
  • This mixture is emulsified in a mixture of 1 .2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51 .6 parts of water until the desired particle size is achieved.
  • To this emulsion a mixture of 2.8 parts 1 ,6- diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
  • the obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent.
  • the capsule suspension formulation contains 28% of the active ingredients.
  • the medium capsule diameter is 8-15 microns.
  • the resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
  • reaction mixture was diluted with water and extracted with ethyl acetate.
  • organic phases were dried over magnesium sulfate, filtered, concentrated and purified by chromatography (silica gel, heptane/ethyl acetate gradient 0-100%) to give the title compound as yellow oil.
  • reaction mixture was then diluted with ethyl acetate, filtered, washed with water and brine, dried over magnesium sulfate, concentrated and purified by combiflash column chromatography (silica gel, heptane/ethyl acetate gradient 0-100%) to give the title compound as yellow oil.
  • N-Ethyl-N-methyl-N'-[8-[(E)-3-methoxyprop-1-enyl]-2-methyl-3-quinolyl]-formamidine (0.17g) was dissolved in methanol (3 mL) and hydrogenated using an H-Cube ® continuous-flow hydrogenation reactor via passage at 55°C with a flow of 1 mL minute and a pressure of 20 bar through a CatCarts® cartridge loaded with palladium 10% on carbon (0.02 g). The tubes were washed with methanol and the combined fractions were concentrated and the residue was purified by combiflash column chromatography (silica gel, heptane/ethyl acetate gradient 0-100%) to give the title compound as light yellow oil.
  • the pH of the reaction mixture was adjusted to pH 8 by addition of aqueous NaOH (2M) and the suspension was extracted with tert-butyl methyl ether. The organic layer was washed with brine, dried over MgS0 4 , and the solids removed by filtration. The solvent was removed at reduced pressure and the residue purified by flash chromatography over silica gel (cyclohexane/ethyl acetategradient from 0% - 40%) to give the title compound as a light brown amorphous solid.

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Abstract

The invention relates to compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7 and R8 are as defined in the claims. The invention further provides compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.

Description

NOVEL FUNGICIDAL QUINOLINYLAMIDINES
The present invention relates to novel microbiocidal, in particular fungicidal, quinolinylamidine compounds.
It further relates to compositions which comprise these compounds, and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.
The present invention relates to compounds of formula (I)
Figure imgf000002_0001
R and R2 independently of each other represent hydrogen, Ci-C4alkyl, Ci-C4fluoroalkyl or C3- C6cycloalkyl; or
R and R2 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom;
R3 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C4 alkyl, C2- C5alkenyl, C2-C5alkynl, Ci-C4haloalkyl, Ci-C4alkoxy or C3-C6 cycloalkyl;
R4 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynl, d-C6 haloalkyl, d-C6 alkoxy or C3-C6 cycloalkyl;
R5 represents R9-(Z)m-;
R6 , R7 ,R8 independently of each other represent hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C4 alkyl, C2-C5alkenyl, C2-C5alkynl, Ci-C4haloalkyl, Ci-C4alkoxy or d- C4haloalkoxy;
m represents 0, 1 or 2;
when m is 0 or 1 , Z represents -C(=0)-, -0-, -S-, -S(=0)-, -S(=0)2-, -N(R10)- or d-d alkyl, wherein the alkyl is optionally substituted by one or more groups independently selected from halogen, CN, OH, Ci-C4 alkylcarbonyl, Ci-C4 alkoxycarbonyl, Ci-C4-haloalkyl, CN, Ci-C4-alkoxy and d-C4- haloalkoxy;
when m is 2, Z represents Ci-C4 alkyl, wherein the alkyl is optionally substituted by one or more groups independently selected from halogen, CN, OH, Ci-C4 alkylcarbonyl, Ci-C4 alkoxycarbonyl, d- C4-haloalkyl, CN, Ci-C4-alkoxy and Ci-C4-haloalkoxy;
R9 represents hydrogen, d-C8alkyl, C3-C8alkenyl or C3-C8alkynyl, wherein the alkyl, alkenyl, alkynyl and cycloalkoxyare optionally substituted by one or more groups independently selected from halogen, hydroxyl, cyano, N02, OH, SH, d-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynl, d-C6 haloalkyl, d-C6 alkoxy, C3-C8 cycloalkyl C3-C8 cycloalkoxy, formyl, C2-C6alkylcarbonyl, Ci-C6alkylthio, Ci-C6alkylsulfinyl and Ci-C6alkylsulfonyl; or
R9 represents D-A-Ci-C6alkyl-, D-A-Ci-C6alkyl-, D-A-C C6alkyl-, D-A-Ci-C6alkyl-, D-A-d- C6alkyl-, D-A-Ci-C6alkyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl- , D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A- C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D-A- C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl- or D-A-C3-C6cycloalkyl-;
R9 represents an three to eight membered monocyclic system which can be aromatic, partially saturated or fully saturated, which optionally contains one or two hetero atoms selected from the group consisting of N, N(R11), O and S, optionally substituted by one or more groups independently selected from the group consisting of hydrogen, halogen, cyano, nitro, mercapto, hydroxy, -CHO, -COOH, - C(=S)NH2, -SF5, d-dalkyl, Ci-C4haloalkyl, C2-C6alkenyl, C2-C5haloalkenyl, C2-C5alkynyl, C2- C5haloalkynyl, Ci-C4alkoxy, Ci-C4haloalkoxy, C3-C6cycloalkyl, C3-C6halocycloalkyl, C3-C4alkenyloxy, C3-C4haloalkenyloxy, C3-C5alkynyloxy, C3-C6cycloalkyloxy,C2-C4alkoxycarbonyl, C2- C4haloalkoxycarbonyl, C2-C5alkylcarbonyl, C2-C5 haloalkylcarbonyl, -N(R 2)(R13), -C(=0)N(R 2)(R13), C(=S)N(R 2)(R13), d-C4alkylthio, d-dalkylsulfinyl, d-dalkylsulfonyl, d-dhaloalkylthio, d- dhaloalkylsulfinyl, d-dhaloalkylsulfonyl and -S(=0)2N(R 2)(R13); or
R9 represents NHR 4;
A represents -C(=0)-, -C(=S)-, -C(=NOR15)-, -C(R 5)=NO-, -ON=C(R15)-, -S(=0)(=NR15)-, - S(=0)(R 5)=N-, -0-C(=0)-, -C(=0)-0-, -0-, -S-, -S(=0)-, -S(=0)2-, -S(=0)(=NR15)-, -N(R10)-, -N(R15)- (C=0)-, -(C=0)-N(R15)-, -N(R 5)-S02- or -S02-N(R15)-;
D represents d-dalkyl, d-dalkenyl, d-dalkynyl, d-dcycloalkyl, benzyl, phenyl each of which are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, mercapto, d-dhaloalkyl, d-dalkoxy, formyl, C2-C5alkylcarbonyl, d-dalkoxycarbonyl, d- dalkylthio, d-dhaloalkylthio, d-dalkylsulfinyl and d-dalkylsulfonyl;
R 0 represents hydrogen, formyl, d-dalkyl, d-dhaloalkyl, C3-C5alkenyl or d-dalkylcarbonyl; each R independently represents hydrogen, formyl, d-dalkyl, d-dhaloalkyl, d-dalkoxy, d-dhaloalkoxy, d-dalkenyl, C3-C5haloalkenyl, d-dalkylcarbonyl, -dalkoxycarbonyl, d-d haloalkylcarbonyl, benzyl, phenyl, d-dalkylsulfinyl, d-dalkylsulfonyl, d-dhaloalkylsulfinyl, d- dhaloalkylsulfonyl -C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) or -S(=0)2N(R 2)(R13), wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, benzyl and phenyl are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, d-dalkyl, d-dhaloalkyl, d-dalkoxy and d- dhaloalkoxy;
each R 2 and R 3 independently of each other represents hydrogen, formyl, d-dalkyl, d- dhaloalkyl, d-dalkylcarbonyl, d-dalkoxycarbonyl, benzyl or phenyl; or
R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom; R 4 represents phenyl optionally substituted by fluoro, CN , OH, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2- CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3;
each R 5 independently represents hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, C3-C5alkenyl, C3- C5haloalkenyl, C3-C5alkynyl, C3-C6cycloalkyl, benzyl or phenyl wherein the alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, cycloalkyl, benzyl and phenyl are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy and d- C4haloalkoxy;
and tautomers/isomers/enantiomers/salts and N-oxides of these compounds.
Substituents at a nitrogen atom are always different from halogen. A hydroxy, mercapto or amino substituent is not to be placed on an ocarbon relative to a heteroatom of a core fragment.
Halogen, either as a lone substituent or in combination with another substituent (e.g. haloalkyl) is generally fluorine, chlorine, bromine or iodine, and usually fluorine, chlorine or bromine.
Each alkyl moiety (including the alkyl moiety of alkoxy, alkylthio, etc.) is a straight or branched chain and, depending on the number of carbon atoms it contains, is, for example, methyl, ethyl, n- propyl, n-butyl, n-pentyl, n-hexyl, /'so-propyl, sec-butyl, /'so-butyl, ieri-butyl, neo-pentyl, n-heptyl or 1 ,3- dimethylbutyl, and usually methyl or ethyl.
The alkenyl and alkynyl groups can be mono- or di-unsatu rated and examples thereof are derived from the above mentioned alkyl groups.
The alkenyl group is an unsaturated straight or branched chain having a carbon-carbon double bond and, depending on the number of carbon atoms it contains, is, for example ethenyl, 1 -propenyl, 2-propenyl, 1 -methyl-ethenyl, 1 -butenyl, 2-butenyl, 3-butenyl, 1 -methyl-1 -propenyl, 2-methyl-1 - propenyl, 2-methyl-2-propenyl, 1 -pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1 -methyl-1 -butenyl, 2- methyl-1 -butenyl, 3-methyl-1 -butenyl, 1 -methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1 - methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1 , 1 -dimethyl-2-propenyl, 1 ,2-dimethyl-1 - propenyl, 1 ,2-dimethyl-2-propenyl, 1 -ethyl-2-propenyl, 1 -hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5- hexenyl, 1 -methyl-1 -pentenyl, 2-methyl-1 -pentenyl, 3-methyl-1 -pentenyl, 4-methyl-1 -pentenyl, 1 - methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1 -methyl-3- pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1 -methyl-4-pentenyl, 2- methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1 , 1 -dimethyl-2-butenyl, 1 , 1 -dimethyl-3- butenyl, 1 ,2-dimethyl-1 -butenyl, 1 ,2-dimethyl-2-butenyl, 1 ,2-dimethyl-3-butenyl, 1 ,3-dimethyl-1 -butenyl, 1 ,3-dimethyl-2-butenyl, 1 ,3-dimethyl-3-butenyl, and usually 2-propenyl, 1 -methyl-2-propenyl, 2- butenyl, 2-methyl-2-propenyl.
The alkynyl group is an unsaturated straight or branched chain having a carbon-carbon triple bond and, depending on the number of carbon atoms it contains, is, for example ethynyl, 1 -propynyl, 2-propynyl, 1 -butynyl, 2-butynyl, 3-butynyl, 1 -methyl-2-propynyl, 1 -pentynyl, 2-pentynyl, 3-pentynyl, 4- pentynyl, 3-methyl-1 -butynyl, 1 -methyl-2-butynyl, 1 -methyl-3-butynyl, 2-methyl-3-butynyl, 1 , 1 -dimethyl- 2-propynyl, 1 -ethyl-2-propynyl, 1 -hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 3-methyl-1 - pentynyl, 4-methyl-1 -pentynyl, 1 -methyl-2-pentynyl, 4-methyl-2-pentynyl, 1 -methyl-3-pentynyl, 2- methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 3-methyl-4-pentynyl, 3,3,-dimethyl-1- butynyl, 1-ethyl-2-butynyl, 1 , 1-dimethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, 1 , 1-dimethyl-3- butynyl, 2,2-dimethyl-3-butynyl, 1 ,2-dimethyl-3-butynyl.
Haloalkyl moieties are alkyl moieties which are substituted by one or more of the same or different halogen atoms and are, for example, monofluoromethyl, difluoromethyl, trifluoromethyl, monochloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2,2-difluoroethyl, 2-fluoroethyl, 1 , 1-difluoroethyl, 1-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1 , 1-difluoro-2,2,2-trichloroethyl, 2,2,3,3- tetrafluoroethyl and 2,2,2-trichloroethyl, and typically trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.
Alkoxy is, for example, methoxy, ethoxy, propoxy, /'so-propoxy, n-butoxy, /'so-butoxy, sec-butoxy and ieri-butoxy, and usually methoxy or ethoxy.
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, and usually difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.
Alkylthio is, for example, methylthio, ethylthio, propylthio, /'so-propylthio, n-butylthio, iso- butylthio, sec-butylthio or ieri-butylthio, and usually methylthio or ethylthio.
Alkylsulphonyl is, for example, methylsulphonyl, ethylsulphonyl, propylsulphonyl, iso- propylsulphonyl, n-butylsulphonyl, /'so-butylsulphonyl, sec-butylsulphonyl or ieri-butylsulphonyl, and usually methylsulphonyl or ethylsulphonyl.
Alkylsulphinyl is, for example, methylsulphinyl, ethylsulphinyl, propylsulphinyl, iso- propylsulphinyl, n-butylsulphinyl, /'so-butylsulphinyl, sec-butylsulphinyl or ieri-butylsulphinyl, and usually methylsulphinyl or ethylsulphinyl.
Cycloalkyl may be saturated or partially unsaturated, preferably fully saturated, and is, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n- propoxymethyl, n-propoxyethyl, /so-propoxymethyl or /'so-propoxyethyl.
Aryl includes phenyl, naphthyl, anthracyl, fluorenyl and indanyl, but is usually phenyl.
Carbocycle includes cycloalkyl groups and aryl groups.
Heterocycloalkyl is a non-aromatic ring that may be saturated or partially unsaturated, preferably fully saturated, containing carbon atoms as ring members and at least one heteroatom selected from O, S and N as ring members. Examples include oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, 1 ,3-dioxolanyl, 1 ,4-dioxanyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, oxazinanyl, morpholinyl, thiomorpholinyl, imidazolidinyl, pyrazolidinyl and piperazinyl, preferably morpholinyl, pyrrolidinyl, piperdinyl and piperazinyl, more preferably morpholinyl and pyrollidinyl.
Heteroaryl is, for example, a monovalent monocyclic or bicyclic aromatic hydrocarbon radical. Examples of monocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, and thiadiazolyl. Examples of bicyclic groups include quinolinyl, cinnolinyl, quinoxalinyl, benzimidazolyl, benzothiophenyl, and benzothiadiazolyl. Monocyclic heteroaryl groups are preferred, preferably pyridyl, pyrrolyl, imidazolyl and triazolyl, e.g. 1 ,2,4 triazolyl, pyridyl and imidazolyl being most preferred.
The terms "heterocycle" and "heterocyclic ring" are used interchangeably and are defined to include heterocycloalkyl and heteroaryl groups. Any reference herein to a heterocycle or heterocyclic ring preferably refers to the specific examples given under the definition of heteroaryl and
heterocycloalkyl above, and are preferably morpholinyl, pyrrolidinyl, piperdinyl, piperazinyl pyridyl, pyrrolyl, imidazolyl and triazolyl, e.g. 1 ,2,4 triazolyl, more preferably morpholinyl, pyrollidinyl, pyridyl and imidazolyl. No heterocycle contains adjacent oxygen atoms, adjacent sulphur atoms, or adjacent oxygen and sulphur atoms.
Where a moiety is indicated as being (optionally) substituted, e.g. alkyl, this includes those moieties where they are part of a larger group, e.g. the alkyl in the alkylthio group. The same applies, e.g. to the phenyl moiety in phenylthio etc. Where a moiety is indicated as being optionally substituted by one or more other groups, preferably there are one to five optional substituents, more preferably one to three optional substituents. Where a moiety is substituted by a cyclic group, e.g. aryl, heteroaryl, cycloalkyl, preferably there are no more than two such substituents, more preferably no more than one such substituent.
The following list provides definitions, including preferred definitions, for substituents R , R2, R3, R4, R5, R6, R7, R9, R9, R10, R11 , R12, R13, R14, R15, R16, R17, R18, A, D, Z and m with reference to compounds of formula (I). For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.
R and R2 independently of each other represent hydrogen, Ci-C4alkyl, Ci-C4fluoroalkyl or C3- C6cycloalkyl; or
R and R2 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom.
Preferably, R and R2 independently of each other represent hydrogen, Ci-C4alkyl or cyclopropyl.
More preferably, R and R2 independently of each other represent hydrogen, methyl, ethyl, isopropyl, n-propyl or cyclopropyl.
Even more preferably, R and R2 independently of each other represent methyl or ethyl.
Most preferably, R represents methyl and R2 represents ethyl.
In one group of compounds, R represents methyl and R2 is as defined above.
R3 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, C1-C4 alkyl, C2- C5alkenyl, C2-C5alkynl, Ci-C4haloalkyl, Ci-C4alkoxy or C3-C6 cycloalkyl.
Preferably, R3 represents hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, vinyl, - C(Me)=CH2, allyl, OMe OEt or cyclopropyl.
More preferably, R3 represents hydrogen, chloro, methyl or ethyl.
Most preferably, R3 represents methyl. R4 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynl, d-C6 haloalkyl, d-C6 alkoxy or C3-C6 cycloalkyl.
Preferably, R4 represents hydrogen, halogen, cyano, hydroxy, Ci-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynl, d-C6 haloalkyl or d-C6 alkoxy.
More preferably, R4 represents hydrogen, halogen, cyano, hydroxy, d-d alkyl or d-C6 haloalkyl.
Most preferably. R4 represents hydrogen.
R5 represents R9-(Z)m-.
m represents 0, 1 or 2.
Most preferably, m represents 0 or 1 .
When m is 0 or 1 , Z represents -C(=0)-, -0-, -S-, -S(=0)-, -S(=0)2-, -N(R10)- or d-d alkyl, wherein the alkyl is optionally substituted by one or more groups independently selected from halogen, CN , OH , d- alkylcarbonyl, d-C4 alkoxycarbonyl, d-d-haloalkyl, CN , d-C4-alkoxy and d-C4- haloalkoxy.
Preferably when m is 0 or 1 , Z represents -C(=0)-, -0-, -S-, -S(=0)-, -S(=0)2-, -N(R10)-, methylene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from fluorine, CN, OH, methyl, ethyl, propyl, iso-propyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, CN, OMe, OEt, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu ;
More preferably when m is 0 or 1 , Z represents -0-, -S-, -C(=0)-, -S(=0)2-, -N(R10)-, methylene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from CN, OH, methyl, ethyl, CF3, OMe, OEt, COMe, COEt, COiPr, C02Me, C02Et and C02iPr.
Most preferably when m is 0 or 1 , Z represents methylene or ethylene, each of which is optionally substituted by one or more methyl groups.
When m is 2, Z represents Ci-C4 alkyl, wherein the alkyl is optionally substituted by one or more groups independently selected from halogen, CN, OH, Ci-C4 alkylcarbonyl, Ci-C4 alkoxycarbonyl, d- C4-haloalkyl, CN , Ci-C4-alkoxy and Ci-C4-haloalkoxy.
Most preferably when m is 2, Z represents methlyene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from fluorine, CN, OH, methyl, ethyl, propyl, iso-propyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, CN, OMe, OEt, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu.
R9 represents d-C8alkyl, C3-C8alkenyl or C3-C8alkynyl, wherein the alkyl, alkenyl, alkynyl and cycloalkoxyare optionally substituted by one or more groups independently selected from halogen, hydroxyl, cyano, N02, OH, SH, Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynl, Ci-C6 haloalkyl, Ci-C6 alkoxy, C3-C8 cycloalkyl C3-C8 cycloalkoxy, formyl, C2-C6alkylcarbonyl, d-C6alkylthio, d-C6alkylsulfinyl and d-C6alkylsulfonyl; or
R9 represents D-A-d-C6alkyl-, D-A-d-C6alkyl-, D-A-C C6alkyl-, D-A-d-C6alkyl-, D-A-C C6alkyl-, D-A-d-C6alkyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl- , D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A- C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D-A- C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl- or D-A-C3-C6cycloalkyl-; or
R9 represents an three to eight membered monocyclic system which can be aromatic, partially saturated or fully saturated, which optionally contains one or two hetero atoms selected from the group consisting of N, N(R11), O and S, optionally substituted by one or more groups independently selected from the group consisting of hydrogen, halogen, cyano, nitro, mercapto, hydroxy, -CHO, -COOH, - C(=S)NH2, -SF5, d-C4alkyl, d-C4haloalkyl, C2-C6 alkenyl, C2-C5haloalkenyl, C2-C5alkynyl, C2- C5haloalkynyl, d-C4alkoxy, Ci-C4haloalkoxy, C3-C6cycloalkyl, C3-C6halocycloalkyl, C3-C4alkenyloxy, C3-C4haloalkenyloxy, C3-C5alkynyloxy, C3-C6cycloalkyloxy,C2-C4alkoxycarbonyl, C2- C4haloalkoxycarbonyl, C2-C5alkylcarbonyl, C2-C5 haloalkylcarbonyl, -N(R 2)(R13), -C(=0)N(R 2)(R13), C(=S)N(R 2)(R13), d-C4alkylthio, d-dalkylsulfinyl, d-dalkylsulfonyl, d-dhaloalkylthio, d- dhaloalkylsulfinyl, d-dhaloalkylsulfonyl and -S(=0)2N(R 2)(R13); or
R9 represents NHR 4.
Preferably, R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or d-C6alkynyl wherein the alkyl, alkenyl and alkynyl are optionally be optionally substituted by one or more groups independently selected from halogen, CN, OH, d-C4alkyl, C2-C4alkenyl, d-C4fluoroalkyl, d-C4alkoxy, and C2- C5alkylcarbonyl; or
R9 represents a five- or six-membered saturated or partially saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R11), O and S, optionally substituted by one or more groups independently selected from the group consisting of halogen, CN, N02, OH, SH, CHO, d-C4alkyl, d-C4haloalkyl, C3-C6cycloalkyl, C2-C5alkenyl, C2-C5alkynyl, C2- C5haloalkynyl, Ci-C4alkoxy, Ci-C4haloalkoxy, C3-C5alkynyloxy, Ci-C4 alkylcarbonyl and Ci-C4 alkoxycarbonyl; or
R9 represents a five- or six-membered aromatic monocyclic system which contains one or two hetero atoms selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from halogen, CN, OH, SH, CHO, COOH, Ci-C4 alkyl, d- dalkoxy, Ci-C4haloalkyl, Ci-C4haloalkoxy, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C2-C5alkoxycarbonyl, d-C4haloalkylthio, C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) and -S(=0)2N(R 2)(R13); or
R9 represents phenyl optionally substituted by one or more groups independently selected from halogen, CN, N02, OH, SH, CHO, COOH, d-C4 alkyl, d-C4 alkoxy, d-C4 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, Ci-C4 haloalkoxy, Ci-C4alkylcarbonyl, d- C4alkylsulfonyl, C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) and -S(=0)2N(R 2)(R13); or
R9 represents a C3-C8 carbocyclic system, which may be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from halogen, CN, N02, OH, SH, CHO, COOH, d-C4 alkyl, d-C4 alkoxy, d-C4 haloalkyl, d-C4 haloalkoxy, C3-C6 cycloalkyl and d-C4 alkylcarbonyl; or
R9 represents NHR14;
More preferably, R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or d-C6alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, and OCF3; or
R9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R11 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, Ci-C4alkyl, Ci-C4fluoroalkyl, d-C4alkoxy, Ci-C4fluoroalkoxy, Ci-C4 alkylcarbonyl and Ci-C4 alkoxycarbonyl; or
R9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, Ci-C4alkyl, Ci-C4fluoroalkyl, Ci-C4alkoxy, Ci-C4fluoroalkoxy, Ci-C4 alkylcarbonyl, and Ci-C4 alkoxycarbonyl; or
R9 represents phenyl optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH , SH , CHO, COOH , d-d alkyl, d-d alkoxy, d-C4 fluoroalkyl, C3- Ce cycloalkyl, C2-C4 alkenyl, d-C4fluoroalkoxy, d-C4alkylsulfonyl, C(=0)N(R 2)(R13) and
S(=0)2N(R 2)(R13); or
R9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4fluoroalkyl and Ci-C4 fluoroalkoxy; or R9 represents NHR 4.
Most preferably, R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or d-C6alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from fluoro, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF- CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr; or
R9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R11 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH , SH , methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2- CH3, CF2-CF3, OMe, OEt, OiPr, OnPr, OCHF2 and OCF3; or
R9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from fluoro, CN, N02, OH, SH, CHO, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2- CF3, OMe, OEt, OiPr, OPr, OCHF2, OCF3, SCHF2, SCF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu ; or
R9 represents phenyl optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH , SH , methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec- butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, OCF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu CONHMe, CONMe2, S(=0)2Me, -S(=0)2Et, S(=0)2NHMe and S(=0)2NMe2; or
R9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from fluoro, CN, N02, OH, SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3; or
R9 represents NHR 4.
R 0 represents hydrogen, formyl, Ci-C4alkyl, Ci-C4haloalkyl, C3-C5alkenyl or C2-C5alkylcarbonyl. Each R independently represents hydrogen, formyl, d-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy,
Ci-C4haloalkoxy, C3-C5alkenyl, C3-C5haloalkenyl, C2-C5alkylcarbonyl,C2-C5alkoxycarbonyl, C2-C4 haloalkylcarbonyl, benzyl, phenyl, Ci-C4alkylsulfinyl, CrC4alkylsulfonyl, Ci-C4haloalkylsulfinyl, d- C4haloalkylsulfonyl -C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) or -S(=0)2N(R 2)(R13), wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, benzyl and phenyl are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy and d- C4haloalkoxy.
Preferably, each R independently represents hydrogen, formyl, Ci-C4alkyl, Ci-C4haloalkyl, d- C4alkoxy, Ci-C4haloalkoxy, C3-C5alkenyl, C3-C5haloalkenyl, C2-C5alkylcarbonyl,C2-C5alkoxycarbonyl, C2-C4 haloalkylcarbonyl, benzyl, phenyl, -S(=0)2Me, -S(=0)2Et, C(=0)N(R 7)(R18), -C(=S)N(R 7)(R18) or -S(=0)2N(R 7)(R18).
More preferably, each R independently represents formyl, Ci-C4alkyl, CH2F, CHF2, CF3, CHF- CH3, CF2-CH3, CF2-CF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu, benzyl, phenyl, -S(=0)2Me, -S(=0)2Et, C(=0)N(R 7)(R18), -C(=S)N(R 7)(R18) or -S(=0)2N(R 7)(R18).
Most preferably, each R independently represents -S(=0)2Me, -S(=0)2Et, C(=0)N(R 7)(R18), - S(=0)2N(R 7)(R18), formyl, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu, benzyl or phenyl.
Each R 2 and R 3 independently of each other represents hydrogen, formyl, Ci-C4alkyl, d- C4haloalkyl, C2-C4alkylcarbonyl, C2-C4alkoxycarbonyl, benzyl or phenyl; or
R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom.
Most preferably, each R 2 and R 3 independently of each other represents hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, benzyl or phenyl; or
R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom.
R 4 represents phenyl optionally substituted by fluoro, CN, OH, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2- CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3.
Each R 5 independently represents hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, C3-C5alkenyl, C3-
C5haloalkenyl, C3-C5alkynyl, C3-C6cycloalkyl, benzyl or phenyl wherein the alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, cycloalkyi, benzyl and phenyl are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy and d- dhaloalkoxy. Each R 6 independently represents formyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu, benzyl, phenyl, -S(=0)2Me, -S(=0)2Et, and -S(=0)2N(R 2)(R13).
Preferably, each R 6 independently represents hydrogen, fluorine, methyl, ethyl, isopropyl, CHF2, CF3, CHO, CO-Me, C02Me, CONHMe, CONMe2, S(=0)2Me, -S(=0)2Et, S(=0)2NHMe, S(=0)2NMe2, benzyl or phenyl.
Each R 7 and R 8 independently of each other represents hydrogen, Ci-C4alkyl, d- C4fluoroalkyl, benzyl or phenyl; or
R 7 and R 8 together with the nitrogen atom to which they are attached form aziridine, azetidine, pyrolidine, piperidine, morpholine, and thiomorpholine.
Preferably, each R 7 and R 8 independently of each other represents hydrogen, methyl, ethyl, propyl, isopropyl, CHF2, CF3, benzyl or phenyl.
Most preferably, each R 7 and R 8 independently of each other represents hydrogen, methyl, ethyl, propyl or isopropyl.
A represents -C(=0)-, -C(=S)-, -C(=NOR15)-, -C(R 5)=NO-, -ON=C(R15)-, -S(=0)(=NR15)-, -
S(=0)(R 5)=N-, -0-C(=0)-, -C(=0)-0-, -0-, -S-, -S(=0)-, -S(=0)2-, -S(=0)(=NR15)-, -N(R10)-, -N(R15)- (C=0)-, -(C=0)-N(R15)-, -N(R 5)-S02- or -S02-N(R15)-.
D represents Ci-C4alkyl, C2-C5alkenyl, C2-C5alkynyl, C3-C6cycloalkyl, benzyl, phenyl each of which are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, mercapto, Ci-C4haloalkyl, Ci-C4alkoxy, formyl, C2-C5alkylcarbonyl, Ci-C4alkoxycarbonyl, d- C4alkylthio, Ci-C4haloalkylthio, C1-C4alkylsulfinyl and Ci-C4alkylsulfonyl.
In one group of compounds of formula (I), when m is 0 or 1 , Z represents -C(=0)-, -0-, -S-, - S(=0)-, -S(=0)2-, -N(R10)-, methylene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from fluorine, CN, OH, methyl, ethyl, propyl, iso-propyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, CN, OMe, OEt, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu;
when m is 2, Z represents methlyene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from fluorine, CN, OH, methyl, ethyl, propyl, iso-propyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, CN, OMe, OEt, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu;
R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or CrC6alkynyl wherein the alkyl, alkenyl and alkynyl are optionally be optionally substituted by one or more groups independently selected from halogen, CN, OH, Ci-C4alkyl, C2-C4alkenyl, Ci-C4fluoroalkyl, Ci-C4alkoxy, and C2-C5alkylcarbonyl; or R9 represents a five- or six-membered saturated or partially saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R11), O and S, optionally substituted by one or more groups independently selected from the group consisting of halogen, CN, N02, OH, SH, CHO, d-C4alkyl, d-C4haloalkyl, C3-C6cycloalkyl, C2-C5alkenyl, C2-C5alkynyl, C2- C5haloalkynyl, Ci-C4alkoxy, Ci-C4haloalkoxy, C3-C5alkynyloxy, Ci-C4 alkylcarbonyl and Ci-C4 alkoxycarbonyl; or R represents a five- or six-membered aromatic monocyclic system which contains one or two hetero atoms selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from halogen, CN, OH, SH, CHO, COOH, C1-C4 alkyl, d- C4alkoxy, Ci-C4haloalkyl, Ci-C4haloalkoxy, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C2-C5alkoxycarbonyl, d-C4haloalkylthio, C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) and -S(=0)2N(R 2)(R13); or
R9 represents phenyl optionally substituted by one or more groups independently selected from halogen, CN, N02, OH, SH, CHO, COOH, d-d alkyl, d-d alkoxy, d-d haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, Ci-C4 haloalkoxy, Ci-C4alkylcarbonyl, d- C4alkylsulfonyl, C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) and -S(=0)2N(R 2)(R13); or
R9 represents a C3-C8 carbocyclic system, which may be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from halogen, CN, N02, OH, SH, CHO, COOH, d-d alkyl, d-d alkoxy, d-d haloalkyl, d-d haloalkoxy, C3-C6 cycloalkyl and Ci-C4 alkylcarbonyl; or
R9 represents NHR 4;
each R independently represents hydrogen, formyl, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy,
Ci-C4haloalkoxy, C3-C5alkenyl, C3-C5haloalkenyl, C2-C5alkylcarbonyl,C2-C5alkoxycarbonyl, C2-C4 haloalkylcarbonyl, benzyl, phenyl, -S(=0)2Me, -S(=0)2Et, C(=0)N(R 7)(R18), -C(=S)N(R 7)(R18) or - S(=0)2N(R 7)(R18);
each R 2 and R 3 independently of each other represents hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, benzyl or phenyl; or
R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom;
each R 6 independently represents formyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu, benzyl, phenyl, -S(=0)2Me, -S(=0)2Et, and -S(=0)2N(R 2)(R13); each R 7 and R 8 independently of each other represents hydrogen, Ci-C4alkyl, d- C4fluoroalkyl, benzyl or phenyl; or
R 7 and R 8 together with the nitrogen atom to which they are attached form aziridine, azetidine, pyrolidine, piperidine, morpholine, and thiomorpholine.
In another group of compounds of formula (I), m represents 0 or 1 ;
Z represents -0-, -S-, -C(=0)-, -S(=0)2-, -N(R10)-, methylene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from CN, OH, methyl, ethyl, CF3, OMe, OEt, COMe, COEt, COiPr, C02Me, C02Et and C02iPr;
R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or d-C6alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, and OCF3;
R9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R11), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, Ci-C4alkyl, Ci-C4fluoroalkyl, d-C4alkoxy, Ci-C4fluoroalkoxy, Ci-C4 alkylcarbonyl and Ci-C4 alkoxycarbonyl; or
R9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, Ci-C4alkyl, Ci-C4fluoroalkyl, Ci-C4alkoxy, Ci-C4fluoroalkoxy, Ci-C4 alkylcarbonyl, and Ci-C4 alkoxycarbonyl; or
R9 represents phenyl optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH , SH , CHO, COOH , d-d alkyl, d-d alkoxy, d-C4 fluoroalkyl, C3- Ce cycloalkyl, C2-C4 alkenyl, d-C4fluoroalkoxy, d-C4alkylsulfonyl, C(=0)N(R 2)(R13) and
S(=0)2N(R 2)(R13); or
R9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, Ci-C4alkyl, Ci-C4alkoxy, Ci-C4fluoroalkyl and Ci-C4 fluoroalkoxy; or
R9 represents NHR 4;
R 0 represents hydrogen or methyl;
each R independently represents formyl, d-C4alkyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu , benzyl, phenyl, -S(=0)2Me, - S(=0)2Et, C(=0)N(R 7)(R18), -C(=S)N(R 7)(R18) or -S(=0)2N(R 7)(R18);
each R 6 independently represents hydrogen, fluorine, methyl, ethyl, isopropyl, CHF2, CF3, CHO, CO-Me, C02Me, CONHMe, CONMe2, S(=0)2Me, -S(=0)2Et, S(=0)2NHMe, S(=0)2NMe2, benzyl or phenyl;
each R 7 and R 8 independently of each other represents hydrogen, methyl, ethyl, propyl, isopropyl, CHF2, CF3, benzyl or phenyl.
In another group of compounds of formula (I), m represents 0 or 1 ;
Z represents methylene or ethylene, each of which is optionally substituted by one or more methyl groups;
R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or d-C6alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from fluoro, CN , OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2- CH3, CF2-CF3 OMe, OEt, OiPr, OPr; or
R9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R11 ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH , SH , methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2- CH3, CF2-CF3, OMe, OEt, OiPr, OnPr, OCHF2 and OCF3; or
R9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from fluoro, CN, N02, OH, SH, CHO, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2- CF3, OMe, OEt, OiPr, OPr, OCHF2, OCF3, SCHF2, SCF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu; or
R9 represents phenyl optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec- butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, OCF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu CONHMe, CONMe2, S(=0)2Me, -S(=0)2Et, S(=0)2NHMe and S(=0)2NMe2; or
R9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from fluoro, CN, N02, OH, SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3; or
R9 represents NHR 4;
each R independently represents -S(=0)2Me, -S(=0)2Et, C(=0)N(R 7)(R18), - S(=0)2N(R 7)(R18), formyl, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu, benzyl or phenyl;
each R 7 and R 8, independently of each other, represents hydrogen, methyl, ethyl, propyl or isopropyl.
In another group of compounds of formula (I), R9 represents hydrogen, d-C8alkyl, C3-C8alkenyl or C3-C8alkynyl, wherein the alkyl, alkenyl, alkynyl and cycloalkoxyare optionally substituted by one or more groups independently selected from halogen, hydroxyl, cyano, N02, OH, SH, d-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynl, d-C6 haloalkyl, d-C6 alkoxy, C3-C8 cycloalkyl C3-C8 cycloalkoxy, formyl, C2- C6alkylcarbonyl, d-C6alkylthio, d-C6alkylsulfinyl and d-C6alkylsulfonyl.
Preferably in this group of compounds, R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or d- C6alkynyl wherein the alkyl, alkenyl and alkynyl are optionally be optionally substituted by one or more groups independently selected from halogen, CN, OH, d-C4alkyl, C2-C4alkenyl, d-C4fluoroalkyl, d- dalkoxy, and C2-C5alkylcarbonyl.
More preferably in this group of compounds, R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or d-C6alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso- butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, and OCF3.
Most preferably in this group of compounds, R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or d-C6alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from fluoro, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr.
Most preferably in this group of compounds, R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or Ci-C6alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from fluoro, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3 In another group of compounds of formula (I), R represents D-A-Ci-C6alkyl-, D-A-Ci-C6alkyl-, D-A-d-C6alkyl-, D-A-Ci-C6alkyl-, D-A-Ci-C6alkyl-, D-A-Ci-C6alkyl-, D-A-C2-C6alkenyl-, D-A-C2- C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2- C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2- C6alkynyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D- A-C3-C6cycloalkyl- or D-A-C3-C6cycloalkyl-, wherein A and D are as described above.
In another group of compounds of formula (I), R9 represents an three to eight membered monocyclic system which can be aromatic, partially saturated or fully saturated , which optionally contains one or two hetero atoms selected from the group consisting of N, N(R11 ), O and S, optionally substituted by one or more groups independently selected from the group consisting of hydrogen, halogen, cyano, nitro, mercapto, hydroxy, -CHO, -COOH, -C(=S)NH2, -SF5, Ci-C4alkyl, Ci-C4haloalkyl, C2-C6 alkenyl, C2-C5haloalkenyl, C2-C5alkynyl, C2-C5haloalkynyl, d-C4alkoxy, Ci-C4haloalkoxy, C3- C6cycloalkyl, C3-C6halocycloalkyl, C3-C4alkenyloxy, C3-C4haloalkenyloxy, C3-C5alkynyloxy, C3- C6cycloalkyloxy,C2-C4alkoxycarbonyl, C2-C4haloalkoxycarbonyl, C2-C5alkylcarbonyl, C2-C5 haloalkylcarbonyl, -N(R 2)(R13), -C(=0)N(R 2)(R13), C(=S)N(R 2)(R13), d-C4alkylthio, d-C4alkylsulfinyl, d-dalkylsulfonyl, d-dhaloalkylthio, d-dhaloalkylsulfinyl, d-dhaloalkylsulfonyl and - S(=0)2N(R 2)(R13), wherein R , R 2 and R 3 are as described above.
Preferably in this group of compounds, R9 represents a five- or six-membered aromatic monocyclic system which contains one or two hetero atoms selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from halogen, CN, OH, SH, CHO, COOH , d-C4 alkyl, d-C4alkoxy, d-C4haloalkyl, d-C4haloalkoxy, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C2-C5alkoxycarbonyl, d-C4haloalkylthio, C(=0)N(R 2)(R13), - C(=S)N(R 2)(R13) and -S(=0)2N(R 2)(R13).
More preferably in this group of compounds, R9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N , N(R ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, d-C4alkyl, d-C4fluoroalkyl, d-C4alkoxy, d-C4fluoroalkoxy, d-C4 alkylcarbonyl and Ci-C4 alkoxycarbonyl.
Most preferably in this group of compounds, R9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N , N(R ), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH , SH , methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert- butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OnPr, OCHF2 and OCF3.
In another group of compounds of formula (I), R9 represents a five- or six-membered aromatic monocyclic system which contains one or two hetero atoms selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from halogen, CN, OH, SH, CHO, COOH , d-C4 alkyl, d-C4alkoxy, d-C4haloalkyl, d-C4haloalkoxy, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C2-C5alkoxycarbonyl, d-C4haloalkylthio, C(=0)N(R 2)(R13), - C(=S)N(R 2)(R13) and -S(=0)2N(R 2)(R13), wherein R 2, R 3 and R 6 are as described above. Preferably in this group of compounds, R represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, d-C4alkyl, Ci-C4fluoroalkyl, d-C4alkoxy, d-C4fluoroalkoxy, Ci-C4 alkylcarbonyl, and Ci-C4alkoxycarbonyl.
Most preferably in this group of compounds, R9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from fluoro, CN, N02, OH, SH, CHO, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, OCF3, SCHF2, SCF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu.
In another group of compounds of formula (I), R9 represents phenyl optionally substituted by one or more groups independently selected from halogen, CN, N02, OH, SH, CHO, COOH, Ci-C4 alkyl, Ci-C4 alkoxy, Ci-C4 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, d-d haloalkoxy, d-d alkylcarbonyl, d-C4alkylsulfonyl, C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) and - S(=0)2N(R 2)(R13), wherein R 2 and R 3 are as described above.
Preferably in this group of compounds, R9 represents phenyl optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, COOH, d- C4 alkyl, Ci-C4 alkoxy, Ci-C4fluoroalkyl, C3-C6 cycloalkyl, C2-C4 alkenyl, Ci-C4fluoroalkoxy, d- dalkylsulfonyl, C(=0)N(R 2)(R13) and S(=0)2N(R 2)(R13).
Most preferably in this group of compounds, R9 represents phenyl optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2- CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, OCF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu CONHMe, CONMe2, S(=0)2Me, -S(=0)2Et, S(=0)2NHMe and S(=0)2NMe2.
In another group of compounds of formula (I), R9 represents a C3-C8 carbocyclic system, which may be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from halogen, CN, N02, OH, SH, CHO, COOH, d-C4 alkyl, d-C4 alkoxy, d- C4 haloalkyl, Ci-C4 haloalkoxy, C3-C6 cycloalkyl and Ci-C4 alkylcarbonyl.
Preferably in this group of compounds, R9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, Ci-C4alkyl, Ci-C4alkoxy, d- dfluoroalkyl and Ci-C4 fluoroalkoxy.
Most preferably in this group of compounds, R9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from fluoro, CN, N02, OH, SH, methyl, ethyl, n-propyl, iso-propyl, n- butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3.
In another group of compounds of formula (I), R9 represents NHR 4, wherein R 4 is as described above. In another group of compounds of formula (I), Z represents methylene or ethylene each of which is optionally substituted by one or more substituents independently selected from methyl, ethyl, OH, CN, CF3, OMe, OEt, C02Me, C02Et and C02iPr;
m represents 0 or 1
R9 represents H, NHR 4, Ci-C6alkyl, Ci-C6alkenyl, Ci-C6 alkoxy, Ci-C6 alkenoxy, C3-
C6cycloalkylmethoxy, phenyl, benzyl or a five- or six-membered saturated or aromatic monocyclic system which contains one or two members selected from the group consisting of N and O, each of which are optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, OCF3;
R 4 represents phenyl optionally substituted by fluoro, CN, OH, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2- CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3.
In another group of compounds of formula (I), Z represents methylene or ethylene each of which is optionally substituted by one or more substituents independently selected from methyl, ethyl, OH, CN, CF3, OMe, OEt, C02Me, C02Et and C02iPr;
m represents 0 or 1
R9 represents NHR14, d-C6alkyl, Ci-C6alkenyl, d-C6 alkoxy, d-C6 alkenoxy, C3- C6cycloalkylmethoxy, phenyl, benzyl or a five- or six-membered saturated or aromatic monocyclic system which contains one or two members selected from the group consisting of N and O, each of which are optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3;
R 4 represents phenyl optionally substituted by fluoro, CN, OH, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2- CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3.
In another group of compounds of formula (I), Z represents methylene or ethylene each of which is optionally substituted by one or more substituents independently selected from methyl, ethyl, OH, CN, CF3, OMe, OEt, C02Me, C02Et and C02iPr;
m represents 0 or 1
R9 represents d-C6alkyl, d-C6alkenyl, d-C6 alkoxy, d-C6 alkenoxy, C3-C6cycloalkylmethoxy, phenyl, benzyl or a five- or six-membered saturated or aromatic monocyclic system which contains one or two members selected from the group consisting of N and O, each of which are optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2- CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3.
In another group of compounds of formula (I), R and R2 independently of each other represent hydrogen, d-C4alkyl or cyclopropyl;
R3 represents hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, vinyl, -C(Me)=CH2, allyl, OMe OEt or cyclopropyl; R4 represents hydrogen;
R6, R7 and R9 independently of each other represent hydrogen, halogen, CN, d-C4alkyl, d- C4alkoxy, Ci-C4haloalkyl or C1-C4 haloalkoxy.
In another group of compounds of formula (I), R and R2 independently of each other represent hydrogen, methyl, ethyl, isopropyl, n-propyl or cyclopropyl;
R3 represents hydrogen, chloro, methyl or ethyl;
R4 represents hydrogen;
R6, R7 and R8 independently of each other represent hydrogen, fluoro, chloro, bromo, CN, methyl, ethyl, propyl, OMe, OEt, CHF2, CF3 or OCHF2.
In another group of compounds of formula (I), R represents methyl;
R2 represents ethyl;
R3 represents methyl;
R4, R6, R7 and R8 represent hydrogen.
The present invention further provides novel intermediate compounds of the formula (XIX")
Figure imgf000018_0001
wherein R3, R4, R6, R7 and R8 are as defined herein for a compound of formula (I) and R is defined as hydrogen or C02tBu; and
and X is CI, Br, I, boronic ester, boronic acid, tri-alkylstannane, CN, CH2OH, CH(Me)OH, CHO, C(0)Me, C02Me, and C02Et.
Preferably in the compounds of formula (XIX"), X is CI, Br, I, CN, CH2OH, CH(Me)OH, CHO, C(0)Me, C02Me, C02Et, B(OH)2, B(OMe)2, B[02C2(Me)4], SnMe3, or SnBu3.
More preferably in the compounds of formula (XIX"), X is CI, Br, I, B(OH)2, B(OMe)2,
B[02C2(Me)4], SnMe3, or SnBu3.
Even more preferably in the compounds of formula (XIX"), X is CI, Br or I.
Most prefereably in the compounds of formula (XIX"), X is bromine.
Preferably in the compounds of formula (XIX"), R is hydrogen.
Prefered definitions of R3, R4, R6 and R8 defined herein for the compounds of formula (I) also apply to the compounds of formula (XIX").
Tables 1 to 16: Compounds of formula (I)
The invention is further illustrated by making available the following individual compounds of formula (I) listed below in Tables 1 to 16. Each of Tables 1 to 16, which follow Table A below, make available 552 compounds of the formula (I) in which R , R2 and R5 are the substituents defined in Table A and the remaining substituents are defined in each of Tables 1 to 16 respectively.
Thus, Table 1 individualises 552 compounds of formula (I) wherein R , R2 and R5 are as defined in each respective row of Table A, and the remaining substituents are as defined in Table 1. Similarly, Table 2 individualises 552 compounds of formula (I) wherein R , R2 and R5 are as defined in each respective row of Table A, and the remaining substituents are as defined in Table 2; and so on for Tables 3 to 16.
Table A discloses 552 sets of meanings of the variables R , R2 and R5 in a compound of formula (IA), as follows:
Table A
R1 R2 R5
A.1 H methyl (5-tert-butyloxazol-2-yl)methyl
A.2 methyl methyl (5-tert-butyloxazol-2-yl)methyl
A.3 H ethyl (5-tert-butyloxazol-2-yl)methyl
A.4 methyl ethyl (5-tert-butyloxazol-2-yl)methyl
A.5 H isopropyl (5-tert-butyloxazol-2-yl)methyl
A.6 methyl isopropyl (5-tert-butyloxazol-2-yl)methyl
A.7 H cyclopropyl (5-tert-butyloxazol-2-yl)methyl
A.8 methyl cyclopropyl (5-tert-butyloxazol-2-yl)methyl
A.9 H methyl (4-tolyl)methyl
A.10 methyl methyl (4-tolyl)methyl
A.1 1 H ethyl (4-tolyl)methyl
A.12 methyl ethyl (4-tolyl)methyl
A.13 H isopropyl (4-tolyl)methyl
A.14 methyl isopropyl (4-tolyl)methyl
A.15 H cyclopropyl (4-tolyl)methyl
A.16 methyl cyclopropyl (4-tolyl)methyl
A.17 H methyl (m-tolyl)methyl
A.18 methyl methyl (m-tolyl)methyl
A.19 H ethyl (m-tolyl)methyl
A.20 methyl ethyl (m-tolyl)methyl
A.21 H isopropyl (m-tolyl)methyl
A.22 methyl isopropyl (m-tolyl)methyl
A.23 H cyclopropyl (m-tolyl)methyl
A.24 methyl cyclopropyl (m-tolyl)methyl
A.25 H methyl (4-chlorophenyl)methyl
A.26 methyl methyl (4-chlorophenyl)methyl
A.27 H ethyl (4-chlorophenyl)methyl
A.28 methyl ethyl (4-chlorophenyl)methyl
A.29 H isopropyl (4-chlorophenyl)methyl
A.30 methyl isopropyl (4-chlorophenyl)methyl
A.31 H cyclopropyl (4-chlorophenyl)methyl R1 R2 R5
A.32 methyl cyclopropyl (4-chlorophenyl)methyl
A.33 H methyl [2-(trifluoromethyl)phenyl]methyl
A.34 methyl methyl [2-(trifluoromethyl)phenyl]methyl
A.35 H ethyl [2-(trifluoromethyl)phenyl]methyl
A.36 methyl ethyl [2-(trifluoromethyl)phenyl]methyl
A.37 H isopropyl [2-(trifluoromethyl)phenyl]methyl
A.38 methyl isopropyl [2-(trifluoromethyl)phenyl]methyl
A.39 H cyclopropyl [2-(trifluoromethyl)phenyl]methyl
A.40 methyl cyclopropyl [2-(trifluoromethyl)phenyl]methyl
A.41 H methyl (2,6-dichlorophenyl)methyl
A.42 methyl methyl (2,6-dichlorophenyl)methyl
A.43 H ethyl (2,6-dichlorophenyl)methyl
A.44 methyl ethyl (2,6-dichlorophenyl)methyl
A.45 H isopropyl (2,6-dichlorophenyl)methyl
A.46 methyl isopropyl (2,6-dichlorophenyl)methyl
A.47 H cyclopropyl (2,6-dichlorophenyl)methyl
A.48 methyl cyclopropyl (2,6-dichlorophenyl)methyl
A.49 H methyl (4-fluorophenyl)methyl
A.50 methyl methyl (4-fluorophenyl)methyl
A.51 H ethyl (4-fluorophenyl)methyl
A.52 methyl ethyl (4-fluorophenyl)methyl
A.53 H isopropyl (4-fluorophenyl)methyl
A.54 methyl isopropyl (4-fluorophenyl)methyl
A.55 H cyclopropyl (4-fluorophenyl)methyl
A.56 methyl cyclopropyl (4-fluorophenyl)methyl
A.57 H methyl (2,6-difluorophenyl)methyl
A.58 methyl methyl (2,6-difluorophenyl)methyl
A.59 H ethyl (2,6-difluorophenyl)methyl
A.60 methyl ethyl (2,6-difluorophenyl)methyl
A.61 H isopropyl (2,6-difluorophenyl)methyl
A.62 methyl isopropyl (2,6-difluorophenyl)methyl
A.63 H cyclopropyl (2,6-difluorophenyl)methyl
A.64 methyl cyclopropyl (2,6-difluorophenyl)methyl
A.65 H methyl [(3-trifluoromethyl)phenyl]methyl
A.66 methyl methyl [(3-trifluoromethyl)phenyl]methyl
A.67 H ethyl [(3-trifluoromethyl)phenyl]methyl
A.68 methyl ethyl [(3-trifluoromethyl)phenyl]methyl
A.69 H isopropyl [(3-trifluoromethyl)phenyl]methyl
A.70 methyl isopropyl [(3-trifluoromethyl)phenyl]methyl
A.71 H cyclopropyl [(3-trifluoromethyl)phenyl]methyl
A.72 methyl cyclopropyl [(3-trifluoromethyl)phenyl]methyl
A.73 H methyl (2-fluorophenyl)methyl
A.74 methyl methyl (2-fluorophenyl)methyl
A.75 H ethyl (2-fluorophenyl)methyl R1 R2 R5
A.76 methyl ethyl (2-fluorophenyl)methyl
A.77 H isopropyl (2-fluorophenyl)methyl
A.78 methyl isopropyl (2-fluorophenyl)methyl
A.79 H cyclopropyl (2-fluorophenyl)methyl
A.80 methyl cyclopropyl (2-fluorophenyl)methyl
A.81 H methyl 3-ethoxypropyl
A.82 methyl methyl 3-ethoxypropyl
A.83 H ethyl 3-ethoxypropyl
A.84 methyl ethyl 3-ethoxypropyl
A.85 H isopropyl 3-ethoxypropyl
A.86 methyl isopropyl 3-ethoxypropyl
A.87 H cyclopropyl 3-ethoxypropyl
A.88 methyl cyclopropyl 3-ethoxypropyl
A.89 H methyl Phenethyl
A.90 methyl methyl Phenethyl
A.91 H ethyl Phenethyl
A.92 methyl ethyl Phenethyl
A.93 H isopropyl Phenethyl
A.94 methyl isopropyl Phenethyl
A.95 H cyclopropyl Phenethyl
A.96 methyl cyclopropyl Phenethyl
A.97 H methyl [(3,5-difluorophenyl)]methyl
A.98 methyl methyl [(3,5-difluorophenyl)]methyl
A.99 H ethyl [(3,5-difluorophenyl)]methyl
A.100 methyl ethyl [(3,5-difluorophenyl)]methyl
A.101 H isopropyl [(3,5-difluorophenyl)]methyl
A.102 methyl isopropyl [(3,5-difluorophenyl)]methyl
A.103 H cyclopropyl [(3,5-difluorophenyl)]methyl
A.104 methyl cyclopropyl [(3,5-difluorophenyl)]methyl
A.105 H methyl benzyl
A.106 methyl methyl benzyl
A.107 H ethyl benzyl
A.108 methyl ethyl benzyl
A.109 H isopropyl benzyl
A.1 10 methyl isopropyl benzyl
A.1 1 1 H cyclopropyl benzyl
A.1 12 methyl cyclopropyl benzyl
A.1 13 H methyl cyclopropoxyethyl
A.1 14 methyl methyl cyclopropoxyethyl
A.1 15 H ethyl cyclopropoxyethyl
A.1 16 methyl ethyl cyclopropoxyethyl
A.1 17 H isopropyl cyclopropoxyethyl
A.1 18 methyl isopropyl cyclopropoxyethyl
A.1 19 H cyclopropyl cyclopropoxyethyl R1 R2 R5
A.120 methyl cyclopropyl cyclopropoxyethyl
A.121 H methyl propoxyethyl
A.122 methyl methyl propoxyethyl
A.123 H ethyl propoxyethyl
A.124 methyl ethyl propoxyethyl
A.125 H isopropyl propoxyethyl
A.126 methyl isopropyl propoxyethyl
A.127 H cyclopropyl propoxyethyl
A.128 methyl cyclopropyl propoxyethyl
A.129 H methyl allyloxymethyl
A.130 methyl methyl allyloxymethyl
A.131 H ethyl allyloxymethyl
A.132 methyl ethyl allyloxymethyl
A.133 H isopropyl allyloxymethyl
A.134 methyl isopropyl allyloxymethyl
A.135 H cyclopropyl allyloxymethyl
A.136 methyl cyclopropyl allyloxymethyl
A.137 H methyl ethoxymethyl
A.138 methyl methyl ethoxymethyl
A.139 H ethyl ethoxymethyl
A.140 methyl ethyl ethoxymethyl
A.141 H isopropyl ethoxymethyl
A.142 methyl isopropyl ethoxymethyl
A.143 H cyclopropyl ethoxymethyl
A.144 methyl cyclopropyl ethoxymethyl
A.145 H methyl isobutoxymethyl
A.146 methyl methyl isobutoxymethyl
A.147 H ethyl isobutoxymethyl
A.148 methyl ethyl isobutoxymethyl
A.149 H isopropyl isobutoxymethyl
A.150 methyl isopropyl isobutoxymethyl
A.151 H cyclopropyl isobutoxymethyl
A.152 methyl cyclopropyl isobutoxymethyl
A.153 H methyl [4-(difluoromethoxy)phenyl]methyl
A.154 methyl methyl [4-(difluoromethoxy)phenyl]methyl
A.155 H ethyl [4-(difluoromethoxy)phenyl]methyl
A.156 methyl ethyl [4-(difluoromethoxy)phenyl]methyl
A.157 H isopropyl [4-(difluoromethoxy)phenyl]methyl
A.158 methyl isopropyl [4-(difluoromethoxy)phenyl]methyl
A.159 H cyclopropyl [4-(difluoromethoxy)phenyl]methyl
A.160 methyl cyclopropyl [4-(difluoromethoxy)phenyl]methyl
A.161 H methyl 2-ethoxyethyl
A.162 methyl methyl 2-ethoxyethyl
A.163 H ethyl 2-ethoxyethyl R1 R2 R5
A.164 methyl ethyl 2-ethoxyethyl
A.165 H isopropyl 2-ethoxyethyl
A.166 methyl isopropyl 2-ethoxyethyl
A.167 H cyclopropyl 2-ethoxyethyl
A.168 methyl cyclopropyl 2-ethoxyethyl
A.169 H methyl 1-ethoxyethyl
A.170 methyl methyl 1-ethoxyethyl
A.171 H ethyl 1-ethoxyethyl
A.172 methyl ethyl 1-ethoxyethyl
A.173 H isopropyl 1-ethoxyethyl
A.174 methyl isopropyl 1-ethoxyethyl
A.175 H cyclopropyl 1-ethoxyethyl
A.176 methyl cyclopropyl 1-ethoxyethyl
A.177 H methyl cyclohexylmethyl
A.178 methyl methyl cyclohexylmethyl
A.179 H ethyl cyclohexylmethyl
A.180 methyl ethyl cyclohexylmethyl
A.181 H isopropyl cyclohexylmethyl
A.182 methyl isopropyl cyclohexylmethyl
A.183 H cyclopropyl cyclohexylmethyl
A.184 methyl cyclopropyl cyclohexylmethyl
A.185 H methyl (4,4-dimethylcyclohexyl)methyl
A.186 methyl methyl (4,4-dimethylcyclohexyl)methyl
A.187 H ethyl (4,4-dimethylcyclohexyl)methyl
A.188 methyl ethyl (4,4-dimethylcyclohexyl)methyl
A.189 H isopropyl (4,4-dimethylcyclohexyl)methyl
A.190 methyl isopropyl (4,4-dimethylcyclohexyl)methyl
A.191 H cyclopropyl (4,4-dimethylcyclohexyl)methyl
A.192 methyl cyclopropyl (4,4-dimethylcyclohexyl)methyl
A.193 H methyl (4,4-difluorocyclohexyl)methyl
A.194 methyl methyl (4,4-difluorocyclohexyl)methyl
A.195 H ethyl (4,4-difluorocyclohexyl)methyl
A.196 methyl ethyl (4,4-difluorocyclohexyl)methyl
A.197 H isopropyl (4,4-difluorocyclohexyl)methyl
A.198 methyl isopropyl (4,4-difluorocyclohexyl)methyl
A.199 H cyclopropyl (4,4-difluorocyclohexyl)methyl
A.200 methyl cyclopropyl (4,4-difluorocyclohexyl)methyl
A.201 H methyl (4-difluoromethoxy)cyclohexylmethyl
A.202 methyl methyl (4-difluoromethoxy)cyclohexylmethyl
A.203 H ethyl (4-difluoromethoxy)cyclohexylmethyl
A.204 methyl ethyl (4-difluoromethoxy)cyclohexylmethyl
A.205 H isopropyl (4-difluoromethoxy)cyclohexylmethyl
A.206 methyl isopropyl (4-difluoromethoxy)cyclohexylmethyl
A.207 H cyclopropyl (4-difluoromethoxy)cyclohexylmethyl R1 R2 R5
A.208 methyl cyclopropyl (4-difluoromethoxy)cyclohexylmethyl
A.209 H methyl 2-(difluoromethoxy)ethyl
A.210 methyl methyl 2-(difluoromethoxy)ethyl
A.21 1 H ethyl 2-(difluoromethoxy)ethyl
A.212 methyl ethyl 2-(difluoromethoxy)ethyl
A.213 H isopropyl 2-(difluoromethoxy)ethyl
A.214 methyl isopropyl 2-(difluoromethoxy)ethyl
A.215 H cyclopropyl 2-(difluoromethoxy)ethyl
A.216 methyl cyclopropyl 2-(difluoromethoxy)ethyl
A.217 H methyl 3-(difluoromethoxy)propyl
A.218 methyl methyl 3-(difluoromethoxy)propyl
A.219 H ethyl 3-(difluoromethoxy)propyl
A.220 methyl ethyl 3-(difluoromethoxy)propyl
A.221 H isopropyl 3-(difluoromethoxy)propyl
A.222 methyl isopropyl 3-(difluoromethoxy)propyl
A.223 H cyclopropyl 3-(difluoromethoxy)propyl
A.224 methyl cyclopropyl 3-(difluoromethoxy)propyl
A.225 H methyl (4-difluoromethyl)cyclohexylmethyl
A.226 methyl methyl (4-difluoromethyl)cyclohexylmethyl
A.227 H ethyl (4-difluoromethyl)cyclohexylmethyl
A.228 methyl ethyl (4-difluoromethyl)cyclohexylmethyl
A.229 H isopropyl (4-difluoromethyl)cyclohexylmethyl
A.230 methyl isopropyl (4-difluoromethyl)cyclohexylmethyl
A.231 H cyclopropyl (4-difluoromethyl)cyclohexylmethyl
A.232 methyl cyclopropyl (4-difluoromethyl)cyclohexylmethyl
A.233 H methyl [1-(ethylsulfamoyl)-4-piperidyl]methyl
A.234 methyl methyl [1-(ethylsulfamoyl)-4-piperidyl]methyl
A.235 H ethyl [1-(ethylsulfamoyl)-4-piperidyl]methyl
A.236 methyl ethyl [1-(ethylsulfamoyl)-4-piperidyl]methyl
A.237 H isopropyl [1-(ethylsulfamoyl)-4-piperidyl]methyl
A.238 methyl isopropyl [1-(ethylsulfamoyl)-4-piperidyl]methyl
A.239 H cyclopropyl [1-(ethylsulfamoyl)-4-piperidyl]methyl
A.240 methyl cyclopropyl [1-(ethylsulfamoyl)-4-piperidyl]methyl
A.241 H methyl [1-[ethyl(methyl)sulfamoyl]-4-piperidyl]methyl
A.242 methyl methyl [1-[ethyl(methyl)sulfamoyl]-4-piperidyl]methyl
A.243 H ethyl [1-[ethyl(methyl)sulfamoyl]-4-piperidyl]methyl
A.244 methyl ethyl [1-[ethyl(methyl)sulfamoyl]-4-piperidyl]methyl
A.245 H isopropyl [1-[ethyl(methyl)sulfamoyl]-4-piperidyl]methyl
A.246 methyl isopropyl [1-[ethyl(methyl)sulfamoyl]-4-piperidyl]methyl
A.247 H cyclopropyl [1-[ethyl(methyl)sulfamoyl]-4-piperidyl]methyl
A.248 methyl cyclopropyl [1-[ethyl(methyl)sulfamoyl]-4-piperidyl]methyl
A.249 H methyl (1-methylsulfonyl-4-piperidyl)methyl
A.250 methyl methyl (1-methylsulfonyl-4-piperidyl)methyl
A.251 H ethyl (1-methylsulfonyl-4-piperidyl)methyl R1 R2 R5
A.252 methyl ethyl (1-methylsulfonyl-4-piperidyl)methyl
A.253 H isopropyl (1-methylsulfonyl-4-piperidyl)methyl
A.254 methyl isopropyl (1-methylsulfonyl-4-piperidyl)methyl
A.255 H cyclopropyl (1-methylsulfonyl-4-piperidyl)methyl
A.256 methyl cyclopropyl (1-methylsulfonyl-4-piperidyl)methyl
A.257 H methyl (1-acetyl-4-piperidyl)methyl
A.258 methyl methyl (1-acetyl-4-piperidyl)methyl
A.259 H ethyl (1-acetyl-4-piperidyl)methyl
A.260 methyl ethyl (1-acetyl-4-piperidyl)methyl
A.261 H isopropyl (1-acetyl-4-piperidyl)methyl
A.262 methyl isopropyl (1-acetyl-4-piperidyl)methyl
A.263 H cyclopropyl (1-acetyl-4-piperidyl)methyl
A.264 methyl cyclopropyl (1-acetyl-4-piperidyl)methyl
A.265 H methyl tert-bu tyl 4-m ethylpi perid i ne- 1 -carboxylate
A.266 methyl methyl tert-bu tyl 4-m ethylpi perid i ne- 1 -carboxylate
A.267 H ethyl tert-bu tyl 4-m ethylpi perid i ne- 1 -carboxylate
A.268 methyl ethyl tert-bu tyl 4-m ethylpi perid i ne- 1 -carboxylate
A.269 H isopropyl tert-bu tyl 4-m ethylpi perid i ne- 1 -carboxylate
A.270 methyl isopropyl tert-bu tyl 4-m ethylpi perid i ne- 1 -carboxylate
A.271 H cyclopropyl tert-bu tyl 4-m ethylpi perid i ne- 1 -carboxylate
A.272 methyl cyclopropyl tert-bu tyl 4-m ethylpi perid i ne- 1 -carboxylate
A.273 H methyl (1-methoxy-4-piperidyl)methyl
A.274 methyl methyl (1-methoxy-4-piperidyl)methyl
A.275 H ethyl (1-methoxy-4-piperidyl)methyl
A.276 methyl ethyl (1-methoxy-4-piperidyl)methyl
A.277 H isopropyl (1-methoxy-4-piperidyl)methyl
A.278 methyl isopropyl (1-methoxy-4-piperidyl)methyl
A.279 H cyclopropyl (1-methoxy-4-piperidyl)methyl
A.280 methyl cyclopropyl (1-methoxy-4-piperidyl)methyl
A.281 H methyl 1-piperidylmethyl
A.282 methyl methyl 1-piperidylmethyl
A.283 H ethyl 1-piperidylmethyl
A.284 methyl ethyl 1-piperidylmethyl
A.285 H isopropyl 1-piperidylmethyl
A.286 methyl isopropyl 1-piperidylmethyl
A.287 H cyclopropyl 1-piperidylmethyl
A.288 methyl cyclopropyl 1-piperidylmethyl
A.289 H methyl (4,4-dimethyl-1-piperidyl)methyl
A.290 methyl methyl (4,4-dimethyl-1-piperidyl)methyl
A.291 H ethyl (4,4-dimethyl-1-piperidyl)methyl
A.292 methyl ethyl (4,4-dimethyl-1-piperidyl)methyl
A.293 H isopropyl (4,4-dimethyl-1-piperidyl)methyl
A.294 methyl isopropyl (4,4-dimethyl-1-piperidyl)methyl
A.295 H cyclopropyl (4,4-dimethyl-1-piperidyl)methyl R1 R2 R5
A.296 methyl cyclopropyl (4,4-dimethyl-1-piperidyl)methyl
A.297 H methyl (morpholino)methyl
A.298 methyl methyl (morpholino)methyl
A.299 H ethyl (morpholino)methyl
A.300 methyl ethyl (morpholino)methyl
A.301 H isopropyl (morpholino)methyl
A.302 methyl isopropyl (morpholino)methyl
A.303 H cyclopropyl (morpholino)methyl
A.304 methyl cyclopropyl (morpholino)methyl
A.305 H methyl (2-chloro-4-pyridyl)methyl
A.306 methyl methyl (2-chloro-4-pyridyl)methyl
A.307 H ethyl (2-chloro-4-pyridyl)methyl
A.308 methyl ethyl (2-chloro-4-pyridyl)methyl
A.309 H isopropyl (2-chloro-4-pyridyl)methyl
A.310 methyl isopropyl (2-chloro-4-pyridyl)methyl
A.31 1 H cyclopropyl (2-chloro-4-pyridyl)methyl
A.312 methyl cyclopropyl (2-chloro-4-pyridyl)methyl
A.313 H methyl (2-methoxy-4-pyridyl)methyl
A.314 methyl methyl (2-methoxy-4-pyridyl)methyl
A.315 H ethyl (2-methoxy-4-pyridyl)methyl
A.316 methyl ethyl (2-methoxy-4-pyridyl)methyl
A.317 H isopropyl (2-methoxy-4-pyridyl)methyl
A.318 methyl isopropyl (2-methoxy-4-pyridyl)methyl
A.319 H cyclopropyl (2-methoxy-4-pyridyl)methyl
A.320 methyl cyclopropyl (2-methoxy-4-pyridyl)methyl
A.321 H methyl (2-difluoromethoxy-4-pyridyl)methyl
A.322 methyl methyl (2-difluoromethoxy-4-pyridyl)methyl
A.323 H ethyl (2-difluoromethoxy-4-pyridyl)methyl
A.324 methyl ethyl (2-difluoromethoxy-4-pyridyl)methyl
A.325 H isopropyl (2-difluoromethoxy-4-pyridyl)methyl
A.326 methyl isopropyl (2-difluoromethoxy-4-pyridyl)methyl
A.327 H cyclopropyl (2-difluoromethoxy-4-pyridyl)methyl
A.328 methyl cyclopropyl (2-difluoromethoxy-4-pyridyl)methyl
A.329 H methyl (6-chloro-2-pyridyl)methyl
A.330 methyl methyl (6-chloro-2-pyridyl)methyl
A.331 H ethyl (6-chloro-2-pyridyl)methyl
A.332 methyl ethyl (6-chloro-2-pyridyl)methyl
A.333 H isopropyl (6-chloro-2-pyridyl)methyl
A.334 methyl isopropyl (6-chloro-2-pyridyl)methyl
A.335 H cyclopropyl (6-chloro-2-pyridyl)methyl
A.336 methyl cyclopropyl (6-chloro-2-pyridyl)methyl
A.337 H methyl (6-methoxy-2-pyridyl)methyl
A.338 methyl methyl (6-methoxy-2-pyridyl)methyl
A.339 H ethyl (6-methoxy-2-pyridyl)methyl R1 R2 R5
A.340 methyl ethyl (6-methoxy-2-pyridyl)methyl
A.341 H isopropyl (6-methoxy-2-pyridyl)methyl
A.342 methyl isopropyl (6-methoxy-2-pyridyl)methyl
A.343 H cyclopropyl (6-methoxy-2-pyridyl)methyl
A.344 methyl cyclopropyl (6-methoxy-2-pyridyl)methyl
A.345 H methyl (6-difluoromethoxy-2-pyridyl)methyl
A.346 methyl methyl (6-difluoromethoxy-2-pyridyl)methyl
A.347 H ethyl (6-difluoromethoxy-2-pyridyl)methyl
A.348 methyl ethyl (6-difluoromethoxy-2-pyridyl)methyl
A.349 H isopropyl (6-difluoromethoxy-2-pyridyl)methyl
A.350 methyl isopropyl (6-difluoromethoxy-2-pyridyl)methyl
A.351 H cyclopropyl (6-difluoromethoxy-2-pyridyl)methyl
A.352 methyl cyclopropyl (6-difluoromethoxy-2-pyridyl)methyl
A.353 H methyl (6-chloro-3-pyridyl)methyl
A.354 methyl methyl (6-chloro-3-pyridyl)methyl
A.355 H ethyl (6-chloro-3-pyridyl)methyl
A.356 methyl ethyl (6-chloro-3-pyridyl)methyl
A.357 H isopropyl (6-chloro-3-pyridyl)methyl
A.358 methyl isopropyl (6-chloro-3-pyridyl)methyl
A.359 H cyclopropyl (6-chloro-3-pyridyl)methyl
A.360 methyl cyclopropyl (6-chloro-3-pyridyl)methyl
A.361 H methyl (6-methoxy-3-pyridyl)methyl
A.362 methyl methyl (6-methoxy-3-pyridyl)methyl
A.363 H ethyl (6-methoxy-3-pyridyl)methyl
A.364 methyl ethyl (6-methoxy-3-pyridyl)methyl
A.365 H isopropyl (6-methoxy-3-pyridyl)methyl
A.366 methyl isopropyl (6-methoxy-3-pyridyl)methyl
A.367 H cyclopropyl (6-methoxy-3-pyridyl)methyl
A.368 methyl cyclopropyl (6-methoxy-3-pyridyl)methyl
A.369 H methyl (6-difluoromethoxy-3-pyridyl)methyl
A.370 methyl methyl (6-difluoromethoxy-3-pyridyl)methyl
A.371 H ethyl (6-difluoromethoxy-3-pyridyl)methyl
A.372 methyl ethyl (6-difluoromethoxy-3-pyridyl)methyl
A.373 H isopropyl (6-difluoromethoxy-3-pyridyl)methyl
A.374 methyl isopropyl (6-difluoromethoxy-3-pyridyl)methyl
A.375 H cyclopropyl (6-difluoromethoxy-3-pyridyl)methyl
A.376 methyl cyclopropyl (6-difluoromethoxy-3-pyridyl)methyl
A.377 H methyl [4-(trifluoromethyl)phenyl]ethyl
A.378 methyl methyl [4-(trifluoromethyl)phenyl]ethyl
A.379 H ethyl [4-(trifluoromethyl)phenyl]ethyl
A.380 methyl ethyl [4-(trifluoromethyl)phenyl]ethyl
A.381 H isopropyl [4-(trifluoromethyl)phenyl]ethyl
A.382 methyl isopropyl [4-(trifluoromethyl)phenyl]ethyl
A.383 H cyclopropyl [4-(trifluoromethyl)phenyl]ethyl R1 R2 R5
A.384 methyl cyclopropyl [4-(trifluoromethyl)phenyl]ethyl
A.385 H methyl [3-(trifluoromethyl)phenyl]ethyl
A.386 methyl methyl [3-(trifluoromethyl)phenyl]ethyl
A.387 H ethyl [3-(trifluoromethyl)phenyl]ethyl
A.388 methyl ethyl [3-(trifluoromethyl)phenyl]ethyl
A.389 H isopropyl [3-(trifluoromethyl)phenyl]ethyl
A.390 methyl isopropyl [3-(trifluoromethyl)phenyl]ethyl
A.391 H cyclopropyl [3-(trifluoromethyl)phenyl]ethyl
A.392 methyl cyclopropyl [3-(trifluoromethyl)phenyl]ethyl
A.393 H methyl [3-(trifluoromethyl)phenyl]ethyl
A.394 methyl methyl [3-(trifluoromethyl)phenyl]ethyl
A.395 H ethyl [3-(trifluoromethyl)phenyl]ethyl
A.396 methyl ethyl [3-(trifluoromethyl)phenyl]ethyl
A.397 H isopropyl [3-(trifluoromethyl)phenyl]ethyl
A.398 methyl isopropyl [3-(trifluoromethyl)phenyl]ethyl
A.399 H cyclopropyl [3-(trifluoromethyl)phenyl]ethyl
A.400 methyl cyclopropyl [3-(trifluoromethyl)phenyl]ethyl
A.401 H methyl [4-(difluoromethyl)phenyl]ethyl
A.402 methyl methyl [4-(difluoromethyl)phenyl]ethyl
A.403 H ethyl [4-(difluoromethyl)phenyl]ethyl
A.404 methyl ethyl [4-(difluoromethyl)phenyl]ethyl
A.405 H isopropyl [4-(difluoromethyl)phenyl]ethyl
A.406 methyl isopropyl [4-(difluoromethyl)phenyl]ethyl
A.407 H cyclopropyl [4-(difluoromethyl)phenyl]ethyl
A.408 methyl cyclopropyl [4-(difluoromethyl)phenyl]ethyl
A.409 H methyl [3-(difluoromethyl)phenyl]ethyl
A.410 methyl methyl [3-(difluoromethyl)phenyl]ethyl
A.41 1 H ethyl [3-(difluoromethyl)phenyl]ethyl
A.412 methyl ethyl [3-(difluoromethyl)phenyl]ethyl
A.413 H isopropyl [3-(difluoromethyl)phenyl]ethyl
A.414 methyl isopropyl [3-(difluoromethyl)phenyl]ethyl
A.415 H cyclopropyl [3-(difluoromethyl)phenyl]ethyl
A.416 methyl cyclopropyl [3-(difluoromethyl)phenyl]ethyl
A.417 H methyl [3-(difluoromethyl)phenyl]ethyl
A.418 methyl methyl [3-(difluoromethyl)phenyl]ethyl
A.419 H ethyl [3-(difluoromethyl)phenyl]ethyl
A.420 methyl ethyl [3-(difluoromethyl)phenyl]ethyl
A.421 H isopropyl [3-(difluoromethyl)phenyl]ethyl
A.422 methyl isopropyl [3-(difluoromethyl)phenyl]ethyl
A.423 H cyclopropyl [3-(difluoromethyl)phenyl]ethyl
A.424 methyl cyclopropyl [3-(difluoromethyl)phenyl]ethyl
A.425 H methyl [4-(difluoromethyl)phenyl]methyl
A.426 methyl methyl [4-(difluoromethyl)phenyl]methyl
A.427 H ethyl [4-(difluoromethyl)phenyl]methyl R1 R2 R5
A.428 methyl ethyl [4-(difluoromethyl)phenyl]methyl
A.429 H isopropyl [4-(difluoromethyl)phenyl]methyl
A.430 methyl isopropyl [4-(difluoromethyl)phenyl]methyl
A.431 H cyclopropyl [4-(difluoromethyl)phenyl]methyl
A.432 methyl cyclopropyl [4-(difluoromethyl)phenyl]methyl
A.433 H methyl [3-(difluoromethyl)phenyl]methyl
A.434 methyl methyl [3-(difluoromethyl)phenyl]methyl
A.435 H ethyl [3-(difluoromethyl)phenyl]methyl
A.436 methyl ethyl [3-(difluoromethyl)phenyl]methyl
A.437 H isopropyl [3-(difluoromethyl)phenyl]methyl
A.438 methyl isopropyl [3-(difluoromethyl)phenyl]methyl
A.439 H cyclopropyl [3-(difluoromethyl)phenyl]methyl
A.440 methyl cyclopropyl [3-(difluoromethyl)phenyl]methyl
A.441 H methyl [3-(difluoromethyl)phenyl]methyl
A.442 methyl methyl [3-(difluoromethyl)phenyl]methyl
A.443 H ethyl [3-(difluoromethyl)phenyl]methyl
A.444 methyl ethyl [3-(difluoromethyl)phenyl]methyl
A.445 H isopropyl [3-(difluoromethyl)phenyl]methyl
A.446 methyl isopropyl [3-(difluoromethyl)phenyl]methyl
A.447 H cyclopropyl [3-(difluoromethyl)phenyl]methyl
A.448 methyl cyclopropyl [3-(difluoromethyl)phenyl]methyl
A.449 H methyl phenoxymethyl
A.450 methyl methyl phenoxymethyl
A.451 H ethyl phenoxymethyl
A.452 methyl ethyl phenoxymethyl
A.453 H isopropyl phenoxymethyl
A.454 methyl isopropyl phenoxymethyl
A.455 H cyclopropyl phenoxymethyl
A.456 methyl cyclopropyl phenoxymethyl
A.457 H methyl [4-(methyl)phenoxy]methyl
A.458 methyl methyl [4-(methyl)phenoxy]methyl
A.459 H ethyl [4-(methyl)phenoxy]methyl
A.460 methyl ethyl [4-(methyl)phenoxy]methyl
A.461 H isopropyl [4-(methyl)phenoxy]methyl
A.462 methyl isopropyl [4-(methyl)phenoxy]methyl
A.463 H cyclopropyl [4-(methyl)phenoxy]methyl
A.464 methyl cyclopropyl [4-(methyl)phenoxy]methyl
A.465 H methyl [2,4-(dimethyl)phenoxy]methyl
A.466 methyl methyl [2,4-(dimethyl)phenoxy]methyl
A.467 H ethyl [2,4-(dimethyl)phenoxy]methyl
A.468 methyl ethyl [2,4-(dimethyl)phenoxy]methyl
A.469 H isopropyl [2,4-(dimethyl)phenoxy]methyl
A.470 methyl isopropyl [2,4-(dimethyl)phenoxy]methyl
A.471 H cyclopropyl [2,4-(dimethyl)phenoxy]methyl R1 R2 R5
A.472 methyl cyclopropyl [2,4-(dimethyl)phenoxy]methyl
A.473 H methyl [4-(trifluoromethyl)phenoxy]methyl
A.474 methyl methyl [4-(trifluoromethyl)phenoxy]methyl
A.475 H ethyl [4-(trifluoromethyl)phenoxy]methyl
A.476 methyl ethyl [4-(trifluoromethyl)phenoxy]methyl
A.477 H isopropyl [4-(trifluoromethyl)phenoxy]methyl
A.478 methyl isopropyl [4-(trifluoromethyl)phenoxy]methyl
A.479 H cyclopropyl [4-(trifluoromethyl)phenoxy]methyl
A.480 methyl cyclopropyl [4-(trifluoromethyl)phenoxy]methyl
A.481 H methyl [4-(difluoromethyl)phenoxy]methyl
A.482 methyl methyl [4-(difluoromethyl)phenoxy]methyl
A.483 H ethyl [4-(difluoromethyl)phenoxy]methyl
A.484 methyl ethyl [4-(difluoromethyl)phenoxy]methyl
A.485 H isopropyl [4-(difluoromethyl)phenoxy]methyl
A.486 methyl isopropyl [4-(difluoromethyl)phenoxy]methyl
A.487 H cyclopropyl [4-(difluoromethyl)phenoxy]methyl
A.488 methyl cyclopropyl [4-(difluoromethyl)phenoxy]methyl
A.489 H methyl [3-(trifluoromethyl)phenoxy]methyl
A.490 methyl methyl [3-(trifluoromethyl)phenoxy]methyl
A.491 H ethyl [3-(trifluoromethyl)phenoxy]methyl
A.492 methyl ethyl [3-(trifluoromethyl)phenoxy]methyl
A.493 H isopropyl [3-(trifluoromethyl)phenoxy]methyl
A.494 methyl isopropyl [3-(trifluoromethyl)phenoxy]methyl
A.495 H cyclopropyl [3-(trifluoromethyl)phenoxy]methyl
A.496 methyl cyclopropyl [3-(trifluoromethyl)phenoxy]methyl
A.497 H methyl [3-(difluoromethyl)phenoxy]methyl
A.498 methyl methyl [3-(difluoromethyl)phenoxy]methyl
A.499 H ethyl [3-(difluoromethyl)phenoxy]methyl
A.500 methyl ethyl [3-(difluoromethyl)phenoxy]methyl
A.501 H isopropyl [3-(difluoromethyl)phenoxy]methyl
A.502 methyl isopropyl [3-(difluoromethyl)phenoxy]methyl
A.503 H cyclopropyl [3-(difluoromethyl)phenoxy]methyl
A.504 methyl cyclopropyl [3-(difluoromethyl)phenoxy]methyl
A.505 H methyl [4-(difluoromethoxy)phenoxy]methyl
A.506 methyl methyl [4-(difluoromethoxy)phenoxy]methyl
A.507 H ethyl [4-(difluoromethoxy)phenoxy]methyl
A.508 methyl ethyl [4-(difluoromethoxy)phenoxy]methyl
A.509 H isopropyl [4-(difluoromethoxy)phenoxy]methyl
A.510 methyl isopropyl [4-(difluoromethoxy)phenoxy]methyl
A.51 1 H cyclopropyl [4-(difluoromethoxy)phenoxy]methyl
A.512 methyl cyclopropyl [4-(difluoromethoxy)phenoxy]methyl
A.513 H methyl [3-(difluoromethoxy)phenoxy]methyl
A.514 methyl methyl [3-(difluoromethoxy)phenoxy]methyl
A.515 H ethyl [3-(difluoromethoxy)phenoxy]methyl R1 R2 R5
A.516 methyl ethyl [3-(difluoromethoxy)phenoxy]methyl
A.517 H isopropyl [3-(difluoromethoxy)phenoxy]methyl
A.518 methyl isopropyl [3-(difluoromethoxy)phenoxy]methyl
A.519 H cyclopropyl [3-(difluoromethoxy)phenoxy]methyl
A.520 methyl cyclopropyl [3-(difluoromethoxy)phenoxy]methyl
A.521 H methyl [4-(fluoromethyl)phenoxy]methyl
A.522 methyl methyl [4-(fluoromethyl)phenoxy]methyl
A.523 H ethyl [4-(fluoromethyl)phenoxy]methyl
A.524 methyl ethyl [4-(fluoromethyl)phenoxy]methyl
A.525 H isopropyl [4-(fluoromethyl)phenoxy]methyl
A.526 methyl isopropyl [4-(fluoromethyl)phenoxy]methyl
A.527 H cyclopropyl [4-(fluoromethyl)phenoxy]methyl
A.528 methyl cyclopropyl [4-(fluoromethyl)phenoxy]methyl
A.529 H methyl [2,4-(difluoromethyl)phenoxy]methyl
A.530 methyl methyl [2,4-(difluoromethyl)phenoxy]methyl
A.531 H ethyl [2,4-(difluoromethyl)phenoxy]methyl
A.532 methyl ethyl [2,4-(difluoromethyl)phenoxy]methyl
A.533 H isopropyl [2,4-(difluoromethyl)phenoxy]methyl
A.534 methyl isopropyl [2,4-(difluoromethyl)phenoxy]methyl
A.535 H cyclopropyl [2,4-(difluoromethyl)phenoxy]methyl
A.536 methyl cyclopropyl [2,4-(difluoromethyl)phenoxy]methyl
A.537 H methyl [3,5-(difluoromethyl)phenoxy]methyl
A.538 methyl methyl [3,5-(difluoromethyl)phenoxy]methyl
A.539 H ethyl [3,5-(difluoromethyl)phenoxy]methyl
A.540 methyl ethyl [3,5-(difluoromethyl)phenoxy]methyl
A.541 H isopropyl [3,5-(difluoromethyl)phenoxy]methyl
A.542 methyl isopropyl [3,5-(difluoromethyl)phenoxy]methyl
A.543 H cyclopropyl [3,5-(difluoromethyl)phenoxy]methyl
A.544 methyl cyclopropyl [3,5-(difluoromethyl)phenoxy]methyl
A.545 H methyl [2,6-(difluoromethyl)phenoxy]methyl
A.546 methyl methyl [2,6-(difluoromethyl)phenoxy]methyl
A.547 H ethyl [2,6-(difluoromethyl)phenoxy]methyl
A.548 methyl ethyl [2,6-(difluoromethyl)phenoxy]methyl
A.549 H isopropyl [2,6-(difluoromethyl)phenoxy]methyl
A.550 methyl isopropyl [2,6-(difluoromethyl)phenoxy]methyl
A.551 H cyclopropyl [2,6-(difluoromethyl)phenoxy]methyl
A.552 methyl cyclopropyl [2,6-(difluoromethyl)phenoxy]methyl
Table 1 : Table 1 discloses 552 compounds of formula (I) wherein each of R3, R4, R6, R7 and R! are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A. For example, compound 1.1 has the following structure:
Figure imgf000032_0001
Table 2: Table 2 discloses 552 compounds of formula (I) wherein R3 is methyl, each of R4, R6, R7 and R8 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 3: Table 3 discloses 552 compounds of formula (I) wherein R3 is ethyl, each of R4, R6, R7 and R8 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 4: Table 4 discloses 552 compounds of formula (I) wherein R3 is cycloproply, each of R4, R6, R7 and R8 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 5: Table 5 discloses 552 compounds of formula (I) wherein R3 is methyl, R8 is chloro, each of R4, R6 and R7 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 6: Table 6 discloses 552 compounds of formula (I) wherein R3 is methyl, R8 is methyl, each of R4, R6 and R7 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 7: Table 7 discloses 552 compounds of formula (I) wherein R3 is methyl, R8 is methoxy, each of R4, R6 and R7 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 8: Table 8 discloses 552 compounds of formula (I) wherein R3 is methyl, R8 is cyano, each of R4, R6 and R7 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 9: Table 9 discloses 552 compounds of formula (I) wherein R3 is methyl, R7 is chloro, each of R4, R6 and R8 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 10: Table 10 discloses 552 compounds of formula (I) wherein R3 is methyl, R7 is methyl, each of R4, R6 and R8 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 1 1 : Table 1 1 discloses 552 compounds of formula (I) wherein R3 is methyl, R8 is methoxy, each of R4, R6 and R7 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 12: Table 12 discloses 552 compounds of formula (I) wherein R3 is methyl, R8 is cyano, each of R4, R6 and R7 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 13: Table 13 discloses 552 compounds of formula (I) wherein R3 is methyl, R6 is chloro, each of R4, R7 and R8 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 14: Table 14 discloses 552 compounds of formula (I) wherein R3 is methyl, R6 is methyl, each of R4, R7 and R8 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 15: Table 15 discloses 552 compounds of formula (I) wherein R3 is methyl, R6 is methoxy, each of R4, R7 and R8 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
Table 16: Table 16 discloses 552 compounds of formula (I) wherein R3 is methyl, R6 is cyano, each of R4, R7 and R8 are hydrogen and each of the variables R , R2 and R5 has the specific meaning given in the corresponding row of Table A.
It has now been found that the compounds of formula (I) according to the invention have, for practical purposes, a very advantageous spectrum of activities for protecting useful plants against diseases that are caused by phytopathogenic microorganisms, such as fungi, bacteria or viruses, in particular against diseases that are caused by fungi.
Compounds of formula I and fungicidal compositions containing them may be used to control plant diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete,
Ascomycete, Oomycete and/or Deuteromycete, Blasocladiomycete, Chrytidiomycete, Glomeromycete and/or Mucoromycete classes.
The invention therefore also relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula (I) is applied as active ingredient to the plants, to parts thereof or the locus thereof.
The term "plants" refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
The term "locus" as used herein means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.
The compounds of formula I can be used in the agricultural sector and related fields of use e.g. as active ingredients for controlling plant pests or on non-living materials for control of spoilage microorganisms or organisms potentially harmful to man.
The compounds of formula (I) according to the invention are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous useful plants. The compounds of formula (I) can be used to inhibit or destroy the diseases that occur on plants or parts of plants of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later from phytopathogenic micro-organisms.
It is possible to use compounds of formula I as fungicide. The term "fungicide" as used herein means a compound that controls, modifies, or prevents the growth of fungi. The term "fungicidally effective amount" means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all deviation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.
A preferred method of applying a compound of formula (I) is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen. However, the compounds of formula (I) may also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
It is also possible to use compounds of formula (I) as dressing agents for the treatment of plant propagation material, in particular of seeds and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.
The propagation material can be treated with a composition comprising a compound of formula I before planting: seed, for example, can be dressed before being sown. The active ingredients according to the invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation. The composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing. The invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.
The term "plant propagation material" denotes all generative parts of a plant, for example seeds or vegetative parts of plants such as cuttings and tubers. It includes seeds in the strict sense, as well as roots, fruits, tubers, bulbs, rhizomes, and parts of plants.
Furthermore the compounds of formula (I) according to the invention may be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene management.
In addition, the invention could be used to protect non-living materials from fungal attack, e.g. lumber, wall boards and paint.
The compounds of formula I are for example, effective against Fungi and fungal vectors of disease as well as phytopathogenic bacteria and viruses. These pathogens may include:
Oomycetes, including Phytophthora diseases such as those caused by Phytophthora capsici, Phytophthora infestans, Phytophthora sojae, Phytophthora fragariae, Phytophthora nicotianae, Phytophthora cinnamomi, Phytophthora citricola, Phytophthora citrophthora and Phytophthora erythroseptica; Pythium diseases such as those caused by Pythium aphanidermatum, Pythium arrhenomanes, Pythium graminicola, Pythium irregulare and Pythium ultimum; diseases caused by Peronosporales such as Peronospora destructor, Peronospora parasitica, Plasmopara viticola, Plasmopara halstedii, Pseudoperonospora cubensis, Albugo Candida, Sclerophthora macrospora and Bremia lactucae; and others such as Aphanomyces cochlioides, Labyrinthula zosterae,
Peronosclerospora sorghi and Sclerospora graminicola.
Ascomycetes, including blotch, spot, blast or blight diseases and/or rots for example those caused by Pleosporales such as Stemphylium solani, Stagonospora tainanensis, Spilocaea oleaginea, Setosphaeria turcica, Pyrenochaeta lycoperisici, Pleospora herbarum, Phoma destructiva,
Phaeosphaeria herpotrichoides, Phaeocryptocus gaeumannii, Ophiosphaerella graminicola,
Ophiobolus graminis, Leptosphaeria maculans, Hendersonia creberrima, Helminthosporium triticirepentis, Setosphaeria turcica, Drechslera glycines, Didymella bryoniae, Cycloconium
oleagineum, Corynespora cassiicola, Cochliobolus sativus, Bipolaris cactivora, Venturia inaequalis, Pyrenophora teres, Pyrenophora tritici-repentis, Alternaria alternata, Alternaria brassicicola, Alternaria solani and Alternaria tomatophila, Capnodiales such as Septoria tritici, Septoria nodorum, Septoria glycines, Cercospora arachidicola, Cercospora sojina, Cercospora zeae-maydis, Cercosporella capsellae and Cercosporella herpotrichoides, Cladosporium carpophilum, Cladosporium effusum, Passalora fulva, Cladosporium oxysporum, Dothistroma septosporum, Isariopsis clavispora,
Mycosphaerella fijiensis, Mycosphaerella graminicola, Mycovellosiella koepkeii, Phaeoisariopsis bataticola, Pseudocercospora vitis, Pseudocercosporella herpotrichoides, Ramularia beticola, Ramularia collo-cygni, Magnaporthales such as Gaeumannomyces graminis, Magnaporthe grisea, Pyricularia oryzae, Diaporthales such as Anisogramma anomala, Apiognomonia errabunda, Cytospora platani, Diaporthe phaseolorum, Discula destructiva, Gnomonia fructicola, Greeneria uvicola, Melanconium juglandinum, Phomopsis viticola, Sirococcus clavigignenti-juglandacearum, Tubakia dryina, Dicarpella spp. , Valsa ceratosperma, and others such as Actinothyrium graminis, Ascochyta pisi, Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Asperisporium caricae, Blumeriella jaapii, Candida spp. , Capnodium ramosum, Cephaloascus spp., Cephalosporium gramineum, Ceratocystis paradoxa, Chaetomium spp., Hymenoscyphus pseudoalbidus, Coccidioides spp., Cylindrosporium padi, Diplocarpon malae, Drepanopeziza campestris, Elsinoe ampelina, Epicoccum nigrum, Epidermophyton spp., Eutypa lata, Geotrichum candidum, Gibellina cerealis, Gloeocercospora sorghi, Gloeodes pomigena, Gloeosporium perennans; Gloeotinia temulenta, Griphospaeria corticola, Kabatiella lini, Leptographium microsporum, Leptosphaerulinia crassiasca, Lophodermium seditiosum, Marssonina graminicola, Microdochium nivale, Monilinia fructicola, Monographella albescens, Monosporascus cannonballus, Naemacyclus spp., Ophiostoma novo-ulmi, Paracoccidioides brasiliensis, Penicillium expansum, Pestalotia rhododendri, Petriellidium spp., Pezicula spp.,
Phialophora gregata, Phyllachora pomigena, Phymatotrichum omnivora, Physalospora abdita, Plectosporium tabacinum, Polyscytalum pustulans, Pseudopeziza medicaginis, Pyrenopeziza brassicae, Ramulispora sorghi, Rhabdocline pseudotsugae, Rhynchosporium secalis, Sacrocladium oryzae, Scedosporium spp., Schizothyrium pomi, Sclerotinia sclerotiorum, Sclerotinia minor,
Sclerotium spp., Typhula ishikariensis, Seimatosporium mariae, Lepteutypa cupressi, Septocyta ruborum, Sphaceloma perseae, Sporonema phacidioides, Stigmina palmivora, Tapesia yallundae, Taphrina bullata, Thielviopsis basicola, Trichoseptoria fructigena, Zygophiala jamaicensis; powdery mildew diseases for example those caused by Erysiphales such as Blumeria graminis, Erysiphe polygoni, Uncinula necator, Sphaerotheca fuligena, Podosphaera leucotricha, Podospaera macularis Golovinomyces cichoracearum, Leveillula taurica, Microsphaera diffusa, Oidiopsis gossypii,
Phyllactinia guttata and Oidium arachidis; molds for example those caused by Botryosphaeriales such as Dothiorella aromatica, Diplodia seriata, Guignardia bidwellii, Botrytis cinerea, Botryotinia allii, Botryotinia fabae, Fusicoccum amygdali, Lasiodiplodia theobromae, Macrophoma theicola,
Macrophomina phaseolina, Phyllosticta cucurbitacearum; anthracnoses for example those caused by Glommerelales such as Colletotrichum gloeosporioides, Colletotrichum lagenarium, Colletotrichum gossypii, Glomerella cingulata, and Colletotrichum graminicola; and wilts or blights for example those caused by Hypocreales such as Acremonium strictum, Claviceps purpurea, Fusarium culmorum, Fusarium graminearum, Fusarium virguliforme, Fusarium oxysporum, Fusarium subglutinans, Fusarium oxysporum f.sp. cubense, Gerlachia nivale, Gibberella fujikuroi, Gibberella zeae,
Gliocladium spp., Myrothecium verrucaria, Nectria ramulariae, Trichoderma viride, Trichothecium roseum, and Verticillium theobromae.
Basidiomycetes, including smuts for example those caused by Ustilaginales such as
Ustilaginoidea virens, Ustilago nuda, Ustilago tritici, Ustilago zeae, rusts for example those caused by Pucciniales such as Cerotelium fici, Chrysomyxa arctostaphyli, Coleosporium ipomoeae, Hemileia vastatrix, Puccinia arachidis, Puccinia cacabata, Puccinia graminis, Puccinia recondita, Puccinia sorghi, Puccinia hordei, Puccinia striiformis f.sp. Hordei, Puccinia striiformis f.sp. Secalis,
Pucciniastrum coryli, or Uredinales such as Cronartium ribicola, Gymnosporangium juniper!- viginianae, Melampsora medusae, Phakopsora pachyrhizi, Phragmidium mucronatum, Physopella ampelosidis, Tranzschelia discolor and Uromyces viciae-fabae; and other rots and diseases such as those caused by Cryptococcus spp., Exobasidium vexans, Marasmiellus inoderma, Mycena spp., Sphacelotheca reiliana, Typhula ishikariensis, Urocystis agropyri, Itersonilia perplexans, Corticium invisum, Laetisaria fuciformis, Waitea circinata, Rhizoctonia solani, Thanetephorus cucurmeris, Entyloma dahliae, Entylomella microspora, Neovossia moliniae and Tilletia caries.
Blastocladiomycetes, such as Physoderma maydis.
Mucoromycetes, such as Choanephora cucurbitarum.; Mucor spp.; Rhizopus arrhizus, As well as diseases caused by other species and genera closely related to those listed above. In addition to their fungicidal activity, the compounds and compositions comprising them may also have activity against bacteria such as Erwinia amylovora, Erwinia caratovora, Xanthomonas campestris, Pseudomonas syringae, Strptomyces scabies and other related species as well as certain protozoa.
Crops of useful plants in which the composition according to the invention can be used include perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass, St. Augustine grass and Zoysia grass; herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme; legumes for example beans, lentils, peas and soya beans; nuts for example almond, cashew, ground nut, hazelnut, peanut, pecan, pistachio and walnut; palms for example oil palm; ornamentals for example flowers, shrubs and trees; other trees, for example cacao, coconut, olive and rubber; vegetables for example asparagus, aubergine, broccoli, cabbage, carrot, cucumber, garlic, lettuce, marrow, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach and tomato; and vines for example grapes.
Crops are to be understood as being those which are naturally occurring, obtained by conventional methods of breeding, or obtained by genetic engineering. They include crops which contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
Crops are to be understood as also including those crops which have been rendered tolerant to herbicides like bromoxynil or classes of herbicides such as ALS-, EPSPS-, GS-, HPPD- and PPO- inhibitors. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer canola. Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.
Crops are also to be understood as being those which naturally are or have been rendered resistant to harmful insects. This includes plants transformed by the use of recombinant DNA techniques, for example, to be capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria. Examples of toxins which can be expressed include δ-endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonising nematodes, and toxins produced by scorpions, arachnids, wasps and fungi.
An example of a crop that has been modified to express the Bacillus thuringiensis toxin is the Bt maize KnockOut® (Syngenta Seeds). An example of a crop comprising more than one gene that codes for insecticidal resistance and thus expresses more than one toxin is VipCot® (Syngenta Seeds). Crops or seed material thereof can also be resistant to multiple types of pests (so-called stacked transgenic events when created by genetic modification). For example, a plant can have the ability to express an insecticidal protein while at the same time being herbicide tolerant, for example Herculex I® (Dow AgroSciences, Pioneer Hi-Bred International).
The compounds of formula (I) can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation.
Therefore the invention also relates to compositions for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula (I) and an inert carrier, and to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a composition, comprising a compound of formula (I) as active ingredient and an inert carrier, is applied to the plants, to parts thereof or the locus thereof.
To this end compounds of formula (I) and inert carriers are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
Suitable carriers and adjuvants (auxiliaries) can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.
A formulation, i.e. a composition comprising the compound of formula (I) and, if desired, a solid or liquid adjuvant, is prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface-active compounds (surfactants).
The agrochemical formulations will usually contain from 0.1 to 99% by weight, preferably from
0.1 to 95% by weight, of the compound of formula (I), 99.9 to 1 % by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.
Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations. Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 20g to 600g a.i./ha. When used as seed drenching agent, convenient rates of application are from 10mg to 1g of active substance per kg of seeds. The rate of application for the desired action can be determined by experiments. It depends for example on the type of action, the developmental stage of the useful plant, and on the application (location, timing, application method) and can, owing to these parameters, vary within wide limits.
Normally, in the management of a crop a grower would use one or more other agronomic chemicals in addition to the compound of the present invention. Examples of agronomic chemicals include insecticides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection, as well as plant nutrients and plant fertilizers.
Accordingly, the present invention provides a composition comprising a compound of formula (I) according to the present invention together with one or more pesticides, plant nutrients or plant fertilizers. The combination may also encompass specific plant traits incorporated into the plant using any means, for example conventional breeding or genetic modification. Such compositions may also contain one or more inert carriers as described above.
The invention also provides for the use of provides a composition comprising a compound of formula (I) according to the present invention together with one or more pesticides, plant nutrients, plant fertilizers, synergists, herbicides or plant growth regulators, where appropriate. The combination may also encompass specific plant traits incorporated into the plant using any means, for example conventional breeding or genetic modification.
Suitable examples of plant nutrients or plant fertilizers are calcium sulfate (CaS04), calcium nitrate (Ca(N03)2.4H20), calcium carbonate (CaC03), potassium nitrate (KN03), magnesium sulfate (MgS04), potassium hydrogen phosphate (KH2P04), manganese sulfate (MnS04), copper sulfate (CuS04), zinc sulfate (ZnS04), nickel chloride (NiCI2), cobalt sulfate (CoS04), potassium hydroxide (KOH), sodium chloride (NaCI), boric acid (H3B03) and metal salts thereof (Na2Mo04). The nutrients may be present in an amount of 5% to 50% by weight, preferably of 10% to 25% by weight or of 15% to 20% by weight each. Preferred additional nutrients are urea ((NH2)2CO), melamine (C3H6N6), potassium oxide (K20), and inorganic nitrates. The most preferred additional plant nutrient is potassium oxide. Where the preferred additional nutrient is urea, it is present in an amount of generally 1 % to 20% by weight, preferably 2% to 10% by weight or of 3% to 7% by weight.
Examples of suitable additional active ingredients include the following acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, anilide fungicides, antibiotic fungicides, aromatic fungicides, arsenical fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged diphenyl fungicides, carbamate fungicides, carbanilate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, , dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, organophosphorous fungicides, organotin fungicides, oxathiin fungicides, oxazole fungicides, phenylsulfamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, strobilurin fungicides, sulfonanilide fungicides, thiadiazole fungicides, thiazole fungicides, thiazolidine fungicides, thiocarbamate fungicides, thiophene fungicides, triazine fungicides, triazole fungicides,
triazolopyrimidine fungicides, urea fungicides, valinamide fungicides, and zinc fungicides.
Examples of suitable additional active ingredients also include the following: 3-difluoromethyl-1- methyl-1 H-pyrazole-4-carboxylic acid (9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano- naphthalen-5-yl)-amide , 3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid methoxy-[1-methyl- 2-(2,4,6-trichlorophenyl)-ethyl]-amide , 1-methyl-3-difluoromethyl-1 H-pyrazole-4-carboxylic acid (2- dichloromethylene-3-ethyl-1-methyl-indan-4-yl)-amide (1072957-71-1 ), 1-methyl-3-difluoromethyl-1 H- pyrazole-4-carboxylic acid (4'-methylsulfanyl-biphenyl-2-yl)-amide, 1-methyl-3-difluoromethyl-4H- pyrazole-4-carboxylic acid [2-(2,4-dichloro-phenyl)-2-methoxy-1-methyl-ethyl]-amide, (5-Chloro-2,4- dimethyl-pyridin-3-yl)-(2,3,4-trimethoxy-6-methyl-phenyl)-methanone, (5-Bromo-4-chloro-2-methoxy- pyridin-3-yl)-(2,3,4-trimethoxy-6-methyl-phenyl)-methanone, 2-{2-[(E)-3-(2,6-Dichloro-phenyl)-1- methyl-prop-2-en-(E)-ylideneaminooxymethyl]-phenyl}-2-[(Z)-methoxyimino]-N-methyl-acetamide, 3-[5- (4-Chloro-phenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine, (E)-N-methyl-2- [2- (2, 5- dimethylphenoxymethyl) phenyl]-2-methoxy-iminoacetamide, 4-bromo-2-cyano-N, N-dimethyl-6- trifluoromethylbenzimidazole-1-sulphonamide, a- [N-(3-chloro-2, 6-xylyl)-2-methoxyacetamido]-y- butyrolactone, 4-chloro-2-cyano-N, - dimethyl-5-p-tolylimidazole-1 -sulfonamide, N-allyl-4, 5,-dimethyl- 2-trimethylsilylthiophene-3-carboxamide, N- (l-cyano-1 , 2-dimethylpropyl)-2- (2, 4-dichlorophenoxy) propionamide, N- (2-methoxy-5-pyridyl)-cyclopropane carboxamide, (.+-.)-cis-1-(4-chlorophenyl)-2- (1 H-1 ,2,4-triazol-1-yl)-cycloheptanol, 2-(1-tert-butyl)-1-(2-chlorophenyl)-3-(1 ,2,4-triazol-1-yl)-propan-2- ol, 2',6'-dibromo-2-methyl-4-trifluoromethoxy-4'-trifluoromethyl-1 ,3-thiazole- 5-carboxanilide, 1- imidazolyl-1-(4'-chlorophenoxy)-3,3-dimethylbutan-2-one, methyl (E)-2-[2-[6-(2- cyanophenoxy)pyrimidin-4-yloxy]phenyl]3-methoxyacrylate, methyl (E)-2-[2-[6-(2- thioamidophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylat e, methyl (E)-2-[2-[6-(2- fluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2,6- difluorophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacryla te, methyl (E)-2-[2-[3-(pyrimidin-2- yloxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(5-methylpyrimidin-2-yloxy)- phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[3-(phenyl-sulphonyloxy)phenoxy]phenyl-3- methoxyacrylate, methyl (E)-2-[2-[3-(4-nitrophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2- [2-phenoxyphenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3,5-dimethyl-benzoyl)pyrrol-1-yl]-3- methoxyacrylate, methyl (E)-2-[2-(3-methoxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2[2-(2- phenylethen-1-yl)-phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3,5-dichlorophenoxy)pyridin-3-yl]-3- methoxyacrylate, methyl (E)-2-(2-(3-(1 , 1 ,2,2-tetrafluoroethoxy)phenoxy)phenyl)-3-methoxyacrylate, methyl (E)-2-(2-[3-(alpha-hydroxybenzyl)phenoxy]phenyl)-3-methoxyacrylate, methyl (E)-2-(2-(4- phenoxypyridin-2-yloxy)phenyl)-3-methoxyacrylate, methyl (E)-2-[2-(3-n-propyloxy-phenoxy)phenyl]3- methoxyacrylate, methyl (E)-2-[2-(3-isopropyloxyphenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2- [3-(2-fluorophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(3-ethoxyphenoxy)phenyl]-3- methoxyacrylate, methyl (E)-2-[2-(4-tert-butyl-pyridin-2-yloxy)phenyl]-3-methoxyacrylate, methyl (E)-2- [2-[3-(3-cyanophenoxy)phenoxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[(3-methyl-pyridin-2- yloxymethyl)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2-methyl-phenoxy)pyrimidin-4- yloxy]phenyl]-3-methoxyacrylate, methyl (E)-2-[2-(5-bromo-pyridin-2-yloxymethyl)phenyl]-3- methoxyacrylate, methyl (E)-2-[2-(3-(3-iodopyridin-2-yloxy)phenoxy)phenyl]-3-methoxyacrylate, methyl (E)-2-[2-[6-(2-chloropyridin-3-yloxy)pyrimidin-4-yloxy]phenyl]-3-methoxyac rylate, methyl (E),(E)-2-[2- (5,6-dimethylpyrazin-2-ylmethyloximinomethyl)phenyl]-3-methox yacrylate, methyl (E)-2-{2-[6-(6- methylpyridin-2-yloxy)pyrimidin-4-yloxy]phenyl}-3-methoxy-a crylate, methyl (E),(E)-2-{ 2-(3- methoxyphenyl)methyloximinomethyl]-phenyl}-3-methoxyacrylate, methyl (E)-2-{2-(6-(2- azidophenoxy)-pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate, methyl (E),(E)-2-{2-[6-phenylpyrimidin-4- yl)-methyloximinomethyl]phenyl}-3-methox yacrylate, methyl (E),(E)-2-{2-[(4-chlorophenyl)- methyloximinomethyl]-phenyl}-3-methoxyacryl ate, methyl (E)-2-{2-[6-(2-n-propylphenoxy)-1 ,3,5- triazin-4-yloxy]phenyl}-3-methoxyacr ylate, methyl (E),(E)-2-{2-[(3- nitrophenyl)methyloximinomethyl]phenyl}-3-methoxyacrylate, 3-chloro-7-(2-aza-2,7,7-trimethyl-oct-3- en-5-ine), 2,6-dichloro-N-(4-trifluoromethylbenzyl)-benzamide, 3-iodo-2-propinyl alcohol, 4- chlorophenyl-3-iodopropargyl formal, 3-bromo-2,3-diiodo-2-propenyl ethylcarbamate, 2,3,3-triiodoallyl alcohol, 3-bromo-2,3-diiodo-2-propenyl alcohol, 3-iodo-2-propinyl n-butylcarbamate, 3-iodo-2-propinyl n-hexylcarbamate, 3-iodo-2-propinyl cyclohexyl-carbamate, 3-iodo-2-propinyl phenylcarbamate;
phenol derivatives, such as tribromophenol, tetrachlorophenol, 3-methyl-4-chlorophenol, 3,5-dimethyl- 4-chlorophenol, phenoxyethanol, dichlorophene, o-phenylphenol, m-phenylphenol, p-phenylphenol, 2- benzyl-4-chlorophenol, 5-hydroxy-2(5H)-furanone; 4,5-dichlorodithiazolinone, 4,5-benzodithiazolinone, 4,5-trimethylenedithiazolinone, 4,5-dichloro-(3H)-1 ,2-dithiol-3-one, 3,5-dimethyl-tetrahydro-1 ,3,5- thiadiazine-2-thione, N-(2-p-chlorobenzoylethyl)-hexaminium chloride, acibenzolar, acypetacs, alanycarb, albendazole, aldimorph, allicin, allyl alcohol, ametoctradin, amisulbrom, amobam, ampropylfos, anilazine, asomate, aureofungin, azaconazole, azafendin, azithiram, azoxystrobin, barium polysulfide, benalaxyl, benalaxyl-M, benodanil, benomyl, benquinox, bentaluron,
benthiavalicarb, benthiazole, benzalkonium chloride, benzamacril, benzamorf, benzohydroxamic acid, berberine, bethoxazin, biloxazol, binapacryl, biphenyl, bitertanol, bithionol, bixafen, blasticidin-S, boscalid, bromothalonil, bromuconazole, bupirimate, buthiobate, butylamine calcium polysulfide, captafol, captan, carbamorph, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chitosan, chlobenthiazone, chloraniformethan, chloranil, chlorfenazole, chloroneb, chloropicrin, chlorothalonil, chlorozolinate, chlozolinate, climbazole, clotrimazole, clozylacon, copper containing compounds such as copper acetate, copper carbonate, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper oxyquinolate, copper silicate, copper sulphate, copper tallate, copper zinc chromate and Bordeaux mixture, cresol, cufraneb, cuprobam, cuprous oxide, cyazofamid, cyclafuramid, cycloheximide, cyflufenamid, cymoxanil, cypendazole, cyproconazole, cyprodinil, dazomet, debacarb, decafentin, dehydroacetic acid, di-2-pyridyl disulphide 1 , 1 '-dioxide, dichlofluanid, diclomezine, dichlone, dicloran, dichlorophen, dichlozoline, diclobutrazol, diclocymet, diethofencarb, difenoconazole, difenzoquat, diflumetorim, O, O-di-iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetachlone, dimetconazole, dimethomorph, dimethirimol, diniconazole, diniconazole-M, dinobuton, dinocap, dinocton, dinopenton, dinosulfon, dinoterbon, diphenylamine, dipyrithione, disulfiram, ditalimfos, dithianon, dithioether, dodecyl dimethyl ammonium chloride, dodemorph, dodicin, dodine, doguadine, drazoxolon, edifenphos, enestroburin, epoxiconazole, etaconazole, etem, ethaboxam, ethirimol, ethoxyquin, ethilicin, ethyl (Z)-N-benzyl-N ([methyl (methyl-thioethylideneamino- oxycarbonyl) amino] Νιίο)-β- alaninate, etridiazole, famoxadone, fenamidone, fenaminosulf, fenapanil, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, flupicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutanil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fuberidazole, furalaxyl, furametpyr, furcarbanil, furconazole, furfural, furmecyclox, furophanate, glyodin, griseofulvin, guazatine, halacrinate, hexa chlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexylthiofos, hydrargaphen, hydroxyisoxazole, hymexazole, imazalil, imazalil sulphate,
imibenconazole, iminoctadine, iminoctadine triacetate, inezin, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isopropanyl butyl carbamate, isoprothiolane, isopyrazam, isotianil, isovaledione, izopamfos, kasugamycin, kresoxim-methyl, LY186054, LY21 1795, LY248908, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid, mefenoxam, mepanipyrim, mepronil, mercuric chloride, mercurous chloride, meptyldinocap, metalaxyl, metalaxyl-M, metam, metazoxolon, metconazole, methasulfocarb, methfuroxam, methyl bromide, methyl iodide, methyl isothiocyanate, metiram, metiram-zinc, metominostrobin, metrafenone, metsulfovax, milneb, moroxydine, myclobutanil, myclozolin, nabam, natamycin, neoasozin, nickel dimethyldithiocarbamate, nitrostyrene, nitrothal-iso- propyl, nuarimol, octhilinone, ofurace, organomercury compounds, orysastrobin, osthol, oxadixyl, oxasulfuron, oxine-copper, oxolinic acid, oxpoconazole, oxycarboxin, parinol, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, penthiopyrad, phenamacril, phenazin oxide, phosdiphen, phosetyl-AI, phosphorus acids, phthalide, picoxystrobin, piperalin, polycarbamate, polyoxin D, polyoxrim, polyram, probenazole, prochloraz, procymidone, propamidine, propamocarb, propiconazole, propineb, propionic acid, proquinazid, prothiocarb, prothioconazole, pyracarbolid, pyraclostrobin, pyrametrostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyroxychlor, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinacetol, quinazamid, quinconazole, quinomethionate, quinoxyfen, quintozene, rabenzazole, santonin, sedaxane, silthiofam, simeconazole, sipconazole, sodium pentachlorophenate, solatenol, spiroxamine, streptomycin, sulphur, sultropen, tebuconazole, tebfloquin, tecloftalam, tecnazene, tecoram, tetraconazole, thiabendazole, thiadifluor, thicyofen, thifluzamide, 2- (thiocyanomethylthio) benzothiazole, thiophanate-methyl, thioquinox, thiram, tiadinil, timibenconazole, tioxymid, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triamiphos, triarimol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumazole, triforine, triflumizole, triticonazole, uniconazole, urbacide, validamycin, valifenalate, vapam, vinclozolin, zarilamid, zineb, ziram, and zoxamide. The compounds of the invention may also be used in combination with anthelmintic agents. Such anthelmintic agents include, compounds selected from the macrocyclic lactone class of compounds such as ivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, moxidectin, nemadectin and milbemycin derivatives as described in EP- 357460, EP- 444964 and EP-594291. Additional anthelmintic agents include semisynthetic and biosynthetic avermectin/milbemycin derivatives such as those described in US-5015630, WO-9415944 and WO- 9522552. Additional anthelmintic agents include the benzimidazoles such as albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, and other members of the class. Additional anthelmintic agents include imidazothiazoles and tetrahydropyrimidines such as tetramisole, levamisole, pyrantel pamoate, oxantel or morantel.
Additional anthelmintic agents include flukicides, such as triclabendazole and clorsulon and the cestocides, such as praziquantel and epsiprantel.
The compounds of the invention may be used in combination with derivatives and analogues of the paraherquamide/marcfortine class of anthelmintic agents, as well as the antiparasitic oxazolines such as those disclosed in US-5478855, US- 4639771 and DE-19520936.
The compounds of the invention may be used in combination with derivatives and analogues of the general class of dioxomorpholine antiparasitic agents as described in WO-9615121 and also with anthelmintic active cyclic depsipeptides such as those described in WO-961 1945, WO-9319053, WO- 9325543, EP-626375, EP-382173, WO-9419334, EP-382173, and EP-503538.
The compounds of the invention may be used in combination with other ectoparasiticides; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as lufenuron;
ecdysone agonists such as tebufenozide and the like; neonicotinoids such as imidacloprid and the like.
The compounds of the invention may be used in combination with terpene alkaloids, for example those described in International Patent Application Publication Numbers W095/19363 or WO04/72086, particularly the compounds disclosed therein.
Other examples of such biologically active compounds that the compounds of the invention may be used in combination with include but are not restricted to the following:
Organophosphates: acephate, azamethiphos, azinphos-ethyl, azinphos- methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl, demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos, fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate, isoxathion, malathion, methacriphos, methamidophos, methidathion, methyl- parathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, paraoxon, parathion, parathion-methyl, phenthoate, phosalone, phosfolan, phosphocarb, phosmet, phosphamidon, phorate, phoxim, pirimiphos, pirimiphos- methyl, profenofos, propaphos, proetamphos, prothiofos, pyraclofos, pyridapenthion, quinalphos, sulprophos, temephos, terbufos, tebupirimfos, tetrachlorvinphos, thimeton, triazophos, trichlorfon, vamidothion. Carbamates: alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb, fenoxycarb, fenthiocarb, furathiocarb, HCN-801 , isoprocarb, indoxacarb, methiocarb, methomyl, 5-methyl-m-cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, UC-51717.
Pyrethroids: acrinathin, allethrin, alphametrin, 5-benzyl-3-furylmethyl (E) -
(1 R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate, bifenthrin, beta -cyfluthrin, cyfluthrin, a-cypermethrin, beta -cypermethrin, bioallethrin, bioallethrin((S)- cyclopentylisomer), bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin, cythithrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, ethofenprox, fenfluthrin, fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (D isomer), imiprothrin, cyhalothrin, lambda- cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrins (natural products), resmethrin, tetramethrin, transfluthrin, theta-cypermethrin, silafluofen, t-fluvalinate, tefluthrin, tralomethrin, Zeta-cypermethrin.
Arthropod growth regulators: a) chitin synthesis inhibitors: benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, buprofezin, diofenolan, hexythiazox, etoxazole, chlorfentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide, tebufenozide; c) juvenoids: pyriproxyfen, methoprene (including S-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors: spirodiclofen.
Other antiparasitics: acequinocyl, amitraz, AKD-1022, ANS-1 18, azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl, bromopropylate, BTG-504, BTG-505, camphechlor, cartap, chlorobenzilate, chlordimeform, chlorfenapyr, chromafenozide, clothianidine, cyromazine, diacloden, diafenthiuron, DBI-3204, dinactin, dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan, ethiprole, ethofenprox, fenazaquin, flumite, MTI- 800, fenpyroximate, fluacrypyrim, flubenzimine, flubrocythrinate, flufenzine, flufenprox, fluproxyfen, halofenprox, hydramethylnon, IKI-220, kanemite, NC-196, neem guard, nidinorterfuran, nitenpyram, SD-35651 , WL-108477, pirydaryl, propargite, protrifenbute, pymethrozine, pyridaben, pyrimidifen, NC-1 1 1 1 , R- 195,RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601 , silafluofen, silomadine, spinosad, tebufenpyrad, tetradifon, tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate, triethoxyspinosyn, trinactin, verbutin, vertalec, YI-5301.
Biological agents: Bacillus thuringiensis ssp aizawai, kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenic bacteria, virus and fungi.
Bactericides: chlortetracycline, oxytetracycline, streptomycin.
Other biological agents: enrofloxacin, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, carprofen, metaflumizone, praziquarantel,
thiabendazole.
Another aspect of invention is related to the use of a compound of formula I or of a preferred individual compound as above-defined, of a composition comprising at least one compound of formula I or at least one preferred individual compound as above-defined, or of a fungicidal or insecticidal mixture comprising at least one compound of formula I or at least one preferred individual compound as above-defined, in admixture with other fungicides or insecticides as described above, for controlling or preventing infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non-living materials by insects or by phytopathogenic microorganisms, preferably fungal organisms.
A further aspect of invention is related to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or of non-living materials by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, which comprises the application of a compound of formula I or of a preferred individual compound as above- defined as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the non-living materials.
Controlling or preventing means reducing infestation by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated.
A preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, or insects which comprises the application of a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen or insect. However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.
A formulation, e.g. a composition containing the compound of formula I, and, if desired, a solid or liquid adjuvant or monomers for encapsulating the compound of formula I, may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface active compounds (surfactants).
Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 20g to 600g a.i./ha. When used as seed drenching agent, convenient dosages are from 10mg to 1g of active substance per kg of seeds.
When the combinations of the present invention are used for treating seed, rates of 0.001 to 50 g of a compound of formula I per kg of seed, preferably from 0.01 to 10g per kg of seed are generally sufficient.
The compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.
Such compositions may be produced in conventional manner, e.g. by mixing the active ingredients with appropriate formulation inerts (diluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects). Also conventional slow release formulations may be employed where long lasting efficacy is intended. Particularly formulations to be applied in spraying forms, such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain surfactants such as wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g. the ondensation product of formaldehyde with naphthalene sulphonate, an alkylarylsulphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol.
A seed dressing formulation is applied in a manner known per se to the seeds employing the combination of the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds. Such seed dressing formulations are known in the art. Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g. as slow release capsules or microcapsules.
In general, the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula I together with component (B) and (C), and optionally other active agents, particularly microbiocides or conservatives or the like.
Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent. Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations.
Compounds of formula (I), as well as the intermediates and reagents used, can be prepared by methods known to a skilled chemist in a variety of ways, or they are commercially available.
Additionally, compounds of formula (I), as well as the intermediates and reagents used, can be prepared in analogous fashion by the methods and the synthetic procedures & schemes described in WO08101682 and/or WO2012146125.
Scheme 1a: Compounds of formula (I) can be prepared by known methods from an amino compound of formula (II), wherein R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R is hydrogen, C02tBu or Ac, and a formamide HC(=0)-N(R )(R2) of formula (III), wherein R and R2 are as defined for a compound of formula (I), via treatment of a compound of formula (III) with an activating reagent, such as POCI3, PCI3, COCI2, PhS02CI, Me2NS02CI, (CF3CO)20 or (MeO)2S02 and then introducing the compound of formula (II).
Scheme 1 b: Compounds of formula (I) can be prepared by known methods from reacting an amino derivative of formula (IV), wherein R3, R4, R5, R6, R7 and R8 are as defined for a compound of formula (I) and R' is defined as hydrogen or C02tBu, with an orthoamide HC(ORz)2-N(R )(R2) of formula (V), wherein R-i and R2 are as defined for a compound of formula (I) and Rz is alkyl, in the presence of an acid.
Figure imgf000047_0001
Scheme 2: A compound of formula (la), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R5a is selected from aryl, heteroaryl, carbocyclic, heterocylic, alkyl, alkenyl or alkynyl groups, can be obtained from a compound of formula (VI), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and X is selected from CI, Br or I, via reaction with a nucleophile of formula (VII), wherein R5a is as defined for a compound of formula (la) and Y is a metal or metalloid group (e.g. tri-alkylstannane, boronic acid or boronic ester), via a metal- catalyzed cross-coupling reaction using a Cu or Pd metal complex at elevated temperatures.
Scheme 2
Figure imgf000047_0002
Scheme 3: A compound of formula (lb), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R5b is selected from aryl, heteroaryl, carbocyclic, heterocylic, alkyl, alkenyl or alkynyl groups, can be obtained from a compound of formula (VIII), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and Y is a metal or metalloid group (e.g. tri- alkylstannane, tri-alkylsilylane, boronic acid, boronic ester or trifluoroborate) via cross-coupling reaction with a compound of formula (IX), wherein R5b is as defined for a compound of formula (lb) and X is selected from CI, Br or I, using metal-catalyzed conditions featuring a Cu or Pd metal complex at elevated temperatures. Scheme 3
Figure imgf000048_0001
Scheme 4: A compound of formula (lc), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R5c is selected from aryl, heteroaryl, carbocyclic, heterocylic or alkyl groups, can be obtained from a compound of formula (VI), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and X is selected from CI, Br or I, via reaction with a nucleophile of formula (X), wherein R5c is as defined for a compound of formula (lc) and Q is a heteroatom (e.g. oxygen, nitrogen or sulfur), using methods that feature a metal (e.g. palladium) catalyst, base, and elevated temperatures.
Figure imgf000048_0002
Scheme 5: A compound of formula (Id), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R5d is selected from aryl, heteroaryl, carbocyclic, heterocylic, alkyl, alkenyl or alkynyl groups, can be obtained from a compound of formula (VI), wherein R , R2, R3, R4, R6, R7 and R8 are as defined herein for a compound of formula (I) and X' is selected from CI, Br, I, boronic ester or tri-alkylstannane, via treatment with an organometallic reagent (e.g. alkyllithium or alkymagnesium) so as to perform a metal halogen exchange or trans-metalation followed by the introduction of an electrophile of formula (XI), wherein R5d is as defined for a compound of formula (I) and T is an aldehyde or activated carboxylic acid derivative (i.e. acyl chloride, ester, acid anhydride or carboxamide).
Scheme 5
Figure imgf000048_0003
Scheme 6: A compound of formula (le), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R5ea is selected from aryl, heteroaryl, carbocyclic, heterocylic or alkyl groups and R5eb is selected from hydrogen or alkyl, can be obtained from a compound of formula (VI), wherein R , R2, R3, R4, R6, R7 and R8 are as defined herein for a compound of formula (I) and X" is a halogen (e.g. CI, Br, or I), via reaction with an alkene of formula (XII), wherein R5ea and R5eb are as defined for a compound of formula (le), using well known Heck reaction conditions in the presence of a palladium catalyst, base, and elevated temperatures.
Figure imgf000049_0001
(le)
Scheme 7: A compound of formula (If), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R5f is selected from a fully or partially saturated group (i.e. carbocyclic, heterocylic, alkyl or alkenyl groups), can be obtained from a compound of formula (XIII), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R5fa is a partially or fully unsaturated group (i.e. carbonyl, benzyloxy, alkynyl, alkeny, cycloalkenyl or heterocyclic) via reaction with a reductant; preferably done with a supported catalyst (eg. Pt, Pd, Rh-metal), molecular hydrogen, and a suitable solvent at ambient or elevated temperatures.
Figure imgf000049_0002
Scheme 8: A compound of formula (Ig), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R5g is selected from aryl, heteroaryl, carbocyclic, heterocylic, alkyl, alkenyl or alkynyl groups, can be obtained from a compound of formula (XIV), wherein R , R2, R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and T' is selected from CH2OH or CH(alkyl)OH, and a compound of formula (XV), wherein R5g is as defined for a compound of formula (Ig) and X'" is selected from CI, Br, I, boronic acid, boronic ester, or trialkylstannane via base promoted substitution reactions or metal-catalyzed coupling reaction using a Pd metal complex, prefereably at elevated temperatures.
Scheme 8
Figure imgf000049_0003
(ig)
Scheme 9: A compound of formula (IV), that is a compound of formula (IV) wherein R'is Hydrogen or Ac, can be prepared from a compound of formula (XVI), wherein R5, R6, R7, and R8 are as defined for a compound of formula (IV), and an N-acyl amino ketone of formula (XVII), wherein R3 is as defined herein for a compound of formula (I), via heating in the presence of base in aquous media followed by acidification and additional heating. Compounds of formula (XVI) are known to be commercially available or can be made by known methods from known compounds. For examples, see: Wang, S. H. et al Med. Chem. Res. (2014), 23, 2161-2168
Scheme 9
Figure imgf000050_0001
(IV)
Scheme 10: A compound of formula (II), wherein R3, R4, R5, R6, R7 and R8 are as defined for a compound of formula (I) and R is Hydrogen or C02tBu, can be prepared from a compound of formula (XVIII), wherein R3, R4, R5, R6, R7 and R8 are as defined herein for a compound of formula (I), using any one of the numerous conditions described in the literature for the Curtius rearrangement involving Ph203PN3. Compounds of formula (XVIII) are known or are commercially available.
(II)
Figure imgf000050_0002
Schemel 1 : A compound of formula (XIX), wherein R3, R4, R6, R7 and R8 are as defined for a compound of formula (I) and R is Hydrogen or C02tBu and X' is is selected from CI, Br, or I can be prepared from a compound of formula (XVIN'), wherein R3, R4, R6, R7 and R8 are as defined herein for a compound of formula (I) and X' is is selected from CI, Br, or I using any one of the numerous conditions described in the literature for the Curtius rearrangement involving Ph203PN3. Compounds of formula (XVIII') are known or are commercially available
Figure imgf000050_0003
Scheme 12: A compound of formula (ΧΙΧ'), wherein R3, R4, R6, R7 and R8 are as defined for a compound of formula (I), R is defined as hydrogen or C02tBu and X'" is CN, CH2OH, CHO, C(0)Me, C02Me, C02Et, or a metal or metalloid (i.e. boronic ester, boronic acid, tri-alkylstannane), can be prepared from a compound of formula (XIX), wherein R3, R4, R6, R7 and R8 are as defined for a compound of formula (I), and X' is selected from CI, Br, or I, via treatment with an organometallic reagent (e.g. alkyllithium or alkymagnesium) followed by the introduction of an electrophile, such as an aldehyde, or an activated carboxylic acid derivative (i.e. acyl chloride, ester, acid anhydride or carboxamide), or via introduction of a Pd catalyst and a organometal or organometaloid (i.e. boronic ester, tri-alkylstannane chloride, or CuCN).
Figure imgf000051_0001
Scheme 13a: A compound of formula (XX) can be prepared from an amino compound of formula (XIX"), wherein R3, R4, R6, R7 and R8 are as defined for a compound of formula (I), X" is CI, Br, I, CN, CH2OH, CHO, C(0)Me, C02Me, C02Et, or a metal or metalloid (i.e. boronic ester, boronic acid, tri-alkylstannane) and R is defined as hydrogen, or C02tBu, via treatment of a formamide HC(=0)-N(R )(R2) of formula (III) with an activating reagent, such as POCI3, PCI3, COCI2, PhS02CI, Me2NS02CI, (CF3CO)20 or (MeO)2S02and then introducing a compound of formula (XIX").
Scheme 13b: A compound of formula (XX) can be prepared from an amino compound of formula (XIX"), wherein R3, R4, R6, R7 and R8 are as defined for a compound of formula (I), X" is CI, Br, I, CN, CH2OH, CHO, C(0)Me, C02Me, C02Et, or a metal or metalloid (i.e. boronic ester, boronic acid, tri-alkylstannane) and R is defined as hydrogen or C02tBu via a reaction with an orthoamide HC(ORz)2-N(R )(R2) of formula (V), wherein R-i and R2 are as defined for a compound of formula (I) and Rz is alkyl, in the presence of an acid.
A compound of formula (XIX") is selected from a compound of formula (XIX) or compound of formula (ΧΙΧ').
Figure imgf000051_0002
EXAMPLES
The following non-limiting Examples illustrate the above-described invention in greater detail without limiting it. Those skilled in the art will promptly recognise appropriate variations from the procedures both as to reactants and as to reaction conditions and techniques. All references mentioned herein are incorporated by reference in their entirety. The compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples, using lower application rates if necessary, for example 50 ppm, 12.5 ppm, 6 ppm, 3 ppm, 1.5 ppm or 0.8 ppm or 0.2 ppm.
Formulation Examples
Wettable powders a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % sodium lignosulfonate 5 % 5 %
sodium lauryl sulfate 3 % - 5 % sodium diisobutylnaphthalenesulfonate - 6 % 10 % phenol polyethylene glycol ether - 2 %
(7-8 mol of ethylene oxide)
highly dispersed silicic acid 5 % 10 % 10 %
Kaolin 62 % 27 %
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
Powders for drv seed treatment a) b) c) active ingredient [compound of formula (1)] 25 % 50 % 75 % light mineral oil 5 % 5 % 5 % highly dispersed silicic acid 5 % 5 % -
Kaolin 65 % 40 % -
Talcum - 20
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
Emulsifiable concentrate
active ingredient [compound of formula (I)] 10 %
octylphenol polyethylene glycol ether 3 %
(4-5 mol of ethylene oxide)
calcium dodecylbenzenesulfonate 3 %
castor oil polyglycol ether (35 mol of ethylene oxide) 4 %
Cyclohexanone 30 %
xylene mixture 50 %
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water. Dusts a) b) c)
Active ingredient [compound of formula (I)] 5 % 6 % 4 % talcum 95 %
Kaolin - 94 %
mineral filler - - 96 %
Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.
Extruder granules
Active ingredient [compound of formula (I)] 15 %
sodium lignosulfonate 2 %
carboxymethylcellulose 1 %
Kaolin 82 %
The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
Coated granules
Active ingredient [compound of formula (I)] 8 %
polyethylene glycol (mol. wt. 200) 3 %
Kaolin 89 %
The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner. Suspension concentrate
active ingredient [compound of formula (I)] 40 %
propylene glycol 10 %
nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 %
Sodium lignosulfonate 10 %
carboxymethylcellulose 1 %
silicone oil (in the form of a 75 % emulsion in water) 1 %
Water 32 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
Flowable concentrate for seed treatment
active ingredient [compound of formula (I)] 40 %
propylene glycol 5 %
copolymer butanol PO/EO 2 % tristyrenephenole with 10-20 moles EO 2 %
1 ,2-benzisothiazolin-3-one (in the form of a 20% solution in water) 0.5 %
monoazo-pigment calcium salt 5 %
Silicone oil (in the form of a 75 % emulsion in water) 0.2 %
Water 45.3 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
Slow Release Capsule Suspension
28 parts of a combination of the compound of formula I are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8: 1 ). This mixture is emulsified in a mixture of 1 .2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51 .6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1 ,6- diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns.
The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
Synthetic Examples
Using techniques described above together with further techniques known to the person skilled in the art, for example as found in WO 08/101682 (pp.22-33), compounds of formula (I) may be prepared.
Preparation of (E)-N-ethyl-N-methyl-N'-[8-[hvdroxy(phenyl)methyll-2-methyl-3-quinolyll- formamidine
Figure imgf000054_0001
(E)-N-Ethyl-N-methyl-N'-(8-bromo-2-methyl-3-quinolyl)-formamidine (0.30 g) in THF (7 mL) was added dropwise at -78°C to a solution of n-butyllithium (0.61 mL, 1.6M solution in hexanes) in THF (10 mL). After 15 minutes at -78°C, benzaldehyde (0.13 g) was added and the reaction mixture was stirred for a further 10 minutes at -78°C then warmed to room temperature. After 10 minutes the reaction mixture was cooled to -5°C and a solution of ammonium chloride (3 mL, 20% in water) was added. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phases were dried over magnesium sulfate, filtered, concentrated and purified by chromatography (silica gel, heptane/ethyl acetate gradient 0-100%) to give the title compound as yellow oil.
H NMR (400 MHz, CDCI3): δ 8.00 (broad s, 1 H), 7.60 (m, 4H), 7.30 (m, 6H), 6.32 (s, 1 H), 3.40 (m, 2H), 3.10 (s, 3H), 2.72 (s, 3H), 1.30 (t, 3H);
Preparation of (E)-N-ethyl-N-methyl-N'-[8-[(E)-3-methoxyprop-1-enyll-2-methyl-3-quinolyll- formamidine
Figure imgf000055_0001
3-Methoxyprop-1-ene (0.25 g), palladium actetate (0.1 1 g), tris(o-tolyl)phosphine (0.29 g,) and triethylamine (0.18 g) were added to a solution of (E)-N-ethyl-N-methyl-N'-(8-bromo-2-methyl-3- quinolyl)-formamidine (0.36 g) in acetonitrile (4 mL) and stirred for 16h at 65°C. The reaction mixture was then diluted with ethyl acetate, filtered, washed with water and brine, dried over magnesium sulfate, concentrated and purified by combiflash column chromatography (silica gel, heptane/ethyl acetate gradient 0-100%) to give the title compound as yellow oil.
H NMR (400 MHz, CDCI3): δ 7.98 (d, 1 H), 7.76 (d, 1 H), 7.60 (m, 3H), 7.39 (t, 1 H), 6.60 (m, 1 H),
4.31 (d, 2H), 3.42 (m, 1 H), 3.48 (s, 3H), 3.38 (m, 1 H), 3.10 (s, 3H), 2.75 (s, 3H), 1.3 (m, 3H);
Preparation of (E)-N-ethyl-N-methyl-N'-[8-(3-methoxypropyl)-2-methyl-3-quinolyll-formamidine
Figure imgf000055_0002
N-Ethyl-N-methyl-N'-[8-[(E)-3-methoxyprop-1-enyl]-2-methyl-3-quinolyl]-formamidine (0.17g) was dissolved in methanol (3 mL) and hydrogenated using an H-Cube® continuous-flow hydrogenation reactor via passage at 55°C with a flow of 1 mL minute and a pressure of 20 bar through a CatCarts® cartridge loaded with palladium 10% on carbon (0.02 g). The tubes were washed with methanol and the combined fractions were concentrated and the residue was purified by combiflash column chromatography (silica gel, heptane/ethyl acetate gradient 0-100%) to give the title compound as light yellow oil.
H NMR (400 MHz, CDCI3): δ 7.54 (broad s, 1 H), 7.49 (d, 1 H), 7.36 (d, 1 H), 7.29 (t, 1 H), 7.26 (s, 1 H), 3.47 (m, 8H), 3.05 (s, 3H), 2.68 (s, 3H), 2.09 (m, 2H), 1.25 (m, 3H);
Preparation of (E)-N'-(8-benzyl-2-methyl-3-quinolyl)-N-ethyl-N-methyl-formamidine
Figure imgf000056_0001
To a solution of 9-methoxy-9-borabicyclo[3.3.1]nonane (0.47 mL) in THF (1 M, 0.90 mL) at -78°C was added under inert atmosphere (Ar) a 2M solution of benzylmagnesium chloride (0.23 mL) in THF over 10 min. The reaction mixture was allowed to warm to the rt and stirred for 30 min. The reaction mixture was then diluted with DMF (3.5 mL) and degassed by 2 freeze-thaw cycles. (E)-N- Ethyl-N-methyl-N'-(8-bromo-2-methyl-3-quinolyl)-formamidine (0.14 g), palladium acetate (0.01 g), and S-Phos (0.04 g) were added and the reaction mixture was stirred at 1 10°C for 4h. The reaction mixture was cooled to room temperature and poured onto ethylacetate and water. The organic phase was washed with brine, dried over anhydrous Na2S04 and filtered. The solvent was removed in vacuo to give a yellow solid, which was purified by combiflash column chromatography (silica gel, heptane/ethyl acetate gradient 0-60%). Suitable fractions were collected and concentrated in vacuo to give the title compound as a yellow solid.
H NMR (400 MHz, CDCI3): δ 7.44 (broad s, 1 H), 7.40 (m, 1 H), 7.25 (m, 2H), 7.17 (m, 6H), 4.57 (s, 2H), 3.35 (m, 2H), 2.95 (broad s, 3H), 2.64 (s, 3H), 1.14 (t, 3H);
Preparation of tert-butyl N-(8-bromo-2-methyl-3-quinolyl)carbamate
Figure imgf000056_0002
To a solution of 8-bromo-2-methyl-quinoline-3-carboxylic acid (7.0 g) in anhydrous t-butanol (25 mL) under inert atmosphere (Ar), was added triethylamine (1 1.4 mL) and the reaction mixture was stirred at 20°C for 30 min. To the reaction mixture was then added [azido(phenoxy)phosphoryl]- oxybenzene (7.4 mL) and stirred at 80°C for 3h. The reaction mixture was cooled to rt and poured onto a sodium carbonate saturated solution and stirred for 30min. The aqueous layer was extracted with ethyl acetate and the organic phase was washed with water and brine, dried over anhydrous sodium sulfate, and filtered. The solvent was removed in vacuo to give a brown solid, which was purified by combiflash column chromatography (silica gel, heptane/ethyl acetate gradient 0-100%). Suitable fractions were collected and concentrated in vacuo to give the title compound as a yellowish solid.
H NMR (400 MHz, CDCI3): δ 8.75 (broad s, 1 H), 7.92 (d, 1 H), 7.74 (d, 1 H), 7.33 (m, 1 H), 6.61 (broad s, 1 H), 2.80 (s, 3H), 1 .60 (s, 9H);
Preparation of tert-butyl N-(2-methyl-8-phenethyl-3-quinolyl)carbamate
Figure imgf000057_0001
To a solution of 9-methoxy-9-borabicyclo[3.3.1 ]nonane (1.42 mL) in THF (1 M, 2.0 mL) at -78°C was added under inert atmosphere (Ar) a 2M solution of bromo(phenethyl)magnesium (5.1 mL) in THF over 10 min. The reaction mixture was allowed to warm up to the rt and stirred at this temperature for 30min. The reaction mixture was then diluted with DMF (9 mL) and degassed by 2 freeze-thaw cycles. tert-Butyl N-(8-bromo-2-methyl-3-quinolyl)carbamate (0.40 g) palladium acetate (0.03 g) and S-Phos (0.10 g) were added and the reaction mixture was stirred at 1 10°C for 6h. The reaction mixture was cooled to room temperature and poured onto ethyl acetate and water. The organic phase was washed with brine, dried over anhydrous Na2S04, and filtered. The solvent was removed in vacuo to give a yellow solid, which was purified by combiflash column chromatography (silica gel, heptane/ethyl acetate gradient 0-30%). Fractions containing the pure compound were collected and concentrated in vacuo to give the title compound as an amorphous solid.
H NMR (400 MHz, CD3OD): δ 8.23 (broad s, 1 H), 7.52 (m, 1 H), 7.25 (m, 8H), 3.46 (m, 2H), 3.04 (m, 2H), 2.69 (s, 3H), 1.55 (s, 9H);
Preparation of 2-methyl-8-phenethyl-quinolin-3-amine hydrochloride
Figure imgf000057_0002
To a solution of tert-butyl N-(2-methyl-8-phenethyl-3-quinolyl)carbamate (0.10 g) in methanol (1.0 mL) was added 4M HCI in dioxane (0.67 mL). The resulting reaction mixture was stirred at rt for 8h. Solvents were evaporated and the resultant solid was dried to give the titled compound as a dark yellow solid.
H NMR (400 MHz, MeOD): δ 7.98 (s, 1 H), 7.77 (m, 1 H), 7.60 (m, 1 H), 7.54 (m, 1 H), 7.15 (m, 3H), 7.03 (m, 2H), 3.65 (broad s, 2H), 3.56 (m, 2H), 3.07 (m, 2H), 2.76 (s, 3H);
Preparation of (E)-N-ethyl-N-methyl-N'-(2-methyl-8-phenethyl-3-quinolyl)formamidine
Figure imgf000058_0001
To a solution of N-ethyl-N-methyl-formamide (0.04 g) in CH2CI2 (2 mL), under inert atmosphere (Ar), was added phosphorusoxychloride (0.04 mL) and the mixture was stirred for 30min at rt. The resulting solution was transferred via syringe to the 2-methyl-8-phenethyl-quinolin-3-amine hydrochloride (0.10 g) previously suspended in CH2CI2 (5 mL). The yellowish solution was stirred for 16h at rt after which the reaction mixture was basified with 2M NaOH (pH = 9) and the organic phase was separated, washed with water and brine, and dried over anhydrous sodium sulfate, and concentrated at reduced pressure to give the title compound as a yellowish oil.
H NMR (400 MHz, CDCI3): δ 7.47 (broad s, 1 H), 7.44 (m, 1 H), 7.20 (m, 7H), 3.46 (dd, 2H), 3.30 (m 2H), 3.02 (dd, 2H), 1.98 (m, 3H), 2.64 (s, 3H), 1.17 (m, 3H);
Preparation of N-ethyl-N-methyl-N'-(8-bromo-2-methyl-3-quinolyl)-formamidine
Figure imgf000058_0002
To a solution of N-ethyl-N-methyl-formamide (0.48 g) in CH2CI2 (10 mL), under inert atmosphere (Ar), was added phosphorusoxychloride (0.52 mL). The mixture was stirred for 30min at rt. The resulting solution was transferred via syringe to the 8-bromo-2-methyl-quinolin-3-amine (1.01 g) previously suspended in CH2CI2 (10 mL). The yellowish solution was stirred for 16h at rt. The reaction mixture was basified with 2M NaOH (pH = 9) and the separated organic phase washed with water and brine, and dried over anhydrous sodium sulfate to give the title compound as a brownish solid.
H NMR (400 MHz, CDCI3): δ 7.83 (d, 1 H), 7.54 (m, 2H), 7.25 (m, 2H), 3.50 (m, 2H), 3.10 (broad s, 3H), 2.79 (s, 3H), 1.29 (m, 3H);
Preparation of (E)-N-ethyl-N-methyl-N'-[2-methyl-8-(3-phenylpropyl)-3-quinolyllformamidine
Figure imgf000058_0003
To a solution of 9-methoxy-9-borabicyclo[3.3.1 ]nonane (0.47 ml.) in THF (1 M, 0.9 ml.) at -78°C was added under inert atmosphere (Ar) a solution of 0.25 M 3-phenpropylmagnesium bromide (2.2 mL) in THF over 10 min. The reaction mixture was allowed to warm up to the rt and stirred for 30min. A solution of (E)-N'-(8-bromo-2-methyl-3-quinolyl)-N-ethyl-N-methyl-formamidine (0.14 g), palladium(ll) acetate (0.01 g) in DMF (3.5 mL) was added to the reaction mixture followed by S-Phos (0.04 g) and the reaction mixture was stirred at 1 10°C for 2.5h followed by cooling to rt and poured onto ethylacetate and water. The organic phase was washed with brine, dried over anhydrous Na2S04 and filtered. The solvent was removed in vacuo to give a yellow oil, which was purified by combiflash column chromatography (silica gel, heptane/ethyl acetate gradient 0-60%) to give the title compound as a yellow oil.
H NMR (400 MHz, CDCI3): δ 7.44 (broad s, 1 H), 7.41 (m, 1 H), 7.28-7.13 (m, 7H), 7.06 (m, 1 H), 3.40 (m, 2H), 3.23 (m, 2H), 2.97 (broad s, 3H), 2.67 (m, 2H), 2.62 (s, 3H), 2.05 (m, 2H), 1 .15 (m, 3H);
Preparation of 8-bromo-2-methyl-quinolin-3-amine
Figure imgf000059_0001
To a suspension of finely ground calcium oxide (0.49 g) in water (18 mL) was added 7- bromoisatin (1.0 g) at rt and the resulting suspension was warmed to 80°C. After aging the mixture for 45min at 80°C, the light brown suspension was cooled to rt and N-acetonylacetamide (0.56 g) was added. The reaction was then warmed again to 80°C and stirred for an additional 2h at 80°C. The resulting slurry was cooled to rt, diluted with aqueous HCI (2M, 45 mL) and heated to reflux temperature. After cooling to rt, the pH of the reaction mixture was adjusted to pH 8 by addition of aqueous NaOH (2M) and the suspension was extracted with tert-butyl methyl ether. The organic layer was washed with brine, dried over MgS04, and the solids removed by filtration. The solvent was removed at reduced pressure and the residue purified by flash chromatography over silica gel (cyclohexane/ethyl acetategradient from 0% - 40%) to give the title compound as a light brown amorphous solid.
H NMR (400 MHz, CDCI3): δ 7.74 (m, 1 H), 7.53 (m, 1 H), 7.22 (m, 1 H), 7.19 (s, 1 H), 3.93 (broad s, 2H), 2.69 (s, 3H);
Preparation of (E)-N-ethyl-N-methyl-N'-(2-methyl-8-phenoxy-3-quinolyl)formamidine
Figure imgf000059_0002
(E)-N-ethyl-N-methyl-N'-(8-bromo-2-methyl-3-quinolyl)-formamidine (0.05 g), Cul (0.01 g), N,N- dimethylglycine hydrochloride (0.014 g), cesium carbonate (0.1 1 g), and phenol (0.03 g) were suspended in 1 ,4-dioxane (0.7 mL) at rt. The resulting mixture was then warmed to 100°C and stirred at this temperature for 18 h. After cooling to rt, the reaction was diluted with ethyl acetate (15 mL) and poured into a saturated aqueous NaHC03 solution. The organic layer was washed with saturated aqueous NaHC03 solution, brine, and then dried over MgS04. The solids were removed by filtration, the solvent evaporated and the residue purified by flash chromatography over silica gel (cyclohexane/ethyl acetate gradient from 0% - 30%) to give the title compound as a light yellow gum.
H NMR (400 MHz, CDCI3): δ 7.59 (broad s, 1 H), 7.35 (m, 4H), 7.23 (m, 1 H), 7.15 (m, 3H), 6.83 (dd, 1 H), 3.59 (broad s, 2H), 3.08 (s, 3H), 2.72 (s, 3H), 1.27 (t, 3H);
Preparation of methyl 2-[3-[(E)-ethyl(methyl)aminolmethyleneaminol-2-methyl-8-quinolyll-2- phenyl-acetate
Figure imgf000060_0001
Methyl 2-phenylacetate (0.05 g) was added dropwise to chloro-(2,2,6,6-tetramethyl-1- piperidyl)zinc chloride - lithium chloride (0.5M in THF, 0.7 mL) at 0°C under argon atmosphere. The resulting solution was aged for 5 min at 0°C and then a solution of (E)-N-ethyl-N-methyl-N'-(8-bromo- 2-methyl-3-quinolyl)- formamidine (0.05 g), palladium acetate (0.004 g) and dicyclohexyl-[2-(2,6- dimethoxyphenyl)phenyl]phosphine (0.013 g) in toluene (0.7 mL) was added at 0°C. The reaction mixture was then warmed to 40°C and aged for 90 min at 40°C. After cooling to rt, the reaction was diluted with ethyl acetate (15 mL) and poured into a saturated aqueous NaHC03 solution. The organic layer was washed with saturated aqueous NaHC03 solution, brine, and then dried over MgS04. The solids were removed by filtration, the solvent evaporated and the residue purified by flash chromatography over silica gel (cyclohexane/ethyl acetate gradient from 0% - 30%) to give the title compound as a light yellow gum.
H NMR (400 MHz, CDCI3): δ 7.52 (m, 4H), 7.35 (m, 4H), 7.15 (m, 1 H), 6.18 (s, 1 H), 3.73 (s, 3H), 3.45 (broad s, 3H), 3.06 (s, 3H), 2.67 (s, 3H), 1.25 (t, 3H);
Preparation of (E)-N-ethyl-N-methyl-N'-[2-methyl-8-(1-phenylethyl)-3-quinolyllformamidine
Figure imgf000060_0002
1-chloroethylbenzene (0.25 g) was added drop wise to a suspension of Mg-turnings (0.1 1 g), anhydrous LiCI (0.09 g) and ZnCI2 (0.27 g) in THF (3.6 mL) at rt. The resulting mixture was then aged for 2 h to give a chloro(1-phenylethyl)zinc (ca. 0.5M in THF, 1.3 mL) which was added to a solution of (E)-N-ethyl-N-methyl-N 8-bromo-2-methyl-3-quinolyl)-formamidine (0.10 g), palladium acetate (0.01 g) and 2-(2-dicyclohexylphosphanylphenyl)-N ,N ,N3,N3-tetramethyl-benzene-1 ,3-diamine (0.02 g) in THF (1 mL) at 5°C. The resulting solution was gradually warmed to 40°C and aged at this temperature for 120min. After cooling to rt, the reaction was diluted with ethyl acetate (15 mL) and poured into a saturated aqueous NaHC03 solution. The organic layer was washed with saturated aqueous NaHC03 solution, brine, and then dried over MgS04. The solids were removed by filtration, the solvent evaporated and the residue purified by flash chromatography over silica gel (cyclohexane/ethyl acetate gradient from 0% - 15%) to give the title compound as a light yellow gum.
H NMR (400 MHz, CDCI3): δ 7.39 (m, 8H), 7.12 (m, 1 H), 5.74 (q, 1 H), 3.42 (broad s, 1 H), 3.06 (s, 3H), 2.70 (s, 3H), 1 .73 (d, 3H), 1.25 (t, 3H).
Preparation of tert-butyl N-[8-(3,5-difluorophenyl)-2-methyl-3-quinolyllcarbamate
Figure imgf000061_0001
XX H
To a solution of tert-butyl N-(8-bromo-2-methyl-3-quinolyl) carbamate (0.10 g), (3,5- difluorophenyl)boronic acid (0.05 g) and [(PPh)3]2PdCI2 (0.02 g) in 1 ,4-dioxane (1 mL, degased) was added Na2C03 (0.09 g) in water (0.1 mL). The reaction mixture was then warmed to 1 10°C and stirred for 16 h. After cooling to rt, the reaction was diluted with EtOAc, filtrated through a pad of celite and the solvent was removed in vacuo. The residue was purified by flash chromatography over silica gel (cyclohexane/ethyl acetate gradient from 0% - 50%) to afford the title compound as an amorphous solid.
H NMR (400 MHz, CDCI3): δ 8.77 (s, 1 H), 7.82 (m, 1 H), 7.62 (m, 1 H), 7.54 (m, 1 H), 7.35 (m,
2H), 6.87 (m, 1 H), 6.58 (broad s, 1 H), 2.69 (s, 3H), 1.61 (s, 9H);
Pre aration of (E)-N'-[8-(3,5-difluorophenyl)-2-methyl-3-quinolyll-N-ethyl-N-methyl-formamidine
Figure imgf000061_0002
To a solution of tert-butyl N-[8-(3,5-difluorophenyl)-2-methyl-3-quinolyl]carbamate (0.08 g) in MeOH (1 mL) was added 4M HCI in 1 ,4-dioxane (0.50 mL) at rt. The reaction mixture was stirred for 16h after which the solvent evaporated and the residue dried in vacuo to afford crude [8-(3,5- difluorophenyl)-2-methyl-3-quinolyl]ammonium chloride. In a separate flask, phosphorusoxychloride (0.03 mL) was added to N-ethyl-N-methyl-formamide (0.02 g) in dichloromethane (1 mL) at rt. The resulting solution was aged for 45min at rt and then added to a solution of crude [8-(3,5- difluorophenyl)-2-methyl-3-quinolyl]ammonium chloride prepared above in dichloromethane (1 mL) at 0°C. Upon end of the addition, the cooling bath was removed and the reaction was allowed to stir for 16h at rt. The reaction mixture was then basified with tertiary amine-resin (pH = 7-8), the resin filtered off, and the filtrate was washed with water and brine. The organic layer was dried over sodium sulfate, filtrated and the solvent was removed under reduced pressure. The residue was purified by combiflash chromatography over silica gel (cyclohexane/ethyl acetate gradient from 0% - 30%) to afford the title compound as a light yellow gum.
H NMR (400 MHz, CDCI3): δ 7.70 (m, 1 H), 7.55 (m, 2H), 7.40 (m, 4H), 6.83 (m, 1 H), 3.38 (broad s, 2H), 3.09 (broad s, 3H), 2.67 (s, 3H), 1.27 (t, 3H);
Preparation of (E)-N-ethyl-N-methyl-N'-[8-(cvclopropylmethoxymethyl)-2-methyl-3- quinolyllformamidine
Figure imgf000062_0001
Sodium hydride (0.02 g) was added portionwise to a solution of (E)-N-ethyl-N-methyl-N'-[8- (hydroxymethyl)-2-methyl-3-quinolyl]-formamidine (0.15 g) in DMF (2 ml_) at 0°C. The reaction mixture was stirred for 15min at 0°C then warmed to rt the after which a deep red colour appeared, lodomethylcyclopropane (0.21 g) was added and the reaction stirred for 2h during which a yellow color was observed. The solution was quenched with a saturated aqueous Na2C03 solution, diluted with ethyl acetate, and the layers were separated. The aqueous phase was extracted with EtOAc (3 x 30 mL) and the combined organic phase was dried over Na2S04 and the solvent was evaporated under reduced pressure. The crude residue was purified by combiflash (heptane/ethyl acetate gradient 0% - 30%) to afford the title compound as a light yellow oil.
H NMR (400 MHz, CDCI3): δ 7.66 (m, 1 H), 7.55 (m, 1 H), 7.52 (m, 1 H), 7.26 (s, 1 H), 5.25 (s, 2H), 3.55 (broad s, 1 H), 3.50 (m, 2H), 3.35 (broad s, 1 H), 3.05 (s, 3H), 2.65 (s, 3H), 1.22 (t, 3H), 1.22 (m, 1 H), 0.55 (m, 2H), 0.26 (m, 2H).
Table Q
This table gives analytical data for compounds of formula (I) prepared using techniq
described above together with further techniques known to the person skilled in the art.
Figure imgf000062_0002
Figure imgf000063_0001
Figure imgf000064_0001
Figure imgf000065_0001
Figure imgf000066_0001
Figure imgf000067_0001
Figure imgf000068_0001
Q.103 quinolyl]-N-ethyl-N-methyl-formamidine 372 (M+H)
Analytical Methods Used
Method 1 : Spectra were recorded on a ZQ Mass Spectrometer from Waters (Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150°C, Desolvation Temperature: 350°C, Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode- array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3 , 1.8 m, 30 x 2.1 mm, Temp: 60°C, DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A = water + 5% MeOH + 0.05 % HCOOH, B= Acetonitrile + 0.05 % HCOOH. Gradient: 0 min 0% B, 100%A; 1 .2-1.5min 100% B: Flow (ml/min) 0.85.
Method 2: Spectra were recorded on a ZQ Mass Spectrometer from Waters (Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 100°C, Desolvation Temperature: 250°C, Cone Gas Flow: 50 L/Hr, Desolvation Gas Flow: 400 L/Hr, Mass range: 100 to 900 Da) and an Agilent 1 100 LC (Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Phenomenex Gemini C18, 3 μητι, 30 x 3 mm, Temp: 60°C, DAD Wavelength range (nm): 210 to 500, Solvent Gradient: A = water + 5% MeOH + 0.05 % HCOOH, B= Acetonitrile + 0.05 % HCOOH: gradient: 0 min 0% B; 2-2.8 min 100% B; 2.9-3 min 0%. Flow (ml/min) 1.7
Biological examples
General examples of leaf disk tests in well plates:
Leaf disks or leaf segments of various plant species are cut from plants grown in a greenhouse. The cut leaf disks or segments are placed in multiwell plates (24-well format) onto water agar. The leaf disks are sprayed with a test solution before (preventative) or after (curative) inoculation. Compounds to be tested are prepared as DMSO solutions (max. 10 mg/ml) which are diluted to the appropriate concentration with 0.025% Tween20 just before spraying. The inoculated leaf disks or segments are incubated under defined conditions (temperature, relative humidity, light, etc.) according to the respective test system. A single evaluation of disease level is carried out 3 to 14 days after inoculation, depending on the pathosystem. Percent disease control relative to the untreated check leaf disks or segments is then calculated.
General examples of liquid culture tests in well plates:
Mycelia fragments or conidia suspensions of a fungus prepared either freshly from liquid cultures of the fungus or from cryogenic storage, are directly mixed into nutrient broth. DMSO solutions of the test compound (max. 10 mg/ml) are diluted with 0.025% Tween20 by a factor of 50 and 10 μΙ of this solution is pipetted into a microtiter plate (96-well format). The nutrient broth containing the fungal spores/mycelia fragments is then added to give an end concentration of the tested compound. The test plates are incubated in the dark at 24°C and 96% relative humidity. The inhibition of fungal growth is determined photometrically after 2 to 7 days, depending on the pathosystem, and percent antifungal activity relative to the untreated check is calculated.
Blumeria graminis f. sp. tritici (Erysiphe graminis f. sp. tritici) I wheat / leaf disc preventative (Powdery mildew on wheat)
Wheat leaf segments cv. Kanzler were placed on agar in a multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated by shaking powdery mildew infected plants above the test plates 1 day after application. The inoculated leaf disks were incubated at 20°C and 60% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate chamber and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check leaf segments (6 - 8 days after application).
The following compounds gave at 200 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development: Q.001 , Q.002, Q.003, Q.004, Q.005, Q.006, Q.014, Q.018, Q.019, Q.020, Q.021 , Q.022, Q.023, Q.025, Q.026, Q.027, Q.028, Q.029, Q.030, Q.031 , Q.032, Q.033, Q.034, Q.035, Q.036, Q.037, Q.038, Q.039, Q.040, Q.042, Q.043, Q.044, Q.045, Q.046, Q.047, Q.048, Q.049, Q.050, Q.052, Q.053, Q.054, Q.055, Q.056, Q.057, Q.058, Q.059, Q.060, Q.061 , Q.064, Q.065, Q.066, Q.067, Q.068, Q.069, Q.070, Q.071 , Q.072, Q.073, Q.076, Q.078, Q.080, Q.081 , Q.082, Q.085, Q.086.
Puccinia recondita f. sp. tritici I wheat / leaf disc preventative (brown rust)
Wheat leaf segments cv. Kanzler were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments were incubated at 19°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7 - 9 days after application).
The following compounds gave at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development:
Q.001 , Q.002, Q.003, Q.004, Q.005, Q.006, Q.007, Q.013, Q.014, Q.016, Q.018, Q.019, Q.020, Q.021 , Q.022, Q.023, Q.024, Q.025, Q.026, Q.027, Q.028, Q.029, Q.030, Q.031 , Q.032, Q.033, Q.034, Q.038, Q.039, Q.040, Q.041 , Q.042, Q.043, Q.044, Q.045, Q.046, Q.048, Q.049, Q.050, Q.051 , Q.052, Q.053, Q.054, Q.055, Q.056, Q.057, Q.058, Q.059, Q.060, Q.061 , Q.062, Q.064, Q.065, Q.066, Q.067, Q.068, Q.069, Q.070, Q.071 , Q.072, Q.073, Q.076, Q.078, Q.079, Q.080, Q.081 , Q.082, Q.085, Q.086. Puccinia recondita f. sp. tritici I wheat / leaf disc curative (Brown rust)
Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format). The leaf segments are inoculated with a spore suspension of the fungus. Plates were stored in darkness at
19°C and 75% rh. The formulated test compound diluted in water was applied 1 day after inoculation.
The leaf segments were incubated at 19°C and 75% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (6 - 8 days after application).
The following compounds gave at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development:
Q.001 , Q.002, Q.003, Q.004, Q.005, Q.006, Q.007, Q.008, Q.014, Q.018, Q.019, Q.020, Q.021 , Q.022, Q.023, Q.024, Q.025, Q.026, Q.027, Q.028, Q.029, Q.030, Q.031 , Q.032, Q.033, Q.034, Q.036, Q.037, Q.038, Q.039, Q.040, Q.042, Q.043, Q.044, Q.045, Q.046, Q.047, Q.048, Q.049, Q.050, Q.051 , Q.052, Q.053, Q.054, Q.055, Q.056, Q.057, Q.058, Q.059, Q.060, Q.061 , Q.062, Q.063, Q.064, Q.065, Q.066, Q.067, Q.068, Q.069, Q.070, Q.071 , Q.072, Q.073, Q.076, Q.078, Q.079, Q.080, Q.081 , Q.082, Q.085, Q.086.
Phakoosora oachyrhizi on soybean, preventive treatment
4-week old soybean plants are sprayed in a spray chamber with the formulated test compound diluted in water. Leaf disks are cut from treated plants and placed on agar into 24-well plates one day after application. Leaf disks are inoculated by spraying them with a spore suspension on their lower leaf surface. After an incubation period in a climate cabinet of 24-36 hours in darkness at 20° C and 75% rh, the leaf disks are then kept at 20° C with 12 h light/day and 75% rh. The percentage leaf disk area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (12 - 14 days after application).
The following compounds gave at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development:
Q.018, Q.021 , Q.022, Q.023, Q.030, Q.032, Q.048, Q.049, Q.051 , Q.052, Q.055, Q.058, Q.059,
Q.060, Q.061 , Q.065, Q.067, Q.069, Q.070, Q.071 , Q.072, Q.076, Q.078, Q.081.
Mycosphaerella arachidis (Cercospora arachidicola) I liquid culture (early leaf spot)
Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically 4-5 days after application.
The following compounds gave at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development:
Q.001 , Q.004, Q.010, Q.01 1 , Q.014, Q.020, Q.026, Q.027, Q.028, Q.029, Q.030, Q.031 , Q.032, Q.033, Q.034, Q.041 , Q.042, Q.044, Q.045, Q.046, Q.047, Q.048, Q.049, Q.050, Q.051 , Q.052, Q.053, Q.054, Q.055, Q.056, Q.057, Q.059, Q.060, Q.067, Q.069, Q.070, Q.071 , Q.072, Q.073, Q.076, Q.078, Q.079, Q.080, Q.081.
Thanatephorus cucumeris (Rhizoctonia solani) I liquid culture (foot rot, dam ping-off)
Mycelia fragments of a newly grown liquid culture of the fungus are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format), the nutrient broth containing the fungal material is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically 3-4 days after application.
The following compounds gave at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development: Q.001 , Q.020, Q.023, Q.026, Q.027, Q.028, Q.031 , Q.032, Q.057, Q.058, Q.060, Q.061 , Q.069, Q.070.
Sclerotinia sclerotiorum I liquid culture (cottony rot)
Mycelia fragments of a newly grown liquid culture of the fungus are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format) the nutrient broth containing the fungal material is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically 3-4 days after application.
The following compounds gave at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development:
Q.001 , Q.004, Q.005, Q.006, Q.007, Q.010, Q.01 1 , Q.018, Q.019, Q.020, Q.021 , Q.022, Q.023, Q.026, Q.027, Q.028, Q.029, Q.030, Q.031 , Q.032, Q.033, Q.034, Q.039, Q.042, Q.043, Q.044, Q.045, Q.046, Q.047, Q.048, Q.049, Q.050, Q.051 , Q.052, Q.054, Q.055, Q.056, Q.057, Q.058, Q.059, Q.060, Q.061 , Q.062, Q.069, Q.070, Q.072, Q.076, Q.078, Q.079, Q.080, Q.085, Q.086.
Mycosphaerella graminicola (Septoria tritici) I liquid culture (Septoria blotch)
Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically 4-5 days after application.
The following compounds gave at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development:
Q.008, Q.017, Q.031 , Q.032, Q.069.

Claims

1. A compound of formula (I)
Figure imgf000073_0001
wherein
R and R2 independently of each other represent hydrogen, Ci-C4alkyl, Ci-C4fluoroalkyl or C3- C6cycloalkyl; or R and R2 together with the nitrogen atom to which they are attached form a three to six-membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom;
R3 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C4 alkyl, C2-
C5alkenyl, C2-C5alkynl, Ci-C4haloalkyl, Ci-C4alkoxy or C3-C6 cycloalkyl;
R4 represents hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynl, d-C6 haloalkyl, d-C6 alkoxy or C3-C6 cycloalkyl;
R6 ,R7 ,R8 independently of each other represent hydrogen, halogen, cyano, hydroxy, formyl, carboxy, amino, Ci-C4alkyl, C2-C5alkenyl, C2-C5alkynl, Ci-C4haloalkyl, Ci-C4alkoxy or d-
C4haloalkoxy;
R5 represents R9-(Z)m-;
m represents 0, 1 or 2;
when m is 0 or 1 , Z represents -C(=0)-, -0-, -S-, -S(=0)-, -S(=0)2-, -N(R10)- or d-d alkyl, wherein the alkyl is optionally substituted by one or more groups independently selected from halogen, CN, OH, Ci-C4 alkylcarbonyl, Ci-C4 alkoxycarbonyl, Ci-C4-haloalkyl, CN, Ci-C4-alkoxy and Ci-C4-haloalkoxy;
when m is 2, Z represents Ci-C4 alkyl, wherein the alkyl is optionally substituted by one or more groups independently selected from halogen, CN, OH, Ci-C4 alkylcarbonyl, Ci-C4
alkoxycarbonyl, Ci-C4-haloalkyl, CN, Ci-C4-alkoxy and Ci-C4-haloalkoxy;
R9 represents d-C8alkyl, C3-C8alkenyl or C3-C8alkynyl, wherein the alkyl, alkenyl, alkynyl and cycloalkoxy are optionally substituted by one or more groups independently selected from halogen, hydroxyl, cyano, N02, OH, SH, d-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynl, d-C6 haloalkyl, d-C6 alkoxy, C3-C8 cycloalkyl C3-C8 cycloalkoxy, formyl, C2-C6alkylcarbonyl, d-C6alkylthio, d- C6alkylsulfinyl and d-C6alkylsulfonyl; or
R9 represents D-A-d-C6alkyl-, D-A-d-C6alkyl-, D-A-C C6alkyl-, D-A-d-C6alkyl-, D-A-C C6alkyl-, D-A-d-C6alkyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2- C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkenyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A- C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C2-C6alkynyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl-, D-A-C3-C6cycloalkyl- or D-A- C3-C6cycloalkyl-; or R represents an three to eight membered monocyclic system which can be aromatic, partially saturated or fully saturated, which optionally contains one or two hetero atoms selected from the group consisting of N, N(R11), O and S, optionally substituted by one or more groups independently selected from the group consisting of hydrogen, halogen, cyano, nitro, mercapto, hydroxy, -CHO, -COOH, -C(=S)NH2, -SF5, d-dalkyl, d-dhaloalkyl, C2-C6 alkenyl, C2- C5haloalkenyl, C2-C5alkynyl, C2-C5haloalkynyl, d-C4alkoxy, Ci-C4haloalkoxy, C3-C6cycloalkyl, C3-C6halocycloalkyl, C3-C4alkenyloxy, C3-C4haloalkenyloxy, C3-C5alkynyloxy, C3- C6cycloalkyloxy,C2-C4alkoxycarbonyl, C2-C4haloalkoxycarbonyl, C2-C5alkylcarbonyl, C2-C5 haloalkylcarbonyl, -N(R 2)(R13), -C(=0)N(R 2)(R13), C(=S)N(R 2)(R13), d-dalkylthio, d- dalkylsulfinyl, d-dalkylsulfonyl, d-dhaloalkylthio, d-dhaloalkylsulfinyl, d- dhaloalkylsulfonyl and -S(=0)2N(R 2)(R13); or
R9 represents NHR 4;
A represents -C(=0)-, -C(=S)-, -C(=NOR15)-, -C(R 5)=NO-, -ON=C(R15)-, -S(=0)(=NR15)-, - S(=0)(R 5)=N-, -0-C(=0)-, -C(=0)-0-, -0-, -S-, -S(=0)-, -S(=0)2-, -S(=0)(=NR15)-, -N(R10)-, - N(R 5)-(C=0)-, -(C=0)-N(R15)-, -N(R 5)-S02- or -S02-N(R15)-;
D represents d-dalkyl, d-dalkenyl, d-dalkynyl, d-dcycloalkyl, benzyl, phenyl each of which are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, mercapto, d-dhaloalkyl, d-dalkoxy, formyl, d-dalkylcarbonyl, d- dalkoxycarbonyl, d-dalkylthio, d-dhaloalkylthio, d-dalkylsulfinyl and d-dalkylsulfonyl; R 0 represents hydrogen, formyl, d-dalkyl, d-dhaloalkyl, d-dalkenyl or d-dalkylcarbonyl; each R independently represents hydrogen, formyl, d-dalkyl, d-C4haloalkyl, d-dalkoxy, d-dhaloalkoxy, d-dalkenyl, d-dhaloalkenyl, d-dalkylcarbonyl, -dalkoxycarbonyl, C2- d haloalkylcarbonyl, benzyl, phenyl, d-dalkylsulfinyl, d-dalkylsulfonyl, d- dhaloalkylsulfinyl, d-dhaloalkylsulfonyl -C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) or - S(=0)2N(R 2)(R13), wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, benzyl and phenyl are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, d-dalkyl, d-dhaloalkyl, d-dalkoxy and d-dhaloalkoxy;
each R 2 and R 3 independently of each other represents hydrogen, formyl, d-dalkyl, d- dhaloalkyl, C2-C4alkylcarbonyl, d-dalkoxycarbonyl, benzyl or phenyl; or
R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom;
R 4 represents phenyl optionally substituted by fluoro, CN, OH, methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3;
each R 5 independently represents hydrogen, d-dalkyl, Crdhaloalkyl, d-dalkenyl, d- dhaloalkenyl, d-dalkynyl, d-dcycloalkyl, benzyl or phenyl wherein the alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, cycloalkyi, benzyl and phenyl are optionally substituted by one or more groups independently selected from halogen, cyano, hydroxy, d-dalkyl, d-dhaloalkyl, Ci-C4alkoxy and Ci-C4haloalkoxy; and tautomers/isomers/enantiomers/salts and N-oxides of these compounds.
A compound according to claim 1 wherein when m is 0 or 1 , Z represents -C(=0)-, -0-, -S-, - S(=0)-, -S(=0)2-, -N(R10)-, methylene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from fluorine, CN, OH, methyl, ethyl, propyl, iso-propyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, CN, OMe, OEt, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu;
when m is 2, Z represents methlyene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from fluorine, CN, OH, methyl, ethyl, propyl, iso-propyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, CN, OMe, OEt, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu;
R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or CrC6alkynyl wherein the alkyl, alkenyl and alkynyl are optionally be optionally substituted by one or more groups independently selected from halogen, CN, OH, d-C4alkyl, C2-C4alkenyl, Ci-C4fluoroalkyl, Ci-C4alkoxy, and C2- C5alkylcarbonyl; or
R9 represents a five- or six-membered saturated or partially saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R11), O and S, optionally substituted by one or more groups independently selected from the group consisting of halogen, CN, N02, OH, SH, CHO, d-C4alkyl, d-C4haloalkyl, C3-C6cycloalkyl, C2-C5alkenyl, C2-C5alkynyl, C2-C5haloalkynyl, Ci-C4alkoxy, Ci-C4haloalkoxy, C3-C5alkynyloxy, Ci-C4 alkylcarbonyl and Ci-C4 alkoxycarbonyl; or
R9 represents a five- or six-membered aromatic monocyclic system which contains one or two hetero atoms selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from halogen, CN, OH, SH, CHO, COOH, Ci-C4 alkyl, Ci-C4alkoxy, Ci-C4haloalkyl, Ci-C4haloalkoxy, C3-C6 cycloalkyl, C2-C4 alkylcarbonyl, C2- C5alkoxycarbonyl, d-C4haloalkylthio, C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) and - S(=0)2N(R 2)(R13); or
R9 represents phenyl optionally substituted by one or more groups independently selected from halogen, CN, N02, OH, SH, CHO, COOH, d-C4 alkyl, d-C4 alkoxy, d-C4 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, Ci-C4 haloalkoxy, Ci-C4 alkylcarbonyl, d-C4alkylsulfonyl, C(=0)N(R 2)(R13), -C(=S)N(R 2)(R13) and -S(=0)2N(R 2)(R13); or
R9 represents a C3-C8 carbocyclic system, which may be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from halogen, CN, N02, OH, SH, CHO, COOH, d-C4 alkyl, d-C4 alkoxy, d-C4 haloalkyl, d-C4 haloalkoxy, C3-C6 cycloalkyl and Ci-C4 alkylcarbonyl; or
R9 represents NHR 4;
each R independently represents hydrogen, formyl, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy, d-C4haloalkoxy, C3-C5alkenyl, C3-C5haloalkenyl, C2-C5alkylcarbonyl,C2-C5alkoxycarbonyl, C2- C4 haloalkylcarbonyl, benzyl, phenyl, -S(=0)2Me, -S(=0)2Et, C(=0)N(R 7)(R18),
C(=S)N(R 7)(R18) or -S(=0)2N(R 7)(R18);
each R 2 and R 3 independently of each other represents hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, benzyl or phenyl; or
R 2 and R 3 together with the nitrogen atom to which they are attached form a three to six- membered saturated cyclic group which optionally contains either one oxygen atom or one sulphur atom;
each R 6 independently represents formyl, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu, benzyl, phenyl, -S(=0)2Me, -S(=0)2Et, and - S(=0)2N(R 2)(R13);
each R 7 and R 8 independently of each other represents hydrogen, Ci-C4alkyl, d- C4fluoroalkyl, benzyl or phenyl; or
R 7 and R 8 together with the nitrogen atom to which they are attached form aziridine, azetidine, pyrolidine, piperidine, morpholine, and thiomorpholine.
A compound according to either claim 1 or claim 2 wherein m represents 0 or 1 ;
Z represents -0-, -S-, -C(=0)-, -S(=0)2-, -N(R10)-, methylene or ethylene, wherein the methlyene and ethylene are optionally substituted by one or more groups independently selected from CN, OH, methyl, ethyl, CF3, OMe, OEt, COMe, COEt, COiPr, C02Me, C02Et and
C02iPr;
R9 represents hydrogen, d-C6alkyl, d-C6alkenyl or CrC6alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from chloro, fluoro, bromo, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, and OCF3; or R9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R11), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, Ci-C4alkyl, Ci-C4fluoroalkyl, Ci-C4alkoxy, Ci-C4fluoroalkoxy, Ci-C4alkylcarbonyl and d- alkoxycarbonyl; or
R9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, d-C4alkyl, Ci-C4fluoroalkyl, Ci-C4alkoxy, Ci-C4fluoroalkoxy, Ci-C4alkylcarbonyl, and Ci-C4 alkoxycarbonyl; or
R9 represents phenyl optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, CHO, COOH, d-C4 alkyl, d-C4 alkoxy, d-C4 fluoroalkyl, C3-C6 cycloalkyl, C2-C4 alkenyl, Ci-C4fluoroalkoxy, Ci-C4alkylsulfonyl,
C(=0)N(R 2)(R13) and S(=0)2N(R 2)(R13); or R represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, Ci-C4alkyl, C C4alkoxy, Ci-C4fluoroalkyl and C1-C4 fluoroalkoxy; or
R9 represents NHR 4;
R 0 represents hydrogen or methyl;
each R independently represents formyl, C C4alkyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu, benzyl, phenyl, - S(=0)2Me, -S(=0)2Et, C(=0)N(R 7)(R18), -C(=S)N(R 7)(R18) or -S(=0)2N(R 7)(R18);
each R 6 independently represents hydrogen, fluorine, methyl, ethyl, isopropyl, CHF2, CF3, CHO, CO-Me, C02Me, CONHMe, CONMe2, S(=0)2Me, -S(=0)2Et, S(=0)2NHMe, S(=0)2NMe2, benzyl or phenyl; and
each R 7 and R 8 independently of each other represents hydrogen, methyl, ethyl, propyl, isopropyl, CHF2, CF3, benzyl or phenyl.
4. A compound according to any preceding claim wherein m represents 0 or 1 ; Z represents
methylene or ethylene, each of which is optionally substituted by one or more methyl groups; R9 represents hydrogen, Ci-C6alkyl, Ci-C6alkenyl or CrC6alkynyl, wherein the alkyl, alkenyl and alkynyl are optionally substituted by one or more groups selected from fluoro, CN, OH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr; or
R9 represents a five- or six-membered saturated monocyclic system which contains one or two members selected from the group consisting of N, N(R11), O and S, optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OnPr, OCHF2 and OCF3; or
R9 represents a five- or six-membered aromatic monocyclic system which contains one or two members selected from the group consisting of N, N(R16), O and S, optionally substituted by one or more groups independently selected from fluoro, CN, N02, OH, SH, CHO, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2- CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, OCF3, SCHF2, SCF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, and C02tBu; or
R9 represents phenyl optionally substituted by one or more groups independently selected from chloro, fluoro, bromo, CN, N02, OH, SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2, OCF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu CONHMe, CONMe2, S(=0)2Me, -S(=0)2Et, S(=0)2NHMe and S(=0)2NMe2; or
R9 represents a five or six membered carbocyclic system which can be partially saturated or fully saturated and is optionally substituted by one or more groups independently selected from fluoro, CN, N02, OH, SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert- butyl, CH2F, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CH3, CF2-CF3, OMe, OEt, OiPr, OPr, OCHF2 and OCF3; or R9 represents NHR 4;
each R independently represents -S(=0)2Me, -S(=0)2Et, C(=0)N(R 7)(R18), - S(=0)2N(R 7)(R18), formyl, CHF2, CF3, CHF-CH3, CF2-CH3, CF2-CF3, COMe, COEt, COiPr, COtBu, C02Me, C02Et, C02iPr, C02tBu, benzyl or phenyl; and
each R 7 and R 8, independently of each other, represents hydrogen, methyl, ethyl, propyl or isopropyl.
A compound according to any preceding claim wherein R and R2 independently of each other represent hydrogen, Ci-C4alkyl or cyclopropyl;
R3 represents hydrogen, halogen, methyl, ethyl, n-propyl, isopropyl, vinyl, -C(Me)=CH2, allyl, OMe OEt or cyclopropyl;
R4 represents hydrogen;
R6, R7 and R8 independently of each other represent hydrogen, halogen, CN, d-C4alkyl, d- C4alkoxy, Ci-C4haloalkyl or Ci-C4 haloalkoxy.
A compound according to any preceding claim wherein
R and R2 independently of each other represent hydrogen, methyl, ethyl, isopropyl, n-propyl or cyclopropyl;
R3 represents hydrogen, chloro, methyl or ethyl;
R4 represents hydrogen;
R6, R7 and R8 independently of each other represent hydrogen, fluoro, chloro, bromo, CN, methyl, ethyl, propyl, OMe, OEt, CHF2, CF3 or OCHF2.
A compound according to any preceding claim wherein R represents methyl; R2 represents ethyl; R3 represents methyl; R4, R6, R7 and R8 represent hydrogen.
A compound of formula (XIX")
Figure imgf000078_0001
wherein R3, R4, R6, R7 and R8 are as defined in claim 1 and R is defined as hydrogen or C02tBu; and
X is CI, Br, I, boronic ester, boronic acid, tri-alkylstannane, CN, CH2OH, CHO, C(0)Me, C02Me, C02Et, and tautomers/isomers/enantiomers/salts and N-oxides of these compounds.
9. A composition comprising a fungicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 7, optionally comprising at least one additional active ingredient and/or a diluent.
10. A method of controlling or preventing phytopathogenic diseases on useful plants or on
propagation material thereof, which comprises applying to the useful plants, the locus thereof propagation material thereof a fungicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 7.
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