New heteroaryl-triazole compounds as pesticides

Abstract

The present invention relates to novel heteroaryl-triazole compounds of general formula (I), in which the structural elements X, R 1 , R 2 , R 3 and R 4 have the meanings given in the description; preparations and compositions comprising said compounds; and their use in plant protection for controlling animal pests including arthropods and insects and their use for controlling ectoparasites of animals.

Description

[0001] The present invention relates to novel heteroaryl-triazole compounds, formulations and compositions comprising said compounds, and their use in plant protection for controlling animal pests including arthropods and insects, and their use for controlling ectoparasites of animals.

[0002] Certain heteroaryl-triazole compounds have been disclosed for controlling ectoparasites of animals (in WO 2017 / 192385) and for controlling animal pests including arthropods and insects in the field of plant protection (in WO2019 / 170626 and WO 2019 / 215198). In addition, patent applications WO 2019 / 197468, WO 2019 / 201835, WO2019 / 202077, WO 2019 / 206799, WO 2021 / 013719 and WO 2021 / 013720 disclose certain heteroaryl-triazole compounds for controlling ectoparasites of animals and for controlling animal pests including arthropods and insects in the field of plant protection. WO 2020 / 002563, WO 2020 / 053364, WO 2020 / 053365, WO 2020 / 079198, WO 2020 / 094363, WO 2020 / 169445, WO 2020 / 182649, WO 2020 / 188014, WO 2020 / 188027 and WO 2020 / 193341 describe that oxazole-amide compounds can all be used as insecticides.

[0003] Modern plant protection products and veterinary ectoparasiticides must meet many requirements, such as regarding efficacy, persistence, spectrum of action and resistance-breaking properties. Issues of toxicity, compatibility with other active compounds or formulation aids also play a role, as do the costs required for synthesizing active compounds. In addition, resistance may occur. For all these reasons, the research on new crop protection compositions or veterinary ectoparasiticides cannot be considered complete, but there is a continuous need for new compounds that have improved properties at least in some aspects compared to known compounds.

[0004] One object of the present invention is to provide compounds that broaden the spectrum of pesticides in all aspects.

[0005] Accordingly, the present invention provides compounds of general formula (I)

[0006]

[0007] wherein (configuration 1-1):

[0008] X is O or S;

[0009] R 1 is hydrogen;

[0010] R 2 is selected from the following substructures Q1 and Q2, wherein the bond connected to the C═X group is marked with #:

[0011]

[0012] wherein

[0013] R 21 is halogen, -CN, -SF 5 , C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 3 haloalkylthio, C 1 -C 3 haloalkylsulfinyl, C 1 -C 3 haloalkylsulfonyl, C 1 -C 3 alkylthio, C 1 -C 3 alkylsulfinyl, C 1 -C 3 alkylsulfonyl, C 3 -C 4 cycloalkylthio, C 3 -C 4 cycloalkylsulfinyl, C 3 -C 4 cycloalkylsulfonyl, phenylsulfonyl, wherein the phenyl is optionally substituted with one or two substituents selected from halogen, -CN, methyl, trifluoromethyl or trifluoromethoxy; or cyclopropyl, wherein the cyclopropyl is optionally substituted with one or two substituents selected from halogen, -CN, methyl or trifluoromethyl;

[0014] R 22 is hydrogen, halogen, -CN, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy or C 1 -C 3 haloalkylsulfonyl;

[0015] R 3 is -CN or a substituent selected from the following substructure S1, wherein the bond connected to pyrimidine is marked with #:

[0016]

[0017] R 31 is hydrogen or C 1 -C 3 alkyl;

[0018] R 32 is hydrogen, C 3 -C 6 cycloalkyl or C 1 -C 3 alkyl, where C 3 -C 6 cycloalkyl and C 1 -C 3 alkyl are optionally substituted by one or two substituents selected from halogen, -CN, C 3 -C 6 cycloalkyl and C 1 -C 3 alkoxy;

[0019] R 4 is hydrogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy or C 3 -C 4 cycloalkyl.

[0020] The compounds of formula (I) also cover any diastereoisomers or enantiomers and E / Z isomers present, as well as salts and N-oxides of the compounds of formula (I), and their use for controlling animal pests.

[0021] Preferred group definitions of the chemical formulas detailed above and below are given below.

[0022] In addition, the present invention also provides compounds of general formula (I)

[0023] wherein (configuration 1-2):

[0024] X is O or S;

[0025] R 1 is hydrogen;

[0026] R 2 is selected from the following substructures Q1 and Q2, where the bond connected to the C═X group is marked with #:

[0027]

[0028] wherein

[0029] R 21 is halogen, -CN, -SF 5 、C 1 -C 3Halogenated alkyl, C 1 -C 3 Halogenated alkoxy, C 1 -C 3 Halogenated alkylthio, C 1 -C 3 Halogenated alkylsulfinyl, C 1 -C 3 Halogenated alkylsulfonyl, C 1 -C 3 Alkylthio, C 1 -C 3 Alkylsulfinyl, C 1 -C 3 Alkylsulfonyl, C 3 -C 4 Cycloalkylthio, C 3 -C 4 Cycloalkylsulfinyl, C 3 -C 4 Cycloalkylsulfonyl, phenylsulfonyl, wherein the phenyl is optionally substituted with one or two substituents selected from halogen, -CN, methyl, trifluoromethyl or trifluoromethoxy; or cyclopropyl, wherein the cyclopropyl is optionally substituted with one or two substituents selected from halogen, -CN, methyl or trifluoromethyl;

[0030] R 22 is hydrogen, halogen, -CN, C 1 -C 3 Halogenated alkyl, C 1 -C 3 Halogenated alkoxy or C 1 -C 3 Halogenated alkylsulfonyl;

[0031] R 3 is -CN or a substituent selected from the following substructure S1, wherein the bond connected to pyrimidine is marked with #:

[0032]

[0033] R 31 is hydrogen or C 1 -C 3 alkyl;

[0034] R 32 is hydrogen, C 3 -C 6 Cycloalkyl or C 1 -C 3 alkyl, wherein C 3 -C 6 Cycloalkyl and C 1 -C 3 alkyl is optionally substituted with one to three substituents selected from halogen, -CN, C3 -C 6 cycloalkyl and C 1 -C 3 substituted by a substituent of an alkoxy group;

[0035] R 4 is hydrogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy or C 3 -C 4 cycloalkyl.

[0036] Preferably (Configuration 2-1) A compound of formula (I), wherein

[0037] X is O or S;

[0038] R 1 is hydrogen;

[0039] R 2 is selected from the following substructures Q1 and Q2, where the bond connected to the C═X group is marked with #:

[0040]

[0041] wherein

[0042] R 21 is fluorine, chlorine, bromine, iodine, -CN, cyclopropyl, 1-cyanocyclopropyl, 2,2-dichlorocyclopropyl, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, 1,1,2,2-tetrafluoro-2-iodoethoxy, difluoromethylthio, trifluoromethylthio, 1,1,2,2-tetrafluoroethylthio, difluoromethylsulfonyl, trifluoromethylsulfonyl, 1,1,2,2-tetrafluoroethylsulfonyl, methylsulfonyl, ethylsulfonyl, cyclopropylsulfonyl or 4-chlorophenylsulfonyl;

[0043] R 22 is hydrogen, fluorine, chlorine, bromine, iodine, -CN, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, difluoromethylsulfonyl, trifluoromethylsulfonyl;

[0044] R 3 is -CN or a substituent selected from the following substructure S1, where the bond connected to the pyrimidine is marked with #:

[0045]

[0046] R 31 is hydrogen or methyl;

[0047] R 32 is hydrogen, cyclopropyl or C1 -C 3 alkyl, wherein C 1 -C 3 alkyl is optionally substituted with a substituent selected from halogen, -CN, cyclopropyl, and methoxy;

[0048] R 4 is hydrogen, methyl, or cyclopropyl.

[0049] Also preferably (Configuration 2-2) A compound of formula (I), wherein

[0050] X is O or S;

[0051] R 1 is hydrogen;

[0052] R 2 is selected from the following substructures Q1 and Q2, wherein the bond connected to the C=X group is marked with #:

[0053]

[0054] wherein

[0055] R 21 is fluorine, chlorine, bromine, iodine, -CN, cyclopropyl, 1-cyanocyclopropyl, 2,2-dichlorocyclopropyl, difluoromethyl, 1,1-difluoroethyl, trifluoromethyl, chlorodifluoromethyl, 2-fluoropropan-2-yl, difluoromethoxy, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, 1,1,2,2-tetrafluoro-2-iodoethoxy, difluoromethylthio, trifluoromethylthio, 1,1,2,2-tetrafluoroethylthio, difluoromethylsulfonyl, trifluoromethylsulfonyl, 1,1,2,2-tetrafluoroethylsulfonyl, methylthio, methylsulfinyl, methylsulfonyl, ethylsulfonyl, cyclopropylsulfonyl, or 4-chlorophenylsulfonyl;

[0056] R 22 is hydrogen, fluorine, chlorine, bromine, iodine, -CN, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, difluoromethylsulfonyl, trifluoromethylsulfonyl;

[0057] R 3 is -CN or a substituent selected from the following substructure S1, wherein the bond connected to pyrimidine is marked with #:

[0058]

[0059] R 31 is hydrogen or methyl;

[0060] R 32 is hydrogen, cyclopropyl, or C 1 -C 3 alkyl, wherein C1 -C 3 The alkyl group is optionally substituted by one to three substituents selected from fluorine, chlorine, -CN, cyclopropyl and methoxy;

[0061] R 4 is hydrogen, methyl or cyclopropyl.

[0062] Further preferably (Configuration 3-1) A compound of formula (I), wherein

[0063] X is O;

[0064] R 1 is hydrogen;

[0065] R 2 is (3,5-dibromophenyl), (3,5-dichlorophenyl), (3-chloro-5-methylsulfonylphenyl), (3-cyano-5-fluorophenyl), (3-fluorophenyl), (3-iodophenyl), 3-(1,1,2,2-tetrafluoroethylthio)phenyl, 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)phenyl, 3-(difluoromethoxy)-5-fluorophenyl, 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)phenyl, 3-(trifluoromethoxy)-5-(trifluoromethylsulfonyl)phenyl, 3-(trifluoromethoxy)phenyl, 3-(trifluoromethyl)phenyl, 3,5-bis(difluoromethoxy)phenyl, 3,5-bis(trifluoromethoxy)phenyl, 3,5-bis(trifluoromethyl)phenyl, 3,5-bis(trifluoromethylsulfonyl)phenyl, 3-bromo-5-(1,1,2,2-tetrafluoroethoxy)phenyl, 3-bromo-5-(2,2-dichlorocyclopropyl)phenyl, 3-bromo-5-(difluoromethoxy)phenyl, 3-bromo-5-(trifluoromethoxy)phenyl, 3-chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)phenyl, 3-chloro-5-(1,1,2,2-tetrafluoroethoxy)phenyl, 3-chloro-5-(4-chlorophenyl)sulfonylphenyl, 3-chloro-5-(difluoromethylsulfonyl)phenyl, 3-chloro-5-(trifluoromethoxy)phenyl, 3-chloro-5-(trifluoromethyl)phenyl, 3-chloro-5-(trifluoromethylsulfonyl)phenyl, 3-chloro-5-(trifluoromethylthio)phenyl, 3-cyano-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(difluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyclopropylsulfonyl-5-(trifluoromethoxy)phenyl, 3-fluor-5-(trifluoromethoxy)phenyl, 3-methylsulfonyl-5-(trifluoromethoxy)phenyl, 3-methylsulfonyl-5-(trifluoromethyl)phenyl or 2-chloro-6-(1-cyanocyclopropyl)pyridin-4-yl.

[0066] R 3is -CN, aminocarbonyl, methylcarbamoyl, [ethyl(methyl)amino]carbonyl, [isopropyl(methyl)amino]carbonyl or [cyclopropylmethyl(methyl)amino]carbonyl;

[0067] R 4 is hydrogen, methyl or cyclopropyl.

[0068] Also further preferably (Configuration 3 - 2) The compound of formula (I), wherein

[0069] X is O;

[0070] R 1 is hydrogen;

[0071] R 2is (3-fluorophenyl), (3-iodophenyl), (3,5-dibromophenyl), (3,5-dichlorophenyl), (3-chloro-5-methylsulfonylphenyl), 3-bromo-5-methylsulfonylphenyl, (3-cyano-5-fluorophenyl), 3-chloro-5-cyanophenyl, 3-bromo-5-cyanophenyl, 3,5-dicyanophenyl, 3-(1,1,2,2-tetrafluoroethylthio)phenyl, 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)phenyl, 3-(difluoromethoxy)-5-fluorophenyl, 3-(difluoromethoxy)-5-iodophenyl, 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)phenyl, 3-(trifluoromethoxy)-5-(trifluoromethylsulfonyl)phenyl, 3-(trifluoromethoxy)phenyl, 3-(trifluoromethyl)phenyl, 3-(trifluoromethylsulfonyl)phenyl, 3,5-bis(difluoromethoxy)phenyl, 3-(2-fluoropropan-2-yl)-5-(trifluoromethoxy)phenyl, 3,5-bis(trifluoromethoxy)phenyl, 3,5-bis(difluoromethyl)phenyl, 3,5-bis(trifluoromethyl)phenyl, 3-(difluoromethoxy)-5-(trifluoromethoxy)phenyl, 3,5-bis(difluoromethylsulfonyl)phenyl, 3,5-bis(trifluoromethylsulfonyl)phenyl, 3-bromo-5-(1,1,2,2-tetrafluoroethoxy)phenyl, 3-bromo-5-(2,2-dichlorocyclopropyl)phenyl, 3-bromo-5-(difluoromethoxy)phenyl, 3-bromo-5-(trifluoromethoxy)phenyl, 3-chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)phenyl, 3-chloro-5-(1,1,2,2-tetrafluoroethoxy)phenyl, 3-chloro-5-(4-chlorophenyl)sulfonylphenyl, 3-chloro-5-(difluoromethylsulfonyl)phenyl, 3-chloro-5-(trifluoromethoxy)phenyl, 3-chloro-5-(trifluoromethyl)phenyl, 3-chloro-5-(1,1-difluoroethyl)phenyl, 3-chloro-5-(chlorodifluoromethyl)phenyl, 3-chloro-5-(trifluoromethylsulfonyl)phenyl, 3-bromo-5-(trifluoromethylsulfonyl)phenyl, 3-chloro-5-(trifluoromethylthio)phenyl, 3-cyano-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(difluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyclopropylsulfonyl-5-(trifluoromethoxy)phenyl, 3-fluoro-5-(trifluoromethoxy)phenyl, 3-methylsulfonylphenyl, 3-(difluoromethoxy)-5-methylthiophenyl, 3-(difluoromethoxy)-5-methylsulfonylphenyl, 3-methylsulfonyl-5-(trifluoromethoxy)phenyl, 3-methylsulfonyl-5-(trifluoromethyl)phenyl, 2,6-dibromopyridin-4-yl, 2-(trifluoromethoxy)pyridin-4-yl, 2-chloro-6-(trifluoromethoxy)pyridin-4-yl, 2-bromo-6-methylsulfonyl-pyridin-4-yl or 2-chloro-6-(1-cyanocyclopropyl)pyridin-4-yl;

[0072] R3 is -CN, aminocarbonyl, methylcarbamoyl, ethylcarbamoyl, (isopropylamino)carbonyl, (difluoroethylamino)carbonyl, (3,3,3 - trifluoropropylamino)carbonyl, (cyclopropylamino)carbonyl, dimethylaminocarbonyl, [ethyl(methyl)amino]carbonyl, [isopropyl(methyl)amino]carbonyl or [cyclopropylmethyl(methyl)amino]carbonyl;

[0073] R 4 is hydrogen, methyl or cyclopropyl.

[0074] In another preferred embodiment, the present invention relates to a compound of formula (I’)

[0075]

[0076] wherein the structural element R 1 、R 2 、R 3 and R 4 has the meaning given in configuration (1 - 1) or the meaning given in configuration (2 - 1) or the meaning given in configuration (3 - 1) or the meaning given in configuration (1 - 2) or the meaning given in configuration (2 - 2) or the meaning given in configuration (3 - 2).

[0077] In another preferred embodiment, the present invention relates to a compound of formula (I”), wherein R 1 is hydrogen and

[0078]

[0079] wherein the structural element R 2 、R 3 and R 4 has the meaning given in configuration (1 - 1) or the meaning given in configuration (2 - 1) or the meaning given in configuration (3 - 1) or the meaning given in configuration (1 - 2) or the meaning given in configuration (2 - 2) or the meaning given in configuration (3 - 2).

[0080] In another preferred embodiment, the present invention relates to a compound of formula (I”’), wherein R 1 is hydrogen and

[0081]

[0082] wherein the structural element R 2 、R 3 and R 4having the meaning given in configuration (1-1) or the meaning given in configuration (2-1) or the meaning given in configuration (3-1) or the meaning given in configuration (1-2) or the meaning given in configuration (2-2) or the meaning given in configuration (3-2).

[0083] According to another aspect, the present invention encompasses intermediate compounds that can be used to prepare the compounds of the above general formula (I).

[0084] In particular, the present invention encompasses intermediate compounds of general formula (a) and their salts:

[0085]

[0086] wherein the structural element R 1 、R 3 and R 4 having the meaning given in configuration (1-1) or the meaning given in configuration (2-1) or the meaning given in configuration (3-1) or the meaning given in configuration (1-2) or the meaning given in configuration (2-2) or the meaning given in configuration (3-2).

[0087] In particular, the present invention encompasses intermediate compounds INT-1 to INT-23, and also includes their salts in the case of amines and acids, and also includes their free amines in the case of amine hydrochlorides (see Table 2):

[0088] INT-1: 6-[5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride

[0089] INT-2: tert-butyl {1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate

[0090] INT-3: tert-butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate

[0091] INT-4: 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile; 2,2,2-trifluoroacetic acid

[0092] INT-5: tert-butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-methyl-1,2,4-triazol-3-yl]ethyl]carbamate

[0093] INT-6: 6-[5-[(1S)-1-aminoethyl]-3-methyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride

[0094] INT-7: tert-Butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate

[0095] INT-8: 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride

[0096] INT-9: 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride INT-10: 6-[5-[(1S)-1-aminoethyl]-3-methyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride

[0097] INT-11: 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride

[0098] INT-17: Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate

[0099] INT-18: tert-Butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate

[0100] INT-19: tert-Butyl N-[(1S)-1-[5-cyclopropyl-2-[6-(methylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamate

[0101] INT-20: tert-Butyl N-[(1S)-1-[5-cyclopropyl-2-[6-(dimethylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamate

[0102] INT-21: 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N-methyl-pyrimidine-4-carboxamide hydrochloride

[0103] INT-22: 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N,N-dimethyl-pyrimidine-4-carboxamide hydrochloride

[0104] INT-12: 2-Chloro-6-(1-cyanocyclopropyl)pyridine-4-carboxylic acid

[0105] INT-13: 3-(Trifluoromethoxy)-5-(trifluoromethylsulfonyl)benzoic acid

[0106] INT-14: 3-Bromo-5-(2,2-dichlorocyclopropyl)benzoic acid

[0107] INT-15: 3-Bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid

[0108] INT-16: 3-(1-Fluoro-1-methylethyl)-5-(trifluoromethoxy)benzoic acid

[0109] INT-23: 3,5-Bis(difluoromethylsulfonyl)benzoic acid

[0110] Depending on the nature of the substituents, the compounds of formula (I) can also be in the form of stereoisomers, i.e., geometric isomers and / or optical isomers or mixtures of isomers with different compositions. The present invention provides pure stereoisomers and any desired mixtures of these isomers, although usually only the compounds of formula (I) discussed herein.

[0111] However, according to the present invention, the optically active stereoisomeric forms of the compounds of formula (I) and their salts are preferably used.

[0112] Therefore, the present invention relates to pure enantiomers and diastereomers and mixtures thereof for controlling animal pests (including arthropods and especially insects).

[0113] If appropriate, the compounds of formula (I) can exist in various polymorphic forms or as mixtures of various polymorphic forms. Pure polymorphs and mixtures of polymorphs are provided by the present invention and can be used according to the present invention.

[0114] Definition

[0115] Those skilled in the art should be aware that, unless otherwise specified, the expressions "a" or "an" used in this application can, depending on the context, mean "one (1)", "one (1) or more", or "at least one (1)".

[0116] For all structures described herein, such as ring systems and groups, adjacent atoms must not be -O-O- or -O-S-.

[0117] Structures with a variable number of possible carbon atoms (C atoms) can be referred to as C 碳原子的下限 -C 碳原子的上限 Structure (C LL -C ULstructure) for more specific definition thereby. Example: An alkyl group may consist of 3 to 10 carbon atoms and in this case corresponds to C 3 -C 10 alkyl. A ring structure composed of carbon atoms and heteroatoms may be referred to as an "LL-membered to UL-membered" structure. An example of a 6-membered ring structure is toluene (a 6-membered ring structure substituted with a methyl group).

[0118] If a collective term for substituents (such as C LL -C UL alkyl) is located at the end of a complex substituent (e.g., C LL -C UL cycloalkyl-C LL -C UL alkyl), the component at the starting end of the complex substituent (e.g., C LL -C UL cycloalkyl) can be mono- or polysubstituted independently and identically or differently by a subsequent substituent (e.g., C LL -C UL alkyl). For chemical groups, cyclic systems, and cyclic groups, all collective terms used in this application can be more specifically defined by adding the word "C LL -C UL " or "LL-membered to UL-membered".

[0119] In the definitions of the symbols given in the above formula, collective terms are used that generally represent the following substituents:

[0120] Halogen refers to the elements of Group VII, preferably fluorine, chlorine, bromine, and iodine, more preferably fluorine, chlorine, and bromine, and even more preferably fluorine and chlorine.

[0121] Examples of heteroatoms are N, O, S, P, B, Si. Preferably, the term "heteroatom" refers to N, S, and O.

[0122] According to the present invention, "alkyl", either by itself or as part of a chemical group, represents a straight-chain or branched hydrocarbon preferably having 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,2-dimethylpropyl, 1,3-dimethylbutyl, 1,4-dimethylbutyl, 2,3-dimethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethylbutyl and 2-ethylbutyl. Also preferred are alkyl groups having 1 to 4 carbon atoms, such as especially methyl, ethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl. The alkyl groups of the present invention may be substituted by one or more identical or different groups.

[0123] According to the present invention, "alkenyl" - either by itself or as part of a chemical group - represents a straight-chain or branched hydrocarbon having preferably 2 to 6 carbon atoms and at least one double bond, such as vinyl, 2-propenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 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-2-propenyl, 1-ethyl-2-propenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-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-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-2-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl and 1-ethyl-2-methyl-2-propenyl. Also preferred are alkenyls having 2 to 4 carbon atoms, such as in particular 2-propenyl, 2-butenyl or 1-methyl-2-propenyl. The alkenyls of the present invention may be substituted by one or more identical or different groups.

[0124] According to the present invention, "alkynyl" - either by itself or as part of a chemical group - represents a straight-chain or branched hydrocarbon preferably having 2 to 6 carbon atoms and at least one triple bond, such as 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-methyl-2-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-4-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, 1-ethyl-1-methyl-2-propynyl and 2,5-hexadiynyl. Also preferred are alkynyl groups having 2 to 4 carbon atoms, such as especially ethynyl, 2-propynyl or 2-butynyl-2-propenyl. The alkynyl groups of the present invention may be substituted by one or more identical or different groups.

[0125] According to the present invention, "cycloalkyl" - either by itself or as part of a chemical group - represents a monocyclic, bicyclic or tricyclic hydrocarbon preferably having 3 to 10 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl or adamantyl. Also preferred are cycloalkyl groups having 3, 4, 5, 6 or 7 carbon atoms, such as especially cyclopropyl or cyclobutyl. The cycloalkyl groups of the present invention may be substituted by one or more identical or different groups.

[0126] According to the present invention, "alkylcycloalkyl" represents a monocyclic, bicyclic or tricyclic alkylcycloalkyl preferably having 4 to 10 or 4 to 7 carbon atoms, such as methylcyclopropyl, ethylcyclopropyl, isopropylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. Also preferred are alkylcycloalkyl groups having 4, 5 or 7 carbon atoms, such as especially ethylcyclopropyl or 4-methylcyclohexyl. The alkylcycloalkyl groups of the present invention may be substituted by one or more identical or different groups.

[0127] According to the present invention, "cycloalkylalkyl" represents a monocyclic, bicyclic or tricyclic cycloalkylalkyl preferably having 4 to 10 or 4 to 7 carbon atoms, such as cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl and cyclopentylethyl. Also preferred are cycloalkylalkyl groups having 4, 5 or 7 carbon atoms, such as especially cyclopropylmethyl or cyclobutylmethyl. The cycloalkylalkyl groups of the present invention may be substituted by one or more identical or different groups.

[0128] According to the present invention, "hydroxyalkyl" represents a straight-chain or branched-chain alcohol preferably having 1 to 6 carbon atoms, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, and tert-butanol. Hydroxyalkyls having 1 to 4 carbon atoms are also preferred. The hydroxyalkyls of the present invention may be substituted by one or more identical or different groups.

[0129] According to the present invention, "alkoxy" represents a straight-chain or branched-chain O-alkyl preferably having 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, and tert-butoxy. Alkoxys having 1 to 4 carbon atoms are also preferred. The alkoxys of the present invention may be substituted by one or more identical or different groups.

[0130] According to the present invention, "alkylthio" or "alkylsulfanyl" represents a straight-chain or branched-chain S-alkyl preferably having 1 to 6 carbon atoms, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, and tert-butylthio. Alkylthios having 1 to 4 carbon atoms are also preferred. The alkylthios of the present invention may be substituted by one or more identical or different groups.

[0131] According to the present invention, "alkylsulfinyl" represents a straight-chain or branched-chain alkylsulfinyl preferably having 1 to 6 carbon atoms, such as methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, and tert-butylsulfinyl. Alkylsulfinyls having 1 to 4 carbon atoms are also preferred. The alkylsulfinyls of the present invention may be substituted by one or more identical or different groups and include two enantiomers.

[0132] According to the present invention, "alkylsulfonyl" represents a straight-chain or branched-chain alkylsulfonyl preferably having 1 to 6 carbon atoms, such as methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, and tert-butylsulfonyl. Alkylsulfonyls having 1 to 4 carbon atoms are also preferred. The alkylsulfonyls of the present invention may be substituted by one or more identical or different groups.

[0133] According to the present invention, "cycloalkylthio" or "cycloalkylsulfanyl" represents an -S-cycloalkyl preferably having 3 to 6 carbon atoms, such as cyclopropylthio, cyclobutylthio, cyclopentylthio, and cyclohexylthio. Cycloalkylthios having 3 to 5 carbon atoms are also preferred. The cycloalkylthios of the present invention may be substituted by one or more identical or different groups.

[0134] According to the present invention, "cycloalkylsulfinyl" represents -S(O)-cycloalkyl preferably having 3 to 6 carbon atoms, such as cyclopropylsulfinyl, cyclobutylsulfinyl, cyclopentylsulfinyl, cyclohexylsulfinyl. Cycloalkylsulfinyl having 3 to 5 carbon atoms is also preferred. The cycloalkylsulfinyl of the present invention can be substituted with one or more identical or different groups and includes two enantiomers.

[0135] According to the present invention, "cycloalkylsulfonyl" represents -SO 2 -cycloalkyl preferably having 3 to 6 carbon atoms, such as cyclopropylsulfonyl, cyclobutylsulfonyl, cyclopentylsulfonyl, cyclohexylsulfonyl. Cycloalkylsulfonyl having 3 to 5 carbon atoms is also preferred. The cycloalkylsulfonyl of the present invention can be substituted with one or more identical or different groups.

[0136] According to the present invention, "phenylthio" or "phenylsulfanyl" represents -S-phenyl, such as phenylthio. The phenylthio of the present invention can be substituted with one or more identical or different groups.

[0137] According to the present invention, "phenylsulfinyl" represents -S(O)-phenyl, such as phenylsulfinyl. The phenylsulfinyl of the present invention can be substituted with one or more identical or different groups and includes two enantiomers.

[0138] According to the present invention, "phenylsulfonyl" represents -SO 2 -phenyl, such as phenylsulfonyl. The phenylsulfonyl of the present invention can be substituted with one or more identical or different groups.

[0139] According to the present invention, "alkylcarbonyl" represents a straight-chain or branched-chain alkyl-C(=O) preferably having 2 to 7 carbon atoms, such as methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, sec-butylcarbonyl and tert-butylcarbonyl. Alkylcarbonyl having 1 to 4 carbon atoms is also preferred. The alkylcarbonyl of the present invention can be substituted with one or more identical or different groups.

[0140] According to the present invention, "alkoxycarbonyl" - either by itself or as part of a chemical group - represents a straight-chain or branched-chain alkoxycarbonyl preferably having 1 to 6 carbon atoms in the alkoxy moiety or having 1 to 4 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, sec-butoxycarbonyl and tert-butoxycarbonyl. The alkoxycarbonyl of the present invention can be substituted with one or more identical or different groups.

[0141] According to the present invention, "alkylaminocarbonyl" represents a straight-chain or branched alkylaminocarbonyl preferably having 1 to 6 carbon atoms or having 1 to 4 carbon atoms in the alkyl moiety, such as methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl, sec-butylaminocarbonyl, and tert-butylaminocarbonyl. The alkylaminocarbonyl of the present invention may be substituted with one or more identical or different groups.

[0142] According to the present invention, "N,N-dialkylaminocarbonyl" represents a straight-chain or branched N,N-dialkylaminocarbonyl preferably having 1 to 6 carbon atoms or having 1 to 4 carbon atoms in the alkyl moiety, such as N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl, N,N-di(n-propylamino)carbonyl, N,N-di(isopropylamino)carbonyl, and N,N-di-(sec-butylamino)carbonyl. The N,N-dialkylaminocarbonyl of the present invention may be substituted with one or more identical or different groups.

[0143] According to the present invention, "aryl" represents a monocyclic, bicyclic, or polycyclic aromatic system preferably having 6 to 14, particularly 6 to 10 ring carbon atoms, such as phenyl, naphthyl, anthryl, phenanthryl, preferably phenyl. In addition, aryl also represents a fused polycyclic system, such as tetrahydronaphthyl, indenyl, indanyl, fluorenyl, biphenyl, wherein the bonding site is on the aromatic system. The aryl of the present invention may be substituted with one or more identical or different groups.

[0144] Examples of substituted aryl are arylalkyls, which may likewise be substituted in the C 1 -C 4 alkyl and / or C 6 -C 14 aryl moiety with one or more identical or different groups. Examples of such arylalkyls include benzyl and phenyl-1-ethyl.

[0145] According to the present invention, the term "polycyclic" ring relates to fused, bridged, and spiro carbocyclic-type rings and heterocyclic-type rings and ring systems connected by single or double bonds.

[0146] According to the present invention, "heterocycle", "heterocyclic ring" or "heterocyclic system" represents a carbocyclic system having at least one ring, wherein at least one carbon atom is replaced by a heteroatom, preferably a heteroatom selected from N, O, S, P, B, Si, Se, and the at least one ring is saturated, unsaturated or heteroaromatic, and may be unsubstituted or substituted, wherein the bonding site is on the ring atom. Unless otherwise differently defined, the heterocycle preferably contains 3 to 9 ring atoms, especially 3 to 6 ring atoms, and one or more, preferably 1 to 4, especially 1, 2 or 3 heteroatoms in the heterocycle are preferably selected from N, O and S, provided that two oxygen atoms should not be directly adjacent. The heterocycle usually contains no more than 4 nitrogen atoms and / or no more than 2 oxygen atoms and / or no more than 2 sulfur atoms. In the case of an optionally substituted heterocyclic group, the present invention also includes polycyclic ring systems, such as 8-azabicyclo[3.2.1]octyl, 1-azabicyclo[2.2.1]heptyl, 1-oxa-5-azaspiro[2.3]hexyl or 2,3-dihydro-1H-indole.

[0147] The heterocyclic groups of the present invention are, for example: piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dihydropyranyl, tetrahydropyranyl, dioxanyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, thiazolidinyl, oxazolidinyl, dioxolanyl, dioxolyl, pyrazolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxetanyl, oxiranyl, azetidinyl, aziridinyl, oxazetidinyl, oxaziridinyl, oxazepanyl, oxazinanyl, azepanyl, oxopyrrolidinyl, dioxopyrrolidinyl, oxomorpholinyl, oxopiperazinyl and oxepanyl.

[0148] Heteroaryl (i.e., heteroaromatic system) is particularly important. According to the present invention, the term "heteroaryl" represents a heteroaromatic compound, i.e., a fully unsaturated aromatic heterocyclic compound covered by the above heterocyclic definition. It preferably has a 5- to 7-membered ring with 1 to 3, preferably 1 or 2, identical or different heteroatoms selected from the above types. The heteroaryl of the present invention is, for example: furyl, thienyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl and 1,2,4-triazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl and 1,2,5-oxadiazolyl, azepinyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl and 1,2,3-triazinyl, 1,2,4-oxazinyl, 1,3,2-oxazinyl, 1,3,6-oxazinyl and 1,2,6-oxazinyl, oxepinyl, thiepinyl, 1,2,4-triazolonyl and 1,2,4-diazepinyl. The heteroaryl of the present invention can also be substituted by one or more identical or different groups.

[0149] According to the present invention, the substituent =O (oxo) can replace two hydrogen atoms of the methylene (CH 2 ) group or only the lone pair of sulfur, nitrogen, and phosphorus atoms bearing substituents other than hydrogen. For example, the group C 2 -alkyl becomes, for example, -COCH 3 by being substituted with =O (oxo), and the heterocyclic thiolane-3-yl- becomes, for example, 1-oxothiolane-3-yl or 1,1-dioxothiolane-3-yl by being substituted with one =O (oxo) group or two =O (oxo) groups, respectively.

[0150] According to the present invention, the substituent =S (thioxo) can replace two hydrogen atoms of the methylene (CH 2 ) group. For example, the group C 2 -alkyl becomes, for example, -CSCH 3 by being substituted with =S (thioxo).

[0151] As used herein, the expression "optionally substituted" means that the optionally substituted group is either substituted by other substituents or not substituted by other substituents.

[0152] The term "optionally substituted in each case" means that a group / substituent, such as an alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cycloalkyl, aryl, phenyl, benzyl, heterocyclic group, and heteroaryl, is substituted, meaning a substituted group derived from, for example, an unsubstituted basic structure, where the substituent is, for example, one (1) substituent or multiple substituents, preferably 1, 2, 3, 4, 5, 6, or 7 substituents selected from the following: amino, hydroxy, halogen, nitro, cyano, isocyano, mercapto, isothiocyanato, C 1 -C 4 carboxy, carbamoyl, SF 5 , aminosulfonyl, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 4 cycloalkyl, C 2 -C 4 alkenyl, C 5 -C 6 cycloalkenyl, C 2 -C 4 alkynyl, N-mono-C 1 -C 4 alkylamino, N,N-di-C 1 -C 4 alkylamino, N-C 1 -C 4 alkanoylamino, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 2 -C 4 alkenyloxy, C 2 -C 4 alkynyloxy, C 3 -C 4 cycloalkoxy, C 5 -C 6 cycloalkenyloxy, C 1 -C 4 alkoxycarbonyl, C 2 -C 4 alkenyloxycarbonyl, C 2 -C 4 alkynyloxycarbonyl, C 6 -aryloxycarbonyl, C 10 -aryloxycarbonyl, C 14 -aryloxycarbonyl, C 1 -C 4 alkanoyl, C 2 -C 4 alkenylcarbonyl, C 2-C 4 alkynylcarbonyl, C 6 -arylcarbonyl, C 10 -arylcarbonyl, C 14 -arylcarbonyl, C 1 -C 4 alkylthio, C 1 -C 4 haloalkylthio, C 3 -C 4 cycloalkylthio, C 2 -C 4 alkenylthio, C 5 -C 6 cycloalkenylthio, C 2 -C 4 alkynylthio, C 1 -C 4 alkylsulfinyl (including the two enantiomers of C 1 -C 4 alkylsulfinyl), C 1 -C 4 haloalkylsulfinyl (including the two enantiomers of C 1 -C 4 haloalkylsulfinyl), C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl, N-mono-C 1 -C 4 alkylaminosulfonyl, N,N-di-C 1 -C 4 alkylaminosulfonyl, C 1 -C 4 alkylphosphinyl, C 1 -C 4 alkylphosphonyl (including C 1 -C 4 alkylphosphinyl and C 1 -C 4 alkylphosphonyl and the two enantiomers of C 1 -C 4 alkylaminocarbonyl, N,N-di-C 1 -C 4 alkylaminocarbonyl, N-C 1 -C 4 alkanoylaminocarbonyl, N-C 1 -C 4 alkanoyl-N-C 1 -C 4 alkylaminocarbonyl, C 6 -aryl, C 10 -aryl, C 14-aryl, C 6 -aryloxy, C 10 -aryloxy, C 14 -aryloxy, benzyl, benzyloxy, benzylthio, C 6 -arylthio, C 10 -arylthio, C 14 -arylthio, C 6 -arylamino, C 10 -arylamino, C 14 -arylamino, benzylamino, heterocyclic group and trialkylsilyl, substituents bonded through a double bond, such as C 1 -C 4 -alkylene (such as methylene or ethylene), oxo group, imino group and substituted imino group. When two or more groups form one or more rings, they can be carbocyclic, heterocyclic, saturated, partially saturated, unsaturated, and also include aromatic rings and further substitutions for example. The substituents mentioned by way of example (“first substituent level”) can—if they contain a hydrocarbon moiety—optionally have further substitutions therein (“second substituent level”), for example be substituted by one or more substituents each independently selected from the following: halogen, hydroxy, amino, nitro, cyano, isocyano, azide, amido, oxo group and imino group. The term “(optionally) substituted” group preferably exactly contains one or two substituent levels.

[0153] The halogen-substituted chemical groups or halo groups (e.g., alkyl or alkoxy) of the present invention are mono- or poly-substituted by halogen up to the maximum possible number of substituents. Such groups are also referred to as halo groups (e.g., haloalkyl). In the case of poly-substitution by halogen, the halogen atoms can be the same or different and can all be bonded to one carbon atom or can all be bonded to multiple carbon atoms. Halogen is particularly fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine and more preferably fluorine. More specifically, the halogen substituents are monohalocycloalkyls, such as 1-fluorocyclopropyl, 2-fluorocyclopropyl or 1-fluorocyclobutyl; monohaloalkyls, such as 2-chloroethyl, 2-fluoroethyl, 1-chloroethyl, 1-fluoroethyl, chloromethyl or fluoromethyl; perhaloalkyls, such as trichloromethyl or trifluoromethyl or CF 2 CF 3; polyhaloalkyl groups such as difluoromethyl, 2-fluoro-2-chloroethyl, dichloromethyl, 1,1,2,2-tetrafluoroethyl or 2,2,2-trifluoroethyl. Other examples of haloalkyl groups are trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, chloromethyl, bromomethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-chloro-2,2-difluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl and pentafluorotert-butyl. Preferred are those haloalkyl groups which have 1 to 4 carbon atoms and 1 to 9, preferably 1 to 5, identical or different halogen atoms selected from fluorine, chlorine and bromine. Particularly preferred are haloalkyl groups having 1 or 2 carbon atoms and 1 to 5 identical or different halogen atoms selected from fluorine and chlorine, such as especially difluoromethyl, trifluoromethyl or 2,2-difluoroethyl. Other examples of halogen-substituted compounds are haloalkoxy groups such as OCF 3 、OCHF 2 、OCH 2 F、OCF 2 CF 3 、OCH 2 CF 3 、OCH 2 CHF 2 and OCH 2 CH 2 Cl; haloalkylthio groups such as difluoromethylthio, trifluoromethylthio, trichloromethylthio, chlorodifluoromethylthio, 1-fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio, 1,1,2,2-tetrafluoroethylthio, 2,2,2-trifluoroethylthio or 2-chloro-1,1,2-trifluoroethylthio; haloalkylsulfinyl groups such as difluoromethylsulfinyl, trifluoromethylsulfinyl, trichloromethylsulfinyl, chlorodifluoromethylsulfinyl, 1-fluoroethylsulfinyl, 2-fluoroethylsulfinyl, 2,2-difluoroethylsulfinyl, 1,1,2,2-tetrafluoroethylsulfinyl, 2,2,2-trifluoroethylsulfinyl and 2-chloro-1,1,2-trifluoroethylsulfinyl; haloalkylsulfonyl groups such as difluoromethylsulfonyl, trifluoromethylsulfonyl, trichloromethylsulfonyl, chlorodifluoromethylsulfonyl, 1-fluoroethylsulfonyl, 2-fluoroethylsulfonyl, 2,2-difluoroethylsulfonyl, 1,1,2,2-tetrafluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl and 2-chloro-1,1,2-trifluoroethylsulfonyl.

[0154] In the case of groups having carbon atoms, those groups preferably having 1 to 4 carbon atoms, especially 1 or 2 carbon atoms, are usually preferred. Substituents selected from the following are generally preferred: halogens such as fluorine and chlorine; (C 1 -C 4 )alkyl, preferably methyl or ethyl; (C 1 -C 4 )haloalkyl, preferably trifluoromethyl; (C 1 -C 4 )alkoxy, preferably methoxy or ethoxy; (C 1 -C 4 )haloalkoxy; nitro and cyano. The following substituents are particularly preferred herein: methyl, methoxy, fluorine and chlorine.

[0155] Substituted amino groups such as mono-substituted or di-substituted amino groups mean substituted amino groups selected from the following, i.e., the amino group is N-substituted by one or two identical or different groups selected from the following: alkyl, hydroxy, amino, alkoxy, acyl and aryl; preferably N-monoalkylamino and N,N-dialkylamino (such as methylamino, ethylamino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino or N,N-dibutylamino), N-monoalkoxyalkylamino or N,N-dialkoxyalkylamino groups (such as N-methoxymethylamino, N-methoxyethylamino, N,N-di(methoxymethyl)amino or N,N-di(methoxyethyl)amino), N-monoarylamino and N,N-diarylamino, such as optionally substituted aniline, acylamino, N,N-diacylamino, N-alkyl-N-arylamino, N-alkyl-N-acylamino and saturated N-heterocycles; herein, alkyl groups having 1 to 4 carbon atoms are preferred; herein, aryl is preferably phenyl or substituted phenyl; for acyl, the definition given further below applies, preferably (C 1 -C 4 )alkanoyl. This also applies to substituted hydroxyamino or hydrazino groups.

[0156] Substituted amino also includes quaternary ammonium compounds (salts) having four organic substituents on the nitrogen atom.

[0157] Optionally substituted phenyl is preferably unsubstituted or mono-substituted or multi-substituted, preferably up to trisubstituted, by the same or different groups selected from the following: halogen, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkoxy, (C1 -C 4 )alkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )haloalkoxy, (C 1 -C 4 )alkylthio, (C 1 -C 4 )haloalkylthio, (C 1 -C 4 )alkylsulfinyl, (C 1 -C 4 )haloalkylsulfinyl, (C 1 -C 4 )alkylsulfonyl, (C 1 -C 4 )haloalkylsulfonyl, cyano, isocyano and nitro, such as o-tolyl, m-tolyl and p-tolyl, dimethylphenyl, 2-chlorophenyl, 3-chlorophenyl and 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl and 4-fluorophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl and 4-trifluoromethylphenyl and 4-trichloromethylphenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 2,5-dichlorophenyl and 2,3-dichlorophenyl, o-methoxyphenyl, m-methoxyphenyl and p-methoxyphenyl, 4-heptafluorophenyl.

[0158] The optionally substituted cycloalkyl is preferably an unsubstituted or mono- or polysubstituted cycloalkyl, preferably up to trisubstituted, with the same or different groups selected from: halogen, cyano, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkoxy, (C 1 -C 4 )alkoxy-(C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl and (C 1 -C 4 )haloalkoxy, especially substituted by one or two (C 1 -C 4 )alkyl groups.

[0159] Preferred embodiments of the compounds of the invention may exist. The individual embodiments described herein may be combined with one another. Combinations that violate the laws of nature and those that a person skilled in the art would rule out based on his / her expert knowledge are excluded. For example, a ring structure having three or more adjacent oxygen atoms is excluded.

[0160] Isomer

[0161] Depending on the nature of the substituents, the compounds of formula (I) may be in the form of geometric isomers and / or optically active isomers or mixtures of isomers having different compositions. These stereoisomers are, for example, enantiomers, diastereomers, atropisomers or geometric isomers. Accordingly, the invention includes pure stereoisomers and mixtures of any of these isomers.

[0162] Methods and uses

[0163] The invention further relates to a method for controlling animal pests, wherein a compound of formula (I) is applied to the animal pests and / or their habitat. The control of animal pests is preferably carried out in agriculture and forestry, as well as in material protection. Methods of surgically or therapeutically treating the human or animal body and diagnostic methods carried out on the human or animal body are preferably excluded therefrom.

[0164] The invention further relates to the use of the compounds of formula (I) as pesticides, in particular as crop protection agents.

[0165] In the context of the present application, the term "pesticide" always also includes the term "crop protection agent" in each case.

[0166] The compounds of formula (I) are suitable for the following uses due to their good plant tolerance, favorable warm-blooded animal toxicity and good environmental compatibility: protecting plants and plant organs against biotic and abiotic stress factors, increasing the harvest yield, improving the quality of the harvested product and controlling animal pests encountered in agriculture, horticulture, animal husbandry, aquaculture, forestry, gardens and leisure facilities, storage products and material protection, and the hygiene field, in particular insects, arachnids, worms (especially nematodes) and mollusks.

[0167] In the context of the present patent application, the term "hygiene" is understood to mean any and all measures, methods and practices aimed at preventing diseases, in particular infectious diseases, and for protecting human and animal health and / or the environment and / or maintaining cleanliness. According to the invention, this particularly includes cleaning, disinfecting and sterilizing, for example, textiles or hard surfaces, in particular glass, wood, concrete, porcelain, ceramics, plastics or metal surfaces, and measures for keeping them free from hygienically harmful substances and / or their secretions. In this regard, the scope of the invention preferably excludes surgical or therapeutic treatment methods for the human or animal body and diagnostic methods carried out on the human or animal body.

[0168] Thus, the term "hygiene sector" includes all areas, technical fields and industrial applications in which these hygiene measures, methods and practices are important, such as hygiene in kitchens, bakeries, airports, bathrooms, swimming pools, department stores, hotels, hospitals, stables, animal husbandry, etc.

[0169] Thus, the term "hygienically harmful substances" is understood to mean one or more such animal harmful substances: the presence of which in the hygiene sector is problematic, in particular for health reasons. Thus, the main aim is to avoid the presence of hygienically harmful substances and / or avoid exposure to these harmful substances in the hygiene sector, or to minimize them. This can in particular be achieved by using pesticides which can be used both for preventing infections and for treating existing infections. Preparations for avoiding or reducing exposure to harmful substances can also be used. For example, hygienically harmful substances include the organisms mentioned below.

[0170] Thus, the term "hygiene protection" encompasses all actions for maintaining and / or improving these hygiene measures, methods and practices.

[0171] The compounds of formula (I) can preferably be used as pesticides. They are active against normally sensitive and resistant species and for all or some stages of development. The above-mentioned harmful substances include:

[0172] Phylum Arthropoda, especially class Arachnida, such as Acarus spp. (e.g., Acarus siro, Aceria kuko, Aceria sheldoni), Aculops spp., Aculus spp. (e.g., Aculus fockeui, Aculus schlechtendali), Amblyomma spp., Amphitetranychus viennensis, Argas spp., Boophilus spp., Brevipalpus spp. (e.g., Brevipalpus phoenicis), Bryobia graminum, Bryobia praetiosa, Centruroides spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Dermacentor spp., Eotetranychus spp. (e.g., Eotetranychus hicoriae), Epitrimerus pyri, Eutetranychus spp. (e.g., Eutetranychus banksi), Eriophyes spp. (e.g., Eriophyes pyri), Glycyphagus domesticus, Halotydeus destructor, Hemitarsonemus spp. (e.g., Hemitarsonemus latus (= Polyphagotarsonemus latus)), Hyalomma spp., Ixodes spp., Latrodectus spp., Loxosceles spp.)、Neutrombicula autumnalis, genus Nuphersa, genus Oligonychus spp. (such as Oligonychus coffeae, Oligonychus coniferarum, Oligonychus ilicis, Oligonychus indicus, Oligonychus mangiferus, Oligonychus pratensis, Oligonychus punicae, Oligonychus yothersi), genus Ornithodorus spp, genus Ornithonyssus spp., genus Panonychus spp. (such as Panonychus citri (= Metatetranychus citri), Panonychus ulmi (= Metatetranychus ulmi)), Phyllocoptruta oleivora, Platytetranychus multidigituli, Polyphagotarsonemus latus, genus Psoroptes spp., genus Rhipicephalus spp., genus Rhizoglyphus spp., genus Sarcoptes spp., Scorpiomaurus, genus Stenotarsonemus spp., Steneotarsonemus spinki, genus Tarsonemus spp. (such as Tarsonemus confusus, Tarsonemus pallidus), genus Tetranychus spp.)(e.g., Tetranychus canadensis, Tetranychus cinnabarinus, Tetranychus turkestani, Tetranychus urticae), Trombicula alfreddugesi, Vaejovis spp., Vasates lycopersici;.

[0173] Chilopoda, e.g., Geophilus spp., Scutigera spp.;

[0174] Collembola, e.g., Onychiurus armatus; Sminthurus viridis;

[0175] Diplopoda, e.g., Blaniulus guttulatus;

[0176] Insecta, e.g., Blattodea, such as Blatta orientalis, Blattella asahinai, Blattella germanica, Leucophaea maderae, Loboptera decipiens, Neostylopyga rhombifolia, Panchlora spp., Parcoblatta spp., Periplaneta spp. (e.g., Periplaneta americana, Periplaneta australasiae), Pycnoscelus surinamensis, Supella longipalpa;

[0177] Coleoptera, such as, Acalymma vittatum, Acanthoscelides obtectus, Adoretus spp., Aethina tumida, Agelastica alni, Agrilus spp. (such as Agrilus planipennis, Agrilus coxalis, Agrilus bilineatus, Agrilus anxius), Agriotes spp. (such as Agriotes linneatus, Agriotes mancus), Agriotes obscurus, Alphitobius diaperinus, Amphimallon solstitialis, Anobium punctatum, Anomala dubia, Anoplophora spp. (such as Anoplophora glabripennis), Anthonomus spp. (such as Anthonomus grandis), Anthrenus spp., Apion spp., Apogonia spp., Athous haemorrhoidales, Atomaria spp. (such as Atomaria linearis), Attagenus spp., Baris caerulescens, Bruchidius obtectus, Bruchus spp. (such as Bruchus pisorum, Bruchus rufimanus), Cassida spp., Cerotoma trifurcata, Ceuthorhynchus spp. (such as Ceutorrhynchus assimilis, Ceutorrhynchus quadridens, Ceutorrhynchus rapae), Chaetocnema spp.(e.g., Chaetocnema confinis, Chaetocnema denticulata, Chaetocnema ectypa), Cleonus mendicus, Conoderus spp., Cosmopolites spp. (e.g., Cosmopolites sordidus), Costelytra zealandica, Ctenicera spp., Curculio spp. (e.g., Curculio caryae, Curculio caryatrypes, Curculio obtusus, Curculio sayi), Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptorhynchus lapathi, Cryptorhynchus mangiferae, Cylindrocopturus spp., Cylindrocopturus adspersus, Cylindrocopturus furnissi, Dendroctonus spp. (e.g., Dendroctonus ponderosae), Dermestes spp., Diabrotica spp. (e.g., Diabrotica balteata, Diabrotica barberi, Diabrotica undecimpunctata howardi, Diabrotica undecimpunctata undecimpunctata, Diabrotica virgifera virgifera, Diabrotica virgifera zeae), Dichocrocis spp., Dicladispa armigera, Diloboderus spp., Epicaerus spp., Epilachna spp.(e.g., Epilachna borealis, Epilachna varivestis), Epitrix spp. (e.g., Epitrix cucumeris, Epitrix fuscula, Epitrix hirtipennis, Epitrix subcrinita, Epitrix tuberis), Faustinus spp., Gibbium psylloides, Gnathocerus cornutus, Hellula undalis, Heteronychus arator, Heteronyx spp., Hoplia argentea, Hylamorpha elegans, Hylotrupes bajulus, Hypera postica, Hypomeces squamosus, Hypothenemus spp. (e.g., Hypothenemus hampei, Hypothenemus obscurus, Hypothenemus pubescens), Lachnosterna consanguinea, Lasioderma serricorne, Latheticus oryzae, Lathridius spp., Lema spp., Leptinotarsa decemlineata, Leucoptera spp. (e.g., Leucoptera coffeella), Limonius ectypus, Lissorhoptrus oryzophilus, Listronotus (=Hyperodes) spp., Lixus spp., Luperodes spp., Luperomorpha xanthodera, Lyctus spp., Megacyllene spp. (e.g., Megacyllene robiniae), Megascelis spp.) Melanotus spp. (e.g., Melanotus longulus oregonensis), Meligethes aeneus, Melolontha spp. (e.g., Melolontha melolontha), Migdolus spp., Monochamus spp., Naupactus xanthographus, Necrobia spp., Neogalerucella spp., Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorrhynchus spp. (e.g., Otiorhynchus cribricollis, Otiorhynchus ligustici, Otiorhynchus ovatus, Otiorhynchus rugosostriarus, Otiorhynchus sulcatus), Oulema spp. (e.g., Oulema melanopus, Oulema oryzae), Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., Phyllophaga helleri, Phyllotreta spp. (e.g., Phyllotreta armoraciae, Phyllotreta pusilla, Phyllotreta ramosa, Phyllotreta striolata), Popillia japonica, Premnotrypes spp., Prostephanus truncatus, Psylliodes spp.)(e.g., Psylliodes affinis, Psylliodes chrysocephala, Psylliodes punctulata), Ptinus spp., Rhizobius ventralis, Rhizopertha dominica, Rhynchophorus spp. (e.g., Rhynchophorus ferrugineus, Rhynchophorus palmarum), Scolytus spp. (e.g., Scolytus multistriatus), Sinoxylon perforans, Sitophilus spp. (e.g., Sitophilus granarius, Sitophilus linearis, Sitophilus oryzae, Sitophilus zeamais), Sphenophorus spp., Stegobium paniceum, Sternechus spp. (e.g., Sternechus paludatus), Symphyletes spp., Tanymecus spp. (e.g., Tanymecus dilaticollis, Tanymecus indicus, Tanymecus palliatus), Tenebrio molitor, Tenebrioides mauretanicus, Tribolium spp. (e.g., Tribolium audax, Tribolium castaneum, Tribolium confusum), Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrus spp. (e.g., Zabrus tenebrioides);.

[0178] Dermaptera, such as, Anisolabis maritime, Forficula auricularia, Labidura riparia;

[0179] Diptera, for example, Aedes spp. (such as Aedes aegypti, Aedes albopictus, Aedes sticticus, Aedes vexans), Agromyza spp. (such as Agromyza frontella, Agromyzaparvicornis), Anastrepha spp., Anopheles spp. (such as Anopheles quadrimaculatus, Anopheles gambiae), Asphondyliaspp., Bactrocera spp. (such as Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera oleae), Bibiohortulanus, Calliphora erythrocephala, Calliphora vicina, Ceratitis capitata, Chironomus spp., Chrysomya spp., Chrysops spp., Chrysozona pluvialis, Cochliomyaspp., Contarinia spp. (such as Contarinia johnsoni, Contarinia nasturtii, Contarinia pyrivora, Contarinia schulzi, Contarinia sorghicola, Contarinia tritici), Cordylobia anthropophaga, Cricotopus sylvestris, Culexspp. (such as Culex pipiens, Culex quinquefasciatus), Culicoides spp., Culiseta spp., Cuterebra spp.)、Olive fruit fly (Dacus oleae), Dasineura spp. (such as Dasineura brassicae), Delia spp. (such as Delia antiqua, Delia coarctata, Delia florilega, Delia platura, Delia radicum), Human botfly (Dermatobia hominis), Drosophila spp. (such as Drosophila melanogaster, Drosophila suzukii), Echinocnemus spp., Euleia heraclei, Fannia spp., Gastrophilus spp., Glossina spp., Haematopota spp., Hydrellia spp. (such as Hydrellia griseola), Hylemya spp., Hippobosca spp., Hypoderma spp., Liriomyza spp. (such as Liriomyza brassicae, Liriomyza huidobrensis, Liriomyza sativae), Lucilia spp. (such as Lucilia cuprina), Lutzomyia spp., Mansonia spp., Musca spp. (such as Musca domestica, Musca domestica vicina), Oestrus spp., Oscinella frit, Paratanytarsus spp., Paralauterborniella subcincta, Pegomya or Pegomyia spp. (such as Pegomya betae, Pegomya hyoscyami, Pegomyia rubivora), Phlebotomus spp.)、Phorbia spp., Phormia spp., Piophila casei, Platyparea poeciloptera, Prodiplosis spp., Psila rosae, Rhagoletis spp. (e.g., Rhagoletis cingulata, Rhagoletis completa, Rhagoletis fausta, Rhagoletis indifferens, Rhagoletis mendax, Rhagoletis pomonella), Sarcophaga spp., Simulium spp. (e.g., Simulium meridionale), Stomoxys spp., Tabanus spp., Tetanops spp., Tipula spp. (e.g., Tipula paludosa, Tipula simplex), Toxotrypana curvicauda;.

[0180] Hemiptera, such as Acizzia acaciaebaileyanae, Acizzia dodonaeae, Acizzia uncatoides, Acrida turrita, Acyrthosipon spp. (such as Acyrthosiphon pisum), Acrogonia spp., Aeneolamia spp., Agonoscena spp., Aleurocanthus spp., Aleyrodes proletella, Aleurolobus barodensis, Aleurothrixus floccosus, Allocaridara malayensis, Amrasca spp. (such as Amrasca bigutulla, Amrasca devastans), Anuraphis cardui, Aonidiella spp. (such as Aonidiella aurantii, Aonidiella citrina, Aonidiella inornata), Aphanostigma piri, Aphis spp. (such as Aphis citricola, Aphis craccivora, Aphis fabae, Aphis forbesi, Aphis glycines, Aphis gossypii, Aphis hederae, Aphis illinoisensis, Aphis middletoni, Aphis nasturtii, Aphis nerii, Aphis pomi, Aphis spiraecola, Aphis viburniphila, Arboridia apicalis, Arytainilla spp., Aspidiella spp., Aspidiotus spp.(e.g., Aspidiotus nerii), Atanus genus, Aulacorthum solani, Bemisia tabaci, Blastopsylla occidentalis, Boreioglycaspis melaleucae, Brachycaudus helichrysii, Brachycolus spp., Brevicoryne brassicae, Cacopsyllaspp. (e.g., Cacopsylla pyricola), Calligypona marginata, Capulinia genus, Carneocephala fulgida, Ceratovacuna lanigera, Cercopidae, Ceroplastes spp., Chaetosiphon fragaefolii, Chionaspis tegalensis, Chlorita onukii, Chondracris rosea, Chromaphis juglandicola, Chrysomphalus aonidum, Chrysomphalus ficus, Cicadulina mbila, Coccomytilus halli, Coccus spp. (e.g., Coccus hesperidum, Coccus longulus, Coccus pseudomagnoliarum, Coccus viridis), Cryptomyzus ribis, Cryptoneossa genus, Ctenarytaina spp., Dalbulus spp., Dialeurodes chittendeni, Dialeurodes citri, Diaphorina citri, Diaspis spp., Diuraphis genus, Doralis genus, Drosicha spp., Dysaphis spp.(e.g., Dysaphis apiifolia, Dysaphis plantaginea, Dysaphis tulipae), Dysmicoccus spp., Empoasca spp. (e.g., Empoasca abrupta, Empoasca fabae, Empoasca maligna, Empoasca solana, Empoasca stevensi), Eriosoma spp. (e.g., Eriosoma americanum, Eriosoma lanigerum, Eriosoma pyricola), Erythroneura spp., Eucalyptolyma spp., Euphyllura spp., Euscelis bilobatus, Ferrisia spp., Fiorinia spp., Furcaspis oceanica, Geococcus coffeae, Glycaspis spp., Heteropsylla cubana, Heteropsylla spinulosa, Homalodisca coagulata, Hyalopterus arundinis, Hyalopterus pruni, Icerya spp. (e.g., Icerya purchasi), Idiocerus spp., Idioscopus spp., Laodelphax striatellus, Lecanium spp. (e.g., Lecanium corni (=Parthenolecanium corni)), Lepidosaphes spp. (e.g., Lepidosaphes ulmi), Lipaphis erysimi, Lopholeucaspis japonica, Lycorma delicatula, Macrosiphum spp.(e.g., Macrosiphum euphorbiae, Macrosiphum lilii, Macrosiphum rosae), Macrosteles facifrons, Mahanarva spp., Melanaphis sacchari, Metcalfiella spp., Metcalfa pruinosa, Metopolophium dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus spp. (e.g., Myzus ascalonicus, Myzus cerasi, Myzus ligustri, Myzus ornatus, Myzus persicae, Myzus nicotianae), Nasonovia ribisnigri, Neomaskellia spp., Nephotettix spp. (e.g., Nephotettix cincticeps, Nephotettix nigropictus), Nettigoniclla spectra, Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Oxya chinensis, Pachypsylla spp., Parabemisia myricae, Paratrioza spp. (e.g., Paratrioza cockerelli), Parlatoria spp., Pemphigus spp. (e.g., Pemphigus bursarius, Pemphigus populivenae), Peregrinus maidis, Perkinsiella spp., Phenacoccus spp. (e.g., Phenacoccus madeirensis), Phloeomyzus passerinii, Phorodon humuli, Phylloxera spp.(e.g., Phylloxera devastatrix, Phylloxera notabilis), Pinnaspis aspidistrae, Planococcus spp. (e.g., Planococcus citri), Prosopidopsylla flava, Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus spp. (e.g., Pseudococcus calceolariae, Pseudococcus comstocki, Pseudococcus longispinus, Pseudococcus maritimus, Pseudococcus viburni), Psyllopsis spp., Psylla spp. (e.g., Psylla buxi, Psylla mali, Psylla pyri), Pteromalus spp., Pulvinaria spp., Pyrilla spp., Quadraspidiotus spp. (e.g., Quadraspidiotus juglansregiae, Quadraspidiotus ostreaeformis, Quadraspidiotus perniciosus), Quesada gigas, Rastrococcus spp., Rhopalosiphum spp. (e.g., Rhopalosiphum maidis, Rhopalosiphum oxyacanthae, Rhopalosiphum padi, Rhopalosiphum rufiabdominale), Saissetia spp.(e.g., Saissetia coffeae, Saissetia miranda, Saissetia neglecta, Saissetia oleae), Scaphoideus titanus, Schizaphis graminum, Selenaspidus articulatus, Sipha flava, Sitobion avenae, Sogata spp., Sogatella furcifera, Sogatodes spp., Stictocephala festina, Siphoninus phillyreae, Tenalaphara malayensis, Tetragonocephela spp., Tinocallis caryaefoliae, Tomaspis spp., Toxoptera spp. (e.g., Toxoptera aurantii, Toxoptera citricidus), Trialeurodes vaporariorum, Trioza spp. (e.g., Trioza diospyri), Typhlocyba spp., Unaspis spp., Viteus vitifolii, Zygina spp.;.

[0181] Heteroptera, for example, genus Aelia, Anasa tristis, Antestiopsis spp., genus Boisea, Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp. (such as Cimex adjunctus, Cimex hemipterus, Cimex lectularius, Cimex pilosellus), Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp. (such as Euschistus heros, Euschistus servus, Euschistus tristigmus, Euschistus variolarius), Eurydema spp., Eurygaster spp., Halyomorpha halys, Heliopeltis spp., Horcias nobilellus, Leptocorisa spp., Leptocoris varicornis, Leptoglossus occidentalis, Leptoglossus phyllopus, Lygocoris spp. (such as Lygocoris pabulinus), Lygus spp. (such as Lygus elisus, Lygus hesperus, Lygus lineolaris), Macropes excavatus, Megacopta cribraria, Miridae, Monalonion atratum, Nezara spp.)(e.g., Nezara viridula), Nysius genus, Oebalus spp., Pentomidae, Piesma quadratum, Piezodorus spp. (e.g., Piezodorus guildinii), Psallus spp., Pseudacysta persea, Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophora spp., Stephanitis nashi, Tibraca genus, Triatoma spp.;

[0182] Hymenoptera, e.g., Acromyrmex spp., Athalia spp. (e.g., Athalia rosae), Atta spp., Camponotus spp., Dolichovespula genus, Diprion spp. (e.g., Diprion similis), Hoplocampa spp. (e.g., Hoplocampa cookei, Hoplocampa testudinea), Lasius spp., Linepithema (Iridiomyrmex) humile, Monomorium pharaonis, Paratrechina spp., Paravespula genus, Plagiolepis genus, Sirex spp. (e.g., Sirex noctilio), Solenopsis invicta, Tapinoma spp., Technomyrmex albipes, Urocerus spp., Vespa spp. (e.g., Vespa crabro), Wasmannia auropunctata, Xeris spp.;

[0183] Isopoda, for example, Armadillidium vulgare, Oniscus asellus, Porcellio scaber;

[0184] Isoptera, for example, Coptotermes spp. (e.g., Coptotermes formosanus), Cornitermes cumulans, Cryptotermes spp., Incisitermes spp., Kalotermes spp., Microtermes obesi, Nasutitermes spp., Odontotermes spp., Porotermes, Reticulitermes spp. (e.g., Reticulitermes flavipes, Reticulitermes hesperus);

[0185] Lepidoptera, for example, Achroia grisella, Acronicta major, Adoxophyes spp. (e.g., Adoxophyes orana), Aedia leucomelas, Agrotis spp. (e.g., Agrotis segetum, Agrotis ipsilon), Alabama spp. (e.g., Alabama argillacea), Amyelois transitella, Anarsia spp., Anticarsia spp. (e.g., Anticarsia gemmatalis), Argyroploce spp., Autographa spp., Barathra brassicae, Blastodacna atra, Borbo cinnara, Bucculatrix thurberiella, Bupalus piniarius, Busseola spp., Cacoecia spp., Caloptilia theivora, Capua reticulana, Carpocapsa pomonella, Carposina niponensis, Cheimatobia brumata, Chilo spp. (e.g., Chilo plejadellus, Chilo suppressalis), Choreutis pariana, Choristoneura spp., Chrysodeixis chalcites, Clysia ambiguella, Cnaphalocerus spp., Cnaphalocrocis medinalis, Cnephasia spp., Conopomorpha spp., Conotrachelus spp., Copitarsia spp., Cydia spp.(e.g., Cydia nigricana, Cydia pomonella), Dalaca noctuides, Diaphania spp., Diparopsis spp., Diatraea saccharalis, Dioryctria spp. (e.g., Dioryctria zimmermani), Earias spp., Ecdytolopha aurantium, Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp. (e.g., Ephestia elutella, Ephestia kuehniella), Epinotia spp., Epiphyas postvittana, Erannis spp., Erschoviella musculana, Etiella spp., Eudocima spp., Eulia spp., Eupoecilia ambiguella, Euproctis spp. (e.g., Euproctis chrysorrhoea), Euxoa spp., Feltia spp., Galleria mellonella, Gracillaria spp., Grapholitha spp. (e.g., Grapholita molesta, Grapholita prunivora), Hedylepta spp., Helicoverpa spp. (e.g., Helicoverpa armigera, Helicoverpa zea), Heliothis spp. (e.g., Heliothis virescens), Hepialus spp. (e.g., Hepialus humuli), Hofmannophila pseudospretella, Homoeosoma spp., Homona spp.)、Hyponomeuta padella, Kakivoria flavofasciata, Lampides spp., Laphygma spp., Laspeyresia molesta, Leucinodes orbonalis, Leucoptera spp. (e.g., Leucoptera coffeella), Lithocolletis spp. (e.g., Lithocolletis blancardella), Lithophane antennata, Lobesia spp. (e.g., Lobesia botrana), Loxagrotis albicosta, Lymantria spp. (e.g., Lymantria dispar), Lyonetia spp. (e.g., Lyonetia clerkella), Malacosoma neustria, Maruca testulalis, Mamestra brassicae, Melanitis leda, Mocis spp., Monopis obviella, Mythimna separata, Nemapogon cloacellus, Nymphula spp., Oiketicus spp., Omphisa spp., Operophtera spp., Oria spp., Orthaga spp., Ostrinia spp. (e.g., Ostrinia nubilalis), Panolis flammea, Parnara spp., Pectinophora spp. (e.g., Pectinophora gossypiella), Perileucoptera spp., Phthorimaea spp.(e.g., potato tuber moth (Phthorimaea operculella)), citrus leafminer (Phyllocnistis citrella), Phyllonorycter spp. (e.g., apple leafminer (Phyllonorycter blancardella), hawthorn leafminer (Phyllonorycter crataegella)), Pieris spp. (e.g., small white (Pieris rapae)), Platynota stultana, Indian meal moth (Plodia interpunctella), Plusia spp., diamondback moth (Plutella xylostella) (= Plutella maculipennis), Podesia spp. (e.g., Podesia syringae), Prays spp., Prodenia spp., Protoparce spp., Pseudaletia spp. (e.g., armyworm (Pseudaletia unipuncta)), soybean looper (Pseudoplusia includens), European corn borer (Pyrausta nubilalis), mint looper (Rachiplusia nu), Schoenobius spp. (e.g., yellow rice borer (Schoenobius bipunctifer)), Scirpophaga spp. (e.g., white rice borer (Scirpophaga innotata)), turnip moth (Scotia segetum), Sesamia spp. (e.g., pink rice borer (Sesamia inferens)), Sparganothis spp., Spodoptera spp. (e.g., Spodoptera eradiana, beet armyworm (Spodoptera exigua), fall armyworm (Spodoptera frugiperda), Spodoptera praefica), Stathmopoda spp., Stenoma spp., peanut leafminer (Stomopteryx subsecivella), Synanthedon spp., Andean potato tuber moth (Tecia solanivora), Thaumetopoea spp.)、Thermesia gemmatalis, Tinea cloacella, Tinea pellionella, Tineola bisselliella, Tortrix spp., Trichophaga tapetzella, Trichoplusia spp. (e.g., Trichoplusia ni), Tryporyza incertulas, Tuta absoluta, Virachola spp.;.

[0186] Orthoptera or Saltatoria, e.g., Acheta domesticus, Dichroplus spp., Gryllotalpa spp. (e.g., Gryllotalpa gryllotalpa), Hieroglyphus spp., Locusta spp. (e.g., Locusta migratoria), Melanoplus spp. (e.g., Melanoplus devastator, Paratlanticus ussuriensis), Schistocerca gregaria;

[0187] Phthiraptera, e.g., Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Phylloxera vastatrix, Phthirus pubis, Trichodectes spp.;

[0188] Psocoptera, e.g., Lepinatus spp., Liposcelis spp.;

[0189] Siphonaptera, e.g., Ceratophyllus spp., Ctenocephalides spp. (e.g., Ctenocephalides canis, Ctenocephalides felis), Pulex irritans, Tunga penetrans, Xenopsylla cheopis;

[0190] Thysanoptera, e.g., Anaphothrips obscurus, Baliothrips biformis, Chaetanaphothrips leeuweni, Drepanothris reuteri, Enneothrips flavens, Frankliniella spp. (e.g., Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella tritici, Frankliniella vaccinii, Frankliniella williamsi), Haplothrips spp., Heliothrips spp., Hercinothrips femoralis, Kakothrips spp., Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamomi, Thrips spp. (e.g., Thrips palmi, Thrips tabaci);

[0191] Zygentoma ( = Thysanura), e.g., Ctenolepisma spp., Lepisma saccharina, Lepismodes inquilinus, Thermobia domestica;

[0192] Symphyla, e.g., Scutigerella spp. (e.g., Scutigerella immaculata);

[0193] Phylum Mollusca, e.g., class Bivalvia, such as Dreissena spp.,

[0194] and class Gastropoda, such as Arion spp. (e.g., Arion ater rufus), Biomphalaria spp., Bulinus spp., Deroceras spp. (e.g., Deroceras laeve), Galba spp., Lymnaea spp., Oncomelania spp., Pomacea spp., Succinea spp.;

[0195] From the phylum Nematoda, namely phytoparasitic nematodes, especially Aglenchus spp. (such as Aglenchus agricola), Anguina spp. (such as Anguina tritici), Aphelenchoides spp. (such as Aphelenchoides arachidis, Aphelenchoides fragariae), Belonolaimus spp. (such as Belonolaimus gracilis, Belonolaimus longicaudatus, Belonolaimus nortoni), Bursaphelenchus spp. (such as Bursaphelenchus cocophilus, Bursaphelenchus eremus, Bursaphelenchus xylophilus), Cacopaurus spp. (such as Cacopaurus pestis), Criconemella spp. (such as Criconemella curvata, Criconemella onoensis, Criconemella ornata, Criconemella rusium, Criconemella xenoplax (=Mesocriconema xenoplax)), Criconemoides spp. (such as Criconemoides ferniae, Criconemoides onoense, Criconemoides ornatum), Ditylenchus spp. (such as Ditylenchus dipsaci), Dolichodorus spp., Globodera spp.)(e.g., *Globodera pallida*, *Globodera rostochiensis*), *Helicotylenchus* spp. (e.g., *Helicotylenchus dihystera*), *Hemicriconemoides* spp., *Hemicycliophora* spp., *Heterodera* spp. (e.g., *Heterodera avenae*, *Heterodera glycines*, *Heterodera schachtii*), *Hirschmaniella* spp., *Hoplolaimus* spp., *Longidorus* spp. (e.g., *Longidorus africanus*), *Meloidogyne* spp. (e.g., *Meloidogyne chitwoodi*, *Meloidogyne fallax*, *Meloidogyne hapla*, *Meloidogyne incognita*), *Meloinema* spp., *Nacobbus* spp., *Neotylenchus* spp., *Paralongidorus* spp., *Paraphelenchus* spp., *Paratrichodorus* spp. (e.g., *Paratrichodorus minor*), *Paratylenchus* spp., *Pratylenchus* spp. (e.g., *Pratylenchus penetrans*), *Pseudohalenchus* genus, *Psilenchus* spp., *Punctodera* spp., *Quinisulcius* spp., *Radopholus* spp. (e.g., *Radopholus citrophilus*, *Radopholus similis*), *Rotylenchulus* spp.) Rotylenchus spp., Scutellonema spp., Subanguina spp., Trichodorus spp. (e.g., Trichodorus obtusus, Trichodorus primitivus), Tylenchorhynchus spp. (e.g., Tylenchorhynchus annulatus), Tylenchulus spp. (e.g., Tylenchulus semipenetrans), Xiphinema spp. (e.g., Xiphinema index).

[0196] At a certain concentration or application rate, the compounds of formula (I) can also optionally be used as herbicides, safeners, growth regulators or agents for improving plant characteristics, as microbicides or gametocides, for example as fungicides, antimycotics, bactericides, virucides (including agents against viroids) or as agents against MLO (mycoplasma-like organisms) and RLO (rickettsia-like organisms). If appropriate, they can also be used as intermediates or precursors for the synthesis of other active compounds.

[0197] Formulation / Use form

[0198] The present invention also relates to formulations, in particular formulations for controlling unwanted animal pests. The formulations can be applied to the animal pests and / or their habitat.

[0199] The formulations of the present invention can be provided to the end user in a "ready-to-use" form of use, i.e., the formulations can be directly applied to plants or seeds by means of a suitable device such as a sprayer or a duster. Alternatively, the formulations can be provided to the end user in the form of a concentrate which must be diluted before use, preferably diluted with water. Thus, unless otherwise stated, the term "formulation" means such a concentrate, and the term "form of use" means that the end user uses it in the form of a "ready-to-use" solution, i.e., usually uses such a diluted formulation.

[0200] The formulations of the present invention can be prepared in a conventional manner, for example by mixing the compounds of the present invention with one or more suitable auxiliaries (such as those disclosed herein).

[0201] The formulations comprise at least one compound of the present invention and at least one agriculturally suitable auxiliary, such as a carrier and / or a surfactant.

[0202] Carriers are usually inert solids or liquids, natural or synthetic, organic or inorganic substances. Carriers usually improve the application of the compound, such as the application to plants, plant parts or seeds. Examples of suitable solid carriers include, but are not limited to, ammonium salts, especially ammonium sulfate, ammonium phosphate and ammonium nitrate; natural rock powders, such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite and diatomaceous earth, silica gel and synthetic rock powders, such as finely ground silica, alumina and silicates. Examples of solid carriers that are usually useful for preparing granule formulations include, but are not limited to, crushed and classified natural rocks, such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic granules of inorganic powders and organic powders and granules of organic materials such as paper, sawdust, coconut husk, corn cobs and tobacco stems. Examples of suitable liquid carriers include, but are not limited to, water, organic solvents and combinations thereof. Examples of suitable solvents include polar and non-polar organic chemical liquids, such as aromatic and non-aromatic hydrocarbons (such as cyclohexane, alkanes, alkylbenzenes, xylenes, toluene, tetrahydronaphthalene, alkylnaphthalenes, chlorinated aromatic hydrocarbons or chlorinated aliphatic hydrocarbons such as chlorobenzene, vinyl chloride or dichloromethane), alcohols and polyols (which may optionally also be substituted, etherified and / or esterified, such as ethanol, propanol, butanol, benzyl alcohol, cyclohexanol or diols), ketones (such as acetone, methyl ethyl ketone, methyl isobutyl ketone, acetophenone or cyclohexanone), esters (including fats and oils) and (poly)ethers, unsubstituted and substituted amines, amides (such as dimethylformamide or fatty amides) and their esters, lactams (such as N-alkylpyrrolidones, especially N-methylpyrrolidone) and lactones, sulfones and sulfoxides (such as dimethyl sulfoxide), vegetable oils or animal oils, nitriles (alkyl nitriles such as acetonitrile, propionitrile, butyronitrile or aromatic nitriles such as benzonitrile), carbonates (cyclic carbonates such as ethylene carbonate, propylene carbonate, butylene carbonate, or dialkyl carbonates such as dimethyl carbonate, diethyl carbonate, dipropyl carbonate, dibutyl carbonate, dioctyl carbonate). The carrier can also be a liquefied gas extender, i.e., a liquid that is gaseous at standard temperature and standard pressure, such as an aerosol propellant, such as a halogenated hydrocarbon, butane, propane, nitrogen and carbon dioxide.

[0203] Preferred solid carriers are selected from clay, talc and silica.

[0204] Preferred liquid carriers are selected from water, fatty acid amides and their esters, aromatic hydrocarbons and non-aromatic hydrocarbons, lactams, lactones, carbonates, ketones and (poly)ethers.

[0205] The amount of the carrier is usually 1 to 99.99% by weight of the formulation, preferably 5 to 99.9% by weight, more preferably 10 to 99.5% by weight, and most preferably 20 to 99% by weight.

[0206] The liquid carrier is usually present in the preparation in an amount of 20 to 90% by weight, for example 30 to 80% by weight.

[0207] The solid carrier is usually present in the preparation in an amount of 0 to 50% by weight, preferably 5 to 45% by weight, for example 10 to 30% by weight.

[0208] If the preparation contains two or more carriers, the defined ranges refer to the total amount of the carriers.

[0209] The surfactant can be an ionic (cationic or anionic), amphoteric or non-ionic surfactant, such as an ionic or non-ionic emulsifier, foaming agent, dispersant, wetting agent, penetration enhancer and any mixture thereof. Examples of suitable surfactants include, but are not limited to, salts of polyacrylic acid; ethoxylated poly(α-substituted) acrylate derivatives; salts of lignosulfonic acid (such as sodium lignosulfonate); salts of phenolsulfonic acid or naphthalenesulfonic acid; condensates of ethylene oxide and / or propylene oxide with or without alcohols; fatty acids or fatty amines (such as polyoxyethylene fatty acid esters such as castor oil ethoxylate, polyoxyethylene fatty alcohol ethers, such as alkylaryl polyglycol ethers); substituted phenols (preferably alkylphenols or arylphenols); salts of sulfosuccinates; taurine derivatives (preferably taurine alkyl esters); phosphates of polyethoxylated alcohols or phenols; fatty acid esters of polyols (such as fatty acid esters of glycerol, sorbitol or sucrose); sulfates (such as alkyl sulfates and alkyl ether sulfates); sulfonates (such as alkyl sulfonates, aryl sulfonates and alkylbenzene sulfonates); sulfonated polymers of naphthalene / formaldehyde; phosphates; protein hydrolysates; lignosulfite waste liquor and methylcellulose. Any reference to salts in this paragraph preferably refers to the corresponding alkali metal salts, alkaline earth metal salts and ammonium salts.

[0210] Preferred surfactants are selected from ethoxylated poly(α-substituted) acrylate derivatives, condensates of ethylene oxide and / or propylene oxide with alcohols, polyoxyethylene fatty acid esters, alkylbenzene sulfonates, sulfonated polymers of naphthalene / formaldehyde; polyoxyethylene fatty acid esters such as castor oil ethoxylate, sodium lignosulfonate and arylphenol ethoxylate.

[0211] The amount of the surfactant is usually 5 to 40% by weight of the preparation, for example 10 to 20% by weight.

[0212] Other examples of suitable auxiliaries include water-repellent substances, desiccants, adhesives (adhesives, tackifiers, fixatives such as carboxymethyl cellulose; natural and synthetic polymers in the form of powders, granules or latexes, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, natural phospholipids such as cephalin and lecithin and synthetic phospholipids, polyvinylpyrrolidone and methylcellulose), thickeners and secondary thickeners (such as cellulose ethers, acrylic derivatives, xanthan gum, modified clays, such as products available under the name Bentone and finely ground silica), stabilizers (such as cold stabilizers, preservatives (such as dichlorophen, benzyl alcohol hemiacetal, 1,2-benzisothiazolin-3-one, 2-methyl-4-isothiazolin-3-one), antioxidants, light stabilizers (especially UV stabilizers or other agents that improve chemical and / or physical stability), dyes or pigments (such as inorganic pigments, such as iron oxide, titanium oxide and Prussian blue; organic pigments such as alizarin, azo and metal phthalocyanine dyes), defoamers (such as silicone defoamers and magnesium stearate), antifreeze agents, tackifiers, gibberellins and processing aids, mineral oils and vegetable oils, fragrances, waxes, nutrients (including micronutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc), protective colloids, thixotropic substances, penetrants, chelating agents and complexing agents).

[0213] The choice of auxiliaries depends on the intended application mode of the compounds of the present invention and / or the physical properties of the compounds. In addition, the auxiliaries can be selected to impart certain special properties (industrial (technical), physical and / or biological properties) to the formulation or the use form prepared therefrom. The choice of auxiliaries allows the formulation to be made according to specific requirements.

[0214] The formulation contains an insecticidal / acaricidal / nematicidal effective amount of the compound of the present invention. The term "effective amount" means an amount sufficient to control harmful insects / acarids / nematodes on cultivated plants or sufficient to protect materials and cause no substantial damage to the treated plants. Such an amount can vary within a wide range and depends on various factors, such as the species of insects / acarids / nematodes to be controlled, the cultivated plants or materials to be treated, the climatic conditions and the specific compound of the present invention used. Generally, the formulations of the present invention contain 0.01 to 99% by weight, preferably 0.05 to 98% by weight, more preferably 0.1 to 95% by weight, even more preferably 0.5 to 90% by weight, most preferably 1 to 80% by weight of the compound of the present invention. The formulation can contain two or more compounds of the present invention. In such cases, the defined range refers to the total amount of the compounds of the present invention.

[0215] The formulations of the present invention can exist in any conventional formulation type, such as solutions (e.g., aqueous solutions), emulsions, water-based and oil-based suspensions, powders (e.g., wettable powders, soluble powders), dusts, pastes, granules (e.g., soluble granules, broadcast granules), suspoemulsion concentrates, natural or synthetic products impregnated with the compounds of the present invention, fertilizers, and microcapsules in polymeric substances. The compounds of the present invention can exist in a suspended, emulsified, or dissolved form. Examples of specific suitable formulation types are solutions, water-soluble concentrates (e.g., SL, LS), dispersible concentrates (DC), suspensions and suspension concentrates (e.g., SC, OD, OF, FS), emulsifiable concentrates (e.g., EC), emulsions (e.g., EW, EO, ES, ME, SE), capsules (e.g., CS, ZC), pastes, tablets, wettable powders or dusts (e.g., WP, SP, WS, DP, DS), compacts (e.g., BR, TB, DT), granules (e.g., WG, SG, GR, FG, GG, MG), insecticidal products (e.g., LN), and gel formulations (e.g., GW, GF) for treating plant propagation materials such as seeds. These and other formulation types have been defined by the Food and Agriculture Organization of the United Nations (FAO). A review is given in "Catalogue of pesticide formulation types and international coding system", Technical Monograph No. 2, 6th Edition, May 2008, Croplife International.

[0216] Preferably, the formulations of the present invention exist in the form of one of the following types: EC, SC, FS, SE, OD, WG, WP, CS, more preferably EC, SC, OD, WG, CS.

[0217] Further details regarding examples of formulation types and their preparation are given below. If there are two or more compounds of the present invention, the defined amounts of the compounds of the present invention refer to the total amount of the compounds of the present invention. This also applies to all other components of the formulation, if there are two or more representatives of such components (e.g., wetting agents or binders).

[0218] i) Water-soluble concentrates (SL, LS)

[0219] 10 - 60% by weight of at least one compound of the present invention and 5 - 15% by weight of a surfactant (e.g., a condensate of ethylene oxide and / or propylene oxide with an alcohol) are dissolved in a certain amount of water and / or a water-soluble solvent (e.g., alcohols such as propylene glycol or carbonates such as propylene carbonate) such that the total is 100%. Before application, the concentrate is diluted with water.

[0220] ii) Dispersible Concentrate (DC)

[0221] Dissolve 5 - 25% by weight of at least one compound of the present invention, 1 - 10% by weight of a surfactant and / or binder (such as polyvinylpyrrolidone) in a certain amount of an organic solvent (such as cyclohexanone) such that the total is 100% by weight. Dilute with water to obtain a dispersion.

[0222] iii) Emulsifiable Concentrate (EC)

[0223] Dissolve 15 - 70% by weight of at least one compound of the present invention, 5 - 10% by weight of a surfactant (such as a mixture of calcium dodecylbenzenesulfonate and castor oil ethoxylate) in a certain amount of a water-insoluble organic solvent (such as aromatic hydrocarbons or fatty acid amides) and other water-soluble solvents (if required) such that the total is 100% by weight. Dilute with water to obtain an emulsion.

[0224] iv) Emulsion (EW, EO, ES)

[0225] Dissolve 5 - 40% by weight of at least one compound of the present invention, 1 - 10% by weight of a surfactant (such as a mixture of calcium dodecylbenzenesulfonate and castor oil ethoxylate, or a condensate of ethylene oxide and / or propylene oxide with or without alcohol) in 20 - 40% by weight of a water-insoluble organic solvent (such as aromatic hydrocarbons). Using an emulsifier, add the mixture to a certain amount of water such that the total is 100% by weight. The resulting formulation is a homogeneous emulsion. Before application, the emulsion can be further diluted with water.

[0226] v) Suspension and Suspension Concentrate

[0227] v - 1) Aqueous-based (SC, FS)

[0228] In a suitable grinding device, such as a stirred ball mill, grind 20 - 60% by weight of at least one compound of the present invention in the presence of 2 - 10% by weight of a surfactant (such as sodium lignosulfonate and polyoxyethylene fatty alcohol ether), 0.1 - 2% by weight of a thickener (such as xanthan gum) and water to obtain a fine suspension of the active substance. Add a certain amount of water such that the total is 100% by weight. Dilute with water to obtain a stable suspension of the active substance. For FS-type formulations, add up to 40% by weight of a binder (such as polyvinyl alcohol).

[0229] v - 2) Oil-based (OD, OF)

[0230] In a suitable grinding device, such as a stirred ball mill, 20 - 60% by weight of at least one compound of the present invention is ground in the presence of 2 - 10% by weight of a surfactant (such as sodium lignosulfonate and polyoxyethylene fatty alcohol ether), 0.1 - 2% by weight of a thickener (such as modified clay, especially Bentone or silica), and an organic carrier to obtain a fine oil suspension of the active substance. The addition of a certain amount of the organic carrier makes the total amount 100% by weight. Dilution with water gives a stable dispersion of the active substance.

[0231] vi) Water - dispersible granules and water - soluble granules (WG, SG)

[0232] 1 - 90% by weight, preferably 20 - 80% by weight, most preferably 50 - 80% by weight of at least one compound of the present invention is finely ground in the presence of a surfactant (such as sodium lignosulfonate and sodium alkylnaphthalene sulfonate) and, optionally, a carrier material, and is converted into water - dispersible or water - soluble granules by typical industrial means (such as extrusion, spray drying, fluidized - bed granulation). The surfactant and the carrier material are used in an amount such that the total amount reaches 100% by weight. Dilution with water gives a stable dispersion or solution of the active substance.

[0233] vii) Water - dispersible powders and water - soluble powders (WP, SP, WS)

[0234] 50 - 80% by weight of at least one compound of the present invention is ground in a rotor - stator mill while adding 1 - 20% by weight of a surfactant (such as sodium lignosulfonate, sodium alkylnaphthalene sulfonate) and a certain amount of a solid carrier (such as silica gel) such that the total amount is 100% by weight. Dilution with water gives a stable dispersion or solution of the active substance.

[0235] viii) Gels (GW, GF)

[0236] In a stirred ball mill, 5 - 25% by weight of at least one compound of the present invention is ground, and 3 - 10% by weight of a surfactant (such as sodium lignosulfonate), 1 - 5% by weight of a binder (such as carboxymethyl cellulose), and a certain amount of water are added such that the total amount is 100% by weight. A fine suspension of the active substance is obtained. Dilution with water gives a stable suspension of the active substance.

[0237] ix) Microemulsions (ME)

[0238] 5-20% by weight of at least one compound of the present invention is added to 5-30% by weight of an organic solvent mixture (such as fatty acid dimethylamide and cyclohexanone), 10-25% by weight of a surfactant mixture (such as polyoxyethylene fatty alcohol ether and arylphenol ethoxylate), and a certain amount of water such that the total is 100% by weight. The mixture is stirred for 1 hour to produce a thermodynamically stable microemulsion that forms spontaneously.

[0239] x) Microcapsules (CS)

[0240] The oil phase containing 5-50% by weight of at least one compound of the present invention, 0-40% by weight of a water-insoluble organic solvent (such as aromatic hydrocarbons), and 2-15% by weight of an acrylic monomer (such as methyl methacrylate, methacrylic acid, and di- or triacrylate) is dispersed in an aqueous solution of a protective colloid (such as polyvinyl alcohol). Free radical polymerization initiated by a free radical initiator results in the formation of poly(meth)acrylate microcapsules. Alternatively, the oil phase containing 5-50% by weight of at least one compound of the present invention, 0-40% by weight of a water-insoluble organic solvent (such as aromatic hydrocarbons), and an isocyanate monomer (such as diphenylmethane 4,4'-diisocyanate) is dispersed in an aqueous solution of a protective colloid (such as polyvinyl alcohol), which results in the formation of polyurea microcapsules. Optionally, a polyamine (such as hexamethylenediamine) is also added to result in the formation of polyurea microcapsules. The monomers account for 1-10% by weight of the total CS formulation.

[0241] xi) Dustable powders (DP, DS)

[0242] 1-10% by weight of at least one compound of the present invention is finely ground and thoroughly mixed with a certain amount of a solid carrier (such as finely dispersed kaolin) such that the total is 100% by weight.

[0243] xii) Granules (GR, FG)

[0244] 0.5-30% by weight of at least one compound of the present invention is finely ground and combined with a certain amount of a solid carrier (such as silicate) such that the total is 100% by weight.

[0245] xiii) Ultra-low volume liquids (UL)

[0246] 1-50% by weight of at least one compound of the present invention is dissolved in a certain amount of an organic solvent (such as aromatic hydrocarbons) such that the total is 100% by weight.

[0247] Formulation types i) to xiii) may optionally contain other auxiliaries, such as 0.1-1% by weight of a preservative, 0.1-1% by weight of an antifoaming agent, 0.1-1% by weight of a dye and / or pigment, and 5-10% by weight of an antifreeze.

[0248] mixture

[0249] The compounds of formula (I) can also be used in admixture with one or more suitable substances such as fungicides, bactericides, acaricides, molluscicides, nematicides, insecticides, microbiological agents, beneficial species, herbicides, fertilizers, bird repellents, phytotonics, reproduction inhibitors, safeners, chemical pheromones and / or plant growth regulators, for example to broaden the spectrum of action, to extend the duration of action, to increase the rate of action, to prevent repellence or to prevent the development of resistance. Additionally, such combinations of active compounds can improve plant growth and / or the tolerance to abiotic factors such as tolerance to high or low temperatures, to drought or to high water content or soil salinity. They can also improve the flowering and fruiting performance, optimize the germination ability and root development, promote harvesting and increase the yield, influence ripening, improve the quality and / or nutritional value of the harvested product, extend the storage period and / or improve the processability of the harvested product.

[0250] Furthermore, the compounds of formula (I) can be present in admixture with other active compounds or chemical pheromones such as attractants and / or bird repellents and / or plant activators and / or growth regulators and / or fertilizers. Similarly, the compounds of formula (I) can be used to improve plant performance such as the growth, yield and quality of the harvested product.

[0251] In a particular embodiment of the invention, the compounds of formula (I) are present in admixture with other compounds (preferably those described below) in a formulation or in a use form prepared from these formulations.

[0252] If one of the compounds mentioned below can exist in different tautomeric forms, then these forms are also included, even if not explicitly mentioned in each case. Additionally, all named mixing partners can optionally form salts with suitable bases or acids if their functional groups are capable of forming salts.

[0253] Insecticide / Acaricide / Nematicide

[0254] The active compounds mentioned herein by their common names are known and are described, for example, in "The Pesticide Manual" (16th Edition, British Crop Protection Council 2012), or can be found on the Internet (e.g., http: / / www.alanwood.net / pesticides). This classification is based on the IRAC mode of action classification scheme current at the time of filing of this patent application.

[0255] (1) Acetylcholinesterase (AChE) inhibitors, preferably carbamates, selected from alanycarb, aldicarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb, XMC, and xylylcarb; or organophosphates, selected from acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, cadusafos, chlorethoxyfos, chlorfenvinphos, chlormephos, chloropyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon, dichlorvos / DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, famphur, fenamiphos, fenitrothion, fenthion, fosthiazate, heptenophos, imicyafos, isofenphos, isopropyl O-(methoxyaminothiophosphoryl) salicylate, isoxathion,Malathion, mecarbam, methamidophos, methidathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion-methyl, phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim, pirimiphos-methyl, profenofos, propetamphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, triclorfon and vamidothion.

[0256] (2) GABA-gated chloride channel blockers, preferably cyclodiene organochlorines, selected from chlordane and endosulfan; or phenylpyrazoles (fiproles), selected from ethiprole and fipronil.

[0257] (3) Sodium channel modulators, preferably pyrethroids, selected from acrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin s-cyclopentenylisomer), bioresmethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin [(1R)-trans-isomer], deltamethrin, empenthrin [(EZ)-(1R)-isomer], esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flucythrinate, flumethrin, tau-fluvalinate, halfenprox, imiprothrin, kadethrin, momfluorothrin, permethrin, phenothrin [(1R)-trans-isomer], prallethrin, pyrethrins, pyrethrum, resmethrin, silafluofen, tefluthrin, tetramethrin, tetramethrin [(1R)-isomer], tralomethrin, and transfluthrin; or DDT; or methoxychlor.

[0258] (4) Nicotinic acetylcholine receptor (nAChR) competitive modulators, preferably neonicotinoids, selected from acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam or nicotine, or sulfoximine selected from sulfoxaflor, or butenolid selected from flupyradifurone, or mesoionic selected from triflumezopyrim.

[0259] (5) Allosteric modulators (site I) of nicotinic acetylcholine receptor (nAChR), preferably spinosyns, selected from spinetoram and spinosad.

[0260] (6) Allosteric modulators of glutamate-gated chloride channels (GluCl), preferably avermectins / milbemycins, selected from abamectin, emamectin benzoate, lepimectin, and milbemectin.

[0261] (7) Juvenile hormone mimics, preferably juvenile hormone analogs, selected from hydroprene, kinoprene, and methoprene or fenoxycarb or pyriproxyfen.

[0262] (8) Other non-specific (multi-site) inhibitors, preferably alkyl halides, selected from methyl bromide and other alkyl halides; or chloropicrine or sulfuryl fluoride or borax or tartar emetic or methyl isocyanate generators, selected from dazomet or metam.

[0263] (9) Chordotonal organ TRPV channel modulators, preferably pyridyl azomethanes selected from pymetrozine and pyrifluquinazone, or pyropenes selected from afidopyropen.

[0264] (10) Mite growth inhibitors that affect CHS1, selected from clofentezine, hexythiazox, diflovidazin or etoxazole.

[0265] (11) Microbial disruptors of the insect midgut membrane, selected from Bacillus thuringiensis subspecies israelensis, Bacillus sphaericus, Bacillus thuringiensis subspecies aizawai, Bacillus thuringiensis subspecies kurstaki, Bacillus thuringiensis subspecies tenebrionis, and B.t. plant proteins, selected from Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb, Cry34Ab1 / 35Ab1.

[0266] (12) Inhibitors of mitochondrial ATP synthase, preferably ATP disruptors, selected from diafenthiuron or organotin compounds, selected from azocyclotin, cyhexatin, and fenbutatinoxide or propargite or tetradifon.

[0267] (13) Uncouplers that block oxidative phosphorylation of the proton gradient, selected from chlorfenapyr, DNOC, and sulphluramid.

[0268] (14) Nicotinic acetylcholine receptor channel blockers, selected from bensultap, cartap hydrochloride, thiocyclam, and thiosultap-sodium.

[0269] (15) Chitin biosynthesis inhibitors affecting CHS1, preferably benzoylureas, selected from bistrifluron, chlofluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, and triflumuron.

[0270] (16) Chitin biosynthesis inhibitors, type 1, selected from buprofezin.

[0271] (17) Molting disruptors (especially for Diptera, i.e., dipteran insects), selected from cyromazine.

[0272] (18) Ecdysone receptor agonists, preferably diacylhydrazine derivatives, selected from chromafenozide, halofenozide, methoxyfenozide, and tebufenozide.

[0273] (19) Octopamine receptor agonists, selected from amitraz.

[0274] (20) Mitochondrial complex III electron transport inhibitors, selected from hydramethylnone, acequinocyl, fluacrypyrim, and bifenazate.

[0275] (21) Mitochondrial complex I electron transport inhibitors, preferably METI acaricides and insecticides, selected from fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, and tolfenpyrad, or rotenone (Derris).

[0276] (22) Voltage-dependent sodium channel blockers, preferably oxadiazines selected from indoxacarb or semicarbazones selected from metaflumizone.

[0277] (23) Acetyl-CoA carboxylase inhibitors, preferably tetronic acid and tetramic acid derivatives, which are selected from spirodiclofen, spiromesifen, spiropidion and spirotetramat.

[0278] (24) Mitochondrial complex IV electron transport inhibitors, preferably phosphides, which are selected from aluminium phosphide, calcium phosphide, phosphine and zinc phosphide; or cyanides, which are selected from calcium cyanide, potassium cyanide and sodium cyanide.

[0279] (25) Mitochondrial complex II electron transport inhibitors, preferably β-ketonitrile derivatives, which are selected from cyenopyrafen and cyflumetofen; or formanilides, which are selected from pyflubumide.

[0280] (28) Ryanodine receptor modulators, preferably diamides, which are selected from chlorantraniliprole, cyantraniliprole, cyclaniliprole, flubendiamide and tetraniliprole.

[0281] (29) Chordotonal organ modulators (with undefined target sites), which are selected from flonicamid.

[0282] (30) Allosteric modulators of GABA-gated chloride channels, preferably m-diamides selected from broflanilide or isoxazoles selected from fluxametamide.

[0283] (31) Baculoviruses, preferably granuloviruses (GV) selected from Cydia pomonella GV and Thaumatotibia leucotreta (GV) or nucleopolyhedroviruses (NPV) selected from Anticarsia gemmatalis MNPV and Helicoverpa armigera NPV.

[0284] (32) Allosteric modulators of nicotinic acetylcholine receptors (site II), which are selected from GS-ω / κ-HXTX-Hv1a peptides.

[0285] (33) Other active compounds selected from Acynonapyr, Afoxolaner, Azadirachtin, Benclothiaz, Benzoximate, Benzpyrimoxan, Bromopropylate, Chinomethionat, Chloroprallethrin, Cryolite, Cyclobutrifluram or Cyclobutrifen (CAS 1460292-16-3), Cycloxaprid, Cyetpyrafen, Cyhalodiamide, Dicloromezotiaz, Dicofol, Dimpropyridaz, epsilon-Metofluthrin, epsilon-Momfluthrin, Flometoquin, Fluazaindolizine, Fluensulfone, Flufenerim, Flufenoxystrobin, Flufiprole, Fluhexafon, Fluopyram, Flupyrimin, Fluralaner, Fufenozide, Fupentiofenox (CAS1472050-04-6), Guadipyr, Heptafluthrin, Imidaclothiz, Iprodione, Isocycloseram, kappa-Bifenthrin, kappa-Tefluthrin, Lotilaner, Meperfluthrin, Oxazosulfyl, Paichongding, Pyridalyl, Pyrifluquinazon, Pyriminostrobin, Sarolaner, Spirobudiclofen, Tetramethylfluthrin, Tetrachlorantraniliprole, Tigolaner, Tioxazafen, Thiofluoximate, Tyclopyrazoflor, iodomethane, Triflupentoxide (CAS 1472050-04-6); and products based on Bacillus firmus, I-1582, Votivo and azadirachtin (BioNeem), and the following compounds: 1-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)sulfinyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-triazol-5-amine (known from WO2006 / 043635) (CAS 885026-50-6), 2-chloro-N-[2-{1-[(2E)-3-(4-chlorophenyl)prop-2-en-1-yl]piperidin-4-yl}-4-(trifluoromethyl)phenyl]isonicotinamide (known from WO2006 / 003494) (CAS 872999-66-1), 3-(4-chloro-2,5-dimethylphenyl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]dec-3-en-2-one (known from WO2010052161) (CAS 1225292-17-0), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-yl ethyl carbonate (known from EP2647626) (CAS 1440516-42-6), PF1364 (known from JP2010 / 018586) (CAS(3E)-3-[1-[(6-chloro-3-pyridinyl)methyl]-2-pyridinylidene]-1,1,1-trifluoro-propan-2-one (known from WO2013 / 144213) (CAS 1461743-15-6), N-[3-(benzylcarbamoyl)-4-chlorophenyl]-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide (known from WO2010 / 051926) (CAS 1226889-14-0), 5-bromo-4-chloro-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloro-2-pyridinyl)pyrazole-3-carboxamide (known from CN103232431) (CAS 1449220-44-3), 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxo-3-thietanyl)-benzamide, 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(trans-1-oxo-3-thietanyl)-benzamide and 4-[(5S)-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxo-3-thietanyl)benzamide (known from WO2013 / 050317 A1) (CAS 1332628-83-7), N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]-propanamide, (+)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]-propanamide and (-)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]-propanamide (known from WO 2013 / 162715 A2, WO2013 / 162716 A2, US 2014 / 0213448 A1) (CAS 1477923-37-7), 5-[[(2E)-3-chloro-2-propen-1-yl]amino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile (known from CN 101337937 A) (CAS 1105672-77-2), 3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)thiomethyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide (liudaibenjiaxuanan, from CN103109816A is known (CAS 1232543-85-9); N-[4-chloro-2-[[(1,1-dimethylethyl)amino]carbonyl]-6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-(fluoromethoxy)-1H-pyrazole-5-carboxamide is known from WO 2012 / 034403 A1 (CAS 1268277-22-0), N-[2-(5-amino-1,3,4-thiadiazol-2-yl)-4-chloro-6-methylphenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide is known from WO 2011 / 085575 A1 (CAS 1233882-22-8), 4-[3-[2,6-dichloro-4-[(3,3-dichloro-2-propen-1-yl)oxy]phenoxy]propoxy]-2-methoxy-6-(trifluoromethyl)-pyrimidine is known from CN 101337940 A (CAS 1108184-52-6); (2E)- and 2(Z)-2-[2-(4-cyanophenyl)-1-[3-(trifluoromethyl)phenyl]ethylidene]-N-[4-(difluoromethoxy)phenyl]-hydrazinecarboxamide is known from CN101715774 A (CAS1232543-85-9); 3-(2,2-dichlorovinyl)-2,2-dimethyl-4-(1H-benzimidazol-2-yl)phenyl-cyclopropanecarboxylate is known from CN 103524422 A (CAS 1542271-46-4); (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-[(trifluoromethyl)thio]phenyl]amino]carbonyl]-indenyl[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylic acid methyl ester is known from CN 102391261 A (CAS 1370358-69-2); 6-deoxy-3-O-ethyl-2,4-di-O-methyl-, 1-[N-[4-[1-[4-(1,1,2,2,2-pentafluoroethoxy)phenyl]-1H-1,2,4-triazol-3-yl]phenyl]carbamate]-α-L-mannopyranose is known from US 2014 / 0275503 A1 (CAS 1181213-14-8); 8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (CAS 1253850-56-4), (8-trans)-8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (CAS(8-cis)-8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (known from WO 2007040280 A1, WO 2007040282 A1) (CAS 934001-66-8), N-[4-(aminothiomethyl)-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxamide (known from CN 103265527 A) (CAS 1452877-50-7), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-1,8-diazaspiro[4.5]decane-2,4-dione (known from WO 2014 / 187846 A1) (CAS 1638765-58-8), ethyl 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-yl carbonate (known from WO 2010 / 066780 A1, WO 2011151146A1) (CAS 1229023-00-0), N-[1-(2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-(trifluoromethyl)benzamide (known from WO 2014 / 053450 A1) (CAS1594624-87-9), N-[2-(2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2-(trifluoromethyl)benzamide (known from WO 2014 / 053450 A1) (CAS 1594637-65-6), N-[1-(3,5-difluoro-2-pyridyl)-1H-pyrazol-3-yl]-2-(trifluoromethyl)benzamide (known from WO 2014 / 053450 A1) (CAS 1594626-19-3).

[0286] Fungicides

[0287] The active ingredients mentioned herein by their common names are known and are described, for example, in The Pesticide Manual (16th Edition, British Crop Protection Council) or can be retrieved on the Internet (e.g., www.alanwood.net / pesticides).

[0288] All named fungicidal mixtures in categories (1) to (15) can optionally form salts with suitable bases or acids if their functional groups are capable of forming salts. All named mixtures in categories (1) to (15) can include tautomeric forms where applicable.

[0289] 1) Ergosterol biosynthesis inhibitors, such as (1.001) cyproconazole, (1.002) difenoconazole, (1.003) epoxiconazole, (1.004) fenhexamid, (1.005) fenpropidin, (1.006) fenpropimorph, (1.007) fenpyrazamine, (1.008) fluquinconazole, (1.009) flutriafol, (1.010) imazalil, (1.011) imazalil sulfate, (1.012) ipconazole, (1.013) metconazole, (1.014) myclobutanil, (1.015) paclobutrazol, (1.016) prochloraz, (1.017) propiconazole, (1.018) prothioconazole, (1.019) pyrisoxazole, (1.020) spiroxamine, (1.021) tebuconazole, (1.022) tetraconazole, (1.023) triadimenol, (1.024) tridemorph, (1.025) triticonazole, (1.026) (1R,2S,5S)-5-(4-chlorobenzyl)-2-(chloromethyl)-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol, (1.027) (1S,2R,5R)-5-(4-chlorobenzyl)-2-(chloromethyl)-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol, (1.028) (2R)-2-(1-chlorocyclopropyl)-4-[(1R)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (1.029) (2R)-2-(1-chlorocyclopropyl)-4-[(1S)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.030) (2R)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.(1.031) (2S)-2-(1-chlorocyclopropyl)-4-[(1R)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.032) (2S)-2-(1-chlorocyclopropyl)-4-[(1S)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.033) (2S)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.034) (R)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-1,2-oxazol-4-yl](pyridin-3-yl)methanol, (1.035) (S)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-1,2-oxazol-4-yl](pyridin-3-yl)methanol, (1.036) [3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-1,2-oxazol-4-yl](pyridin-3-yl)methanol, (1.037) 1-({(2R,4S)-2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl}methyl)-1H-1,2,4-triazole, (1.038) 1-({(2S,4S)-2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl}methyl)-1H-1,2,4-triazole, (1.039) 1-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiranyl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.040) 1-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiranyl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.041) 1-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiranyl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.042) 2-[(2R,4R,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylhept-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.043) 2-[(2R,4R,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylhept-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.044) 2-[(2R,4S,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylhept-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.045) 2-[(2R,4S,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.046) 2-[(2S,4R,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.047) 2-[(2S,4R,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.048) 2-[(2S,4S,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.049) 2-[(2S,4S,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.050) 2-[1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.051) 2-[2-chloro-4-(2,4-dichlorophenoxy)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.052) 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.053) 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.054) 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)pentan-2-ol, (1.055) mefentrifluconazole, (1.056) 2-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.057) 2-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.058) 2-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.059) 5-(4-chlorobenzyl)-2-(chloromethyl)-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol, (1.060) 5-(allylthio)-1-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-1H-1,2,4-triazole, (1.061) 5-(allylthio)-1-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-1H-1,2,4-triazole, (1.062) 5-(allylthio)-1-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-1H-1,2,4-triazole, (1.063) N'-(2,5-dimethyl-4-{[3-(1,1,2,2-tetrafluoroethoxy)phenyl]thio}phenyl)-N-ethyl-N-methylformimidamide, (1.064) N'-(2,5-dimethyl-4-{[3-(2,2,2-trifluoroethoxy)phenyl]thio}phenyl)-N-ethyl-N-methylformimidamide, (1.065) N'-(2,5-dimethyl-4-{[3-(2,2,3,3-tetrafluoropropoxy)phenyl]thio}phenyl)-N-ethyl-N-methylformimidamide, (1.066) N'-(2,5-dimethyl-4-{[3-(pentafluoroethoxy)phenyl]thio}phenyl)-N-ethyl-N-methylformimidamide, (1.067) N'-(2,5-dimethyl-4-{3-[(1,1,2,2-tetrafluoroethyl)thio]phenoxy}phenyl)-N-ethyl-N-methylformimidamide, (1.068) N'-(2,5-dimethyl-4-{3-[(2,2,2-trifluoroethyl)thio]phenoxy}phenyl)-N-ethyl-N-methylformimidamide, (1.069) N'-(2,5-dimethyl-4-{3-[(2,2,3,3-tetrafluoropropyl)thio]phenoxy}phenyl)-N-ethyl-N-methylformimidamide, (1.070) N'-(2,5-dimethyl-4-{3-[(pentafluoroethyl)thio]phenoxy}phenyl)-N-ethyl-N-methylformimidamide, (1.071) N'-(2,5-dimethyl-4-phenoxyphenyl)-N-ethyl-N-methylformimidamide, (1.072) N'-(4-{[3-(difluoromethoxy)phenyl]thio}-2,5-dimethylphenyl)-N-ethyl-N-methylformimidamide, (1.073) N'-(4-{3-[(difluoromethyl)thio]phenoxy}-2,5-dimethylphenyl)-N-ethyl-N-methylformimidamide, (1.N'-[5-bromo-6-(2,3-dihydro-1H-inden-2-yloxy)-2-methylpyridin-3-yl]-N-ethyl-N-methylformamidine, (1.075) N'-{4-[(4,5-dichloro-1,3-thiazol-2-yl)oxy]-2,5-dimethylphenyl}-N-ethyl-N-methylformamidine, (1.076) N'-{5-bromo-6-[(1R)-1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformamidine, (1.077) N'-{5-bromo-6-[(1S)-1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformamidine, (1.078) N'-{5-bromo-6-[(cis-4-isopropylcyclohexyl)oxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformamidine, (1.079) N'-{5-bromo-6-[(trans-4-isopropylcyclohexyl)oxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformamidine, (1.080) N'-{5-bromo-6-[1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformamidine, (1.081) ipfentrifluconazole, (1.082) 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.083) 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol, (1.084) 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol, (1.085) 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluorophenyl)-2-hydroxypropyl]imidazole-4-carbonitrile and (1.086) 4-[[6-[rac-(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile.

[0290] 2) Inhibitors of respiratory chain complex I or II, such as (2.001) benzovindiflupyr, (2.002) bixafen, (2.003) boscalid, (2.004) carboxin, (2.005) fluopyram, (2.006) flutolanil, (2.007) fluxapyroxad, (2.008) furametpyr, (2.009) Isofetamid, (2.010) isopyrazam (trans-diastereomeric enantiomer 1R,4S,9S), (2.011) isopyrazam (trans-diastereomeric enantiomer 1S,4R,9R), (2.012) isopyrazam (trans-diastereomeric racemate 1RS,4SR,9SR), (2.013) isopyrazam (mixture of cis-diastereomeric racemate 1RS,4SR,9RS and trans-diastereomeric racemate 1RS,4SR,9SR), (2.014) isopyrazam (cis-diastereomeric enantiomer 1R,4S,9R), (2.015) isopyrazam (cis-diastereomeric enantiomer 1S,4R,9S), (2.016) isopyrazam (cis-diastereomeric racemate 1RS,4SR,9RS), (2.017) penflufen, (2.018) penthiopyrad, (2.019) pydiflumetofen, (2.020) Pyraziflumid, (2.021) sedaxane, (2.022) 1,3-dimethyl-N-(1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl)-1H-pyrazole-4-carboxamide, (2.023) 1,3-dimethyl-N-[(3R)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1H-pyrazole-4-carboxamide, (2.024) 1,3-dimethyl-N-[(3S)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1H-pyrazole-4-carboxamide, (2.025) 1-methyl-3-(trifluoromethyl)-N-[2'-(trifluoromethyl)biphenyl-2-yl]-1H-pyrazole-4-carboxamide, (2.026) 2-fluoro-6-(trifluoromethyl)-N-(1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl)benzamide, (2.027) 3-(difluoromethyl)-1-methyl-N-(1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl)-1H-pyrazole-4-carboxamide, (2.(2.028) inpyrfluxam, (2.029) 3-(difluoromethyl)-1-methyl-N-[(3S)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1H-pyrazole-4-carboxamide, (2.030) fluindapyr, (2.031) 3-(difluoromethyl)-N-[(3R)-7-fluoro-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1-methyl-1H-pyrazole-4-carboxamide, (2.032) 3-(difluoromethyl)-N-[(3S)-7-fluoro-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1-methyl-1H-pyrazole-4-carboxamide, (2.033) 5,8-difluoro-N-[2-(2-fluoro-4-{[4-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)ethyl]quinazolin-4-amine, (2.034) N-(2-cyclopentyl-5-fluorobenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.035) N-(2-tert-butyl-5-methylbenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.036) N-(2-tert-butylbenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.037) N-(5-chloro-2-ethylbenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.038) N-(5-chloro-2-isopropylbenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.039) N-[(1R,4S)-9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.040) N-[(1S,4R)-9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.041) N-[1-(2,4-dichlorophenyl)-1-methoxypropan-2-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.042) N-[2-chloro-6-(trifluoromethyl)benzyl]-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.043) N-[3-chloro-2-fluoro-6-(trifluoromethyl)benzyl]-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.044) N-[5-chloro-2-(trifluoromethyl)benzyl]-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.045) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-N-[5-methyl-2-(trifluoromethyl)benzyl]-1H-pyrazole-4-carboxamide, (2.046) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(2-fluoro-6-isopropylbenzyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.047) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(2-isopropyl-5-methylbenzyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.048) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(2-isopropylbenzyl)-1-methyl-1H-pyrazole-4-thiocarboxamide, (2.049) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(2-isopropylbenzyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.050) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(5-fluoro-2-isopropylbenzyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.051) N-cyclopropyl-3-(difluoromethyl)-N-(2-ethyl-4,5-dimethylbenzyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.052) N-cyclopropyl-3-(difluoromethyl)-N-(2-ethyl-5-fluorobenzyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.053) N-cyclopropyl-3-(difluoromethyl)-N-(2-ethyl-5-methylbenzyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.054) N-cyclopropyl-N-(2-cyclopropyl-5-fluorobenzyl)-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.055) N-cyclopropyl-N-(2-cyclopropyl-5-methylbenzyl)-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.056) N-cyclopropyl-N-(2-cyclopropylbenzyl)-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.057) pyrapropoyne.

[0291] 3) Inhibitors of respiratory chain complex III, such as (3.001) ametoctradin, (3.002) amisulbrom, (3.003) azoxystrobin, (3.004) coumethoxystrobin, (3.005) coumoxystrobin, (3.006) cyazofamid, (3.007) dimoxystrobin, (3.008) enoxastrobin, (3.009) famoxadone, (3.010) fenamidone, (3.011) flufenoxystrobin, (3.012) fluoxastrobin, (3.013) kresoxim-methyl, (3.014) metominostrobin, (3.015) orysastrobin, (3.016) picoxystrobin, (3.017) pyraclostrobin, (3.018) pyrametostrobin, (3.019) pyraoxystrobin, (3.020) trifloxystrobin, (3.021) (2E)-2-{2-[({[(1E)-1-(3-{[(E)-1-fluoro-2-phenylethenyl]oxy}phenyl)ethylidene]amino}oxy)methyl]phenyl}-2-(methoxyimino)-N-methylacetamide, (3.022) (2E,3Z)-5-{[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy}-2-(methoxyimino)-N,3-dimethylpent-3-enamide, (3.023) (2R)-2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N-methylacetamide, (3.024) (2S)-2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N-methylacetamide, (3.025) fenpicoxamid, (3.026) mandestrobin, (3.027) N-(3-ethyl-3,5,5-trimethylcyclohexyl)-3-formamido-2-hydroxybenzamide, (3.028) (2E,3Z)-5-{[1-(4-chloro-2-fluorophenyl)-1H-pyrazol-3-yl]oxy}-2-(methoxyimino)-N,3-dimethylpent-3-enamide, (3.Methyl {5-[3-(2,4-dimethylphenyl)-1H-pyrazol-1-yl]-2-methylbenzyl}carbamate, (3.030) metyltetraprole, (3.031) florylpicoxamid.

[0292] 4) Mitotic and cell division inhibitors, such as (4.001) carbendazim, (4.002) diethofencarb, (4.003) ethaboxam, (4.004) fluopicolide, (4.005) pencycuron, (4.006) thiabendazole, (4.007) thiophanate-methyl, (4.008) zoxamide, (4.009) 3-chloro-4-(2,6-difluorophenyl)-6-methyl-5-phenylpyridazine, (4.010) 3-chloro-5-(4-chlorophenyl)-4-(2,6-difluorophenyl)-6-methylpyridazine, (4.011) 3-chloro-5-(6-chloropyridin-3-yl)-6-methyl-4-(2,4,6-trifluorophenyl)pyridazine, (4.012) 4-(2-bromo-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.013) 4-(2-bromo-4-fluorophenyl)-N-(2-bromo-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.014) 4-(2-bromo-4-fluorophenyl)-N-(2-bromophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.015) 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.016) 4-(2-bromo-4-fluorophenyl)-N-(2-chlorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.017) 4-(2-bromo-4-fluorophenyl)-N-(2-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.018) 4-(2-chloro-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.019) 4-(2-chloro-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.020) 4-(2-chloro-4-fluorophenyl)-N-(2-chlorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.021) 4-(2-chloro-4-fluorophenyl)-N-(2-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.022) 4-(4-chlorophenyl)-5-(2,6-difluorophenyl)-3,6-dimethylpyridazine, (4.023) N-(2-bromo-6-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.024) N-(2-bromophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.025) N-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine.

[0293] 5) Compounds capable of having multi-site activity, such as (5.001) Bordeaux mixture, (5.002) captafol, (5.003) captan, (5.004) chlorothalonil, (5.005) copper hydroxide, (5.006) copper naphthenate, (5.007) copper oxide, (5.008) copper oxychloride, (5.009) copper(2+) sulfate, (5.010) dithianon, (5.011) dodine, (5.012) folpet, (5.013) mancozeb, (5.014) maneb, (5.015) metiram, (5.016) metiram zinc, (5.017) oxine-copper, (5.018) propineb, (5.019) sulfur and sulfur preparations (including calcium polysulfide), (5.020) thiram, (5.021) zineb, (5.022) ziram, (5.023) 6-ethyl-5,7-dioxo-6,7-dihydro-5H-pyrrolo[3’,4’:5,6][1,4]dithiino[2,3-c][1,2]thiazole-3-carbonitrile.

[0294] 6) Compounds capable of eliciting host defense, such as (6.001) acibenzolar-S-methyl, (6.002) isotianil, (6.003) probenazole, (6.004) tiadinil.

[0295] 7) Amino acid and / or protein biosynthesis inhibitors, such as (7.001) cyprodinil, (7.002) kasugamycin, (7.003) kasugamycin hydrochloride hydrate, (7.004) oxytetracycline, (7.005) pyrimethanil, (7.006) 3-(5-fluoro-3,3,4,4-tetramethyl-3,4-dihydroisoquinolin-1-yl)quinoline.

[0296] 8) ATP generation inhibitors, such as (8.001) silthiofam.

[0297] 9) Cell wall synthesis inhibitors, such as (9.001) benthiavalicarb, (9.002) dimethomorph, (9.003) flumorph, (9.004) iprovalicarb, (9.005) mandipropamid, (9.006) pyrimorph, (9.007) valifenalate, (9.008) (2E)-3-(4-tert-butylphenyl)-3-(2-chloropyridin-4-yl)-1-(morpholin-4-yl)prop-2-en-1-one, (9.009) (2Z)-3-(4-tert-butylphenyl)-3-(2-chloropyridin-4-yl)-1-(morpholin-4-yl)prop-2-en-1-one.

[0298] 10) Lipid and membrane synthesis inhibitors, such as (10.001) propamocarb, (10.002) propamocarb hydrochloride, (10.003) tolclofos-methyl.

[0299] 11) Melanin biosynthesis inhibitors, such as (11.001) tricyclazole, (11.002) 2,2,2-trifluoroethyl {3-methyl-1-[(4-methylbenzoyl)amino]butan-2-yl}carbamate.

[0300] 12) Nucleic acid synthesis inhibitors, such as (12.001) benalaxyl, (12.002) benalaxyl-M (kiralaxyl), (12.003) metalaxyl, (12.004) metalaxyl-M (mefenoxam).

[0301] 13) Signal transduction inhibitors, such as (13.001) fludioxonil, (13.002) iprodione, (13.003) procymidone, (13.004) proquinazid, (13.005) quinoxyfen, (13.006) vinclozolin.

[0302] 14) Compounds that can act as uncoupling agents, such as (14.001) fluazinam, (14.002) meptyldinocap.

[0303] 15) Other fungicides selected from (15.001) abscisic acid, (15.002) benthiazole, (15.003) bethoxazin, (15.004) capsimycin, (15.005) carvone, (15.006) chinomethionat, (15.007) cufraneb, (15.008) cyflufenamid, (15.009) cymoxanil, (15.010) cyprosulfamide, (15.011) flutianil, (15.012) fosetyl-aluminium, (15.013) fosetyl-calcium, (15.014) fosetyl-sodium, (15.015) methyl isothiocyanate, (15.016) metrafenon, (15.017) mildiomycin, (15.018) natamycin, (15.019) nickeldimethyldithiocarbamate, (15.020) nitrothal-isopropyl, (15.021) oxamocarb, (15.022) Oxathiapiprolin, (15.023) oxyfenthiin, (15.024) pentachlorophenol and its salts, (15.025) phosphorous acid and its salts, (15.026) propamocarb-fosetylate, (15.027) pyriofenone (chlazafenone), (15.028) tebufloquin, (15.029) tecloftalam, (15.030) tolnifanide, (15.031) 1-(4-{4-[(5R)-5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, (15.032) 1-(4-{4-[(5S)-5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, (15.033) 2-(6-benzylpyridin-2-yl)quinazoline, (15.034) dipymetitrone, (15.035) 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-[4-(4-{5-[2-(prop-2-yn-1-yloxy)phenyl]-4,5-dihydro-1,2-oxazol-3-yl}-1,3-thiazol-2-yl)piperidin-1-yl]ethanone, (15.036) 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-[4-(4-{5-[2-chloro-6-(prop-2-yn-1-yloxy)phenyl]-4,5-dihydro-1,2-oxazol-3-yl}-1,3-thiazol-2-yl)piperidin-1-yl]ethanone, (15.037) 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-[4-(4-{5-[2-fluoro-6-(prop-2-yn-1-yloxy)phenyl]-4,5-dihydro-1,2-oxazol-3-yl}-1,3-thiazol-2-yl)piperidin-1-yl]ethanone, (15.038) 2-[6-(3-fluoro-4-methoxyphenyl)-5-methylpyridin-2-yl]quinazoline, (15.039) 2-{(5R)-3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-3-chlorophenyl methanesulfonate, (15.040) 2-{(5S)-3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-3-chlorophenyl methanesulfonate, (15.041) Ipflufenoquin, (15.042) 2-{2-fluoro-6-[(8-fluoro-2-methylquinolin-3-yl)oxy]phenyl}propan-2-ol, (15.043) fluoxapiprolin, (15.044) 2-{3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}phenyl methanesulfonate, (15.045) 2-phenylphenol and salts, (15.046) 3-(4,4,5-trifluoro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)quinoline, (15.047) quinofumelin, (15.048) 4-Amino-5-fluoropyrimidin-2-ol (tautomeric form: 4-amino-5-fluoropyrimidin-2(1H)-one), (15.049) 4-oxo-4-[(2-phenylethyl)amino]butanoic acid, (15.050) 5-amino-1,3,4-thiadiazole-2-thiol, (15.051) 5-chloro-N'-phenyl-N'-(prop-2-yn-1-yl)thiophene-2-sulfonylhydrazide, (15.052) 5-fluoro-2-[(4-fluorobenzyl)oxy]pyrimidin-4-amine, (15.053) 5-fluoro-2-[(4-methylbenzyl)oxy]pyrimidin-4-amine, (15.054) 9-fluoro-2,2-dimethyl-5-(quinolin-3-yl)-2,3-dihydro-1,4-benzoxazepine, (15.055) {6-[({[(Z)-(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]pyridin-2-yl}but-3-yn-1-yl carbamate, (15.056) (2Z)-3-amino-2-cyano-3-phenylacrylic acid ethyl ester, (15.057) phenazine-1-carboxylic acid, (15.058) propyl 3,4,5-trihydroxybenzoate, (15.059) quinolin-8-ol, (15.060) quinolin-8-ol sulfate (2:1), (15.061) {6-[({[(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]pyridin-2-yl}tert-butyl carbamate, (15.062) 5-fluoro-4-imino-3-methyl-1-[(4-methylphenyl)sulfonyl]-3,4-dihydropyrimidin-2(1H)-one, (15.063) aminopyrifen, (15.064) (N'-[2-chloro-4-(2-fluorophenoxy)-5-methylphenyl]-N-ethyl-N-methylformimidamide), (15.065) (N'-(2-chloro-5-methyl-4-phenoxyphenyl)-N-ethyl-N-methylformimidamide), (15.066) (2-{2-[(7,8-difluoro-2-methylquinolin-3-yl)oxy]-6-fluorophenyl}propan-2-ol), (15.067) (5-bromo-1-(5,6-dimethylpyridin-3-yl)-3,3-dimethyl-3,4-dihydroisoquinoline), (15.068) (3-(4,4-difluoro-5,5-dimethyl-4,5-dihydrothieno[2,3-c]pyridin-7-yl)quinoline), (15.069) (1-(4,5-dimethyl-1H-benzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinoline), (15.070) 8-fluoro-3-(5-fluoro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)quinolone, (15.071) 8-fluoro-3-(5-fluoro-3,3,4,4-tetramethyl-3,4-dihydroisoquinolin-1-yl)quinolone, (15.072) 3-(4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-8-fluoroquinoline, (15.073) (N-methyl-N-phenyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide), (15.074) (methyl {4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl}carbamate), (15.075) (N-{4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl}cyclopropanecarboxamide), (15.076) N-methyl-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.077) N-[(E)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.078) N-[(Z)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.079) N-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]cyclopropanecarboxamide, (15.080) N-(2-fluorophenyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.081) 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide, (15.082) N-allyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl]methyl]acetamide, (15.083) N-[(E)-N-methoxy-C-methyl-carboximidoyl]-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.084) N-[(Z)-N-methoxy-C-methyl-carboximidoyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.085) N-allyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide, (15.086) 4,4-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrrolidin-2-one, (15.087) N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]thiobenzamide, (15.088) 5-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrrolidin-2-one, (15.089) N-((2,3-difluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-3,3,3-trifluoropropanamide, (15.090) 1-Methoxy-1-methyl-3-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.091) 1,1-Diethyl-3-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.092) N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide, (15.093) N-Methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide, (15.094) 1-Methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.095) N-Methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl)cyclopropanecarboxamide, (15.096) N,2-Dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide, (15.097) N-Ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl]methyl]propanamide, (15.098) 1-Methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.099) 1,3-Dimethoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.100) 3-Ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.101) 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]piperidin-2-one, (15.102) 4,4-Dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, (15.103) 5,5-Dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, (15.104) 3,3-Dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]piperidin-2-one, (15.105) 1-[[3-Fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl]methyl]azepan-2-one, (15.106) 4,4-Dimethyl-2-[[4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, (15.107) 5,5-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, (15.108) ethyl (1-{4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl}-1H-pyrazol-4-yl)acetate, (15.109) N,N-dimethyl-1-{4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl}-1H-1,2,4-triazol-3-amine and (15.110) N-{2,3-difluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl}butanamide.

[0304] Biological pesticides as a mixed component

[0305] The compounds of formula (I) can be combined with biological pesticides.

[0306] Biological pesticides especially include bacteria, fungi, yeasts, plant extracts and products formed by microorganisms, including proteins and secondary metabolites.

[0307] Biological pesticides include bacteria such as spore-forming bacteria, root-colonizing bacteria and bacteria that act as biological insecticides, fungicides or nematicides.

[0308] Examples of such bacteria used or useful as biological pesticides are:

[0309] Bacillus amyloliquefaciens, strain FZB42 (DSM231179); or Bacillus cereus, in particular Bacillus cereus strain CNCM I-1562; or Bacillus firmus, strain I-1582 (accession number CNCM I-1582); or Bacillus pumilus, in particular strain GB34 (accession number ATCC 700814) and strain QST2808 (accession number NRRL B-30087); or Bacillus subtilis, in particular strain GB03 (accession number ATCC SD-1397), or Bacillus subtilis strain QST713 (accession number NRRL B-21661) or Bacillus subtilis strain OST 30002 (accession number NRRL B-50421); Bacillus thuringiensis, in particular Bacillus thuringiensis subspecies israelensis (serotype H-14), strain AM65-52 (accession number ATCC 1276), or Bacillus thuringiensis subsp. aizawai, in particular strain ABTS-1857 (SD-1372), or Bacillus thuringiensis subsp. kurstaki strain HD-1, or Bacillus thuringiensis subsp. tenebrionis strain NB 176 (SD-5428); Pasteuria penetrans, Pasteuria spp. (Rotylenchulus reniformis nematode) - PR3 (accession number ATCC SD-5834); Streptomyces microflavus strain AQ6121 (= QRD 31.013, NRRL B-50550); Streptomyces galbus strain AQ 6047 (accession number NRRL 30232).

[0310] Examples of fungi and yeasts that are used or can be used as biological pesticides are:

[0311] Beauveria bassiana, especially strain ATCC 74040; Coniothyrium minitans, especially strain CON / M / 91-8 (accession number DSM-9660); Lecanicillium spp., especially strain HRO LEC 12; Lecanicillium lecanii, (formerly known as Verticillium lecanii), especially strain KV01; Metarhizium anisopliae, especially strain F52 (DSM3884 / ATCC 90448); Metschnikowia fructicola, especially strain NRRL Y-30752; Paecilomyces fumosoroseus (current name: Isaria fumosorosea), especially strain IFPC 200613, or strain Apopka 97 (accession number ATCC 20874); Paecilomyces lilacinus, especially Paecilomyces lilacinus strain 251 (AGAL 89 / 030550); Talaromyces flavus, especially strain V117b; Trichoderma atroviride, especially strain SC1 (accession number CBS 122089); Trichoderma harzianum, especially Trichoderma harzianum T39 (accession number CNCM I-952).

[0312] Examples of viruses that are used or can be used as biological pesticides are:

[0313] Granulovirus (GV) of Adoxophyes orana (summer fruit tortrix), Granulovirus (GV) of Cydia pomonella (codling moth), Nuclear Polyhedrosis Virus (NPV) of Helicoverpa armigera (cotton bollworm), mNPV of Spodoptera exigua (beet armyworm), mNPV of Spodoptera frugiperda (fall armyworm), NPV of Spodoptera littoralis (African cotton leafworm).

[0314] It also includes bacteria and fungi added as "inoculants" to plants or plant parts or plant organs, which promote plant growth and plant health through their specific properties. Examples that can be mentioned are:

[0315] Agrobacterium spp., Azorhizobium caulinodans, Azospirillum spp., Azotobacter spp., Bradyrhizobium spp., Burkholderia spp., especially Burkholderia cepacia (formerly known as Pseudomonas cepacia), Gigaspora spp., or Gigaspora monosporum, Glomus spp., Laccaria spp., Lactobacillus buchneri, Paraglomus spp., Pisolithus tinctorius, Pseudomonas spp., Rhizobium spp., especially Rhizobium trifolii, Rhizopogon spp., Scleroderma spp., Suillus spp., Streptomyces spp.

[0316] Examples of plant extracts and products formed by microorganisms (including proteins and secondary metabolites) that are used or can be used as biological pesticides are:

[0317] Garlic (Allium sativum), Wormwood (Artemisia absinthium), Azadirachtin, Biokeeper WP, Cassia nigricans, Celastrus angulatus, Chenopodium anthelminticum, Chitin, Armour-Zen, Dryopteris filix-mas, Equisetum arvense, Fortune Aza, Fungastop, Heads Up (saponin extract of Chenopodium quinoa), Pyrethrum / pyrethroids, Quassia amara, Quercus, Quillaja, Regalia, "Requiem TM Insecticide", Rotenone, Ryanodine, Symphytum officinale, Tanacetum vulgare, Thymol, Triact 70, TriCon, Tropaeulum majus, Urtica dioica, Veratrin, Viscum album, Brassicaceae extracts, especially rapeseed powder or mustard powder, and bio-insecticidal / acaricidal active substances obtained from olive oil, especially unsaturated fatty acids / carboxylic acids with a C 16 -C 20 carbon chain length, such as those contained in products sold under the name .

[0318] Safeners as mixed components

[0319] The compounds of formula (I) can be combined with a safener, which is, for example, benoxacor, cloquintocet (-mexyl), cyometrinil, cyprosulfamide, dichlormid, fenchlorazole (-ethyl), fenclorim, flurazole, fluxofenim, furilazole, isoxadifen (-ethyl), mefenpyr (-diethyl), naphthalic anhydride, oxabetrinil, 2-methoxy-N-{4-[(methylcarbamoyl)amino]phenyl}sulfonyl)benzamide (CAS 129531-12-0), 4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (CAS 71526-07-3), 2,2,5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine (CAS 52836-31-4).

[0320] Plants and plant parts

[0321] All plants and plant parts can be treated according to the invention. For the purposes of the present invention, plants are to be understood as meaning all plants and plant parts, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants), for example cereals (wheat, rice, triticale, barley, rye, oats), maize, soybeans, potatoes, sugar beet, sugar cane, tomatoes, peppers, cucumbers, melons, carrots, watermelons, onions, lettuce, spinach, leeks, beans, brassicas (such as cabbages) and other vegetable varieties, cotton, tobacco, oilseed rape, and fruit plants (the fruits being apples, pears, citrus fruits and grapes). Crop plants can be plants which are obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including transgenic plants and plant varieties which may or may not be protected by varietal property rights. Plants are to be understood as meaning all developmental stages, such as seeds, seedlings and young (immature) plants up to mature plants. Plant parts are to be understood as meaning all parts and organs above and below the ground of plants, such as shoots, leaves, flowers and roots, examples being leaves, needles, stems, branches, flowers, fruiting bodies, fruits and seeds, and tubers, roots and rhizomes. Plant parts also include harvested plants or harvested plant parts and asexual and sexual propagation material, such as seedlings, tubers, rhizomes, cuttings and seeds.

[0322] The treatment of plants and plant parts with the compounds of formula (I) according to the invention is effected directly by conventional treatment methods or by allowing the compounds to act on the environment, habitat or storage space, said conventional treatment methods being, for example, dipping, spraying, evaporation, fogging, scattering, painting, injection and, in the case of propagation material, in particular seeds, also by applying one or more coatings.

[0323] As mentioned above, all plants and their parts can be treated according to the invention. In a preferred embodiment, wild plant varieties and plant cultivars, or those plants and their parts obtained by conventional biological breeding methods such as crossing or protoplast fusion are treated. In another preferred embodiment, transgenic plants and plant cultivars (genetically modified organisms) obtained by genetic engineering methods - if appropriate, in combination with conventional methods - and their parts are treated. The terms "parts" or "parts of plants" or "plant parts" have been explained above. The invention is used in particular preferably for treating plants of the conventional cultivars commercially available or those plants in use. Plant cultivars are to be understood as meaning plants which have new properties ("traits") and have been obtained by conventional breeding, by mutagenesis or by recombinant DNA technology. They can be cultivars, varieties, biotypes or genotypes.

[0324] Transgenic plants, seed treatment and events

[0325] According to the present invention, the compounds of formula (I) can advantageously be used for treating transgenic plants, plant cultivars or plant parts that have received genetic material which confers advantageous and / or useful characteristics (traits) to these plants, plant cultivars and plant parts. Thus, it is contemplated that the present invention can be combined with one or more recombinant traits or transgenic lines or combinations thereof. For the purposes of the present application, a transgenic line is caused by inserting a specific recombinant DNA molecule into a specific location (locus) in the chromosomes of the plant genome. The insertion results in a new DNA sequence, called a "line", which is characterized by the inserted recombinant DNA molecule and a certain amount of genomic DNA flanking / on both sides of the inserted DNA at the ends of the insertion. Such traits or transgenic lines include, but are not limited to, pest resistance, water use efficiency, yield performance, drought tolerance, seed quality, improved nutritional quality, hybrid seed production and herbicide tolerance, where the traits are measured relative to plants lacking such traits or such transgenic lines. Specific examples of such advantageous and / or useful characteristics (traits) are better plant growth, vigor, stress tolerance, standability, lodging resistance, nutrient uptake, plant nutrition and / or yield, in particular improved growth, increased tolerance to high or low temperatures, increased tolerance to drought or water levels or soil salt content, enhanced flowering performance, easier harvesting, accelerated ripening, higher yields, higher quality and / or higher nutritional value of the harvested product, better storage life and / or better processability of the harvested product, and increased resistance or tolerance to animal or microbial pests (such as insects, arachnids, nematodes, mites, slugs and snails).

[0326] Among DNA sequences encoding proteins conferring resistance or tolerance characteristics to pests (especially insects) in such animals or microorganisms, particular mention is made of genetic material from Bacillus thuringiensis encoding Bt proteins, which is widely documented in the literature and well-known to those skilled in the art. Also to be mentioned are proteins extracted from bacteria such as Photorhabdus (WO97 / 17432 and WO98 / 08932). In particular, mention is made of Bt Cry or VIP proteins, which include CrylA, CryIAb, CryIAc, CryIIA, CryIIIA, CryIIIB2, Cry9c, Cry2Ab, Cry3Bb and CryIF proteins or their toxic fragments; and other hybrids or combinations thereof, in particular Cry1F proteins or hybrids derived from Cry1F proteins (e.g., hybrid Cry1A-Cry1F proteins or their toxic fragments); Cry1A-type proteins or their toxic fragments, preferably Cry1Ac proteins or hybrids derived from Cry1Ac proteins (e.g., hybrid Cry1Ab-CryAc proteins) or CryAb or Bt2 proteins or their toxic fragments; Cry2Ae, Cry2Af or Cry2Ag proteins or their toxic fragments; Cry1A.105 proteins or their toxic fragments; VIP3Aa19 proteins, VIP3Aa20 proteins, VIP3A proteins produced in COT202 or COT203 cotton lines; VIP3Aa proteins or their toxic fragments, as described in Estruch et al. (1996), Proc Natl AcadSci USA. 28; 93(11):5389-94; Cry proteins, as described in WO2001 / 47952; insecticidal proteins obtained from Xenorhabdus (described in WO98 / 50427), Serratia (especially obtained from S. entomophila) or strains of the genus Photorhabdus, such as the Tc protein obtained from Photorhabdus, as described in WO98 / 08932. Also included are any variants or mutants of any of these proteins that differ in some amino acids (1-10, preferably 1-5) from the sequences named above (especially from the sequences of their toxic fragments) or are fused to a transit peptide (such as a plastid transit peptide) or another protein or peptide.

[0327] Another and particularly emphasized example of these properties is the conferral of tolerance to one or more herbicides, such as imidazolinones, sulphonylureas, glyphosate or phosphinothricin. Among the DNA sequences encoding proteins that confer tolerance to certain herbicides in transformed plant cells and plants, particular mention is made of: the bar gene or the PAT gene or the Streptomyces coelicolor gene, which is described in WO2009 / 152359 and confers tolerance to the glufosinate herbicide; genes encoding a suitable EPSPS (5-enolpyruvylshikimate 3-phosphate synthase), which confers tolerance to herbicides targeting EPSPS, particularly, for example, glyphosate and its salts; genes encoding glyphosate-N-acetyltransferase or genes encoding glyphosate oxidoreductase. Other suitable herbicide tolerance traits include at least one ALS (acetolactate synthase) inhibitor (e.g., WO2007 / 024782), mutant Arabidopsis ALS / AHAS genes (e.g., U.S. Patent 6,855,533), genes encoding 2,4-D monooxygenase that confers tolerance to 2,4-D (2,4-dichlorophenoxyacetic acid) and genes encoding dicamba monooxygenase that confers tolerance to dicamba (3,6-dichloro-2-methoxybenzoic acid).

[0328] Another and particularly emphasized example of these properties is the increased resistance to plant pathogenic fungi, bacteria and / or viruses caused, for example, by systemic acquired resistance (SAR), systemin, phytoalexins, elicitors, and resistance genes and the correspondingly expressed proteins and toxins.

[0329] Particularly useful transgenic lines of transgenic plants or plant cultivars that can preferably be processed according to the present invention include: line 531 / PV-GHBK04 (cotton, insect control, described in WO2002 / 040677), line 1143-14A (cotton, insect control, not deposited, described in WO2006 / 128569); line 1143-51B (cotton, insect control, not deposited, described in WO2006 / 128570); line 1445 (cotton, herbicide tolerance, not deposited, described in US-A 2002-120964 or WO2002 / 034946); line 17053 (rice, herbicide tolerance, deposited as PTA-9843, described in WO2010 / 117737); line 17314 (rice, herbicide tolerance, deposited as PTA-9844, described in WO2010 / 117735); line 281-24-236 (cotton, insect control - herbicide tolerance, deposited as PTA-6233, described in WO2005 / 103266 or US-A 2005-216969); line 3006-210-23 (cotton, insect control - herbicide tolerance, deposited as PTA-6233, described in US-A 2007-143876 or WO2005 / 103266); line 3272 (maize, quality trait, deposited as PTA-9972, described in WO2006 / 098952 or US-A 2006-230473); line 33391 (wheat, herbicide tolerance, deposited as PTA-2347, described in WO2002 / 027004), line 40416 (maize, insect control - herbicide tolerance, deposited as ATCC PTA-11508, described in WO 11 / 075593); line 43A47 (maize, insect control - herbicide tolerance, deposited as ATCC PTA-11509, described in WO2011 / 075595); line 5307 (maize, insect control, deposited as ATCC PTA-9561, described in WO2010 / 077816); line ASR-368 (bent grass, herbicide tolerance, deposited as ATCC PTA-4816, described in US-A 2006-162007 or WO2004 / 053062); line B16 (maize, herbicide tolerance, not deposited, described in US-A 2003-126634); line BPS-CV127-9 (soybean, herbicide tolerance, deposited as NCIMB No.41603, described in WO2010 / 080829);Line BLR1 (rape, restoration of male sterile line, deposited as NCIMB 41193, described in WO2005 / 074671), line CE43-67B (cotton, insect control, deposited as DSM ACC2724, described in US-A 2009-217423 or WO2006 / 128573); line CE44-69D (cotton, insect control, not deposited, described in US-A 2010-0024077); line CE44-69D (cotton, insect control, not deposited, described in WO2006 / 128571); line CE46-02A (cotton, insect control, not deposited, described in WO2006 / 128572); line COT102 (cotton, insect control, not deposited, described in US-A 2006-130175 or WO2004 / 039986); line COT202 (cotton, insect control, not deposited, described in US-A 2007-067868 or WO2005 / 054479); line COT203 (cotton, insect control, not deposited, described in WO2005 / 054480); line DAS21606-3 / 1606 (soybean, herbicide tolerance, deposited as PTA-11028, described in WO2012 / 033794), line DAS40278 (maize, herbicide tolerance, deposited as ATCC PTA-10244, described in WO2011 / 022469); line DAS-44406-6 / pDAB8264.44.06.l (soybean, herbicide tolerance, deposited as PTA-11336, described in WO2012 / 075426), line DAS-14536-7 / pDAB8291.45.36.2 (soybean, herbicide tolerance, deposited as PTA-11335, described in WO2012 / 075429), line DAS-59122-7 (maize, insect control-herbicide tolerance, deposited as ATCC PTA11384, described in US-A 2006-070139); line DAS-59132 (maize, insect control-herbicide tolerance, not deposited, described in WO2009 / 100188); line DAS68416 (soybean, herbicide tolerance, deposited as ATCC PTA-10442, described in WO2011 / 066384 or WO2011 / 066360); line DP-098140-6 (maize, herbicide tolerance, deposited as ATCC PTA-8296, described in US-A 2009-137395 or WO 08 / 112019); line DP-305423-1 (soybean, qualitative trait, not deposited, described in US-A 2008-312082 or WO2008 / 054747);Line DP-32138-1 (maize, hybrid system, deposited as ATCC PTA-9158, described in US-A2009-0210970 or WO2009 / 103049); Line DP-356043-5 (soybean, herbicide tolerance, deposited as ATCC PTA-8287, described in US-A 2010-0184079 or WO2008 / 002872); Line EE-I (eggplant, insect control, not deposited, described in WO 07 / 091277); Line Fil 17 (maize, herbicide tolerance, deposited as ATCC 209031, described in US-A 2006-059581 or WO 98 / 044140); Line FG72 (soybean, herbicide tolerance, deposited as PTA-11041, described in WO2011 / 063413), Line GA21 (maize, herbicide tolerance, deposited as ATCC 209033, described in US-A 2005-086719 or WO 98 / 044140); Line GG25 (maize, herbicide tolerance, deposited as ATCC 209032, described in US-A 2005-188434 or WO98 / 044140); Line GHB119 (cotton, insect control-herbicide tolerance, deposited as ATCC PTA-8398, described in WO2008 / 151780); Line GHB614 (cotton, herbicide tolerance, deposited as ATCC PTA-6878, described in US-A 2010-050282 or WO2007 / 017186); Line GJ11 (maize, herbicide tolerance, deposited as ATCC209030, described in US-A 2005-188434 or WO98 / 044140); Line GM RZ13 (sugar beet, virus resistance, deposited as NCIMB-41601, described in WO2010 / 076212); Line H7-1 (sugar beet, herbicide tolerance, deposited as NCIMB 41158 or NCIMB 41159, described in US-A 2004-172669 or WO 2004 / 074492); Line JOPLIN1 (wheat, disease resistance, not deposited, described in US-A 2008-064032); Line LL27 (soybean, herbicide tolerance, deposited as NCIMB41658, described in WO2006 / 108674 or US-A 2008-320616); Line LL55 (soybean, herbicide tolerance, deposited as NCIMB 41660, described in WO 2006 / 108675 or US-A 2008-196127);Line LLcotton25 (cotton, herbicide tolerance, deposited as ATCC PTA-3343, described in WO2003 / 013224 or USA2003-097687); Line LLRICE06 (rice, herbicide tolerance, deposited as ATCC 203353, described in US 6,468,747 or WO2000 / 026345); Line LLRice62 (rice, herbicide tolerance, deposited as ATCC 203352, described in WO2000 / 026345), Line LLRICE601 (rice, herbicide tolerance, deposited as ATCC PTA-2600, described in US-A2008-2289060 or WO2000 / 026356); Line LY038 (maize, qualitative trait, deposited as ATCC PTA-5623, described in US-A 2007-028322 or WO2005 / 061720); Line MIR162 (maize, insect control, deposited as PTA-8166, described in US-A 2009-300784 or WO2007 / 142840); Line MIR604 (maize, insect control, not deposited, described in US-A 2008-167456 or WO2005 / 103301); Line MON15985 (cotton, insect control, deposited as ATCC PTA-2516, described in US-A 2004-250317 or WO2002 / 100163); Line MON810 (maize, insect control, not deposited, described in US-A 2002-102582); Line MON863 (maize, insect control, deposited as ATCC PTA-2605, described in WO2004 / 011601 or US-A 2006-095986); Line MON87427 (maize, pollination control, deposited as ATCC PTA-7899, described in WO2011 / 062904); Line MON87460 (maize, stress tolerance, deposited as ATCC PTA-8910, described in WO2009 / 111263 or US-A 2011-0138504); Line MON87701 (soybean, insect control, deposited as ATCC PTA-8194, described in US-A 2009-130071 or WO2009 / 064652); Line MON87705 (soybean, qualitative trait - herbicide tolerance, deposited as ATCC PTA-9241, described in US-A 2010-0080887 or WO2010 / 037016); Line MON87708 (soybean, herbicide tolerance, deposited as ATCC PTA-9670, described in WO2011 / 034704);Line MON87712 (soybean, yield, deposited as PTA-10296, described in WO2012 / 051199); Line MON87754 (soybean, qualitative trait, deposited as ATCC PTA-9385, described in WO2010 / 024976); Line MON87769 (soybean, qualitative trait, deposited as ATCC PTA-8911, described in US-A2011-0067141 or WO2009 / 102873); Line MON88017 (maize, insect control-herbicide tolerance, deposited as ATCC PTA-5582, described in US-A 2008-028482 or WO2005 / 059103); Line MON88913 (cotton, herbicide tolerance, deposited as ATCC PTA-4854, described in WO2004 / 072235 or US-A 2006-059590); Line MON88302 (rapeseed, herbicide tolerance, deposited as PTA-10955, described in WO2011 / 153186), Line MON88701 (cotton, herbicide tolerance, deposited as PTA-11754, described in WO2012 / 134808), Line MON89034 (maize, insect control, deposited as ATCC PTA-7455, described in WO 07 / 140256 or US-A2008-260932); Line MON89788 (soybean, herbicide tolerance, deposited as ATCC PTA-6708, described in US-A 2006-282915 or WO2006 / 130436); Line MS11 (rapeseed, pollination control-herbicide tolerance, deposited as ATCC PTA-850 or PTA-2485, described in WO2001 / 031042); Line MS8 (rapeseed, pollination control-herbicide tolerance, deposited as ATCC PTA-730, described in WO2001 / 041558 or US-A 2003-188347); Line NK603 (maize, herbicide tolerance, deposited as ATCC PTA-2478, described in US-A 2007-292854); Line PE-7 (rice, insect control, not deposited, described in WO2008 / 114282); Line RF3 (rapeseed, pollination control-herbicide tolerance, deposited as ATCC PTA-730, described in WO2001 / 041558 or US-A2003-188347); Line RT73 (rapeseed, herbicide tolerance, not deposited, described in WO2002 / 036831 or US-A2008-070260);Line SYHT0H2 / SYN-000H2-5 (soybean, herbicide tolerance, deposited as PTA-11226, described in WO2012 / 082548); Line T227-1 (sugar beet, herbicide tolerance, not deposited, described in WO2002 / 44407 or US-A 2009-265817); Line T25 (maize, herbicide tolerance, not deposited, described in US-A 2001-029014 or WO2001 / 051654); Line T304-40 (cotton, insect control-herbicide tolerance, deposited as ATCC PTA-8171, described in US-A 2010-077501 or WO2008 / 122406); Line T342-142 (cotton, insect control, not deposited, described in WO2006 / 128568); Line TC1507 (maize, insect control-herbicide tolerance, not deposited, described in US-A2005-039226 or WO2004 / 099447); Line VIP1034 (maize, insect control-herbicide tolerance, deposited as ATCC PTA-3925, described in WO2003 / 052073); Line 32316 (maize, insect control-herbicide tolerance, deposited as PTA-11507, described in WO2011 / 084632); Line 4114 (maize, insect control-herbicide tolerance, deposited as PTA-11506, described in WO2011 / 084621); Line EE-GM3 / FG72 (soybean, herbicide tolerance, ATCC accession number PTA-11041) optionally stacked with Line EE-GM1 / LL27 or Line EE-GM2 / LL55 (WO2011 / 063413A2); Line DAS-68416-4 (soybean, herbicide tolerance, ATCC accession number PTA-10442, WO2011 / 066360Al); Line DAS-68416-4 (soybean, herbicide tolerance, ATCC accession number PTA-10442, WO2011 / 066384Al); Line DP-040416-8 (maize, insect control, ATCC accession number PTA-11508, WO2011 / 075593Al); Line DP-043A47-3 (maize, insect control, ATCC accession number PTA-11509, WO2011 / 075595Al); Line DP-004114-3 (maize, insect control, ATCC accession number PTA-11506, WO2011 / 084621Al); Line DP-032316-8 (maize, insect control, ATCC accession number PTA-11507, WO2011 / 084632Al);Line MON-88302-9 (rape, herbicide tolerance, ATCC accession number PTA-10955, WO2011 / 153186Al); Line DAS-21606-3 (soybean, herbicide tolerance, ATCC accession number PTA-11028, WO2012 / 033794A2); Line MON-87712-4 (soybean, qualitative trait, ATCC accession number PTA-10296, WO2012 / 051199A2); Line DAS-44406-6 (soybean, stacked herbicide tolerance, ATCC accession number PTA-11336, WO2012 / 075426Al); Line DAS-14536-7 (soybean, stacked herbicide tolerance, ATCC accession number PTA-11335, WO2012 / 075429Al); Line SYN-000H2-5 (soybean, herbicide tolerance, ATCC accession number PTA-11226, WO2012 / 082548A2); Line DP-061061-7 (rape, herbicide tolerance, no deposit number, WO2012071039A1); Line DP-073496-4 (rape, herbicide tolerance, no deposit number, US2012131692); Line 8264.44.06.1 (soybean, stacked herbicide tolerance, accession number PTA-11336, WO2012075426A2); Line 8291.45.36.2 (soybean, stacked herbicide tolerance, accession number PTA-11335, WO2012075429A2); Line SYHT0H2 (soybean, ATCC accession number PTA-11226, WO2012 / 082548A2); Line MON88701 (cotton, ATCC accession number PTA-11754, WO2012 / 134808Al); Line KK179-2 (alfalfa, ATCC accession number PTA-11833, WO2013 / 003558Al); Line pDAB8264.42.32.1 (soybean, stacked herbicide tolerance, ATCC accession number PTA-11993, WO2013 / 010094Al), Line MZDT09Y (maize, ATCC accession number PTA-13025, WO2013 / 012775Al).;

[0330] In addition, a list of such transgenic lines is provided by the Animal and Plant Health Inspection Service (APHIS) of the United States Department of Agriculture (USDA) and can be found on its World Wide Web site at aphis.usda.gov. For the purposes of this application, the status of the list itself as of the filing date of this application is relevant.

[0331] In transgenic plants, the genes / lines conferring the desired traits in question can also be present in combination with one another. Examples of transgenic plants that may be mentioned include important crop plants such as cereals (wheat, rice, triticale, barley, rye, oats), maize, soybeans, potatoes, sugar beet, sugar cane, tomatoes, peas and other vegetable species, cotton, tobacco, oilseed rape, and fruit plants (the fruits being apples, pears, citrus fruits and grapes), with particular emphasis on maize, soybeans, wheat, rice, potatoes, cotton, sugar cane, tobacco and oilseed rape. Particular emphasis is placed on the traits of increased resistance of the plants to insects, arachnids, nematodes and slugs and snails, and increased resistance of the plants to one or more herbicides.

[0332] Examples of commercially available instances of such plants, plant parts or plant seeds that can be preferably treated according to the invention include commercial products such as plant seeds sold or distributed under the following trade names: RIB ROUNDUP VT DOUBLE VT TRIPLE BOLLGARD ROUNDUPREADY 2 ROUNDUP 2 XTEN DTM , INTACTA RR2 VISTIVE and / or XTENDFLEX TM .

[0333] Crop protection - Type of treatment

[0334] The plants and plant parts are directly treated with the compounds of formula (I) using conventional treatment methods or treated by acting on their environment, habitat or storage space, said conventional treatment methods being, for example, dipping, spraying, atomizing, irrigation, evaporation, dusting, fogging, broadcasting, foaming, spreading-on, injection, watering (soaking), drip irrigation, and in the case of propagation material, especially seeds, also dry seed treatment as a powder, wet seed treatment as a solution, slurry treatment as a water-soluble powder, treatment by crusting, treatment by coating with one or more layers, etc. The compounds of formula (I) can also be applied by the ultra-low volume method or the application form or the compounds of formula (I) themselves can be injected into the soil.

[0335] A preferred direct treatment of the plants is foliar application, i.e. applying the compounds of formula (I) to the leaf surface, in which case the treatment frequency and application rate should be adjusted according to the infestation level of the pests.

[0336] In the case of systemic active compounds, the compounds of the formula (I) also enter the plant via the root system. The plant is then treated by acting on the habitat of the plant with the compounds of the formula (I). This can be done, for example, by soaking; or by mixing into the soil or nutrient solution, i.e., the growth site of the plant (such as soil or hydroponic system) is impregnated with the compounds of the formula (I) in liquid form; or by soil application, i.e., the compounds of the formula (I) according to the invention are introduced in solid form (such as in the form of granules) into the growth site of the plant; or by drip irrigation application (usually also called "chemigation"), i.e., the compounds of the formula (I) according to the invention are applied in liquid form from surface or subsurface drip lines over a certain period of time, while different amounts of water are applied at defined locations near the plants. In the case of rice crops, it can also be done by metering the compounds of the formula (I) in solid application form (such as as granules) into flooded rice fields.

[0337] Digital technology

[0338] The compounds of the invention can be combined with models, for example, embedded in computer programs, for site-specific crop plant management, satellite farming, precision farming or precision agriculture. Such models use data from different sources to support site-specific management of agricultural sites, with the aim of optimizing profitability, sustainability and environmental protection, and the sources are, for example, soil, weather, crops (such as type, growth stage, plant health), weeds (such as type, growth stage), diseases, pests, nutrients, water, humidity, biomass, satellite data, yield, etc. In particular, such models can help to optimize agronomic decisions, control the precision of pesticide application and record the operations carried out.

[0339] As an example, if the model simulates the growth of pests and calculates that a threshold has been reached at which it is recommended to apply the compounds of the invention to the crop plants, the compounds of the invention can be applied to the crop plants according to a suitable dosage regime.

[0340] Commercially available systems including agronomic models are, for example, FieldScriptsTM from The Climate Corporation, XarvioTM from BASF, AGLogicTM from John Deere, etc.

[0341] In addition, the compounds of the present invention can be used in combination with intelligent spraying devices, such as spot spraying or precision spraying devices attached to or installed inside agricultural vehicles, such as tractors, robots, helicopters, airplanes, unmanned vehicles (UAVs) (such as drones, etc.). Such devices generally include input sensors (such as cameras) and a processing unit configured to analyze the input data and configured to provide decisions based on the analysis of the input data for applying the compounds of the present invention to crop plants (and correspondingly weeds) in a specific and precise manner. The use of such intelligent spraying devices generally also requires: a positioning system (such as a GPS receiver) to locate the recorded data and maneuver or control the agricultural vehicle; a geographic information system (GIS) to represent the information on an understandable map; and a suitable agricultural vehicle to perform the required agricultural activities (such as spraying).

[0342] In one example, pests can be detected from the photos obtained by the camera. In one example, pests can be identified and / or classified based on the photo. Such identification and / or classification can employ image processing algorithms. Such algorithms for image processing can utilize algorithms of machine learning, such as trained neural networks, decision trees and utilize artificial intelligence algorithms. In this way, the compounds described herein can be applied only where they are needed.

[0343] Seed treatment

[0344] It has long been known to control animal pests by treating plant seeds and this has been the subject of continuous improvement. However, seed treatment involves a series of problems that cannot always be solved in a satisfactory manner. Therefore, there is a need to develop methods for protecting seeds and germinating plants that do not require or at least significantly reduce the additional application of pesticides during storage, after sowing or after emergence of the plants. There is also a need to optimize the amount of the active compounds used in order to provide optimal protection for the seeds and germinating plants against animal pests, while the active compounds used do not damage the plants themselves. In particular, the method of treating seeds should also take into account the inherent insecticidal or nematicidal properties of pest-resistant or pest-tolerant transgenic plants in order to achieve optimal protection for the seeds and germinating plants with the smallest amount of pesticides.

[0345] Therefore, in particular, the present invention also relates to a method for protecting seeds and germinating plants from pests by treating the seeds with one of the compounds of formula (I). The method of the present invention for protecting seeds and germinating plants from pests also includes a method of treating the seeds by using the compound of formula (I) and a mixing component simultaneously or sequentially in one operation. This also includes a method of treating the seeds by using the compound of formula (I) and the mixing component at different times.

[0346] The invention further relates to the use of a compound of formula (I) for treating seeds to protect the seeds and the resulting plants against animal pests.

[0347] Furthermore, the invention relates to seeds treated with a compound of formula (I) according to the invention to provide protection against animal pests. The invention also relates to seeds treated simultaneously with a compound of formula (I) and a mixing component. The invention also relates to seeds treated with a compound of formula (I) and a mixing component at different times. In the case of seeds treated with a compound of formula (I) and a mixing component at different time points, the substances may be present on the seeds in different layers. Herein, the layer containing the compound of formula (I) and the mixing component may optionally be separated by an intermediate layer. The invention also relates to seeds on which a compound of formula (I) and a mixing component are applied as components of a coating or as another layer or other layers in addition to the coating.

[0348] Furthermore, the invention relates to seeds which are film-coated after treatment with a compound of formula (I) to prevent the seeds from suffering from dust abrasion.

[0349] When the compound of formula (I) acts systemically, one of the advantages is that by treating the seeds, not only the seeds themselves are protected, but also the plants obtained therefrom are protected against animal pests after emergence. In this way, it is not necessary to immediately treat the crop at the time of sowing or shortly thereafter.

[0350] Another advantage that must be considered is that treating seeds with a compound of formula (I) can promote the germination and emergence of the treated seeds.

[0351] It is also considered advantageous that the compound of formula (I) can also be particularly used for transgenic seeds.

[0352] Furthermore, the compound of formula (I) can be used in combination with signaling technology compositions or compounds, so as to enable better colonization by symbionts (such as rhizobia, mycorrhizae and / or endophytic bacteria or fungi) and / or optimize nitrogen fixation.

[0353] The compound of formula (I) is suitable for protecting the seeds of any plant variety used in agriculture, greenhouses, forestry or horticulture. In particular, it takes the form of seeds of the following plants: cereals (such as wheat, barley, rye, millet and oats), maize, cotton, soybeans, rice, potatoes, sunflowers, coffee, tobacco, canola, rapeseed, sugar beets (such as sugar beets and fodder beets), peanuts, vegetables (such as tomatoes, cucumbers, beans, cruciferous vegetables, onions and lettuce), fruit plants, lawn plants and ornamental plants. It is particularly important to treat the seeds of cereals (wheat, barley, rye, oats), maize, soybeans, cotton, canola, rapeseed, vegetables and rice.

[0354] As described above, it is also particularly important to treat transgenic seeds with the compounds of formula (I). This takes the form of seeds of plants which usually contain at least one heterologous gene which controls the expression of polypeptides having in particular insecticidal and / or nematicidal properties. The heterologous genes in transgenic seeds can be derived from microorganisms such as Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus or Gliocladium. The present invention is particularly suitable for treating transgenic seeds which contain at least one heterologous gene derived from the genus Bacillus. Heterologous genes derived from Bacillus thuringiensis are particularly preferred.

[0355] In the context of the present invention, the compounds of formula (I) are applied to the seeds. The seeds are preferably treated in a state such that they are stable enough to avoid damage during the treatment. Usually, the seeds can be treated at any time point between harvesting and sowing. Seeds which have been separated from the plant and from which the ear axis, husk, stem, pod, hair or pulp have been removed are generally used. For example, seeds which have been harvested, cleaned and dried to a moisture content which permits storage can be used. Alternatively, seeds which have been treated with water, for example, after drying and then redried (for example primed) can also be used. In the case of rice seeds, seeds which have been soaked in water until they reach a certain stage of the rice embryo ('pigeon breast' stage) can also be used, which stimulates germination and gives more uniform emergence.

[0356] When treating seeds, it is generally necessary to pay attention to selecting the amount of the compound of formula (I) and / or the amount of other additives applied to the seeds so as not to have an adverse effect on the germination of the seeds or to damage the resulting plants. This must be particularly ensured for active compounds which may exhibit phytotoxic effects at certain application rates.

[0357] Generally, the compounds of formula (I) are applied to the seeds in a suitable formulation. Suitable formulations and methods for seed treatment are known to those skilled in the art.

[0358] The compounds of formula (I) can be converted into conventional seed dressing formulations, such as solutions, emulsions, suspensions, powders, foams, slurries or other seed coating compositions, as well as ULV formulations.

[0359] These formulations are prepared in a known manner by mixing the compounds of formula (I) with conventional additives, such as conventional extenders and solvents or diluents, colorants, wetting agents, dispersants, emulsifiers, defoamers, preservatives, secondary thickeners, adhesives, gibberellins, and water.

[0360] Colorants which can be present in the seed dressing formulations which can be used according to the invention are all colorants which are customarily used for this purpose. Pigments which are sparingly soluble in water or dyes which are soluble in water can be used. Examples include the dyes known under the names Rhodamine B, C.I. Pigment Red 112, and C.I. Solvent Red 1.

[0361] Useful wetting agents which can be present in the seed dressing formulations which can be used according to the invention are all substances which promote wetting and are customarily used for formulating agrochemically active compounds. Alkyl naphthalenesulfonates, such as diisopropyl naphthalenesulfonate or diisobutyl naphthalenesulfonate, are preferably used.

[0362] Useful dispersants and / or emulsifiers which can be present in the seed dressing formulations which can be used according to the invention are all nonionic, anionic, and cationic dispersants which are customarily used for formulating agrochemically active ingredients. Nonionic or anionic dispersants, or mixtures of nonionic or anionic dispersants, are preferably used. Suitable nonionic dispersants include, in particular, ethylene oxide / propylene oxide block polymers, alkylphenol polyglycol ethers, and triphenylvinylphenol polyglycol ethers, and phosphorylated or sulfated derivatives thereof. Suitable anionic dispersants are, in particular, lignosulfonates, polyacrylates, and arylsulfonates / formaldehyde condensates.

[0363] Defoamers which can be present in the seed dressing formulations which can be used according to the invention are all foam-inhibiting substances which are customarily used for formulating agrochemically active ingredients. Silicone defoamers and magnesium stearate are preferably used.

[0364] Preservatives which can be present in the seed dressing formulations which can be used according to the invention are all substances which can be used for this purpose in agrochemical compositions. Examples include dichlorophen and benzyl alcohol hemiformal.

[0365] Secondary thickeners which can be present in the seed dressing formulations which can be used according to the invention are all substances which can be used for this purpose in agrochemical compositions. Cellulose derivatives, acrylic derivatives, xanthan gum, modified clays, and finely divided silica are preferred.

[0366] Adhesives which can be present in the seed dressing formulations which can be used according to the invention are all conventional binders which can be used for seed dressing products. Polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, and methyl cellulose (tylose) can be considered to be preferred.

[0367] The gibberellins that can be present in the seed dressing preparations that can be used according to the present invention are preferably gibberellin A1, A3 (= gibberellic acid), A4 and A7; gibberellic acid is particularly preferably used. The said gibberellins are known (see R. Wegler "Chemie der Pflanzenschutz - and ", Volume 2, Springer Verlag, 1970, pages 401 - 412).

[0368] The seed dressing preparations that can be used according to the present invention can be used, directly or after prior dilution with water, to treat various different types of seeds. For example, the concentrate or the preparation obtained therefrom by dilution with water can be used for dressing the seeds of the following plants: cereals (such as wheat, barley, rye, oats and triticale), as well as maize, rice, rape, peas, beans, cotton, sunflower, soybeans and sugar beet, or various different vegetables. The seed dressing preparations that can be used according to the present invention or their diluted use forms can also be used for dressing the seeds of genetically modified plants.

[0369] For treating seeds with the seed dressing preparations that can be used according to the present invention or the use forms prepared therefrom by adding water, all conventional mixing devices for seed dressing are useful. Specifically, the seed dressing process is to place the seeds in a mixer operating in batch or continuous mode; add the specifically required amount of the seed dressing preparation (either in itself or after prior dilution with water); and mix until the preparation is evenly distributed on the seeds. If appropriate, a drying operation is carried out afterwards.

[0370] The application rate of the seed dressing preparations that can be used according to the present invention can vary within a wide range. This is determined by the specific content of the compound of formula (I) in the preparation and the seeds. The application rate of the compound of formula (I) is generally 0.001 to 50 g / kg of seeds, preferably 0.01 to 15 g / kg of seeds.

[0371] Animal Health

[0372] In the field of animal health, i.e., the field of veterinary medicine, the compounds of formula (I) are active against animal parasites, especially ectoparasites or endoparasites. The term "endoparasite" particularly includes worms and protozoa, such as coccidia. Ectoparasites are generally and preferably arthropods, especially insects or mites.

[0373] In the field of veterinary medicine, the compounds of formula (I) having favorable warm - blooded animal toxicity are suitable for controlling parasites that occur in animal breeding and animal reproduction of domestic animals, breeding animals, zoo animals, laboratory animals, experimental animals and domestic pets. They are active against all or specific developmental stages of the parasites.

[0374] Agricultural livestock includes, for example, mammals such as sheep, goats, horses, donkeys, camels, water buffalo, rabbits, reindeer, moose, especially cattle and pigs; or poultry such as turkeys, ducks, geese, especially chickens; or fish or crustaceans as in aquaculture; or, as the case may be, insects such as bees.

[0375] Domestic animals include, for example, mammals such as hamsters, guinea pigs, rats, mice, chinchillas, ferrets, especially dogs, cats, caged birds; reptiles, amphibians or ornamental fish.

[0376] According to a specific embodiment, the compound of formula (I) is administered to a mammal.

[0377] According to another specific embodiment, the compound of formula (I) is administered to birds, i.e., caged birds or especially poultry.

[0378] By using the compound of formula (I) to control animal parasites, it is intended to reduce or prevent diseases, death cases and performance decline (in the case of meat, milk, wool, skin, eggs, honey, etc.), thereby making animal husbandry more economical and simpler and achieving better animal health.

[0379] In the field of animal health, the term "control" (control or controlling) as used herein means that the compound of formula (I) effectively reduces the incidence of various parasites in animals infected with parasites to a harmless level. More specifically, "control" as used herein means that the compound of formula (I) effectively kills various parasites, inhibits their growth or inhibits their proliferation.

[0380] Exemplary arthropods include, but are not limited to:

[0381] Order Anoplurida, such as genera Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp. and Solenopotes spp.;

[0382] Order Mallophagida and suborders Amblycerina and Ischnocerina, such as genera Bovicola spp., Damalina spp., Felicola spp., Lepikentron spp., Menopon spp., Trichodectes spp., Trimenopon spp., Trinoton spp., Werneckiella spp.;

[0383] Diptera, Nematocerina, Brachycerina, such as Aedes spp., Anopheles spp., Atylotus spp., Braula spp., Calliphora spp., Chrysomyia spp., Chrysops spp., Culex spp., Culicoides spp., Eusimulium spp., Fannia spp., Gasterophilus spp., Glossina spp., Haematobia spp., Haematopota spp., Hippobosca spp., Hybomitra spp., Hydrotaea spp., Hypoderma spp., Lipoptena spp., Lucilia spp., Lutzomyia spp., Melophagus spp., Morellia spp., Musca spp., Odagmia spp., Oestrus spp., Philipomyia, Phlebotomus spp., Rhinoestrus spp., Sarcophaga spp., Simulium spp., Stomoxys spp., Tabanus spp., Tipula spp., Wilhelmia spp., Wohlfahrtia spp.;

[0384] Siphonapterida, such as Ceratophyllus spp., Ctenocephalides spp., Pulex spp., Tunga spp., Xenopsylla spp.;

[0385] Heteropterida, such as Cimex spp., Panstrongylus spp., Rhodnius spp., Triatoma spp.; and annoying pests and hygiene pests from Blattarida.

[0386] Furthermore, in the case of arthropods, mention should be made of, for example but not limited to, the following Acari:

[0387] Subclass Acari (Order Acarina) and Suborder Metastigmata, such as family Argasidae like Argas spp., Ornithodorus spp., Otobius spp.; family Ixodidae like Amblyomma spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Ixodes spp., Rhipicephalus (Boophilus) spp., Rhipicephalus spp. (the original genus of multi-host ticks); Suborder Mesostigmata such as Dermanyssus spp., Ornithonyssus spp., Pneumonyssus spp., Raillietia spp., Sternostoma spp., Tropilaelaps spp., Varroa spp.; Order Actinedida (Prostigmata), such as Acarapis spp., Cheyletiella spp., Demodex spp., Listrophorus spp., Myobia spp., Neotrombicula spp., Ornithocheyletia spp., Psorergates spp., Trombicula spp.; and Order Acaridida (Astigmata), such as Acarus spp., Caloglyphus spp., Chorioptes spp., Cytodites spp., Hypodectes spp., Knemidocoptes spp., Laminosioptes spp., Notoedres spp., Otodectes spp., Psoroptes spp., Pterolichus spp.) Sarcoptes spp., Trixacarus spp., Tyrophagus spp.

[0388] Exemplary parasitic protozoa include, but are not limited to:

[0389] Mastigophora (Flagellata), for example:

[0390] Metamonada: Diplomonadida, such as Giardia spp., Spironucleus spp.

[0391] Parabasala: Trichomonadida, such as Histomonas spp., Pentatrichomonas spp., Tetratrichomonas spp., Trichomonas spp., Tritrichomonas spp.

[0392] Euglenozoa: Trypanosomatida, such as Leishmania spp., Trypanosoma spp.

[0393] Sarcomastigophora (Rhizopoda), for example Entamoebidae, such as Entamoeba spp., Centramoebidae, such as Acanthamoeba sp., Euamoebidae, such as Harmanella sp.

[0394] Alveolata, such as Apicomplexa (Sporozoa): such as Cryptosporidium spp.; Eimeriida, for example Besnoitia spp., Cystoisospora spp., Eimeria spp., Hammondia spp., Isospora spp., Neospora spp., Sarcocystis spp., Toxoplasma spp.; Adeleida, for example Hepatozoon spp., Klossiella spp.; Haemosporida, for example Leucocytozoon spp., Plasmodium spp.; Piroplasmida, for example Babesia spp., Ciliophora spp., Echinozoon, Theileria spp.; Vesibuliferida, for example Balantidium spp., Buxtonella spp.

[0395] Microspora, such as Encephalitozoon spp., Enterocytozoon spp., Globidium spp., Nosema spp., and for example Myxozoa spp.

[0396] Worms pathogenic to humans or animals include, for example, Acanthocephala, Nematoda, Pentastomida, and Platyhelminthes (e.g., Monogenea, Cestodes, and Trematodes).

[0397] Exemplary worms include, but are not limited to:

[0398] Monogenea: e.g., Dactylogyrus spp., Gyrodactylus spp., Microbothrium spp., Polystoma spp., Troglecephalus spp.;

[0399] Cestoda: Pseudophyllidea, e.g., Bothridium spp., Diphyllobothrium spp., Diplogonoporus spp., Ichthyobothrium spp., Ligula spp., Schistocephalus spp., Spirometra spp.;

[0400] Cyclophyllidea, e.g., Andyra spp., Anoplocephala spp., Avitellina spp., Bertiella spp., Cittotaenia spp., Davainea spp., Diorchis spp., Diplopylidium spp., Dipylidium spp., Echinococcus spp., Echinocotyle spp., Echinolepis spp., Hydatigera spp., Hymenolepis spp., Joyeuxiella spp., Mesocestoides spp., Moniezia spp., Paranoplocehala spp., Raillietina spp., Stilesia spp., Taenia spp., Thysaniezia spp., Thysanosoma spp.;

[0401] Trematodes: selected from the class Digenea, such as: Austrobilharzia spp., Brachylaima spp., Calicophoron spp., Catatropis spp., Clonorchis spp., Collyriclum spp., Cotylophoron spp., Cyclocoelum spp., Dicrocoelium spp., Diplostomum spp., Echinochasmus spp., Echinoparyphium spp., Echinostoma spp., Eurytema spp., Fasciola spp., Fascioloides spp., Fasciolopsis spp., Fischoederius spp., Gastrothylacus spp., Gigantobilharzia spp., Gigantoctyle spp., Heterophyes spp., Hypoderaeum spp., Leucochloridium spp., Metagonimus spp., Metorchis spp., Nanophyetus spp., Notocotylus spp., Opisthorchis spp., Ornithobilharzia spp., Paragonimus spp., Paramphistomum spp., Plagiorchis spp., Posthodiplostomum spp., Prosthogonimus spp., Schistosoma spp., Trichobilharzia spp., Troglotrema spp., Typhlocoelum spp.;

[0402] Nematodes: Nematodes from the order Trichinellida, such as: Capillaria spp., Eucoleus spp., Paracapillaria spp., Trichinella spp., Trichomosoides spp., Trichuris spp.;

[0403] Nematodes from the order Tylenchida, such as: Micronema spp., Parastrongyloides spp., Strongyloides spp.;

[0404] Nematodes from the order Rhabditina, such as: Aelurostrongylus spp., Amidostomum spp., Ancylostoma spp., Angiostrongylus spp., Bronchonema spp., Bunostomum spp., Chabertia spp., Cooperia spp., Cooperioides spp., Crenosoma spp., Cyathostomum spp., Cyclococercus spp., Cyclodontostomum spp., Cylicocyclus spp., Cylicostephanus spp., Cylindropharynx spp., Cystocaulus spp., Dictyocaulus spp., Elaphostrongylus spp., Filaroides spp., Globocephalus spp., Graphidium spp., Gyalocephalus spp., Haemonchus spp., Heligmosomoides spp., Hyostrongylus spp., Marshallagia spp., Metastrongylus spp., Muellerius spp., Necator spp., Nematodirus spp., Neostrongylus spp., Nippostrongylus spp., Obeliscoides spp., Oesophagodontus spp., Oesophagostomum spp., Ollulanus spp.; Ornithostrongylus spp., Oslerus spp., Ostertagia spp., Paracooperia spp.) Paracrenosoma, Parafilaroides spp., Parelaphostrongylus spp., Pneumocaulus, Pneumostrongylus spp., Poteriostomum spp., Protostrongylus spp., Spicocaulus spp., Stephanurus spp., Strongylus spp., Syngamus spp., Teladorsagia spp., Trichonema spp., Trichostrongylus spp., Triodontophorus spp., Troglostrongylus, Uncinaria spp.;.

[0405] Nematodes from the order Spirurida, such as: Acanthocheilonema spp., Anisakis spp., Ascaridia spp.; Ascaris spp., Ascarops spp., Aspiculuris spp., Baylisascaris spp., Brugia spp., Cercopithifilaria spp., Crassicauda spp., Dipetalonema spp., Dirofilaria spp., Dracunculus spp.; Draschia spp., Enterobius spp., Filaria spp., Gnathostoma spp., Gongylonema spp., Habronema spp., Heterakis spp.; Litomosoides spp., Loa spp., Onchocerca spp., Oxyuris spp., Parabronema spp., Parafilaria spp., Parascaris spp., Passalurus spp., Physaloptera spp., Probstmayria spp., Pseudofilaria spp., Setaria spp., Skjrabinema spp., Spirocerca spp., Stephanofilaria spp., Strongyluris spp., Syphacia spp., Thelazia spp., Toxascaris spp., Toxocara spp., Wuchereria spp.

[0406] Acanthocephala: Oligacanthorhynchida, such as Macracanthorhynchus spp., Prosthenorchis spp.; Moniliformida, such as Moniliformis spp.;

[0407] Polymorphida, such as Filicollis spp.; Echinorhynchida, such as Acanthocephalus spp., Echinorhynchus spp., Leptorhynchoides spp.;

[0408] Pentastomida: Porocephalida, such as Linguatula spp.

[0409] In the field of veterinary medicine and animal husbandry, the compounds of formula (I) are administered in a suitable formulation by methods commonly known in the art (such as by enteral, parenteral, dermal or nasal routes). The administration can be carried out prophylactically, metaphylactically or therapeutically.

[0410] Accordingly, one embodiment of the present invention relates to the compounds of formula (I) for use as medicaments.

[0411] Another aspect relates to the compounds of formula (I) for use as anti-endoparasitic agents.

[0412] Another specific aspect relates to the compounds of formula (I) for use as anthelmintics, more particularly as nematocides, trematocides, acanthocidies or pentastomicides.

[0413] Another specific aspect relates to the compounds of formula (I) for use as antiprotozoal agents.

[0414] Another aspect relates to the compounds of formula (I) for use as anti-ectoparasitic agents, especially as arthropodicides, more particularly as insecticides or acaricides.

[0415] Other aspects of the invention are veterinary preparations which comprise an effective amount of at least one compound of formula (I) and at least one of the following: a pharmaceutically acceptable excipient (such as a solid or liquid diluent), a pharmaceutically acceptable adjuvant (such as a surfactant), in particular a pharmaceutically acceptable excipient and / or a pharmaceutically acceptable adjuvant commonly used in veterinary preparations.

[0416] A related aspect of the invention is a process for preparing a veterinary preparation as described herein, which comprises the step of mixing at least one compound of formula (I) with a pharmaceutically acceptable excipient and / or adjuvant, in particular with a pharmaceutically acceptable excipient and / or adjuvant commonly used in veterinary preparations.

[0417] Another specific aspect of the invention is a veterinary preparation and a process for its preparation, the veterinary preparation being selected from ectoparasiticide preparations and endoparasiticide preparations, more particularly from anthelmintic, antiprotozoal and arthropodicide preparations of the above aspects, and even more particularly from nematocidal, trematocidal, acanthocephalocidal, linguatulicidal, insecticidal and acaricidal preparations.

[0418] Another aspect relates to a method for treating a parasitic infection, in particular an infection caused by a parasite selected from the ectoparasites and endoparasites mentioned herein, by administering to an animal in need of treatment, in particular a non-human animal, an effective amount of a compound of formula (I).

[0419] Another aspect relates to a method for treating a parasitic infection, in particular an infection caused by a parasite selected from the ectoparasites and endoparasites mentioned herein, by administering to an animal in need of treatment, in particular a non-human animal, a veterinary preparation as defined herein.

[0420] Another aspect relates to the use of a compound of formula (I) in the treatment of parasitic infections in animals, in particular non-human animals, in particular infections caused by parasites selected from the ectoparasites and endoparasites mentioned herein.

[0421] In the context of the animal health or veterinary field of the present invention, the term "treatment" includes prophylactic, remedial or therapeutic treatment.

[0422] In a specific embodiment, there is provided a mixture of at least one compound of formula (I) with other active ingredients, in particular with endoparasiticides and ectoparasiticides, for use in the veterinary field.

[0423] In the field of animal health, a "mixture" not only refers to the formulation of two (or more) different active ingredients as a combined preparation and their corresponding administration together, but also to a product containing separate preparations of each active compound. Thus, when more than two active compounds are administered, all the active compounds can be formulated as a combined preparation or all the active compounds can be formulated as separate preparations; it can also be in a mixed form, where some active compounds are formulated in combination and some are formulated separately. The separate preparations can administer the active compounds either separately or sequentially.

[0424] The active compounds mentioned herein by their common names are known and are described, for example, in the Pesticide Manual (see above), or can be retrieved on the Internet (such as http: / / www.alanwood.net / pesticides).

[0425] Exemplary active ingredients of the ectoparasiticide class as mixed compatibilities include, but are not limited to, the insecticides and acaricides listed in detail above. Other active ingredients that can be used are listed below according to the above classification based on the current IRAC mode of action classification scheme: (1) acetylcholinesterase (AChE) inhibitors; (2) GABA-gated chloride channel blockers; (3) sodium channel modulators; (4) nicotinic acetylcholine receptor (nAChR) competitive modulators; (5) nicotinic acetylcholine receptor (nAChR) allosteric modulators; (6) glutamate-gated chloride channel (GluCl) allosteric modulators; (7) juvenile hormone mimics; (8) other non-specific (multi-site) inhibitors; (9) scolopale organ modulators; (10) mite growth inhibitors; (12) mitochondrial ATP synthase inhibitors, such as ATP disruptors; (13) uncouplers that block oxidative phosphorylation by disrupting the proton gradient; (14) nicotinic acetylcholine receptor channel blockers; (15) chitin biosynthesis inhibitors, type 0; (16) chitin biosynthesis inhibitors, type 1; (17) molting disruptors (especially for Diptera, i.e., two-winged insects); (18) ecdysteroid receptor agonists; (19) octopamine receptor agonists; (21) mitochondrial complex I electron transport inhibitors; (25) mitochondrial complex II electron transport inhibitors; (20) mitochondrial complex III electron transport inhibitors; (22) voltage-dependent sodium channel blockers; (23) acetyl-CoA carboxylase inhibitors; (28) ryanodine receptor modulators; (30) GABA-gated chloride channel allosteric modulators.

[0426] Active compounds with unknown or non-specific modes of action, such as fentrifanil, fenoxacrim, cycloprene, chlorobenzilate, chlordimeform, flubenzimine, dicyclanil, amidoflumet, quinomethionate, triarathene, clothiazoben, tetrasul, potassium oleate, petroleum, metoxadiazone, gossyplure, flutenzin, brompropylate, cryolite;

[0427] Other kinds of compounds, such as butacarb, dimetilan, cloethocarb, phosphocarb, pirimiphos (-ethyl), parathion (-ethyl), methacrifos, isopropylo-salicylate, trichlorfon, tigolaner, sulprofos, propaphos, sebufos, pyridathion, prothoate, dichlofenthion, demeton-S-methylsulphone, isazofos, cyanofenphos, dialifos, carbophenothion, autathiofos, aromfenvinfos (-methyl), azinphos (-ethyl), chlorpyrifos (-ethyl), fosmethilan, iodofenphos, dioxabenzofos, formothion, fonofos, flupyrazofos, fensulfothion, etrimfos;

[0428] Organochlorines, such as camphechlor, lindane, heptachlor; or phenylpyrazoles, such as acetoprole, pyrafluprole, pyriprole, vaniliprole, sisapronil; or isoxazolines, such as sarolaner, afoxolaner, lotilaner, fluralaner;

[0429] Pyrethroids, such as (cis-, trans-) metofluthrin, profluthrin, flufenprox, flubrocythrinate, fubfenprox, fenfluthrin, protrifenbute, pyresmethrin, RU15525, terallethrin, cis-resmethrin, heptafluthrin, bioethanomethrin, biopermethrin, fenpyrithrin, cis-cypermethrin, cis-permethrin, clocythrin, cyhalothrin (lambda-), chlovaporthrin, or halogenated hydrocarbons (HCH),

[0430] Neonicotinoids, such as nithiazine

[0431] Dicloromezotiaz, triflumezopyrim

[0432] Macrolides, such as nemadectin, ivermectin, latidectin, moxidectin, selamectin, eprinomectin, doramectin, emamectin benzoate; milbemycin oxime

[0433] Triprene, epofenonane, diofenolan;

[0434] Biological agents, hormones or pheromones, such as natural products, such as thuringiensin, codlemone or neem components

[0435] Dinitrophenols, such as dinocap, dinobuton, binapacryl;

[0436] Benzoylureas such as fluazuron, penfluron, amidine derivatives such as chlormebuform, cymiazole, demiditraz

[0437] Bee hive varroa acaricides such as organic acids such as formic acid, oxalic acid.

[0438] Exemplary active ingredients of endoparasiticides as a mixed formulation include but are not limited to active anthelmintic compounds and active antiprotozoal compounds.

[0439] Active anthelmintic compounds include but are not limited to the following active nematocidal, trematicidally and / or cestocidally compounds:

[0440] Macrolides such as eprinomectin, abamectin, nemadectin, moxidectin, doramectin, selamectin, lepimectin, latidectin, milbemectin, ivermectin, emamectin, milbemycin;

[0441] Benzimidazoles and probenzimidazoles such as oxibendazole, mebendazole, triclabendazole, thiophanate, parbendazole, oxfendazole, netobimin, fenbendazole, febantel, thiabendazole, cyclobendazole, cambendazole, albendazole-sulphoxide, albendazole, flubendazole;

[0442] Cyclic peptides, preferably cyclic peptides, especially 24-membered cyclic peptides, such as emodepside, PF1022A;

[0443] Tetrahydropyrimidines, such as morantel, pyrantel, oxantel;

[0444] Imidazothiazoles, such as butamisole, levamisole, tetramisole;

[0445] Aminophenylamidines, such as amidantel, deacylated amidantel (dAMD), tribendimidine;

[0446] Aminoacetonitriles, such as monepantel;

[0447] Paraherquamides, such as paraherquamide, derquantel;

[0448] Salicylanilides, such as tribromsalan, bromoxanide, brotianide, clioxanide, closantel, niclosamide, oxyclozanide, rafoxanide;

[0449] Substituted phenols, such as nitroxynil, bithionol, disophenol, hexachlorophen, niclofolan, meniclopholan;

[0450] Organophosphates, such as trichlorfon, naphthalofos, dichlorvos / DDVP, crufomate, coumaphos, haloxon;

[0451] Piperazinone / quinolines, such as praziquantel, epsiprantel;

[0452] Piperazines, such as: piperazine, hydroxyzine;

[0453] Tetracyclines, such as: tetracyclin, chlorotetracycline, doxycyclin, oxytetracyclin, rolitetracyclin;

[0454] Various other types, such as: bunamidine, niridazole, resorantel, omphalotin, oltipraz, nitroscanate, nitroxynile, oxamniquine, mirasan, miracil, lucanthone, hycanthone, hetolin, emetine, diethylcarbamazine, dichlorophen, diamfenetide, clonazepam, bephenium, amoscanate, clorsulon.

[0455] Active anti - protozoal compounds include, but are not limited to, the following active compounds:

[0456] Triazines, such as: diclazuril, ponazuril, letrazuril, toltrazuril;

[0457] Polyether ionophores, such as: monensin, salinomycin, maduramicin, narasin;

[0458] Macrolides, such as: milbemycin, erythromycin;

[0459] Quinolones, such as: enrofloxacin, pradofloxacin;

[0460] Quinine - like, such as: chloroquine;

[0461] Pyrimidines, such as: pyrimethamine;

[0462] Sulfonamides, such as: sulfaquinoxaline, trimethoprim, sulfaclozin;

[0463] Thiamines, such as: amprolium;

[0464] Lincosamides, such as: clindamycin;

[0465] Carbonanilides, such as: imidocarb;

[0466] Nitrofurans, such as: nifurtimox;

[0467] Quinazolinone alkaloids, such as: halofuginon;

[0468] Various other types, such as: oxamniquin, paromomycin;

[0469] Vaccines or antigens from microorganisms, said microorganisms being, for example: Babesia canis rossi, Eimeria tenella, Eimeria praecox, Eimeria necatrix, Eimeria mitis, Eimeria maxima, Eimeria brunetti, Eimeria acervulina, Babesia canis vogeli, Leishmania infantum, Babesia canis canis, Dictyocaulus viviparus.

[0470] All named mixtures can - if their functional groups are capable of forming salts - optionally form salts with suitable bases or acids.

[0471] Vector control

[0472] The compounds of formula (I) can also be used for vector control. For the purposes of the present invention, a vector is an arthropod, in particular an insect or an arachnid, which is capable of transmitting pathogens such as viruses, worms, unicellular organisms and bacteria from a reservoir (plant, animal, human, etc.) to a host. The pathogen can be transmitted mechanically to the host (e.g., trachoma is transmitted by non-stinging flies), or can be transmitted by injection to the host (e.g., Plasmodium is transmitted by mosquitoes).

[0473] Examples of vectors and the diseases or pathogens they transmit are:

[0474] 1) Mosquitoes

[0475] - Anopheles: malaria, filariasis;

[0476] - Culex: Japanese encephalitis, other viral diseases, filariasis, other worm transmissions;

[0477] - Aedes: yellow fever, dengue fever, other viral diseases, filariasis;

[0478] - Simuliidae: worm transmission, especially Onchocerca volvulus;

[0479] - Psychodidae: Leishmaniasis transmission;

[0480] 2) Lice: skin infections, epidemic typhus;

[0481] 3) Fleas: plague, endemic typhus, tapeworms;

[0482] 4) Flies: sleeping sickness (trypanosomiasis); cholera, other bacterial diseases;

[0483] 5) Mites: tick-borne diseases, epidemic typhus, rickettsialpox, tularemia, Saint Louis encephalitis, tick-borne encephalitis (TBE), Crimean-Congo haemorrhagic fever, borreliosis;

[0484] 6) Ticks: borellioses, such as Borrelia bungdorferi sensu lato., Borrelia duttoni, tick-borne encephalitis, Q fever (Coxiella burnetii), babesioses (Babesia canis canis), ehrlichiosis.

[0485] For the purposes of the present invention, examples of vectors are insects such as aphids, flies, leafhoppers or thrips, which can transmit plant viruses to plants. Other vectors capable of transmitting plant viruses are spider mites, lice, beetles and nematodes.

[0486] For the purposes of the present invention, other examples of vectors are insects and arachnids such as mosquitoes, in particular of the genera Aedes, Anopheles, such as Anopheles gambiae, Anopheles arabiensis, Anopheles funestus, Anopheles dirus (malaria) and Culex, Psychodidae such as Phlebotomus, Lutzomyia, lice, fleas, flies, mites and ticks, which can transmit pathogens to animals and / or humans.

[0487] Vector control is also possible if the compounds of formula (I) are resistance-breaking.

[0488] The compounds of formula (I) are suitable for preventing vector-borne diseases and / or pathogens. Accordingly, another aspect of the present invention is the use of the compounds of formula (I) for vector control, for example in agriculture, horticulture, landscaping and leisure equipment, and in the protection of materials and storage products.

[0489] Protection of industrial materials

[0490] The compounds of formula (I) are suitable for protecting industrial materials against attack or damage by insects such as those from Coleoptera, Hymenoptera, Isoptera, Lepidoptera, Psocoptera and Zygentoma.

[0491] In the context of the present invention, industrial materials are to be understood as meaning inanimate materials, for example, preferably plastics, adhesives, pastes, paper and cardboard, leather, wood, processed wood products and coating compositions. The use of the present invention for protecting wood is particularly preferred.

[0492] In another embodiment, the compounds of formula (I) are used together with at least one other insecticide and / or at least one fungicide.

[0493] In another embodiment, the compound of formula (I) is present as a ready-to-use pesticide, i.e., it can be applied to the material without further modification. Other suitable insecticides or fungicides are in particular those mentioned above.

[0494] Surprisingly, it has also been found that the compounds of formula (I) can be used to protect objects in contact with salt water or brackish water from contamination, in particular ship hulls, partitions, nets, buildings, mooring equipment and signalling systems. Likewise, the compounds of formula (I) can be used as antifouling agents either alone or in combination with other active compounds.

[0495] Control of animal pests in the hygiene field

[0496] The compounds of formula (I) are suitable for controlling animal pests in the hygiene field. In particular, the invention can be used in the indoor field, the hygiene field and the protection of stored products, in particular for controlling insects, arachnids, ticks and mites encountered in enclosed spaces such as dwellings, factory halls, offices, vehicle cabins, livestock farming. For controlling animal pests, the compounds of formula (I) are used alone or in combination with other active compounds and / or auxiliaries. They are preferably used in indoor insecticide products. The compounds of formula (I) are effective against sensitive and resistant species, and all their developmental stages.

[0497] These pests include, for example, the following pests: Arachnida, Scorpiones, Araneae and Opiliones; Chilopoda and Diplopoda; Insecta, Blattodea, Coleoptera, Dermaptera, Diptera, Heteroptera, Hymenoptera, Isoptera, Lepidoptera, Phthiraptera, Psocoptera, Saltatoria or Orthoptera, Siphonaptera and Zygentoma; Malacostraca, Isopoda.

[0498] They are used, for example, in aerosols, non-pressurized spray products such as pump sprays and atomizer sprays, automatic atomizing systems, sprays, foams, gels, evaporation products with evaporation tablets made of cellulose or plastic, liquid evaporants, gel and film evaporants, propellant-driven evaporants, energy-free or passive evaporation systems, moth papers, moth bags and moth glues, as granulates or dusts, in baits for spreading or bait stations.

[0499] Abbreviations and symbols

[0500] AcOH: acetic acid

[0501] aq.: aqueous

[0502] br.: broad peak

[0503] d: doublet

[0504] DABCO 1,4-Diazabicyclo[2.2.2]octane

[0505] DCC: N,N’-Dicyclohexylcarbodiimide

[0506] DCM: Dichloromethane

[0507] DIPEA: N,N-Diisopropylethylamine

[0508] DMF: N,N-Dimethylformamide

[0509] DMSO: Dimethyl sulfoxide

[0510] ee: Enantiomeric excess

[0511] eq.: Equivalent

[0512] ES: Electrospray ionization

[0513] Et 3 N Triethylamine

[0514] EtOAc: Ethyl acetate

[0515] h(rs) hour

[0516] HATU: 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate

[0517] HOBt: 1-Hydroxybenzotriazole hydrate

[0518] HPLC: High performance liquid chromatography

[0519] iPrOH: Isopropyl alcohol

[0520] J: Coupling constant

[0521] LCMS: Liquid chromatography - mass spectrometry

[0522] m / z: Mass-to-charge ratio

[0523] M: Molarity

[0524] m: Multiplet

[0525] MeCN Acetonitrile

[0526] MeOH: Methanol

[0527] NaH 2 PO 4 Sodium dihydrogen phosphate

[0528] NaOH Sodium hydroxide

[0529] Na 2 SO 4 Sodium sulfate

[0530] NH 4 Cl Ammonium chloride

[0531] NMR: Nuclear magnetic resonance

[0532] q: Quartet

[0533] r.t.: Room temperature

[0534] R t : Retention time

[0535] s: Singlet

[0536] sat.: Saturated

[0537] T: Temperature

[0538] t: Triplet

[0539] Propylphosphonic anhydride

[0540] THF: Tetrahydrofuran

[0541] TMSOK Potassium trimethylsilanolate

[0542] wt.: Weight

[0543] xantphos: 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene

[0544] δ: Chemical shift

[0545] λ: Wavelength

[0546] Description of methods and intermediates

[0547] The compound of formula (I’) can be prepared as shown in Scheme 1 below, where R 1 、R 2 、R 3 and R 4 are as defined above, and X represents OH or Cl.

[0548] Scheme 1

[0549]

[0550] X 1 = OH: Reacting the triazole compound of formula (1) with the carboxylic acid of formula (2a) (X 1react with (—OH) to form a compound of formula (I′). For example, a mixture of a triazole of formula (1), a carboxylic acid of formula (2a) (X 1 = —OH), a suitable coupling agent (e.g., HATU or DCC / HOBt), a suitable base (e.g., triethylamine or DIPEA) in a suitable solvent (e.g., ethyl acetate or DMF) is mixed at a temperature of about 0 to 100° C. to provide a compound of formula (I′), which is then isolated and, if desired and wanted, purified using techniques well known in the art (e.g., chromatography).

[0551] X 1 = Cl: React the triazole compound of formula (1) with a carboxylic acid chloride of formula (2b) (X 1 = —Cl) to form a compound of formula (I′). For example, a mixture of a triazole of formula (1), a carboxylic acid of formula (2b) (X 1 = —Cl), a suitable base (e.g., triethylamine or DIPEA) in a suitable solvent (e.g., dichloromethane or THF) is mixed at a temperature of about 0 to 100° C. to provide a compound of formula (I′), which is then isolated and, if desired and wanted, purified using techniques well known in the art (e.g., chromatography).

[0552] The thioamide of formula (I) (wherein X = S) can be obtained by treating the compound of formula (I′) with Lawesson's reagent in boiling toluene, as described, for example, in WO 2005009435.

[0553] The carboxylic acid of formula (2a) (X 1 = —OH) and the carboxylic acid chloride of formula (2b) (X 1 = —Cl) are commercially available or can be synthesized by methods known to those of ordinary skill in the art. The synthesis of certain carboxylic acids of formula (2a) (X 1 = —OH) has been described in WO 2019 / 197468.

[0554] 3-[(1,1,2,2-Tetrafluoroethyl)thio]benzoic acid: The synthesis is described in J. Org. Chem. 1964, vol 29, 895 - 898. Another synthesis starts from 3-mercaptobenzoic acid, which is converted to the methyl ester with HCl in MeOH and then alkylated with 1,2-dibromo-1,1,2,2-tetrafluoroethane in DMSO in the presence of cesium carbonate at 60° C. The resulting methyl 3-[(2-bromo-1,1,2,2-tetrafluoroethyl)thio]benzoate is debrominated with Zn in AcOH at 50° C. Hydrolysis of the methyl ester gives 3-[(1,1,2,2-tetrafluoroethyl)thio]benzoic acid.

[0555] The compound of formula (1) can be prepared as shown in Scheme 2 below, where R 1 and R 3 are as defined above, R 4 is hydrogen or C 1 -C 3 alkyl.

[0556] Scheme 2

[0557]

[0558] React the amide of formula (3) with N,N-dimethylformamide dimethyl acetal of formula (4) to form a compound of formula (5), which is then reacted with a substituted hydrazine of formula (6) or a suitable salt thereof (such as the hydrochloride salt) under acidic conditions to form a compound of formula (7). For example, react the compound of formula (3) and N,N-dimethylformamide dimethyl acetal of formula (4) in a suitable solvent (such as CH 2 Cl 2 ) under reflux to provide the compound of formula (5). After removing the solvent, react the compound of formula (5) with a substituted hydrazine of formula (6) or a suitable salt thereof (such as the hydrochloride salt) in a suitable solvent (such as 1,4-dioxane, acetic acid or a mixture of these solvents) at a temperature of about 20 to 80 °C. The resulting compound of formula (7) can then be isolated and, if desired and necessary, purified using techniques well known in the art (such as chromatography).

[0559] Treat the carbamate of formula (7) with an acid to form the amine of formula (1). For example, react the carbamate of formula (7) and a suitable acid (such as hydrochloric acid or trifluoroacetic acid) at a temperature of about 0 to 80 °C in a suitable solvent (such as 1,4-dioxane) or, in the case of trifluoroacetic acid, without using an additional solvent. The resulting amine of formula (1) can then be isolated in the form of their acid salts or, after base treatment, in the form of the free amine, and, if desired and necessary, purified using techniques well known in the art (such as chromatography).

[0560] The necessary amide of formula (3) and hydrazine of formula (6) or a suitable salt thereof (such as the hydrochloride salt) are commercially available or can be synthesized by the methods described in this application or by methods known to those skilled in the art.

[0561] For example, the hydrazine of formula (6) can be obtained as follows:

[0562] 6-Hydroxypyrimidine-4-carboxylic acid is obtained as described in J. Org. Chem. 1961, 2755; WO2010 / 20432A2; US2011 / 21500A1 or US2007 / 259860 A1 and is converted to 6-chloropyrimidine-4-carbonyl chloride similar to WO2010 / 20432A2. Then the acyl chloride functional group of the latter is converted to an amide by reaction with a suitable amine in a solvent (such as THF) at 0 °C. If the reaction amine is different from ammonia, only one equivalent of the reaction amine is used and a suitable base (such as triethylamine) is additionally used. Amides of this type are known from Chemistry of heterocyclic compounds 1972, vol8, p509. Finally, similar to Ukrainskii Khimicheskii Zhurnal 1982, 48(1), 67-69, the chloropyrimidine functional group is converted to hydrazinopyrimidine by reaction with hydrazine hydrate in a solvent (such as methanol) at RT or at elevated temperatures up to 65 °C.

[0563] Alternatively, the compounds of formula (I’) can be prepared as shown in Scheme 3 below, where R 1 , R 2 , R 3 and R 4 are as defined above, and R 5 is hydrogen or C 1 -C 3 alkyl.

[0564] Scheme 3

[0565]

[0566] The amide of formula (8) is reacted with N,N-dimethylamidedimethylacetal of formula (4) to form a compound of formula (9), which is then reacted with a substituted hydrazine of formula (6) or a suitable salt thereof (such as the hydrochloride) under acidic conditions to form a compound of formula (I’). For example, the compound of formula (8) and N,N-dimethylamidedimethylacetal of formula (4) are reacted in a suitable solvent (such as CH 2 Cl 2 ) under reflux to give a compound of formula (9). After removal of the solvent, the compound of formula (9) is reacted with a substituted hydrazine of formula (6) or a suitable salt thereof (such as the hydrochloride) in a suitable solvent (such as 1,4-dioxane, acetic acid or a mixture of these solvents) at a temperature of about 20 to 100 °C. The resulting compound of formula (I’) can then be isolated and, if desired and wanted, purified using techniques well known in the art (such as chromatography).

[0567] The required hydrazine of formula (6) or a suitable salt thereof (e.g., hydrochloride) is commercially available or can be synthesized by the methods described in this application or by methods known to those skilled in the art.

[0568] The required amide of formula (8) can be prepared as shown in Scheme 4 below, where R 1 and R 2 as described above (see also WO2017 / 192385).

[0569] Scheme 4

[0570]

[0571] React the amino amide of formula (10) with the carboxylic acid of formula (2a) (X 1 = OH) to form a compound of formula (8). For example, mix a mixture of the amino amide of formula (10), the carboxylic acid (2a) (X 1 = OH), a suitable coupling agent (such as HATU or DCC / HOBt), a suitable base (such as triethylamine or DIPEA) in a suitable solvent (such as ethyl acetate or DMF) at a temperature of about 0 to 100 °C to provide a compound of formula (8), which can then be isolated and, if desired and needed, purified using techniques well known in the art (e.g., chromatography).

[0572] Alternatively, react the amino amide of formula (10) with the carboxylic acid chloride of formula (2b) (X 1 = Cl) to form a compound of formula (8). For example, mix a mixture of the amino amide of formula (10), the carboxylic acid chloride of formula (2b) (X 1 = Cl), a suitable base (such as triethylamine or DIPEA) in a suitable solvent (such as dichloromethane or THF) at a temperature of about 0 to 100 °C to provide a compound of formula (8), which can then be isolated and, if desired and needed, purified using techniques well known in the art (e.g., chromatography).

[0573] The compound of formula (10) is commercially available or can be synthesized by methods known to those skilled in the art. The carboxylic acid of formula (2a) (X 1 = OH) and the carboxylic acid chloride of formula (2b) (X 1 = Cl) are commercially available or can be synthesized by methods known to those skilled in the art. The synthesis of certain carboxylic acids of formula (2a) (X 1 = OH) has been described in WO2019 / 197468.

[0574] Scheme 5 illustrates the preparation of amines (1a) containing alkyl triazole and cycloalkyl triazole, where R 4 is C1 -C 3 alkyl or C 3 -C 4 cycloalkyl. Z is NH 2 or OC 1 -C 6 alkyl.

[0575] Scheme 5

[0576]

[0577] React N-(tert-butoxycarbonyl)-alanine (3a) with an alkyl amidine (11a, Z = NH 2 ) or an alkyl iminoester (11b, Z = OC 1 -C 6 alkyl) to form an intermediate of formula (12), which is then reacted with a substituted hydrazine of formula (6) to form an alkyl triazole of formula (7a).

[0578] For example, in the case of (11a, Z = NH 2 ) (compare J. Org. Chem. 2011, 76, 1177 - 1179), react N-(tert-butoxycarbonyl)-alanine and an alkyl amidine of formula (11a) in the presence of a suitable coupling agent (such as HATU), a suitable base (such as triethylamine or DIPEA), in a suitable solvent (such as DMF), at a temperature of 0 to 50 °C to form an acyl amidine intermediate of formula (12). After removing the solvent, react the intermediate of formula (12) with a substituted hydrazine of formula (6) or a suitable salt thereof (such as the hydrochloride salt) in a suitable solvent (such as acetic acid), at a temperature of about 20 to 80 °C. The resulting alkyl triazole of formula (7a) can then be isolated and, if desired and necessary, purified using techniques well known in the art (such as chromatography).

[0579] In the case where Z = OC 1 -C 6 alkyl N-(tert-butoxycarbonyl)-alanine, react an alkyl iminoester of formula (11b) or a suitable salt thereof in the presence of a suitable coupling agent (such as HATU), a suitable base (such as triethylamine or DIPEA), in a suitable solvent (such as THF), at a temperature of about 0 to 25 °C to form an acyl iminoester intermediate of formula (12b). After adding a substituted hydrazine of formula (6) or a suitable salt thereof (such as the hydrochloride salt), react the intermediate of formula (12b) at a temperature of about 20 to 80 °C to obtain an alkyl triazole of formula (7a), which can then be isolated and, if desired and necessary, purified using techniques well known in the art (such as chromatography).

[0580] The amine of formula (1a) or a related salt as described in Scheme 2 in which the carbamate of formula (7a) is treated with an acid to form the amine of formula (1).

[0581] The necessary alkyl amidine (11a) and alkyl iminoester (11b) or their suitable salts and the hydrazine of formula (6) or its suitable salts (such as hydrochloride) are commercially available or can be synthesized by the methods described in this application or methods known to those skilled in the art (for the synthesis of methyl cyclopropanecarboximidate hydrochloride, see, for example, WO 2011 / 133447).

[0582] The compound of formula (1b) wherein the alkyl is C 1 -C 3 alkyl, R 3 as defined previously) can be prepared as shown in Scheme 6 below.

[0583] Scheme 6

[0584]

[0585] 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl chloride (13) prepared from 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoic acid and oxalyl chloride according to Tetrahedron: Asymmetry, 21(8), 936 - 942, 2010 is reacted with potassium thiocyanate (KSCN) in acetone to produce the corresponding isocyanate intermediate (14), which is treated with the corresponding alcohol (alkylOH) in the next step to give O-alkyl [2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl]thiocarbamate (15). The reaction of the intermediate of formula (15) with the hydrazine of formula (6) or its hydrohalide in ethanol gives the cyclized product of formula (16) as described in Bioorganic & Medicinal Chemistry 26(2018)3321–3344. In the last step, the phthalimide protecting group is removed by reaction with hydrazine hydrate in a suitable solvent (such as ethanol) as described in WO 2018 / 086605. The resulting amine (1b) is then reacted with the carboxylic acid described in Scheme 1 to form the example compound.

[0586] The compound of formula (21) can be prepared as shown in Scheme 7 below, where E is H or C 1 -C 6 alkyl, Hal is bromine or iodine, R 22 as described previously, G is cyclopropyl, where the cyclopropyl is optionally substituted with one to two substituents selected from halogen, -CN, methyl or trifluoromethyl.

[0587] Scheme 7

[0588]

[0589] React the halogen-containing compound of formula (19) with boric acid of formula (20) or the corresponding borate ester to form the compound of formula (21). For example, react a mixture of the halogen-containing compound of formula (19), boric acid (20), a suitable catalyst (such as palladium(II) acetate), tricyclohexylphosphine, and a suitable base (such as tripotassium phosphate) in a suitable solvent or solvent mixture (such as toluene and water) at a temperature of about 0 to 100 °C to produce the compound of formula (21), which can then be isolated and, if desired and needed, purified using techniques well known in the art (such as chromatography). Wherein E is C 1 -C 6 The compound of formula (21) wherein E is an alkyl group can be converted to the compound of formula (21) wherein E is H by treatment with an alkali metal hydroxide in a suitable solvent or solvent mixture (such as / containing tetrahydrofuran, ethanol or water) at a temperature of about 0 to 100 °C.

[0590] The compound of formula (23) can be prepared as shown in Scheme 8 below, wherein E is H or C 1 -C 6 alkyl, Hal is iodine or bromine, Ra is C 1 -C 3 alkyl or cyclopropyl, R 22 as described above.

[0591] Scheme 8

[0592]

[0593] React the aryl halide of formula (20) with the sulfinate of formula (22) under the catalysis of a copper salt to form the sulfone of formula (23).

[0594] For example, react a mixture of the compound of formula (20), the sodium sulfinate salt of formula (22), copper(I) iodide, proline, and sodium hydroxide in a suitable solvent (such as dimethyl sulfoxide) at a temperature of 40 to 140 °C (compare WO 2019 / 197468). In another method, react a mixture of the compound of formula (20), the sodium sulfinate salt of formula (22), copper(I) iodide, trans-N,N-dimethylcyclohexane-1,2-diamine, and cesium carbonate in a suitable solvent (such as DMF) at a temperature of 40 to 140 °C.

[0595] The resulting compound of formula (23) can then be isolated and, if desired and needed, purified using techniques well known in the art (such as chromatography). Wherein E is C1 -C 6 The compound of formula (23) wherein E is an alkyl group can be converted to the compound of formula (23) wherein E is H by treatment with an alkali hydroxide in a suitable solvent or solvent mixture (such as containing tetrahydrofuran, ethanol or water) at a temperature of about 0 to 100 °C. In the case where E is tert-butyl, the ester can be cleaved under acidic conditions in a suitable solvent (such as dichloromethane) in the presence of a suitable acid (such as trifluoroacetic acid) at a temperature of 0 - 40 °C.

[0596] The aryl halide (20) and the sulfite of formula (22) are commercially available or can be synthesized by methods known to those skilled in the art.

[0597] In another method, the compound of formula (23a) can be prepared as shown in Scheme 9a below, where Hal is fluorine or chlorine and Ra is C 1 -C 3 alkyl or cyclopropyl, R 22 as described above.

[0598] Scheme 9a

[0599]

[0600] React the aryl halide of formula (24) with the thiolate of formula (25) to form the thioether of formula (26), which is then hydrolyzed to form the carboxylic acid of formula (27). In the third step, the thioether of formula (27) is oxidized to the sulfone of formula (23a).

[0601] For example, react a mixture of the halide of formula (24) and sodium thiolate of formula (25) in a suitable solvent (such as N,N-dimethylformamide) at a temperature of -20 to 50 °C. Then hydrolyze the resulting nitrile of formula (26) under basic conditions using, for example, aqueous sodium hydroxide in a suitable solvent or solvent mixture (such as isopropanol or methanol / THF) at a temperature of 40 to 100 °C or under acidic conditions in a suitable strong acid (such as sulfuric acid or hydrochloric acid, pure or diluted with a suitable diluent (such as water)) at a temperature of 40 to 100 °C. Then, if desired and wanted, purify the obtained carboxylic acid (27) using techniques well known in the art (such as chromatography) (see the synthesis of 3-chloro-5-(difluoromethyl)benzoic acid described in this application, the conditions for which are basic hydrolysis and US20060276536, the conditions for which are acidic hydrolysis).

[0602] The compound of formula (27) containing a thioether is reacted with an oxidizing agent (such as 3-chloroperoxybenzoic acid or a combination of formic acid and hydrogen peroxide) in a suitable solvent (such as dichloromethane) at a temperature of 0 to 50 °C to form the sulfone of formula (23). Then, if necessary and desired, the obtained sulfone of formula (23a) is purified by techniques known in the art (such as chromatography).

[0603] The necessary aryl halide (24) and the thiolate of formula (25) are commercially available or can be synthesized by methods known to those skilled in the art (such as the synthesis of cyclopropanethiol in WO 2013 / 049250). The thiolate can be synthesized from the corresponding thiol by deprotonation with sodium hydride in a suitable solvent (such as N,N-dimethylformamide).

[0604] In another alternative method, the compound of formula (23b) can be prepared as shown in Scheme 9b below, where Hal is chlorine, bromine or iodine, and Ra is C 1 -C 3 alkyl or C 1 -C 3 haloalkyl, R 22 as described above.

[0605] Scheme 9b

[0606]

[0607] As described in WO2009148052, the dibromobenzene of formula (43) can be lithiated at a low temperature of -78 to 0 °C in the presence of a lithium transfer reagent (such as n-butyllithium), and then reacted with sulfur. The resulting thiol of formula (45) can be alkylated with an alkylating agent (46) in the presence of a base and, in the case of CF 3 Hal, in the presence of a phase transfer catalyst (such as 1,1'-dimethyl-[4,4'-bipyridinium]-1,1'-dichloride).

[0608] The resulting thioalkane of formula (47) can be carbonylated and then oxidized by methods known to those skilled in the art to obtain the sulfone of formula (23b).

[0609] The compound of formula (34) can be prepared as shown in Scheme 10 below. R f is C 1 -C 3 haloalkyl, R 21 as described above. When R f is difluoromethyl, Hal is iodine or chlorine. If R 21 is iodine or bromine, it can be converted to an optionally substituted cyclopropyl as described in Scheme 7.

[0610] Scheme 10

[0611]

[0612] The aryl fluoride of formula (28) is reacted with sodium sulfide (29) to form a thiol of formula (30) as described in Tetrahedron Letters, 2012, 53(20), 2548-2551. Subsequently, a haloalkyl thioether (32) is formed using, for example, a haloalkyl iodide or dichlorofluoromethane and a suitable base under alkylation conditions. In the case of trifluoromethyl iodide, an additional catalyst as described, for example, in WO 2015035223 is used. Then the nitrile functional group is hydrolyzed to form a carboxylic acid of formula (33). In another step, the thioether of formula (33) is oxidized to a sulfone of formula (34).

[0613] For example, a mixture of the aryl fluoride of formula (28) and sodium sulfide (29) is reacted in a suitable solvent (such as N,N-dimethylformamide) at a temperature of -20 to 50 °C. Then the resulting thiol of formula (30) is alkylated with trifluoromethyl iodide in a suitable solvent (such as N,N-dimethylformamide) at a temperature of -20 to 50 °C in the presence of, for example, triethylamine and 1,1'-dimethyl-4,4'-bipyridinium dichloride.

[0614] The obtained thioether of formula (32) is hydrolyzed under basic conditions using, for example, aqueous sodium hydroxide in a suitable solvent (such as methanol) at a temperature of 40 to 100 °C, or under acidic conditions in a suitable strong acid (such as sulfuric acid or hydrochloric acid, pure or diluted with a suitable diluent (such as water)) at a temperature of 40 to 100 °C. Then, if desired and wanted, the obtained carboxylic acid (33) is purified by techniques known in the art (such as chromatography).

[0615] The compound of formula (33) containing a thioether is reacted with an oxidizing agent (such as 3-chloroperoxybenzoic acid) in a suitable solvent (such as a combination of dichloromethane or acetic acid and hydrogen peroxide) at a temperature of 0 to 50 °C to form a sulfone of formula (34). Then, if desired and wanted, the obtained sulfone of formula (34) is purified by techniques known in the art (such as chromatography).

[0616] The necessary aryl fluoride (28) is commercially available or can be synthesized by methods known to those skilled in the art.

[0617] In another method, an acid of formula (38) containing a substituted cyclopropyl can be prepared as shown in Scheme 11 below, where R 22 As described above, Z 1 is -CN or -CO 2 C 1 -C 6 alkyl. Z2 and Z 3 are independently selected from hydrogen, halogen, -CN, methyl or trifluoromethyl, provided that at most three of the substituents Z 2 and Z 3 are different from hydrogen. L is iodine or trifluoroacetate. M is a transition metal complex fragment containing iron, copper, palladium or rhodium and suitable ligand substituents.

[0618] Scheme 11

[0619]

[0620] Reacting the olefin-containing compound of formula (35) with free carbene compound (36a), zinc carbene species (36c) and certain transition metal carbene complexes (36b) gives the cyclopropyl-containing compound of formula (37). Then they can be converted to the acid of formula (38) by ester cleavage (in the case where Z 1 is -CO 2 C 1 -C 6 alkyl) or by hydrolysis of the cyano group (in the case where Z 1 is -CN). Different cyclopropanation reactions are known to those skilled in the art and have been reviewed in the literature (for example in Chem. Rev. 2017, 117, 11651–11679).

[0621] For the reaction with zinc carbene species (36c), first react Et 2 Zn with trifluoroacetic acid in a suitable solvent (such as anhydrous dichloromethane) at 0 °C, and then generate the zinc carbene species by adding CH 2 I 2 . After adding the olefin (35), react the preformed zinc carbene species with the olefin at a temperature of 20 - 40 °C to form cyclopropane (see also WO 2012 / 139775).

[0622] It has been found that different transition metal carbene complexes (36b) are suitable for the cyclopropanation reaction. Examples of suitable precursors of such complexes are CuBr, Pd(OAc) 2 , Rh(OAc) 4 or iron(III)-5,10,15,20-tetraphenyl-porphyrin (Fe(TPP)Cl).

[0623] For the reaction through a palladium carbene complex, a solution of the olefin (35) in a suitable solvent (such as tetrahydrofuran or diethyl ether) is reacted with a suitable palladium salt (such as Pd(OAc) 2) in the presence of, at a temperature of 0 °C - 20 °C, treated with a solution of diazomethane in a suitable solvent (such as diethyl ether) (see also WO 2014 / 023367). The trifluoromethyl-substituted cyclopropyl can be obtained by reacting an alkene (35) with an iron carbene complex obtained from in-situ generated trifluoromethyldiazomethane and Fe(TPP)Cl, as described in Angew. Chem. Int. Ed. 2010, 49, 938 - 941.

[0624] For the reaction with free carbene (36a), a solution of alkene (35) in a suitable solvent is mixed with a carbene precursor that generates free carbene in-situ. For example, a solution of alkene (35) in diglyme is heated at a temperature of 60 - 80 °C in the presence of sodium bromodifluoroacetate. An alternative carbene precursor is, for example, trimethyl(trifluoromethyl)silane used in combination with sodium iodide (as described in WO 2017 / 040742).

[0625] Finally, the hydrolysis of the cyano group to the corresponding acid (38) can be carried out under basic or acidic conditions as described in Scheme 9. The hydrolysis of the ester can be carried out as described in Scheme 8.

[0626] The necessary reagents for the generation of the alkene (35) and free carbene (36a), zinc carbene species (36c) and certain transition metal carbene complexes (36b) are commercially available or can be synthesized by methods known to those skilled in the art. For the synthesis of substituted alkenes (35) by palladium-catalyzed coupling reactions, see, for example, WO 2013 / 178362 (1-bromo-3-(1,1-dimethylethyl)-5-(1-methylethenyl)benzene) and WO 2012 / 035011 (1,5-dichloro-2-fluoro-3-(3,3,3-trifluoroprop-1-en-2-yl)benzene).

[0627] The following preparation and use examples illustrate the invention but do not limit the invention.

[0628] Scheme 12 illustrates the preparation of the triazole-containing amine (1b), where R 4 、R 31 and R 32 As described above, Alk is C 1 -C 3 alkyl, and Hal is chlorine, bromine or iodine.

[0629] The intermediate of formula (5a) or (12) is reacted with a substituted hydrazine of formula (39) or a suitable salt thereof (such as the hydrochloride) in a suitable solvent (such as acetic acid) at a temperature of about 20 to 80 °C. The resulting 4-halo-pyrimidin-6-yl-triazole of formula (40) can then be isolated and, if desired and wanted, purified using techniques well known in the art (such as chromatography).

[0630] Subsequently, in the presence of a palladium catalyst (e.g., dichlorobis(1,1'-bis(diphenylphosphino)ferrocene)palladium), 4-halo-pyrimidin-6-yl-triazole of formula (40) is pressurized with carbon monoxide in a suitable C 1 -C 3 -alcohol (such as methanol or ethanol), as described in WO 2012 / 035039. The resulting ester of formula (41) can be converted to the amide of formula (42) by the methods described in this application or methods known to those skilled in the art.

[0631] The carbamate of formula (42) is treated with an acid to form the amine of formula (1b) or a related salt as described in Scheme 2 for the formation of the amine of general formula (1).

[0632] The necessary amidine (5a) and iminoester (12) are described in Scheme 2 and Scheme 5. The hydrazine of formula (39) or a suitable salt thereof (e.g., hydrochloride) is commercially available or can be synthesized by the methods described in this application or methods known to those skilled in the art.

[0633] Scheme 12

[0634]

[0635] The compound of formula (53) can be prepared as shown in Scheme 13 below. R 22 As described above.

[0636] Scheme 13

[0637]

[0638] The aryl bromide of formula (49) is readily converted to the 1-hydroxy-1-methyl-ethyl aryl compound of formula (50) using a Grignard reagent (such as isopropylmagnesium chloride) and acetone as an electrophile, as described in WO 2017 / 055859. The resulting compound (50) can be carbonylated, subsequently fluorinated (fluorination: see, for example, Journal of Medicinal Chemistry (2019), 62(9), 4350 - 4369), and hydrolyzed by methods known to those skilled in the art to obtain the benzoic acid of formula (52).

[0639] The compound of formula (59) can be prepared as shown in Scheme 14 below. R f is C 1 -C 3 -haloalkyl, LG represents a leaving group, such as chlorine, bromine, iodine, or methyl sulfonate.

[0640] Scheme 14

[0641]

[0642] Methyl 3,5-dimercaptobenzoate (57) can be easily prepared according to the known methods described in US 20020072583. For example, WO 2004 / 007444 describes haloalkylation with R f LG, or WO 2020 / 002563 describes haloalkylation with CF 2 ClCO 2 Na. The resulting thioether compound (58) can be oxidized and then hydrolyzed by methods known to those skilled in the art to obtain benzoic acid of formula (59).

[0643] Preparation of examples

[0644] Synthesis of 3-bromo-N-{(1S)-1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethoxy)benzamide (Example I-1)

[0645] Step 1: 2N-[(2S)-1-Amino-1-oxopropan-2-yl]-3-bromo-5-(trifluoromethoxy)benzamide

[0646]

[0647] 1.75 g (14.0 mmol) of L-alaninamide hydrochloride, 1.0 g (3.5 mmol) of 3-bromo-5-(trifluoromethoxy)benzoic acid and 3.1 mL of triethylamine were stirred in 10 mL of DMF under ice-water cooling. 3.1 ml (5.3 mmol) of 50% T3P (cyclopropylphosphonic anhydride) in EtOAc was added to the mixture. The mixture was stirred at room temperature overnight. Water was added to the reaction mixture that formed a white precipitate. The precipitate was separated by filtration and dissolved in ethyl acetate. The solution was washed successively with dilute hydrochloric acid (10%), water, saturated NaHCO 3 aqueous solution and brine. The solvent was evaporated to give 1.13 g of N-[(2S)-1-amino-1-oxopropan-2-yl]-3-bromo-5-(trifluoromethoxy)benzamide.

[0648] ESI mass [m / z]: 355.0 [M+H] +

[0649] Step 2: 3-bromo-N-{(1S)-1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethoxy)benzamide (Example I-1)

[0650]

[0651] To a solution of 160 mg (0.45 mmol) of N-[(2S)-1-amino-1-oxopropan-2-yl]-3-bromo-5-(trifluoromethoxy)benzamide in 3 mL of CH 2 Cl 2 was added 0.09 mL (0.67 mmol) of N,N-dimethylformamide dimethyl acetal. The solution was heated under reflux for 2 h and then the solvent was removed under reduced pressure. The residue was dissolved in 3 mL of glacial acetic acid. 93 mg (0.54 mmol) of 6-hydrazinylpyrimidine-4-carbonitrile hydrochloride was added and the mixture was stirred at 80 °C for 2 h. Then the solvent was removed under reduced pressure and the residue was purified by reverse-phase chromatography (water / acetonitrile) to give 159 mg of 3-bromo-N-{(1S)-1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}-5-(trifluoromethoxy)benzamide.

[0652] 1 H-NMR (400 MHz, DMSO-d 6 ): δ = 9.42 (d, J = 6.8 Hz, 1H), 9.38 (d, J = 1.2 Hz, 1H), 8.61 (d, J = 1.2 Hz, 1H), 8.36 (s, 1H), 8.14 (s, 1H), 7.90 (s, 1H), 7.80 (s, 1H), 6.22–6.13 (m, 1H), 1.63 (d, J = 6.8 Hz, 3H).

[0653] ESI mass [m / z]: 484.1 [M+H] +

[0654] Synthesis of N-{1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}-3-cyclopropyl-5-(trifluoromethoxy)benzamide (Example I-8)

[0655] Step 1: 6-Hydrazinylpyrimidine-4-carbonitrile

[0656]

[0657] A mixture of 500 mg (3.58 mmol) of 6-chloropyrimidine-4-carbonitrile and 7.2 mL (7.2 mmol) of a 1 M solution of hydrazine in THF was refluxed for 2 h and then stirred at room temperature overnight. After cooling to room temperature, the mixture was evaporated and the residue was suspended in 15 mL of hot water. After cooling to room temperature, the resulting precipitate was separated by filtration, washed with water, dissolved in acetonitrile and dried in vacuo to give 159 mg of 6-hydrazinylpyrimidine-4-carbonitrile hydrochloride. Then with NaHCO3 The aqueous solution alkalizes the mother liquor obtained from the filtration step. This causes some of the solid precipitates formed after filtration to not dissolve completely. The complete suspension is transferred to a separatory funnel and extracted three times with ethyl acetate. The combined organic layers are washed with brine and dried over Na 2 SO 4 filtered. The solvent is evaporated under reduced pressure to isolate 120 mg of 6-hydrazinylpyrimidine-4-carbonitrile. The obtained 6-hydrazinylpyrimidine-4-carbonitrile hydrochloride and 6-hydrazinylpyrimidine-4-carbonitrile are combined and used in the next step without further purification.

[0658] ESI mass [m / z]: 136.1 [M+H] +

[0659] Step 2: tert-Butyl {1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate

[0660]

[0661] To a solution of 0.26 g (1.35 mmol) of N 2 -(tert-butoxycarbonyl)-propanamide in 10 mL of CH 2 Cl 2 is added 0.27 mL (2.0 mmol) of N,N-dimethylformamide dimethyl acetal. The solution is heated under reflux for 2 h, and then the solvent is removed under reduced pressure. The residue is dissolved in a mixture of 3 mL of glacial acetic acid and 3 mL of 1,4-dioxane. A mixture of 0.27 g of the 6-hydrazinylpyrimidine-4-carbonitrile and 6-hydrazinylpyrimidine-4-carbonitrile hydrochloride obtained in the first step is added as a solution to a mixture of 2 mL of glacial acetic acid and 2 mL of 1,4-dioxane. The mixture is stirred at room temperature for 72 h. Then the solvent is removed under reduced pressure, and the residue is purified by silica gel chromatography (ethyl acetate / cyclohexane) to give 201 mg of tert-butyl {1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate.

[0662] 1 H-NMR (400 MHz, DMSO-d 6 ): δ = 9.38 (s, 1H), 8.58 (s, 1H), 8.33 (s, 1H), 7.61 (d, J = 7.6 Hz, 1H), 5.78–5.68 (m, 1H), 1.44 (d, J = 7.6 Hz, 3H), 1.33 (s, 9H).

[0663] ESI mass [m / z]: 316.1 [M+H] +

[0664] Step 3: 6-[5-(1-Aminoethyl)-1H-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride

[0665]

[0666] To a solution of 100 mg (0.31 mmol) of tert-butyl {1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate in 3 ml of 1,4-dioxane was added 0.79 ml (3.2 mmol) of a 4 M solution of HCl in 1,4-dioxane, and the mixture was stirred overnight at room temperature. Then 0.50 ml (2.0 mmol) of a 4 M solution of HCl in 1,4-dioxane was added, and the mixture was stirred overnight at room temperature. The reaction mixture was evaporated to give the title compound (100 mg, 80% purity), which was used in the next step without further purification.

[0667] 1 H-NMR (400 MHz, DMSO-d 6 ): δ = 9.42 (d, J = 1.2 Hz, 1H), 8.74 (brs, 3H), 8.67 (d, J = 1.2 Hz, 1H), 8.56 (s, 1H), 5.50–5.40 (m, 1H), 1.64 (d, J = 6.8 Hz, 3H).

[0668] ESI mass [m / z]: 216.1 [amine + H] +

[0669] Step 4: N-{1-[1-(6-Cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}-3-cyclopropyl-5-(trifluoromethoxy)benzamide (Example I-8)

[0670]

[0671] To a solution of 67 mg (64% purity, 0.18 mmol) of 3-cyclopropyl-5-(trifluoromethoxy)benzoic acid in 2 mL of N,N-dimethylformamide (DMF) was added 0.1 mL (0.6 mmol) of N,N-diisopropylethylamine (Hünig's base) and 121 mg (318 μmol) of [O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate] (HATU). The mixture was stirred at room temperature for 1 h. Then 50 mg (80% purity, 0.15 mmol) of 6-[5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride was added, and the reaction mixture was stirred at room temperature for 3 days. The reaction mixture was then purified directly by reverse-phase chromatography (water / acetonitrile) to give 31 mg of the title compound.

[0672] ESI mass [m / z]: 444.1 [M+H] +

[0673] 1 1H-NMR (400 MHz, DMSO-d 6 ): δ = 9.38 (d, J = 0.8 Hz, 1H), 9.24 (d, J = 6.8 Hz, 1H), 8.61 (d, J = 0.8 Hz, 1H), 8.35 (s, 1H), 7.54 (s, 1H), 7.52 (s, 1H), 7.28 (s, 1H), 6.22–6.12 (m, 1H), 2.10–2.00 (m, 1H), 1.63 (d, J = 7.2 Hz, 3H), 1.07–1.00 (m, 2H), 0.81–0.75 (m, 2H).

[0674] Synthesis of methyl 3-bromo-5-(difluoromethoxy)benzoate

[0675] Step 1: Methyl 3-bromo-5-hydroxybenzoate

[0676]

[0677] The solution of 3-bromo-5-hydroxybenzoic acid (49.9 g, 230 mmol) in MeOH (325 mL) was cooled to 7-8 °C with an ice bath. Then SOCl 2 (27.4 g, 16.79 mL, 230 mmol) was added dropwise to this solution over 25 min. The reaction mixture was heated to room temperature, stirred at reflux for 3 h, cooled to room temperature, and then stirred at this temperature for another 48 h. All volatiles were removed in vacuo, and the residue was dissolved in ethyl acetate (400 mL). The solution was washed with NaHCO 3 , brine, and with Na 2SO 4 Dry and remove volatiles under reduced pressure. Grind the residue with hexane (400 mL). Filter off the precipitate, wash with hexane / diethyl ether (1:1), and dry at 110 °C to obtain 3-bromo-5-hydroxybenzoic acid methyl ester (50.5 g) as a dark yellow powder.

[0678] 1 H NMR (400 MHz, CDCl 3 ) δ = 7.73 (m, 1H), 7.51 (m, 1H), 7.26 (s, 1H), 7.23 (t, J = 2.1 Hz, 1H), 6.05 (br s, 1H), 3.92 (s, 3H). Recorded on a Varian Gemini 2000 machine.

[0679] Step 2: Methyl 3-bromo-5-(difluoromethoxy)benzoate

[0680]

[0681] A mixture of methyl 3-bromo-5-hydroxybenzoate (23.1 g, 100 mmol), K 2 CO 3 (41.5 g, 300 mmol) and ClF 2 CCOONa (45.7 g, 300 mmol) in DMF (350 mL) was stirred at 60 - 65 °C for 2 h. Then the precipitate was separated, washed with acetone, and the filtrate was evaporated under reduced pressure. The residue was dissolved in diethyl ether (300 mL), and the solution was left standing at r.t. for 12 h. The formed precipitate was filtered off and washed with water. The filtrate was washed with brine (300 mL), and the organic layer was evaporated under reduced pressure. The oily residue was dissolved in hexane (250 mL) and kept at r.t. for 2 h. The formed precipitate was removed by filtration, and the filtrate was evaporated under reduced pressure. The residue was distilled under reduced pressure (3 Torr), and the fraction with a boiling point between 80 and 85 °C was collected to obtain 15.75 g of methyl 3-bromo-5-(difluoromethoxy)benzoate.

[0682] 1 H NMR (400 MHz, CDCl 3 ) δ = 8.03 (t, J = 1.6 Hz, 1H), 7.75–7.70 (m, 1H), 7.49 (t, J = 2.1 Hz, 1H), 6.55 (t, J = 72.6 Hz, 1H), 3.93 (s, 3H). Recorded on a Varian Gemini 2000 machine.

[0683] 19 F NMR (376 MHz, CDCl 3) δ = -84.89 (d, J = 72.7 Hz). (Recorded on a Varian Gemini 2000 machine)

[0684] Synthesis of 3-Methylsulfonyl-5-(trifluoromethoxy)benzoic Acid

[0685]

[0686] A mixture of 2.95 g (17.5 mmol) of trans-N,N-dimethylcyclohexane-1,2-diamine and 11.4 g (35 mmol) of cesium carbonate in 60 mL of DMF was purged with argon for 30 min. 5 g (17.5 mmol) of 3-bromo-5-(trifluoromethoxy)benzoic acid, 3.58 g (35 mmol) of sodium methylsulfinate, and 3.34 g (17.5 mmol) of copper(I) iodide were added, and the mixture was further purged with argon for 5 min. The mixture was stirred at 120 °C overnight, cooled to room temperature, and then extracted three times with dichloromethane. The aqueous layer was acidified to pH 2 with concentrated hydrochloric acid and extracted again with dichloromethane. The dichloromethane phase was washed several times with brine. The layers were separated, and the combined organic layers were dried over anhydrous Na 2 SO 4 dried and filtered. The solvent was removed under reduced pressure, and the residue was triturated with n-pentane, filtered off, and dried to give 3.2 g of 3-methylsulfonyl-5-(trifluoromethoxy)benzoic acid.

[0687] 1 1H NMR (DMSO-d 6 , 400 MHz): δ = 14.00 (br s, 1H, COOH), 8.42 (s, 1H), 8.20 (s, 1H), 8.14 (s, 1H), 3.39 (s, 3H).

[0688] ESI mass [m / z]: 285.0 [M+H] +

[0689] In a similar manner, the following intermediates were prepared:

[0690] 3-(Cyclopropylsulfonyl)-5-(trifluoromethoxy)benzoic Acid

[0691] ESI mass [m / z]: 311.0 [M+H] +

[0692] 3-Chloro-5-(4-chlorophenyl)sulfonyl-benzoic Acid

[0693] ESI mass [m / z]: 331.0 [M+H] +

[0694] Synthesis of 3-(difluoromethoxy)-5-methylsulfonyl-benzoic acid

[0695] Step 1: Methyl 3-(trifluoromethoxy)-5-triisopropylsilylthio-benzoate

[0696]

[0697] Under an argon stream, NaH (5.03 g, 122 mmol, 60% dispersed in oil) was added portionwise to a stirred solution of triisopropylsilanethiol (21.45 g, 112 mmol) in toluene (500 mL). The mixture was stirred until no more gas was evolved. Then methyl 3-bromo-5-(trifluoromethoxy)benzoate (CAS: 1306763-53-0) (30 g, 100 mmol), XantPhos (6.13 g, 11.2 mmol), and Pd 2 (dba) 3 (4.85 g, 5.3 mmol) were added to the reaction mixture in sequence. The mixture was stirred at 100 °C overnight, cooled to r.t., diluted with EtOAc (500 mL), and filtered through a thin pad of silica gel. After evaporation, crude methyl 3-(trifluoromethoxy)-5-triisopropylsilylthio-benzoate (50 g, 50% purity by LC / MS, 64 mmol, 57% yield) was obtained, which was used in the next step without further purification.

[0698] Step 2: Methyl 3-(difluoromethylthio)-5-(trifluoromethoxy)benzoate

[0699]

[0700] Under an argon stream, sodium 2-chloro-2,2-difluoroacetate (29.27 g, 192 mmol) and cesium carbonate (62.55 g, 192 mmol) were added to a stirred solution of crude methyl 3-(trifluoromethoxy)-5-triisopropylsilylthio-benzoate (50 g, 50% purity by LC / MS, 64 mmol) in DMF (1000 mL). The mixture was stirred at 100 °C overnight, cooled to r.t., and evaporated under reduced pressure. The residue was dissolved in water (1000 mL) and extracted with EtOAc (5 × 250 mL). After column chromatography, methyl 3-(difluoromethylthio)-5-(trifluoromethoxy)benzoate (10.5 g, 34.7 mmol, 54.3% yield) was obtained.

[0701] Step 3: Methyl 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoate

[0702]

[0703] Under an argon stream at 0 °C, mCPBA (16.35 g, 93.9 mmol, 75% purity) was added portionwise to a solution of methyl 3-(difluoromethylthio)-5-(trifluoromethoxy)benzoate (10.5 g, 34.7 mmol) in dichloromethane (200 mL). The mixture was stirred overnight at room temperature and evaporated under reduced pressure. After silica gel column chromatography, methyl 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoate (6.8 g, 20.34 mmol, 58.63%) was obtained.

[0704] Step 4: 3-(Difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoic acid

[0705]

[0706] At 0 °C, lithium hydroxide monohydrate (1.146 g, 27.459 mmol) was added to a stirred solution of methyl 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoate (6.8 g, 20.34 mmol) in a THF (80 mL) / water (20 mL) mixture, and the mixture was stirred overnight at r.t. The THF was evaporated under reduced pressure, the aqueous phase was acidified to pH = 3, and extracted with MTBE (5 × 10 mL). After recrystallization from 30% aqueous EtOH, pure 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoic acid as a white solid (3 g, 9.37 mmol, 34.12% yield) was obtained.

[0707] 1 H NMR (DMSO-d 6 , 400 MHz): δ = 7.47 (t, 1H), 8.21 (s, 1H), 8.32 (s, 1H), 8.40 (s, 1H), 13.79 (s, 1H).

[0708] ESI mass [m / z]: 319.0 [M+H] +

[0709] Synthesis of 2-chloro-6-(1-cyanocyclopropyl)-N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]pyridine-4-carboxamide (I-35)

[0710] Step 1: 2-Chloro-6-(cyanomethyl)pyridine-4-carboxylic acid

[0711]

[0712] n-BuLi (91.14 ml, 2 M, 183.3 mmol) was diluted in anhydrous THF (150 ml) and cooled to -78 °C under argon. A solution of anhydrous acetonitrile (11.4 ml, 218.8 mmol) in anhydrous THF (30 mL) was added dropwise, and the reaction mixture was kept at -78 °C for 30 min. A solution of 2,6-dichloropyridine-4-carboxylic acid (7 g, 36.5 mmol) in THF (200 ml) was added dropwise over 1 hour, and the reaction mixture was stirred at -78 °C for another 45 min and then at room temperature for 1 h. The reaction mixture was then quenched with saturated aqueous citric acid (200 mL) and extracted with EtOAc (3 x 250 mL). The organic layer was washed with water (3 x 300 mL) and then with brine solution (200 mL) and dried over anhydrous Na 2 SO 4 and the solvent was removed under reduced pressure. The residue was purified by flash silica gel chromatography using a gradient of 0% to 10% acetone in DCM. The obtained solid was triturated with 50% diethyl ether in n-pentane to give 4.2 g (58% yield) of a pale grey solid of 2-chloro-6-(cyanomethyl)pyridine-4-carboxylic acid.

[0713] 1 1H NMR (400 MHz, D6-DMSO): δ = 7.87 (s, 1H), 7.82 (s, 1H), 4.27 (s, 2H). COOH was not detected.

[0714] ESI mass [m / z]: 195.0 [M-H] -

[0715] Step 2: 2-Chloro-6-(1-cyanocyclopropyl)pyridine-4-carboxylic acid (INT-12)

[0716]

[0717] Under nitrogen, tetrabutylammonium bromide (5.74 g, 17.8 mmol) was added to a stirred solution of 2-chloro-6-(cyanomethyl)pyridine-4-carboxylic acid (3.5 g, 17.8 mmol) in acetonitrile (50 mL). Then 1,2-dibromoethane (3.68 g, 19.6 mmol) was added dropwise at room temperature, and the reaction mixture was stirred at room temperature for another 30 min. The reaction mixture was cooled to 0 °C. 7.5 mL of aqueous NaOH solution (50%) was added dropwise slowly within 20 min. Then the reaction mixture was warmed to room temperature and stirred for another 24 h. The reaction mixture was concentrated in vacuo at room temperature. The remaining residue was diluted with water, acidified with citric acid (pH ~ 5), and extracted with EtOAc (3 x 150 mL). The combined organic layers were washed with water (3 x 100 mL) and sodium thiosulfate solution (100 mL), and then washed with brine solution (150 mL). The organic layer was dried over anhydrous Na 2 SO 4 and then the solvent was removed under reduced pressure. The crude material was purified by flash silica gel chromatography using a gradient of 0% to 10% acetone in DCM. The obtained solid was washed with n-pentane to give 2 g (50% yield) of off-white solid of 2-chloro-6-(1-cyanocyclopropyl)pyridine-4-carboxylic acid (INT-12).

[0718] 1 H NMR (400 MHz, DMSO-d 6 ): δ = 14.20 (bs, 1H, COOH), 7.89 (s, 1H), 7.53 (s, 1H), 1.94–1.91 m, 2H), 1.76–1.73 (m, 2H).

[0719] ESI mass [m / z]: 221.0 [M-H] -

[0720] Step 3: tert-Butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxoethyl]carbamate

[0721]

[0722] Dissolve tert-butyl N-[(1S)-2-amino-1-methyl-2-oxoethyl]carbamate (40.0 g, 213 mmol) in DCM (400 mL). Add dimethylformamide dimethyl acetal (38.0 g, 319 mmol, 42.4 mL) to the mixture. Stir the reaction mixture at 40 °C for 2 h. Concentrate the reaction mixture under reduced pressure. The obtained tert-butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxoethyl]carbamate (50.0 g, crude) is a colorless oil and used as the crude material for the next step.

[0723] Step 4: tert-Butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (INT-3)

[0724]

[0725] Dissolve tert-butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxoethyl]carbamate (36.1 g, 267 mmol) in dioxane (400 mL). Dissolve 6-hydrazinylpyrimidine-4-carbonitrile (50.0 g, 206 mmol) in AcOH (400 mL) and add it to the mixture. Stir the reaction mixture at 20 °C for 16 h. Concentrate the reaction mixture in vacuo. Purify the residue by column chromatography (SiO 2 , petroleum ether / EtOAc = 50 / 1 to 0 / 1). Grind the crude product with MTBE (750 mL) at 20 °C for 30 min. Obtain tert-butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (INT-3) as a white solid (8.50 g, 27.0 mmol, 13.1% yield).

[0726] The enantiomeric excess of INT-3 was determined by screening OD_RH (acid): ee-value = 95%; R t = 9.49 min. Method: chiral HPLC; Chiralcel OD-RH column (4.6 mm x 150 mm x 5 μm), room temperature, eluted with 0.1% phosphoric acid (A) and acetonitrile (B), gradient A:B 95 / 5 to 10 / 90, detected at λ = 210 nm.

[0727] 11H NMR (400 MHz, CDCl3): δ = 1.43 (s, 9H), 1.58 (d, J = 6.8 Hz, 3H), 5.45 - 5.58 (m, 1H), 5.97 - 6.10 (m, 1H), 8.02 (s, 1H), 8.32 (d, J = 0.8 Hz, 1H), 9.24 (d, J = 1.2 Hz, 1H). Measured using Bruker AVANCE III 400 MHz.

[0728] ESI mass [m / z]: 260.1 [M - C 4 H 8 + H] +

[0729] Step 5: 6 - [5 - [(1S) - 1 - aminoethyl] - 1,2,4 - triazol - 1 - yl]pyrimidine - 4 - carbonitrile; 2,2,2 - trifluoroacetic acid (INT - 4)

[0730]

[0731] Dissolve tert - butyl - N - [(1S) - 1 - [2 - (6 - cyanopyrimidin - 4 - yl) - 1,2,4 - triazol - 3 - yl]ethyl]carbamate (2 g, 6.34 mmol) in 20 mL of dichloromethane. Slowly add trifluoroacetic acid (3.62 g, 31.7 mmol), then stir the reaction mixture overnight at r.t., and then heat to 40 °C and maintain for 3 hours to complete the reaction. Evaporate the reaction mixture under reduced pressure and use it as the crude material in the next step.

[0732] ESI mass [m / z]: 216.1 [amine + H] +

[0733] Step 5: 2 - chloro - 6 - (1 - cyanocyclopropyl) - N - [(1S) - 1 - [2 - (6 - cyanopyrimidin - 4 - yl) - 1,2,4 - triazol - 3 - yl]ethyl]pyridine - 4 - carboxamide (I - 35)

[0734]

[0735] 2-Chloro-6-(1-cyanocyclopropyl)pyridine-4-carboxylic acid (88 mg, 0.39 mmol) was dissolved in 10 mL of dichloromethane, 2 drops of DMF were added, and then oxalyl chloride (114 mg, 0.9 mmol) was added. The reaction mixture was stirred until gas evolution ceased. The reaction mixture was then evaporated under reduced pressure and dissolved in acetonitrile. This solution was slowly added dropwise to another acetonitrile solution prepared at r.t. as a mixture of 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile (2,2,2-trifluoroacetate) (197 mg 60% purity, 0.36 mmol) and DIPEA (140 mg, 1.08 mmol). The reaction mixture was stirred overnight at r.t., then diluted with water and dichloromethane, the organic layer was separated and evaporated under reduced pressure. The remaining residue was purified by HPLC to give the title compound as an off-white solid (86 mg, 56% yield).

[0736] 1 The H NMR is shown in the peak list in Table 1.

[0737] ESI mass [m / z]: 420.3 [M+H] +

[0738] Synthesis of 3-bromo-N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]-5-(trifluoromethoxy)benzamide (I-15) and 6-[5-[(1S)-1-[[3-bromo-5-(trifluoromethoxy)benzoyl]amino]ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (I-13)

[0739] Step 1: Ethyl cyclopropanecarboximidate hydrochloride

[0740]

[0741] Cyclopropanecarbonitrile (10.0 g, 149 mmol, 11.0 mL) was dissolved in HCl / dioxane (70.0 mL). EtOH (6.87 g, 149 mmol, 8.71 mL) was slowly added dropwise at 0 °C. The mixture was stirred at 25 °C for 16 h. The reaction mixture was concentrated under reduced pressure to remove HCl / dioxane. The crude product was triturated with MTBE at 25 °C for 30 min and then filtered. The filter cake was dried under reduced pressure using a rotary evaporator. The crude product as a white solid (21.0 g, 140 mmol, 94.2% yield, HCl salt) was obtained and used in the next step without further purification.

[0742] Step 2:(Z)-N-[(2S)-2-(tert-Butoxycarbonylamino)propanoyl]cyclopropanecarboximidic acid ethyl ester

[0743]

[0744] Dissolve tert-butyl N-[(1S)-2-amino-1-methyl-2-oxo-ethyl]carbamate (15.1 g, 79.7 mmol) in THF (180 mL). Add ethyl cyclopropanecarboximidate hydrochloride (17.8 g, 119 mmol), DIPEA (46.1 g, 357 mmol, 62.1 mL), and finally HATU (49.7 g, 131 mmol). Stir the mixture at 25 °C for 3 h. Obtain (Z)-N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidic acid ethyl ester (22.5 g, crude) as a yellow liquid in THF, which is used as a solution in the next step without further treatment and purification.

[0745] Step 3: tert-Butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate (INT-7)

[0746]

[0747] Slowly add 6-hydrazinylpyrimidine-4-carbonitrile (7.13 g, 52.8 mmol) to a solution of (Z)-N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidic acid ethyl ester (15.0 g, 52.8 mmol) in THF at 0 °C. Stir the mixture at 25 °C for 16 h. Quench the reaction mixture with H 2 O (200 mL), then extract with ethyl acetate (3 x 50 mL). Wash the combined organic layers with brine (200 mL), dry over anhydrous Na 2 SO 4 and filter and concentrate in vacuo. Purify the obtained residue by column chromatography (SiO2, petroleum ether / ethyl acetate = 50 / 1 to 3 / 1) to obtain tert-butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate (INT-7, 5.60 g, 15.6 mmol, 29.6% yield, 99.1% purity) as a white solid.

[0748] By screening OD_RH (acid): ee-value = 92.5%; R tThe enantiomeric excess of INT-7 was determined at 14.45 min. Method: chiral HPLC; Chiralcel OD-RH column (4.6 mm x 150 mm x 5 m), at room temperature, eluted with 0.1% phosphoric acid (A) and acetonitrile (B), gradient A:B 95 / 5 to 10 / 90, detected at λ = 210 nm.

[0749] 1 1H NMR (400 MHz, MeOD): δ = 9.21 (s, 1H), 8.36 (s, 1H), 5.82 (q, J = 6.8 Hz, 1H), 2.15 - 2.04 (m, 1H), 1.52 (d, J = 6.8 Hz, 3H), 1.40 (br s, 9H), 1.09 - 0.98 (m, 4H). Measured with Bruker AVANCE III 400 MHz.

[0750] ESI mass [m / z]: 356.0 [M + H] +

[0751] Step 4: 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride (INT-8) and 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-11)

[0752]

[0753] tert-Butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate (5.0 g, 14 mmol) was dissolved in 4M HCl / dioxane (35.0 mL) and stirred overnight at r.t. HCl / dioxane was removed under reduced pressure. The remaining solid was a mixture of 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride (INT-8) and 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-11), which was used in the next step without further purification.

[0754] 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride (INT-8)

[0755] ESI mass [m / z]: 256.2 [amine + H] +

[0756] 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-11)

[0757] ESI mass [m / z]: 274.2 [amine + H] +

[0758] Step 5: 3-Bromo-N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]-5-(trifluoromethoxy)benzamide (I-15) and 6-[5-[(1S)-1-[[3-bromo-5-(trifluoromethoxy)benzoyl]amino]ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (I-13)

[0759]

[0760] A mixture of 101 mg (0.28 mmol) of 3-bromo-5-(trifluoromethoxy)benzoic acid, 245 mg (0.65 mmol) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), 146 mg (1.13 mmol) of N,N-diisopropylethylamine, and 1.3 mL of DMF was stirred at room temperature for 60 min. 100 mg of the mixture from Step 4 was added, and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with water and extracted with DCM. The DCM phase was separated, washed with brine, concentrated under reduced pressure, and purified by preparative HPLC chromatography to give 11 mg (6.5% yield) of 3-bromo-N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]-5-(trifluoromethoxy)benzamide (I-15) and 94.5 mg (54.2% yield) of 6-[5-[(1S)-1-[[3-bromo-5-(trifluoromethoxy)benzoyl]amino]ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (I-13).

[0761] 3-Bromo-N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]-5-(trifluoromethoxy)benzamide (I-15)

[0762] 1 See the peak list in Table 1 for 1H NMR.

[0763] ESI mass [m / z]: 524.1 [M + H]+

[0764] 6-[5-[(1S)-1-[[3-Bromo-5-(trifluoromethoxy)benzoyl]amino]ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (I-13)

[0765] 1 The H NMR is shown in the peak list in Table 1.

[0766] ESI mass [m / z]: 542.1 [M+H] +

[0767] Synthesis of intermediate 6-hydrazinylpyrimidine-4-carboxamide / (6-hydrazinyl-1,6-dihydropyrimidine-4-carboxamide)

[0768] Step 1: 6-Chloropyrimidine-4-carbonyl chloride

[0769]

[0770] Oxalyl chloride (26.0 mL, 297.0 mmol) was added to a heated mixture of 6-hydroxypyrimidine-4-carboxylic acid (13.86 g, 9.98 mmol) and DMF (0.13 mmol, 0.01 mL) in 80 mL of ethyl acetate over 1 h. Heating was continued under reflux for 3 h. The volatiles were distilled off at atmospheric pressure and then under reduced pressure. Kugelrohr distillation (diaphragm pump vacuum, 6 mbar, oven temperature 110 °C) gave 11.03 g (63% of theory).

[0771] Step 2: 6-Chloropyrimidine-4-carboxamide

[0772]

[0773] 6-Chloropyrimidine-4-carbonyl chloride (11.03 g, 62.32 mmol) in THF (50 mL) was added to aqueous ammonia (33%, 20 ml, 341 mmol) in a mixture of THF / ice water (0.3 L) under ice / water cooling over 10 min, and the mixture was then stirred for 1 h. The mixture was acidified with aqueous HCl, and the organic solvents were removed under reduced pressure. The precipitate formed was filtered off, washed with water and dried, giving 7.6 g (76% of theory, purity corrected).

[0774] ESI mass [m / z]: 158.1 [M+H] +

[0775] 1 H NMR (400 MHz, D 6-DMSO): δ = 8.1 (m, 2H), 8.45 (br, 1H), 9.2 (s, 1H).

[0776] Step 3: 6-Hydrazinylpyrimidine-4-carboxamide / (6-Hydrazono-1,6-dihydropyrimidine-4-carboxamide)

[0777]

[0778] 6-Chloropyrimidine-4-carboxamide (7.06 g, 48.24 mmol) and hydrazine hydrate (64%, 10.32 g, 206.1 mmol, 10.0 mL) in MeOH (250 mL) were stirred at 65 °C for 4 h. Water was added and MeOH was evaporated under reduced pressure. Aqueous HCl and aqueous K 2 CO 3 were added until pH 8. The formed precipitate was filtered off, washed with water and dried to give 7.03 g (95% of theory, purity corrected).

[0779] ESI mass [m / z]: 154.1 [M + H] +

[0780] 1 1H NMR (400 MHz, D 6 -DMSO): δ = 4.5 (br, 2H), 7.3 (br, 1H), 7.7 (br, 1H), 8.0 (br, 1H), 8.4 (br, 1H), 8.7 (br, 1H).

[0781] Synthesis of 6-[5-[(1S)-1-[(3,5-Dibromobenzoyl)amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (I-34)

[0782] Step 1: 3,5-Dibromo-N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]benzamide

[0783]

[0784] 0.5 g (1.4 mmol) of N-[(2S)-1-amino-1-oxopropan-2-yl]-3,5-dibromobenzamide and 3 ml of DMF-DMA (22.6 mmol) in 40 mL of THF were stirred in a water bath of a rotary evaporator at a water bath temperature of 65 °C for 10 min and then evaporated under reduced pressure to give 0.61 g, which was used directly in the subsequent step.

[0785] Step 2:6-[5-[(1S)-1-[(3,5-Dibromobenzoyl)amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (I-34)

[0786]

[0787] 0.61 g (1.5 mmol) of 3,5-dibromo-N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]benzamide and 0.25 g (1.6 mmol) of 6-hydrazinylpyrimidine-4-carboxamide were stirred in 60 mL of AcOH at 85 °C for 0.5 h. The mixture was evaporated under reduced pressure, and aqueous K 2 CO 3 , aqueous NaCl, and EtOAc were added. The aqueous layer was extracted three times with THF / EtOAc. The combined organic layers were dried over Na 2 SO 4 and evaporated under reduced pressure. The residue was crystallized from MeOH (including heating with activated carbon and hot filtration) to give 0.24 g (32%).

[0788] The analytical data are shown in Table 1.

[0789] Synthesis of 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-9)

[0790] Step 1: tert-Butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate

[0791]

[0792] tert-Butyl N-[(1S)-2-amino-1-methyl-2-oxo-ethyl]carbamate (150 g, 797 mmol, 1.00 eq) was dissolved in dioxane (1.50 L). N,N-Dimethylformamide dimethyl acetal (142 g, 1.20 mol, 159 mL, 1.50 eq) was added to the mixture. The reaction mixture was stirred at 25 °C for 3 h. TLC (dichloromethane:methanol = 10:1, Rf = 0.67) showed that the starting material had been consumed. The crude product in dioxane (193 g, calculated) was used in the next step without further purification.

[0793] Step 2: tert-Butyl N-[(1S)-1-[2-(6-chloropyrimidine-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate

[0794]

[0795] The reaction mixture of tert-butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxoethyl]carbamate (193 g, 793 mmol, 1.00 eq) was added dropwise to a mixture of (6-chloropyrimidin-4-yl)hydrazine (126 g, 873 mmol, 1.10 eq) dissolved in AcOH (1900 mL). The reaction mixture was stirred at 25 °C for 16 h. TLC (petroleum ether:ethyl acetate = 3:1, Rf = 0.22) showed that the starting materials had been completely consumed. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether / ethyl acetate = 50 / 1 to 3 / 1). tert-Butyl N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate as a white solid (160 g, 493 mmol, 62.1% yield) was obtained.

[0796] Step 3: Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate

[0797]

[0798] Under nitrogen, triethylamine (49.9 g, 493 mmol, 68.6 mL, 2.00 eq) and Pd(dppf)Cl 2 (18.0 g, 24.6 mmol, 0.100 eq) were added to a solution of tert-butyl N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (80.0 g, 246 mmol, 1.00 eq) in MeOH (1.50 L). The suspension was degassed in vacuo and purged with CO (carbon monoxide) several times. The mixture was stirred at 40 °C under CO (246 mmol, 1.00 eq) (50.0 psi) for 16 h. TLC (petroleum ether:ethyl acetate = 1:1, Rf = 0.27) showed that the starting materials had been consumed. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether / ethyl acetate = 50 / 1 to 1 / 1). Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate as a white solid (80.0 g, 230 mmol, 46.6% yield) was obtained.

[0799] 1 H NMR (DMSO-d 6) δ = 9.29 (s, 1H), 8.63 (s, 1H), 8.02 (s, 1H), 7.27 (s, 1H), 6.09–6.06 (m, 1H), 5.58–5.56 (d, 1H), 1.60–1.58 (d, 3H), 1.42 (s, 9H).

[0800] Step 4: tert-Butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate

[0801]

[0802] Dissolve methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate (40.0 g, 115 mmol, 1.00 eq) in THF (240 mL) and MeOH (80.0 mL). Add NH 4 OH (96.6 g, 689 mmol, 106 mL, 25.0% purity, 6.00 eq) to the mixture. Stir the reaction mixture at 25 °C for 6 h. TLC (petroleum ether:ethyl acetate = 3:1, Rf = 0.1) shows that the starting material has been completely consumed. Concentrate the reaction mixture. Grind the crude product with MTBE (300 mL) at 25 °C for 30 min. Obtain tert-Butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate as a white solid (64.0 g, 189 mmol, 82.1% yield, 98.2% purity).

[0803] 1 1H NMR (DMSO-d 6 ) δ = 9.30 (s, 1H), 8.47 (s, 1H), 8.35 (s, 1H), 8.28 (s, 1H), 8.12 (s, 1H), 5.80–5.76 (m, 1H), 1.46–1.44 (d, 3H), 1.32 (s, 9H).

[0804] Step 5: 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-9)

[0805]

[0806] tert-Butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (1 g, 3 mmol) was dissolved in 30 mL of dioxane, and then 4 M HCl / dioxane (7.5 mL) was added. The mixture was stirred at 50 °C for 7 h and then stirred at r.t. for another 4 days. The mixture was evaporated under reduced pressure to give 1.02 g of the crude product (INT-9).

[0807] ESI mass [m / z]: 234.2 [amine + H] +

[0808] 1 H NMR (DMSO-d 6 ) δ = 9.36 (s, 1H), 8.78 (s, 2H, NH 2 ), 8.52 (s, 1H), 8.50 (bs, 1H), 8.39 (s, 1H), 8.17 (bs, 1H), 5.07–5.45 (m, 1H), 1.67–1.65 (d, 3H).

[0809] Synthesis of 3-(trifluoromethoxy)-5-(trifluoromethylsulfonyl)benzoic acid (INT-13)

[0810] Step 1: 3-Bromo-5-(trifluoromethoxy)benzenethiol

[0811]

[0812] At -65 °C, a solution of 2.5 M n-BuLi in hexane (77 mL, 191 mmol) was added dropwise to a stirred solution of 1,3-dibromo-5-(trifluoromethoxy)benzene (48.9 g, 153 mmol) in anhydrous diethyl ether (430 mL). The reaction mixture was stirred at -65 °C for 50 min. Then, ground sulfur (7.11 g, 222 mmol) was added in portions at -65 °C. The reaction mixture was stirred at -65 °C for 1.5 h. Then, glacial acetic acid (35 mL) was added to the stirred reaction mixture. The mixture was brought to 0 °C. The reaction mixture was concentrated under reduced pressure to a volume of 50 mL. The residue was triturated with deionized water (500 mL), and the resulting emulsion was extracted with diethyl ether (2 × 300 mL). The combined diethyl ether layers were washed successively with water and brine, and the solution was dried over sodium sulfate. The solvent was removed under reduced pressure to give a brown oil. The oil was vacuum distilled at a pressure of 13 mm Hg. The colorless fraction was collected at 94 - 98 °C. Yield 27.7 g (66%).

[0813] 1 H-NMR (400 MHz, CDCl 3): δ = 7.35 (t, J = 1.6 Hz, 1H), 7.19–7.16 (m, 1H), 7.08–7.05 (m, 1H), 3.61 (s, 1H). 19 F-NMR (376 MHz, CDCl 3 ): δ = -57.80. Recorded on a Varian Gemini 2000 machine 1 H and 19 F NMR spectra.

[0814] Step 2: 1-Bromo-3-(trifluoromethoxy)-5-(trifluoromethylthio)benzene

[0815]

[0816] Under argon, triethylamine (27.2 mL, 195 mmol) was added to a degassed solution of 3-bromo-5-(trifluoromethoxy)benzenethiol (17.75 g, 65 mmol) in DMF (175 mL). The stirred mixture was cooled to 0 °C and blown with trifluoromethyliodide until the weight increased by 38 g. Then 1,1'-dimethyl-[4,4'-bipyridinium]-1,1'-dichloride (3.34 g, 13 mmol) was added to the stirred reaction mixture. The reaction mixture was stirred at room temperature overnight. The mixture was poured into deionized water (800 mL), and the resulting emulsion was extracted with diethyl ether (2 × 350 mL). The combined diethyl ether layers were washed successively with water and brine, and the solution was dried over sodium sulfate. The solvent was removed under reduced pressure to give a dark brown oil. The oil was vacuum distilled at a pressure of 20 mm Hg. The colorless fraction was collected at 87 - 89 °C. Yield 23.4 g (83%).

[0817] 1 H-NMR (400 MHz, CDCl 3 ): δ = 7.76 (t, J = 1.6 Hz, 1H), 7.54–7.51 (m, 1H), 7.49–7.47 (m, 1H). 19 F-NMR (376 MHz, CDCl 3 ): δ = -41.92, -58.01. Recorded on a Varian Gemini 2000 machine 1 H and 19 F NMR spectra.

[0818] Step 3: 3-(Trifluoromethoxy)-5-(trifluoromethylthio)benzoic acid

[0819]

[0820] A mixture of stirred 1-bromo-3-(trifluoromethoxy)-5-(trifluoromethylthio)benzene (5.12 g, 15 mmol), ground potassium carbonate (10.4, 75 mmol), palladium(II) acetate (168 mg, 0.75 mmol) and xanthos (868 mg, 1.5 mmol) in DMF (75 mL) was heated at 100 °C for 19 h under a carbon monoxide atmosphere. Deionized water (75 mL) was added to the reaction mixture at room temperature. The solvent was removed under reduced pressure. The residue was dissolved in deionized water (70 mL) and extracted with diethyl ether (2 × 50 mL). The aqueous layer was separated and its pH was adjusted to 4 with aqueous HCl. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (Combiflash). Yield 3 g (65%).

[0821] 1 H-NMR (400 MHz, DMSO-d 6 ): δ=13.94 (s, 1H), 8.19 (t, J=1.5 Hz, 1H), 8.07–8.04 (m, 1H), 8.03–8.00 (m, 1H). 19 F-NMR (376 MHz, DMSO-d 6 ): δ=-44.12, -59.52. Recorded on a Varian Gemini2000 machine 1 H and 19 F NMR spectra.

[0822] Step 4: 3-(Trifluoromethoxy)-5-(trifluoromethylsulfonyl)benzoic acid (INT-13)

[0823]

[0824] An aqueous solution of hydrogen peroxide (40%, 20 mL, 100 mmol) was added dropwise to a stirred solution of TFA (0.3 mL) in acetic anhydride (50 mL) over 1.5 h at 0 °C. 3-(Trifluoromethoxy)-5-(trifluoromethylthio)benzoic acid (3.06 g, 10 mmol) was added at 0 °C. The resulting solution was brought to room temperature. The reaction mixture was stirred at 55 °C for 4 h and then stirred overnight at room temperature. The reaction mixture was diluted with deionized water to a volume of 250 mL. The mixture was cooled to 0 °C, giving a white solid precipitate. The precipitate was filtered, washed successively with water and hexane, and dried in vacuo. Yield 3.2 g (95%).

[0825] ESI mass [m / z]: 337.0 [M-H] -

[0826] 1¹H NMR (400 MHz, DMSO-d 6 ): δ = 14.37 (bs, 1H, COOH), 8.48 (s, 1H), 8.46 (s, 1H), 8.42 (s, 1H).

[0827] Synthesis of 3-Bromo-5-(2,2-dichlorocyclopropyl)benzoic acid (INT-14)

[0828] Step 1: 3-Bromo-5-(2,2-dichlorocyclopropyl)benzonitrile

[0829]

[0830] At room temperature, powdered potassium hydroxide (15 g, 260 mmol) was added portionwise over 30 min to a stirred solution of 3-bromo-5-vinylbenzonitrile (5.41 g, 26 mmol) and 18-crown-6 (1.03 g, 3.9 mmol) in chloroform (225 mL). The reaction mixture was stirred at room temperature for 48 h. The reaction mixture was diluted with dichloromethane to a volume of 400 mL. The solution was washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure to give a black oil. The oil was purified by flash chromatography (Combiflash) to give 4.55 g (60%).

[0831] 1 ¹H-NMR (400 MHz, CDCl 3 ): δ = 7.73–7.71 (m, 1H), 7.64–7.62 (m, 1H), 7.47–7.45 (m, 1H), 2.93–2.83 (m, 1H), 2.06 (dd, J = 10.5, 7.7 Hz, 1H), 1.90–1.81 (m, 1H). The spectrum was recorded on a Varian Gemini2000.

[0832] Step 2: 3-Bromo-5-(2,2-dichlorocyclopropyl)benzoic acid (INT-14)

[0833]

[0834] At 0 °C, thionyl chloride (16.42 mL, 225 mmol) was added dropwise to a stirred solution of 3-bromo-5-(2,2-dichlorocyclopropyl)benzonitrile (4.36 g, 15 mmol) in methanol (100 mL). The reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with water to a volume of 300 mL, and the resulting emulsion was extracted with diethyl ether (2 × 75 mL). The organic phase was separated, washed with brine, and dried over sodium sulfate. The solvent was removed under reduced pressure to give a pale yellow oil (4.55 g). The oil was dissolved in isopropanol (35 mL), and the solution was added dropwise to a stirred solution of lithium hydroxide (1.26 g, 30 mmol) in deionized water (20 mL) at room temperature, and the reaction mixture was stirred for 5 h. The reaction mixture was diluted with water to a volume of 100 mL. Isopropanol was removed under reduced pressure. The remaining aqueous fraction was washed with diethyl ether (2 × 40 mL). Then a solution of concentrated aqueous HCl in deionized water (20 mL) was added to the aqueous fraction, giving a white solid precipitate. The precipitate was filtered, washed successively with water and hexane, and dried in an oven at 65 °C to give 3.2 g (69%) of the title compound.

[0835] ESI mass [m / z]: 311.0 [M+H] +

[0836] 1 H-NMR (400 MHz, DMSO-d 6 ): δ = 13.45 (s, 1H), 7.97 (s, 1H), 7.87 (s, 1H), 7.81 (s, 1H), 3.27 (dd, J = 10.9, 8.5 Hz, 1H), 2.40–2.28 (m, 1H), 2.17–2.06 (m, 1H). The spectrum was recorded on a Varian Gemini2000.

[0837] Synthesis of 3-bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid (INT-15)

[0838] Step 1: Mixture of methyl 3-bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoate and methyl 3-bromo-5-(2-bromo-1,1,2,2-tetrafluoroethoxy)benzoate

[0839]

[0840] To a solution of 1,2-dibromo-1,1,2,2-tetrafluoroethane (18.0 g, 77.9 mmol, 1.0 eq) in DMSO (100 mL) was added Cs 2 CO 3(38.1 g, 116 mmol, 1.5 eq) and methyl 3-bromo-5-hydroxybenzoate (commercially available, 40.4 g, 155 mmol, 2.0 eq), and the mixture was stirred at 60 °C for 12 h. H 2 O (200 mL) was added to the reaction mixture and it was extracted with ethyl acetate (150 mL × 3). The organic phase was dried and concentrated to give a product mixture as a yellow oil (22.0 g, 1:1).

[0841] Step 2: Methyl 3-bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoate

[0842]

[0843] At 50 °C, Zn (10.5 g, 161 mmol, 3.0 eq) was added to a solution of the mixture from the previous step (22.0 g, 53.6 mmol, 1.0 eq) in AcOH (100 mL), and the mixture was stirred at 50 °C for 12 h. The reaction mixture was filtered and concentrated under reduced pressure to give a residue. A pale yellow liquid (16.5 g, crude) was obtained.

[0844] Step 3: 3-Bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid (INT-15)

[0845]

[0846] To a solution of methyl 3-bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoate (16.5 g, 49.8 mmol, 1.0 eq) from the previous step in THF (100 mL) was added LiOH·H 2 O (2.0 M, 49.8 mL, 2.0 eq), and the mixture was stirred at 25 °C for 2 h. The reaction was concentrated under reduced pressure to give a residue, which was diluted with water (50 mL), adjusted to pH = 4 with 2 M KHSO 4 solution, extracted with DCM (30 mL × 2), the combined organic layers were washed with brine (50 mL), dried over MgSO 4 and filtered and concentrated under reduced pressure to give a white solid (10.0 g, 31.5 mmol, 63.3%).

[0847] ESI mass [m / z]: 314.9 [M-H] -

[0848] 1 H-NMR: (400 MHz CDCl 3): δ = 10.69 (br s, 1H), 8.17 (d, J = 1.2 Hz, 1H), 7.89 (s, 1H), 7.64 (s, 1H), 5.78 - 6.12 (m, 1H).

[0849] Synthesis of 6-(5-{(1S)-1-[3-chloro-5-(1,1,2,2-tetrafluoroethoxy)benzamido]ethyl}-1H-1,2,4-triazol-1-yl)pyrimidine-4-carboxamide (I-113)

[0850] Step 1: Mixture of 3-chloro-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid and 3-chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)benzoic acid

[0851]

[0852] 3-Chloro-5-hydroxybenzoic acid (commercially available, 9.3 g, 54 mmol), 1-chloro-1,1,2,2-tetrafluoro-2-iodoethane (10.5 g, 40 mmol), and potassium carbonate (25 g, 181 mmol) in 50 ml of DMSO were stirred in a thick-walled reaction tube equipped with a pressure relief valve at 60 °C for 3 d. The mixture was evaporated under reduced pressure. The residue was dissolved in aqueous citric acid / ethyl acetate, and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate and evaporated to give 19.5 g of a crude product. Chromatography (silica gel, petroleum ether / acetone) gave 10.3 g of a fraction consisting mainly of 3-chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)benzoic acid and an impure fraction containing 3-chloro-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid, which was used directly in the subsequent step.

[0853] Step 2: 6-(5-{(1S)-1-[3-chloro-5-(1,1,2,2-tetrafluoroethoxy)benzamido]ethyl}-1H-1,2,4-triazol-1-yl)pyrimidine-4-carboxamide (I-113)

[0854]

[0855] 3-Chloro-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid (0.19 g, 0.45 mmol) was stirred with HATU (0.34 g, 0.89 mmol) and 6-{5-[(1S)-1-aminoethyl]-1H-1,2,4-triazol-1-yl}pyrimidine-4-carboxamide hydrochloride (0.12 g (0.45 mmol) and N,N-diisopropylamine (0.31 ml, 1.78 mmol) in 1.5 ml of DMF for 1 h respectively. The two solutions were combined and stirred at r.t. for 16 h. Purification of the reaction mixture by chromatography (RP18, water / ACN containing 0.1% HCOOH) gave 92 mg (42% of theory).

[0856] The analytical data are shown in Table 1.

[0857] Synthesis of 6-(5-{(1S)-1-[3-chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)benzamido]ethyl}-1H-1,2,4-triazol-1-yl)pyrimidine-4-carboxamide (I-114)

[0858]

[0859] 3-Chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)benzoic acid (from the previous sequence, 0.18 g, 0.45 mmol) was stirred with HATU (0.34 g, 0.89 mmol) and 6-{5-[(1S)-1-aminoethyl]-1H-1,2,4-triazol-1-yl}pyrimidine-4-carboxamide hydrochloride (0.12 g (0.45 mmol) and N,N-diisopropylamine (0.31 ml, 1.78 mmol) in 1.5 ml of DMF for 1 h respectively. The two solutions were combined and stirred at r.t. for 16 h. Purification of the reaction mixture by chromatography (RP18, water / ACN containing 0.1% HCOOH) gave 106 mg (39% of theory).

[0860] The analytical data are shown in Table 1.

[0861] Synthesis of 3-(1-fluoro-1-methylethyl)-5-(trifluoromethoxy)benzoic acid (INT-16)

[0862] Step 1: 2-[3-Bromo-5-(trifluoromethoxy)phenyl]propan-2-ol

[0863]

[0864] Under argon, at -5 °C, i-PrMgCl (1.9 M in THF, 36 mL, 73.2 mmol) was added dropwise to a solution of 1,3-dibromo-5-(trifluoromethoxy)benzene (20 g, 62.4 mmol) in THF (160 mL). The mixture was stirred at the same temperature for 45 min, then acetone (9 g, 156 mmol) was added dropwise. The reaction mixture was stirred for an additional 30 min, MTBE (200 mL) was added, and then 10% citric acid (200 mL) was added. The organic phase was separated, washed with brine (3 × 100 mL), dried, and concentrated under reduced pressure. After purification by MPLC, 2-[3-bromo-5-(trifluoromethoxy)phenyl]propan-2-ol (10.14 g, 33.91 mmol, 54.3% yield) was obtained.

[0865] Step 2: Methyl 3-(1-hydroxy-1-methylethyl)-5-(trifluoromethoxy)benzoate

[0866]

[0867] To a solution of 2-[3-bromo-5-(trifluoromethoxy)phenyl]propan-2-ol (10.14 g, 33.91 mmol) in MeOH (110 mL) was added Et 3 N (6.833 g, 67.82 mmol) and Pd(dppf)Cl2 (2.47 g, 3.391 mmol). The mixture was stirred at 130 °C under a CO (10 Torr) pressure for 48 h, diluted with EtOAc (600 mL), filtered through a Celite pad, and concentrated under reduced pressure. The residue was dissolved in EtOAc (300 mL) and washed with water (2 × 200 mL). The organic phase was dried over Na2SO4 and concentrated under reduced pressure to give methyl 3-(1-hydroxy-1-methylethyl)-5-(trifluoromethoxy)benzoate (8.96 g, 32.21 mmol, 95% yield).

[0868] Step 3: Methyl 3-(1-fluoro-1-methylethyl)-5-(trifluoromethoxy)benzoate

[0869]

[0870] At -60 °C, Morph-DAST (6.2 g, 35.435 mmol) was added dropwise to a solution of methyl 3-(1-hydroxy-1-methyl-ethyl)-5-(trifluoromethoxy)benzoate (8.96 g, 32.21 mmol) in dichloromethane (100 mL). The mixture was stirred overnight at room temperature and poured into aqueous sodium bicarbonate. The organic layer was separated, dried over sodium sulfate, and concentrated under reduced pressure. After MPLC, pure methyl 3-(1-fluoro-1-methyl-ethyl)-5-(trifluoromethoxy)benzoate (3.8 g, 13.56 mmol, 42% yield) was obtained.

[0871] Step 4: 3-(1-Fluoro-1-methyl-ethyl)-5-(trifluoromethoxy)benzoic acid (INT-16)

[0872]

[0873] At 0 °C, lithium hydroxide monohydrate (0.766 g, 18.306 mmol) was added to a stirred solution of methyl 3-(1-fluoro-1-methyl-ethyl)-5-(trifluoromethoxy)benzoate (3.8 g, 13.56 mmol) in a mixture of THF (40 mL) / H 2 O (12.5 mL), and the mixture was stirred overnight at r.t. THF was evaporated under reduced pressure, the water was acidified to pH = 4.5, and extracted with MTBE (2 × 25 mL). After recrystallization from 30% aqueous EtOH (3.17 g, 11.9 mmol, 87.76% yield), pure 3-(1-fluoro-1-methyl-ethyl)-5-(trifluoromethoxy)benzoic acid as a yellow solid was obtained.

[0874] ESI mass [m / z neg.]: 265.1 [M-H] +

[0875] 1 H-NMR (400 MHz, DMSO-d 6 ): δ = 1.66 (s, 3H), 1.72 (s, 3H), 7.66 (s, 1H), 7.75 (m, 1H), 7.99 (m, 1H), 13.56 (s, 1H). The spectrum was recorded on a Bruker AVANCE III 400 MHz.

[0876] 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride Alternative synthesis of (INT-11)

[0877] Step 1: tert-Butyl N-[(1S)-2-chloro-1-methyl-2-oxo-ethyl]carbamate

[0878]

[0879] To a solution of (2S)-2-(tert-butoxycarbonylamino)propanoic acid (90.0 g, 476 mmol, 1.00 eq) in DCM (900 mL) was added Et 3 N (44.7 g, 442 mmol, 61.6 mL, 0.930 eq). Trimethylacetyl chloride (57.4 g, 476 mmol, 58.5 mL, 1.00 eq) was added dropwise at 0 °C. After addition, the reaction mixture was stirred at 20 °C for 16 h. tert-Butyl N-[(1S)-2-chloro-1-methyl-2-oxo-ethyl]carbamate (98.8 g, crude) in DCM (900 mL) as a colorless liquid was obtained for the next step.

[0880] Step 2: (Z)-Ethyl N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidate

[0881]

[0882] To a solution of tert-Butyl N-[(1S)-2-chloro-1-methyl-2-oxo-ethyl]carbamate (98.8 g, 476 mmol, 1.00 eq) in DCM (900 mL) was added Et 3 N (116 g, 1.14 mol, 159 mL, 2.40 eq). Then ethyl cyclopropanecarboximidate hydrochloride (71.1 g, 476 mmol, 1.00 eq) was added portionwise at 20 °C. After addition, the mixture was stirred at 20 °C for 16 h. (Z)-Ethyl N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidate (135 g, crude) in DCM as a colorless liquid was obtained for the next step.

[0883] Step 3: tert-Butyl N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate

[0884]

[0885] Below 20 °C, (6-Chloropyrimidin-4-yl)hydrazine (68.7 g, 475 mmol, 1.00 eq) was added portionwise to a solution of (Z)-Ethyl N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidate (135 g, 475 mmol, 1.00 eq) in DCM (900 mL). After addition, the mixture was stirred at 20 °C for 16 h. To the reaction mixture was added H 2O (500 mL), the separated organic phase was washed with brine (200 mL), dried and concentrated. The residue was purified by column chromatography (silica gel, petroleum ether / ethyl acetate = 20 / 1 to 3 / 1). N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamic acid tert-butyl ester as a yellow solid (48.0 g, 132 mmol, 27.7% yield over three steps) was obtained.

[0886] Step 4: Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate (INT-17)

[0887]

[0888] To a solution of N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamic acid tert-butyl ester (48.0 g, 132 mmol, 1.00 eq) in MeOH (1.00 L) was added Et 3 N (26.6 g, 263 mmol, 36.6 mL, 2.00 eq) and Pd(dppf)Cl 2 (9.63 g, 13.2 mmol, 0.100 eq). The suspension was degassed under vacuum and purged with CO several times. The mixture was stirred at 40 °C under CO (50 psi) for 16 h. The reaction mixture was concentrated. The residue was purified by column chromatography (silica gel, petroleum ether / ethyl acetate = 20 / 1 to 1 / 1). Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate as a pale yellow solid (41.0 g, 106 mmol, 80.2% yield) was obtained.

[0889] Step 5: N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamic acid tert-butyl ester (INT-18)

[0890]

[0891] Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate (25.0 g, 64.4 mmol, 1.00 eq) was dissolved in THF (150 mL) and MeOH (50 mL). NH 4OH (54.1 g, 386 mmol, 59.5 mL, 25% purity, 6.00 eq). After addition, the mixture was stirred at 20 °C for 5 h. The reaction mixture was concentrated. N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamic acid tert-butyl ester as a light yellow solid (24.0 g, 60.4 mmol, 93.8% yield, 94% purity) was obtained and used for the next step.

[0892] 1 H NMR (400 MHz, CDCl 3 ): δ 9.08 (d, J = 0.73 Hz, 1H), 8.65 (s, 1H), 7.79 (br s, 1H), 5.96 - 6.07 (m, 1H), 5.81 (br s, 1H), 5.56 - 5.71 (m, 1H), 2.02 - 2.12 (m, 1H), 1.55 (d, J = 6.8 Hz, 3H), 1.44 (s, 9H), 0.98 - 1.11 (m, 4H).

[0893] Step 6: 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-11)

[0894]

[0895] N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamic acid tert-butyl ester (8.00 g, 21.4 mmol, 1.00 eq) in DCM (20.0 mL) was added to HCl / dioxane (80.0 mL, 4 M). The mixture was stirred at 20 °C for 2 h. The reaction mixture was concentrated. The crude product was triturated with DCM (50.0 mL) at 20 °C for 1 h and filtered. 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride as a white solid (5.54 g, 17.01 mmol, 79.4% yield, 95.1% purity) was obtained.

[0896] ESI mass [m / z]: 274.2 [amine + H] +

[0897] 1 H-NMR (400 MHz, DMSO-d 6): δ 9.30 (s, 1H), 8.75 (bs, 2H, NH2), 8.48 (s, 1H), 8.32 (s, 1H), 8.15 (s, 1H), 5.44–5.41 (m, 1H), 2.20–2.14 (m, 1H), 1.64–1.61 (d, 3H), 1.12–1.07 (m, 2H), 1.03–0.98 (m, 2H).

[0898] Synthesis of 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N-methyl-pyrimidine-4-carboxamide Hydrochloride (INT-21)

[0899] Step 1: tert-Butyl N-[(1S)-1-[5-cyclopropyl-2-[6-(methylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamate (INT-19)

[0900]

[0901] To a solution of methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate (9.00 g, 23.2 mmol, 1.00 eq) in THF (45.0 mL) was added methylamine (2 M in THF, 34.7 mL, 3.00 eq). The mixture was stirred at 20 °C for 4 h. After completion of the reaction, the reaction mixture was concentrated. The residue was purified by column chromatography (silica gel, petroleum ether / ethyl acetate = 20 / 1 to 1 / 1). tert-Butyl N-[(1S)-1-[5-cyclopropyl-2-[6-(methylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamate as a pale yellow solid was obtained (8.50 g, 20.8 mmol, 89.9% yield, 95% purity).

[0902] 1 H NMR (400 MHz, CDCl 3 ): δ 9.04 (s, 1H), 8.63 (s, 1H), 7.98 (d, 1H), 6.02–5.99 (m, 1H), 5.63 (d, 1H), 3.09 (d, 3H), 2.10–2.06 (m, 1H), 1.54 (d, 1H), 1.44 (s, 9H), 1.07–1.02 (m, 4H).

[0903] Step 2: 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N-methyl-pyrimidine-4-carboxamide Hydrochloride (INT-21)

[0904]

[0905] Trimethylsilyl chloride (7.07 g, 65.0 mmol, 8.26 mL, 3.00 eq) was added to CF 3 CH 2 OH (84.0 mL) and the mixture was stirred for 30 mins. N-[(1S)-1-[5-Cyclopropyl-2-[6-(methylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamic acid tert-butyl ester (8.40 g, 21.7 mmol, 1.00 eq) in CF 3 CH 2 OH (84.0 mL) was added dropwise to the above solution at below 20 °C. After addition, the mixture was stirred at 20 °C for 1 h. The reaction mixture was concentrated. 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N-methyl-pyrimidine-4-carboxamide hydrochloride (6.60 g, 19.7 mmol, 91.0% yield, 96.8% purity, HCl) as a pale yellow solid was obtained.

[0906] 1 1H NMR (400 MHz, MeOD): δ 9.19 (d, J = 1.00 Hz, 1H), 8.52 (d, J = 1.00 Hz, 1H), 5.59 (q, J = 6.71 Hz, 1H), 3.25 - 3.38 (m, 2H), 3.00 (s, 3H), 2.11 - 2.24 (m, 1H), 1.75 (d, J = 6.75 Hz, 3H), 1.01 - 1.16 (m, 4H).

[0907] Synthesis of 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N,N-dimethyl-pyrimidine- 4-carboxamide hydrochloride (INT-22)

[0908] Step 1: N-[(1S)-1-[5-Cyclopropyl-2-[6-(dimethylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamic acid tert-butyl ester (INT-20)

[0909]

[0910] To a solution of methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate (14.0 g, 36.0 mmol, 1.00 eq) was added a solution of dimethylamine (2 M in THF, 108 mL, 6.00 eq) in THF. The reaction mixture was stirred at 60 °C for 16 h. The reaction mixture was concentrated. The residue was purified by column chromatography (silica gel, petroleum ether / ethyl acetate = 20 / 1 to 1 / 1). Yellow gummy N-[(1S)-1-[5-cyclopropyl-2-[6-(dimethylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamic acid tert-butyl ester (11.6 g, 27.4 mmol, 76.2% yield, 95% purity) was obtained.

[0911] 1 H NMR(400MHz,CDCl 3 ):δ9.07(s,1H),8.12(s,1H),6.02–5.99(m,1H),5.62(d,1H),3.16(s,3H),3.08(s,3H),2.07–2.00(m,1H),1.55(d,1H),1.44(s,9H),1.04–1.00(m,4H).

[0912] Step 2: 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N,N-dimethyl-pyrimidine- 4-carboxamide hydrochloride (INT-22)

[0913]

[0914] Trimethylsilyl chloride (8.93 g, 82.2 mmol, 10.4 mL, 3.00 eq) was added to CF 3 CH 2 OH(110mL) and stirred for 30 mins. N-[(1S)-1-[5-cyclopropyl-2-[6-(dimethylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamic acid tert-butyl ester (11.0 g, 27.4 mmol, 1.00 eq) in CF 3 CH 2 OH(84.0mL) was added dropwise to the above solution below 20 °C. After addition, the mixture was stirred at 20 °C for 1 h. The reaction mixture was concentrated. 6 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N,N-dimethyl-pyrimidine-4-carboxamide hydrochloride as a pale yellow solid (8.20 g, 23.6 mmol, 86.3% yield, 97.4% purity) was obtained.

[0915] 11H NMR (400 MHz, MeOD): δ 9.17 (d, J = 1.00 Hz, 1H), 8.13 (d, J = 1.00 Hz, 1H), 5.61 (q, J = 6.67 Hz, 1H), 3.18 (s, 3H), 3.10 (s, 3H), 2.11 - 2.24 (m, 1H), 1.78 (d, J = 6.75 Hz, 3H), 1.05 - 1.14 (m, 4H).

[0916] Synthesis of 3,5 - bis(difluoromethylsulfonyl)benzoic acid (INT - 23)

[0917] Step 1: Methyl 3,5 - bis(dimethylthiocarbamoyloxy)benzoate

[0918]

[0919] Under a nitrogen atmosphere, methyl 3,5 - dihydroxybenzoate (50 g, 300 mmol) was dissolved in anhydrous DMF (200 mL). The solution was cooled to 0 °C, and DABCO (133 g, 1190 mmol) was added in portions. At 0 - 5 °C, a solution of N,N - dimethylthiocarbamoyl chloride (147 g, 1190 mmol) in DMF (200 mL) was added dropwise to the resulting suspension. When the reaction mixture solidified, more DMF was added to effect efficient stirring. The suspension was heated to room temperature and stirred for 24 h. The reaction mixture was poured into water (2000 mL), filtered, and the residue was washed with ethanol to give methyl 3,5 - bis(dimethylthiocarbamoyloxy)benzoate as a white crystalline powder (92 g, 90% yield), which was used as such in the next step.

[0920] Step 2: Methyl 3,5 - bis(dimethylaminocarbamothioyl)benzoate

[0921]

[0922] Methyl 3,5 - bis(dimethylthiocarbamoyloxy)benzoate (8.0 g, 23.3 mmol) was suspended in diphenyl ether (80 mL) and heated to 230 - 240 °C in a sand bath under a nitrogen atmosphere and maintained for 3 h. After the reaction mixture was cooled to 30 - 40 °C, it was poured into hexane (160 mL) and slowly cooled to 4 °C. After filtration and thorough washing with warm hexane, methyl 3,5 - bis(dimethylaminocarbamothioyl)benzoate as a light beige crystal was obtained (7.37 g, 92% yield), which was used as such in the next step.

[0923] Step 3: Methyl 3,5 - bis(thiol)benzoate

[0924]

[0925] Under a nitrogen atmosphere, methyl 3,5-bis(dimethylcarbamoylthio)benzoate (34.2 g, 100 mmol) was suspended in a mixture of 28% sodium methoxide (43 g, 230 mmol) solution and methanol (150 mL), and the reaction mixture was stirred overnight at r.t. Ice water (500 mL) was added, and then neutralized with concentrated hydrochloric acid. The precipitate was filtered, washed with water, and dried in vacuo to give methyl 3,5-bis(thio)benzoate as a white powder (12.5 g, 62% yield), which was used as such for the next step.

[0926] Step 4: Methyl 3,5-bis(difluoromethylthio)benzoate

[0927]

[0928] To a solution of methyl 3,5-bis(thio)benzoate (4 g, 20 mmol) in N,N-dimethylformamide (50 mL) was added potassium carbonate (11.4 g, 80 mmol) and sodium chlorodifluoroacetate (11.2 g, 80 mmol). The reaction mixture was heated to 95 °C for 3 h, diluted with water, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with water and brine, dried over sodium sulfate, filtered, and then concentrated to give methyl 3,5-bis(difluoromethylthio)benzoate as an off-white powder (3.72 g, 62% yield).

[0929] 1 H NMR (400 MHz, CDCl 3 ): δ 8.30 (s, 2H), 7.99 (s, 1H), 7.04–6.75 (t, 1H), 3.97 (s, 3H). Measured on a Bruker AVANCE III 400 MHz machine.

[0930] Step 5: Methyl 3,5-bis(difluoromethylsulfonyl)benzoate

[0931]

[0932] To a solution of methyl 3,5-bis(difluoromethylthio)benzoate (3.72 g, 12.5 mmol) in a mixture of carbon tetrachloride (15 mL), acetonitrile (15 mL), and water (35 mL) was added sodium periodate (26.4 g, 120 mmol) and ruthenium trichloride hydrate (0.1 g, 0.47 mmol). The reaction mixture was stirred at r.t. for 30 min, diluted with water and extracted with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to give methyl 3,5-bis(difluoromethylsulfonyl)benzoate as an off-white powder (2.3 g, 51% yield).

[0933] 1 H NMR (400 MHz, CDCl 3 ): δ 9.00 (s, 2H), 8.74 (s, 1H), 6.48–6.21 (t, 1H), 4.08 (s, 3H). Measured on a Bruker AVANCE III 400 MHz machine.

[0934] Step 5: 3,5-Bis(difluoromethylsulfonyl)benzoic acid (INT-23)

[0935]

[0936] Methyl 3,5-bis(difluoromethylsulfonyl)benzoate (2.3 g, 6.3 mmol) was added to a mixture of lithium hydroxide (0.76 g, 12.6 mmol), THF (12 mL), and water (6 mL). The reaction was stirred at r.t. for 4 h, acidified with 1 M hydrochloric acid, and the aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to give 3,5-bis(difluoromethylsulfonyl)benzoic acid as an off-white powder (2.03 g, 92% yield).

[0937] ESI mass [m / z]: 349.0 [M-H] -

[0938] 1 H NMR (400 MHz, DMSO-d6): δ 7.53 (t, 2H), 8.57 (s, 1H), 8.79 (s, 2H), ...

Claims

1. A compound of formula (I) wherein X is O or S; R 1 is hydrogen; R 2 selected from the following substructures Q1 and Q2, where the bond connected to the C═X group is marked with #: wherein R 21 is halogen, -CN, -SF 5 , C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 3 haloalkylthio, C 1 -C 3 haloalkylsulfinyl, C 1 -C 3 haloalkylsulfonyl, C 1 -C 3 alkylthio, C 1 -C 3 alkylsulfinyl, C 1 -C 3 alkylsulfonyl, C 3 -C 4 cycloalkylthio, C 3 -C 4 cycloalkylsulfinyl, C 3 -C 4 cycloalkylsulfonyl, phenylsulfonyl, wherein the phenyl is optionally substituted with one or two substituents selected from halogen, -CN, methyl, trifluoromethyl or trifluoromethoxy; or cyclopropyl, wherein the cyclopropyl is optionally substituted with one or two substituents selected from halogen, -CN, methyl or trifluoromethyl; R 22 is hydrogen, halogen, -CN, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy or C 1 -C 3 haloalkylsulfonyl; R 3 is -CN or a substituent selected from the following substructures S1, where the bond connecting to pyrimidine is marked with #: R 31 is hydrogen or C 1 -C 3 alkyl; R 32 is hydrogen, C 3 -C 6 -cycloalkyl or C 1 -C 3 -alkyl, where C 3 -C 6 -cycloalkyl and C 1 -C 3 -alkyl are optionally substituted with one to three substituents selected from halogen, -CN, C 3 -C 6 -cycloalkyl and C 1 -C 3 -alkoxy; R 4 is hydrogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy or C 3 -C 4 cycloalkyl.

2. The compound according to claim 1, wherein X is O or S; R 1 is hydrogen; R 2 selected from the following substructures Q1 and Q2, wherein the bond connected to the C═X group is marked with #: wherein R 21 is fluorine, chlorine, bromine, iodine, -CN, cyclopropyl, 1-cyanocyclopropyl, 2,2-dichlorocyclopropyl, difluoromethyl, 1,1-difluoroethyl, trifluoromethyl, chlorodifluoromethyl, 2-fluoropropan-2-yl, difluoromethoxy, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, 1,1,2,2-tetrafluoro-2-iodoethoxy, difluoromethylthio, trifluoromethylthio, 1,1,2,2-tetrafluoroethylthio, difluoromethylsulfonyl, trifluoromethylsulfonyl, 1,1,2,2-tetrafluoroethylsulfonyl, methylthio, methylsulfinyl, methylsulfonyl, ethylsulfonyl, cyclopropylsulfonyl or 4-chlorophenylsulfonyl; R 22 is hydrogen, fluorine, chlorine, bromine, iodine, -CN, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, difluoromethylsulfonyl, trifluoromethylsulfonyl; R 3 is -CN or a substituent selected from the following substructures S1, where the bond connecting to the pyrimidine is marked with #: R 31 is hydrogen or methyl; R 32 is hydrogen, cyclopropyl or C 1 -C 3 -alkyl, wherein the C 1 -C 3 -alkyl is optionally substituted with one to three substituents selected from fluorine, chlorine, -CN, cyclopropyl and methoxy; R 4 is hydrogen, methyl or cyclopropyl.

3. The compound according to claim 1 or 2, wherein X is O; R 1 is hydrogen; R 2 is (3,5-dibromophenyl), (3,5-dichlorophenyl), (3-chloro-5-methylsulfonylphenyl), 3-bromo-5-methylsulfonylphenyl, (3-cyano-5-fluorophenyl), 3-chloro-5-cyanophenyl, 3-bromo-5-cyanophenyl, 3,5-dicyanophenyl, 3-(1,1,2,2-tetrafluoroethylthio)phenyl, 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)phenyl, 3-(difluoromethoxy)-5-fluorophenyl, 3-(difluoromethoxy)-5-iodophenyl, 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)phenyl, 3-(trifluoromethoxy)-5-(trifluoromethylsulfonyl)phenyl, 3-(trifluoromethoxy)phenyl, 3-(trifluoromethyl)phenyl, 3-(trifluoromethylsulfonyl)phenyl, 3,5-bis(difluoromethoxy)phenyl, 3-(2-fluoropropan-2-yl)-5-(trifluoromethoxy)phenyl, 3,5-bis(trifluoromethoxy)phenyl, 3,5-bis(difluoromethyl)phenyl, 3,5-bis(trifluoromethyl)phenyl, 3-(difluoromethoxy)-5-(trifluoromethoxy)phenyl, 3,5-bis(difluoromethylsulfonyl)phenyl, 3,5-bis(trifluoromethylsulfonyl)phenyl, 3-bromo-5-(1,1,2,2-tetrafluoroethoxy)phenyl, 3-bromo-5-(2,2-dichlorocyclopropyl)phenyl, 3-bromo-5-(difluoromethoxy)phenyl, 3-bromo-5-(trifluoromethoxy)phenyl, 3-chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)phenyl, 3-chloro-5-(1,1,2,2-tetrafluoroethoxy)phenyl, 3-chloro-5-(4-chlorophenyl)sulfonylphenyl, 3-chloro-5-(difluoromethylsulfonyl)phenyl, 3-chloro-5-(trifluoromethoxy)phenyl, 3-chloro-5-(trifluoromethyl)phenyl, 3-chloro-5-(1,1-difluoroethyl)phenyl, 3-chloro-5-(chlorodifluoromethyl)phenyl, 3-chloro-5-(trifluoromethylsulfonyl)phenyl, 3-bromo-5-(trifluoromethylsulfonyl)phenyl, 3-chloro-5-(trifluoromethylthio)phenyl, 3-cyano-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(difluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyclopropylsulfonyl-5-(trifluoromethoxy)phenyl, 3-fluor-5-(trifluoromethoxy)phenyl, 3-methylsulfonylphenyl, 3-(difluoromethoxy)-5-methylthiophenyl, 3-(difluoromethoxy)-5-methylsulfonylphenyl, 3-methylsulfonyl-5-(trifluoromethoxy)phenyl, 3-methylsulfonyl-5-(trifluoromethyl)phenyl, 2,6-dibromopyridin-4-yl, 2-(trifluoromethoxy)pyridin-4-yl, 2-chloro-6-(trifluoromethoxy)pyridin-4-yl, 2-bromo-6-methylsulfonyl-pyridin-4-yl or 2-chloro-6-(1-cyanocyclopropyl)pyridin-4-yl; R 3 is -CN, aminocarbonyl, methylcarbamoyl, ethylcarbamoyl, (isopropylamino)carbonyl, (difluoroethylamino)carbonyl, (3,3,3-trifluoropropylamino)carbonyl, (cyclopropylamino)carbonyl, dimethylcarbamoyl, [ethyl(methyl)amino]carbonyl, [isopropyl(methyl)amino]carbonyl or [cyclopropylmethyl(methyl)amino]carbonyl; R 4 is hydrogen, methyl or cyclopropyl.

4. The compound according to any one of claims 1 to 3, characterized in that it has a structure according to formula (I’) where the structural elements R 1 , R 2 , R 3 and R 4 have the meaning given in claim 1 or the meaning given in claim 2 or the meaning given in claim 3.

5. The compound according to any one of claims 1 to 3, characterized in that it has a structure according to formula (I’’), wherein R 1 is hydrogen, and wherein the structural element R 2 , R 3 and R 4 have the meaning given in claim 1 or the meaning given in claim 2 or the meaning given in claim 3.

6. The compound according to any one of claims 1 to 3, characterized in that it has a structure according to formula (I’’’), where R 1 is hydrogen, and where the structural element R 2 , R 3 and R 4 have the meaning given in claim 1 or the meaning given in claim 2 or the meaning given in claim 3.

7. A compound of formula (a) wherein R 1 , R 3 and R 4 have the meaning given in claim 1 or the meaning given in claim 2 or the meaning given in claim 3.

8. 6-[5-(1-Aminoethyl)-1H-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride, tert-butyl {1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate, tert-butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate, tert-butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-methyl-1,2,4-triazol-3-yl]ethyl]carbamate, 6-[5-[(1S)-1-aminoethyl]-3-methyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride, tert-butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate, 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride, 6-[5-[(1S)-1-aminoethyl]-3-methyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride, 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride, 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride, methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate, tert-butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate, tert-butyl N-[(1S)-1-[5-cyclopropyl-2-[6-(methylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamate, tert-butyl N-[(1S)-1-[5-cyclopropyl-2-[6-(dimethylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamate, 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N-methyl-pyrimidine-4-carboxamide hydrochloride, 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N,N-dimethyl-pyrimidine-4-carboxamide hydrochloride, in the case of amines also including their salts, and in the case of amine hydrochlorides also including their free amines.

9. An agrochemical formulation comprising at least one compound of formula (I) according to any one of claims 1 to 6.

10. The formulation according to claim 9, further comprising at least one extender and / or at least one surface-active substance.

11. The formulation according to claim 9 or 10, characterized in that The compound of formula (I) is mixed with at least one other active compound.

12. A method for controlling animal pests, characterized in that a compound of formula (I) according to any one of claims 1 to 6 or a preparation according to any one of claims 9 to 11 is allowed to act on the pests and / or their habitat, the method excluding methods for surgically or therapeutically treating the human or animal body and diagnostic methods carried out on the human or animal body.

13. The method according to claim 12, characterized in that the animal pests are insects, arachnids or nematodes.

14. Use of a compound of formula (I) according to any one of claims 1 to 6 or a preparation according to any one of claims 9 to 11 for controlling animal pests, the use excluding uses for surgically or therapeutically treating the human or animal body and diagnostic uses carried out on the human or animal body.

15. The use according to claim 14, characterized in that the animal pests are insects, arachnids or nematodes.

16. The use according to claim 14 or 15, for crop protection.

17. A method for protecting seeds or germinating plants against animal pests, comprising the method step of bringing the seeds into contact with a compound of formula (I) according to any one of claims 1 to 6 or with a preparation according to any one of claims 9 to 11.

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