Novel heteroaryl-triazole compounds as insecticides

Abstract

The present invention relates to novel heteroaryl-triazole compounds of general formula (I) (structural elements X, R 1 , R 2 , R 3 and R 4 has the meaning given in the specification), to formulations and compositions containing such compounds and their use in controlling pests such as arthropods and insects in plant protection, and for controlling ectoparasites in animals. [Formula 1] TIFF2023523856000324.tif33158

Description

Technical Field

[0001] The present invention relates to novel heteroaryl triazole compounds, formulations and compositions containing such compounds, and their use in the control of pests such as arthropods and insects in plant protection, and their use for the control of external parasites on animals.

Background Art

[0002] Certain heteroaryl-triazole compounds are disclosed in WO2017 / 192385 for use in controlling external parasites on animals, and in WO2019 / 170626 and WO2019 / 215198 for use in controlling pests such as arthropods and insects in the field of plant protection. Furthermore, patent applications WO2019 / 197468, WO2019 / 201835, WO2019 / 202077, WO2019 / 206799, WO2021 / 013719 and WO2021 / 013720 disclose certain heteroaryl-triazole compounds for use in controlling external parasites on animals and for controlling pests including arthropods and insects in the field of plant protection. WO2020 / 002563, WO2020 / 053364, WO2020 / 053365, WO2020 / 079198, WO2020 / 094363, WO2020 / 169445, WO2020 / 182649, WO2020 / 188014, WO2020 / 188027 and WO2020 / 193341 all describe azole-amide compounds that can be used as insecticides.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

[0004] Modern plant protection products and external parasiticides for animals must meet many requirements, for example, with regard to efficacy, persistence, spectrum and resistance-breaking properties. Questions regarding toxicity, the possibility of combination with other active compounds or formulation auxiliaries become important, and further questions regarding the costs required for the synthesis of the active compounds become important. Furthermore, resistance may occur. For all these reasons, it cannot be considered that the search for new crop protection compositions or external parasiticides for animals has been completed, and there is always a need for new compounds that have improved properties at least with regard to individual aspects compared to known compounds.

[0005] The object of the present invention was to provide a compound that broadens the spectrum of pesticides in various aspects.

Means for Solving the Problems

[0006] Accordingly, the present invention provides a compound of the following general formula (I).

Chemical formula

Chemical formula

Chemical formula

[0007] The compounds of formula (I) likewise include all diastereomers or enantiomers and E / Z isomers present, as well as salts and N-oxides of the compounds of formula (I), and their use for the control of diseased animals.

[0008] Preferred definitions of the groups for the formulas specified above and below are provided below.

[0009] The present invention further provides (Configuration 1-2): X is O or S; R 1 is hydrogen; R 2 is selected from the following substructures Q1 and Q2, where the bond to the C=X-group is marked with #:

[0010]

Chemical formula

Chemical formula

[0011] Preferred (Constitution 2-1) is that X is O or S; R 1 is hydrogen; R 2 is selected from the following substructures Q1 and Q2, where the bond to the C=X group is marked with #:

Chemical formula

[0012] Also preferred (Constitution 2-2) are X is O or S; R 1 is hydrogen; R 2 is selected from the following substructures Q1 and Q2, where the bond to the C=X-group is marked with #:

[0013] [Chemical formula] where 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-iodoethoxydifluoromethylthio, trifluoromethylthio, 1,1,2,2-tetrafluoroethylthio, difluoromethylsulfonyl, trifluoromethylsulfonyl, 1,1,2,2-tetrafluoroethylsulfonyl, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfonyl, cyclopropylsulfonyl or 4-chlorophenyl-sulfonyl; R 22is hydrogen, fluorine, chlorine, bromine, iodine, -CN, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, difluoromethylsulfonyl, or trifluoromethylsulfonyl; R 3 is a substituent selected from -CN or the following substructure S1, where the bond to pyrimidine is marked with #:

Chemical formula

[0014] A further preferred one (Constitution 3-1) is X is O; R 1 is hydrogen; R 2is (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-fluoro-5-(trifluoromethoxy)phenyl, 3-methylsulfonyl-5-(trifluoromethoxy)phenyl, 3-methylsulfonyl-5-(trifluoromethyl)phenyl or 2-chloro-6-(1-cyanocyclopropyl)pyridin-4-yl; R3 is -CN, aminocarbonyl, methylcarbamoyl, [ethyl(methyl)amino]carbonyl, [isopropyl(methyl)amino]carbonyl or [cyclopropylmethyl(methyl)amino]carbonyl; R 4 is hydrogen, methyl or cyclopropyl, and is a compound of formula (I).

[0015] Also, further preferred (Constitution 3-2) is X is O; R 1 is hydrogen; 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-methylsulfanylphenyl, 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, dimethylaminocarbonyl, [ethyl(methyl)amino]carbonyl, [isopropyl(methyl)amino]carbonyl or [cyclopropylmethyl(methyl)amino]carbonyl; R 4 is hydrogen, methyl or cyclopropyl, and is a compound of formula (I).

[0016] In a further preferred embodiment, the present invention relates to a compound of formula (I');

Chemical formula

[0017] In a further preferred embodiment, the present invention relates to R 1 being hydrogen, and the structural elements R 2 , R 3 and R 4 having the meaning provided in Configuration (1-1) or the meaning provided in Configuration (2-1) or the meaning provided in Configuration (3-1) or the meaning provided in Configuration (1-2) or the meaning provided in Configuration (2-2) or the meaning provided in Configuration (3-2), to a compound of formula (I″).

Chemical formula

[0018] In a further preferred embodiment, the present invention relates to R 1 being hydrogen, and the structural elements R 2 , R 3 and R 4 having the meaning provided in Configuration (1-1) or the meaning provided in Configuration (2-1) or the meaning provided in Configuration (3-1) or the meaning provided in Configuration (1-2) or the meaning provided in Configuration (2-2) or the meaning provided in Configuration (3-2), to a compound of formula (I″′).

Chemical formula

[0019] According to a further aspect, the present invention includes intermediate compounds useful for the production of the compounds of the above general formula (I).

[0020] In particular, the present invention includes intermediate compounds of general formula (a) and salts thereof;

Chemical formula

[0021] In particular, the present invention includes intermediate compounds INT-1 to INT-23, their salts in the case of amines and acids, and the free amines in the case of amine hydrochlorides (see Table 2).

[0022] INT-1: 6-[5-(1-Aminoethyl)-1H-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride INT-2: tert-Butyl {1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate INT-3: tert-Butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate INT-4: 6-[5-[(1S)-1-Aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile; 2,2,2-trifluoroacetic acid INT-5: tert-Butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-methyl-1,2,4-triazol-3-yl]ethyl]carbamate INT-6: 6-[5-[(1S)-1-Aminoethyl]-3-methyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride INT-7: tert-Butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]-carbamate INT-8: 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride 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 INT-11: 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride INT-17: Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate INT-18: tert-Butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate INT-19: tert-Butyl N-[(1S)-1-[5-cyclopropyl-2-[6-(methylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamate INT-20: tert-Butyl N-[(1S)-1-[5-cyclopropyl-2-[6-(dimethylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamate INT-21: 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N-methyl-pyrimidine-4-carboxamide hydrochloride INT-22: 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N,N-dimethyl-pyrimidine-4-carboxamide hydrochloride INT-12: 2-Chloro-6-(1-cyanocyclopropyl)pyridine-4-carboxylic acid INT-13: 3-(Trifluoromethoxy)-5-(trifluoromethylsulfonyl)benzoic acid INT-14: 3-Bromo-5-(2,2-dichlorocyclopropyl)benzoic acid INT-15: 3-Bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid INT-16: 3-(1-Fluoro-1-methylethyl)-5-(trifluoromethoxy)benzoic acid INT-23: 3,5-Bis(difluoromethylsulfonyl)benzoic acid.

[0023] Depending on the nature of the substituents, the compounds of formula (I) can also exist in the form of stereoisomers, i.e., geometric isomers and / or optical isomers or mixtures of isomers of various compositions. Even only the compounds of formula (I) discussed herein, the present invention provides both pure stereoisomers and any desired mixtures of these isomers.

[0024] However, according to the present invention, it is preferred to use the optically active stereoisomeric forms of the compounds of formula (I) and their salts.

[0025] Therefore, the present invention relates to both pure enantiomers and diastereomers, and mixtures thereof, for controlling pest animals such as arthropods, especially insects.

[0026] Where appropriate, the compounds of formula (I) can exist in various polymorphic forms or as mixtures of various polymorphic forms Both pure polymorphs and mixtures of polymorphs are provided by the present invention and can be used according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0027] Definition Those skilled in the art will understand that, unless explicitly stated otherwise, the expressions "a" or "an" as used in this application can mean "1", "1 or more" or "at least 1", depending on the context.

[0028] In all structures described herein, such as ring systems and groups, adjacent atoms must not be -O-O- or -O-S-.

[0029] Structures having a variable possible number of carbon atoms (C atoms) are, in the present application, C 炭素原子の下限 -C 炭素原子の上限 structures (C LL -C UL structures) and can be more specifically defined by doing so. Example: An alkyl group can consist of 3 to 10 carbon atoms, in which case it corresponds to C3-C 10 alkyl. A ring structure composed of carbon atoms and heteroatoms may be called an "LL- to UL-member" structure. An example of a 6-member ring structure is toluene (a 6-member ring structure substituted by a methyl group).

[0030] A general term for substituents, for example C LL -C UL alkyl, when at the end of a complex substituent such as, for example, C LL -C UL cycloalkyl-C LL -C UL alkyl, the components at the starting part of the complex substituent, for example C LL -C UL cycloalkyl can be mono- or polysubstituted, identically or differently and independently, by the latter substituent, for example, C LL -C UL alkyl. All general terms used in the present application for chemical groups, ring systems and cyclic groups can be more specifically defined by adding "C LL ~C UL " or "LL- to UL-member". 。

[0031] In the definitions of the symbols given in the above formula, collective terms generally representing the following substituents were used.

[0032] Halogen relates to the elements of Group 7, preferably fluorine, chlorine, bromine and iodine, more preferably fluorine, chlorine and bromine, and even more preferably fluorine and chlorine.

[0033] Examples of heteroatoms are N, O, S, P, B, Si. Preferably, the term "heteroatom" relates to N, S and O.

[0034] According to the present invention, "alkyl" by itself or as part of a chemical group preferably represents a straight-chain or branched hydrocarbon having 1 to 6 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-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. Preferred are also alkyls having 1 to 4 carbon atoms, in particular, for example, methyl, ethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl or t-butyl. The alkyl of the present invention may be substituted with one or more identical or different groups.

[0035] According to the present invention, "alkenyl", by itself or as part of a chemical group, preferably represents a straight-chain or branched hydrocarbon having 2 to 6 carbon atoms and at least one double bond. For example, 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. Preferred are also alkenyls having 2 to 4 carbon atoms, particularly, for example, 2-propenyl, 2-butenyl or 1-methyl-2-propenyl. The alkenyl of the present invention may be substituted with one or more identical or different groups.

[0036] According to the present invention, "alkynyl", by itself or as part of a chemical group, preferably represents a linear or branched hydrocarbon having 2 to 6 carbon atoms and at least one triple bond. For example, 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. Preferred are also alkynyls having 2 to 4 carbon atoms, particularly, for example, ethynyl, 2-propynyl or 2-butynyl-2-propenyl. The alkynyl of the present invention may be substituted with one or more identical or different groups.

[0037] According to the present invention, "cycloalkyl", by itself or as part of a chemical group, preferably represents a monocyclic, bicyclic or tricyclic hydrocarbon having 3 to 10 carbons. For example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl or adamantyl. Preferred are also alkenyls having 3, 4, 5, 6 or 7 carbon atoms, particularly, for example, cyclopropyl or cyclobutyl. The cycloalkyl of the present invention may be substituted with one or more identical or different groups.

[0038] According to the present invention, "alkylcycloalkyl" preferably represents a monocyclic, bicyclic or tricyclic alkylcycloalkyl having 4 to 10 or 4 to 7 carbon atoms, for example, methylcyclopropyl, ethylcyclopropyl, isopropylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. Preferred are also alkylcycloalkyls having 4, 5 or 7 carbon atoms, particularly, for example, ethylcyclopropyl or 4-methylcyclohexyl. The alkylcycloalkyl of the present invention may be substituted with one or more identical or different groups.

[0039] According to the present invention, "cycloalkylalkyl" preferably represents a monocyclic, bicyclic or tricyclic cycloalkylalkyl having 4 to 10 or 4 to 7 carbon atoms, for example, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl and cyclopentylethyl. Preferred are also cycloalkylalkyls having 4, 5 or 7 carbon atoms, particularly, for example, cyclopropylmethyl or cyclobutylmethyl. The cycloalkylalkyl of the present invention may be substituted with one or more identical or different groups.

[0040] According to the present invention, "hydroxyalkyl" preferably represents a straight-chain or branched alcohol having 1 to 6 carbon atoms, for example, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, s-butanol and t-butanol. Preferred are also hydroxyalkyl groups having 1 to 4 carbon atoms. The hydroxyalkyl group of the present invention may be substituted with one or more identical or different groups.

[0041] According to the present invention, "alkoxy" preferably represents a linear or branched O-alkyl having 1 to 6 carbon atoms, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy and t-butoxy. Preferably, there is also an alkoxy group having 1 to 4 carbon atoms. The alkoxy group of the present invention may be substituted by one or more identical or different groups.

[0042] According to the present invention, "alkylthio" or "alkylsulfanyl" preferably represents a linear or branched S-alkyl having 1 to 6 carbon atoms, for example, methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, s-butylthio and t-butylthio. Preferably, there is also an alkylthio group having 1 to 4 carbon atoms. The alkylthio group of the present invention may be substituted by one or more identical or different groups.

[0043] According to the present invention, "alkylsulfinyl" preferably represents a linear or branched alkylsulfinyl having 1 to 6 carbon atoms, for example, methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, s-butylsulfinyl and t-butylsulfinyl. Preferably, there is also an alkylsulfinyl group having 1 to 4 carbon atoms. The alkylsulfinyl group of the present invention may be substituted by one or more identical or different groups and includes both enantiomers.

[0044] According to the present invention, "alkylsulfonyl" preferably represents a linear or branched alkylsulfonyl having 1 to 6 carbon atoms, for example, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, s-butylsulfonyl and t-butylsulfonyl. Preferably, there is also an alkylsulfonyl group having 1 to 4 carbon atoms. The alkylsulfonyl group of the present invention may be substituted by one or more identical or different groups.

[0045] According to the present invention, "cycloalkylthio" or "cycloalkylsulfanyl" preferably represents -S-cycloalkyl having 3 to 6 carbon atoms, for example, cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio. Preferably, there is also a cycloalkylthio group having 3 to 5 carbon atoms. The cycloalkylthio group of the present invention may be substituted by one or more identical or different groups.

[0046] According to the present invention, "cycloalkylsulfinyl" preferably represents -S(O)-cycloalkyl having 3 to 6 carbon atoms, for example, cyclopropylsulfinyl, cyclobutylsulfinyl, cyclopentylsulfinyl, cyclohexylsulfinyl. Preferably, there is also a cycloalkylsulfinyl group having 3 to 5 carbon atoms. The cycloalkylsulfinyl group of the present invention may be substituted by one or more identical or different groups and includes both enantiomers.

[0047] According to the present invention, "cycloalkylsulfonyl" preferably represents -SO2-cycloalkyl having 3 to 6 carbon atoms, for example, cyclopropylsulfonyl, cyclobutylsulfonyl, cyclopentylsulfonyl, cyclohexylsulfonyl. Preferably, there is also a cycloalkylsulfonyl group having 3 to 5 carbon atoms. The cycloalkylsulfonyl group of the present invention may be substituted by one or more identical or different groups.

[0048] According to the present invention, "phenylthio" or "phenylsulfanyl" represents -S-phenyl, for example, phenylthio. The phenylthio group of the present invention may be substituted by one or more identical or different groups.

[0049] According to the present invention, "phenylsulfinyl" represents -S(O)-phenyl, for example, phenylsulfinyl. The phenylsulfinyl group of the present invention may be substituted by one or more identical or different groups and includes both enantiomers.

[0050] According to the present invention, "phenylsulfonyl" represents -SO2-phenyl, for example, phenylsulfonyl. The phenylsulfonyl group of the present invention may be substituted by one or more identical or different groups.

[0051] According to the present invention, "alkylcarbonyl" preferably represents a straight-chain or branched alkyl-C(=O) having 2 to 7 carbon atoms, for example, methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, s-butylcarbonyl and t-butylcarbonyl. Preferably, there is also an alkylcarbonyl having 1 to 4 carbon atoms. The alkylcarbonyl of the present invention may be substituted by one or more identical or different groups.

[0052] According to the present invention, "alkoxycarbonyl", alone or as a component of a chemical group, preferably represents a straight-chain or branched alkoxycarbonyl having 1 to 6 carbon atoms or 1 to 4 carbon atoms in the alkoxy moiety, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, s-butoxycarbonyl and t-butoxycarbonyl. The alkoxycarbonyl group of the present invention may be substituted by one or more identical or different groups.

[0053] According to the present invention, "alkylaminocarbonyl" preferably represents a linear or branched alkylaminocarbonyl having 1 to 6 or 1 to 4 carbon atoms in the alkyl moiety, for example, methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl, s-butylaminocarbonyl, and t-butylaminocarbonyl. The alkylaminocarbonyl group of the present invention may be substituted by one or more identical or different groups.

[0054] According to the present invention, "N,N-dialkylaminocarbonyl" preferably represents a linear or branched N,N-dialkylaminocarbonyl having 1 to 6 or 1 to 4 carbon atoms in the alkyl moiety, for example, N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl, N,N-di(n-propylamino)carbonyl, N,N-di(isopropylamino)carbonyl, and N,N-di-(s-butylamino)carbonyl. The N,N-dialkylaminocarbonyl group of the present invention may be substituted by one or more identical or different groups.

[0055] According to the present invention, "aryl" preferably represents a monocyclic, bicyclic, or polycyclic aromatic system having 6 to 14, particularly 6 to 10, ring carbon atoms, for example, phenyl, naphthyl, anthryl, phenanthrenyl, preferably phenyl. Further, aryl also represents a condensed polycyclic system such as tetrahydronaphthyl, indenyl, indanyl, fluorenyl, biphenyl, etc., where the bonding site is on the aromatic system. The aryl group of the present invention may be substituted by one or more identical or different groups.

[0056] An example of a substituted aryl is arylalkyl, which can likewise be substituted by one or more identical or different groups in the C1-C4 alkyl and / or C6-C 14 aryl moiety. Examples of such arylalkyl include benzyl and phenyl-1-ethyl.

[0057] According to the present invention, the term "polycyclic" ring refers to fused, bridged and spiro cyclic carbocyclic and heterocyclic rings and ring systems linked via single or double bonds.

[0058] According to the present invention, "heterocyclic", "heterocyclic ring" or "heterocyclic ring system" means that at least one carbon atom is replaced by a heteroatom, preferably a heteroatom from the group consisting of N, O, S, P, B, Si, Se, and is saturated, unsaturated or heteroaromatic, which may or may not be substituted, and represents a carbocyclic system having at least one ring with a bonding site on a ring atom. Unless otherwise defined, the heterocyclic ring preferably has 3 to 9 ring atoms, particularly 3 to 6 ring atoms, and contains 1 or more, preferably 1 to 4, particularly 1, 2 or 3 heteroatoms from the group consisting of N, O and S in the heterocyclic ring, provided that two oxygen atoms shall not be directly adjacent. The heterocyclic ring usually contains 4 or fewer nitrogen atoms and / or 2 or fewer oxygen atoms and / or 2 or fewer sulfur atoms. In the case of a heterocyclic ring which may be substituted, the present invention also encompasses polycyclic ring systems, for example, 8-azabicyclo[3.2.1]octanyl, 1-azabicyclo[2.2.1]heptyl, 1-oxa-5-azaspiro[2. 3]hexyl or 2,3-dihydro-1H-indole.

[0059] 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 oxazepanyl.

[0060] Particularly important is heteroaryl, i.e., heteroaromatic. According to the present invention, the term heteroaryl represents a heteroaromatic compound, i.e., a fully unsaturated aromatic heterocyclic compound corresponding to the above definition of a heterocyclic ring. Preferred are 5- to 7-membered rings having 1 to 3, preferably 1 or 2, identical or different heteroatoms from the above group. The heteroaryl of the present invention is, for example, furyl, thienyl, pyrazolyl, imidazolyl, 1,2,3- and 1,2,4-triazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-, 1,3,4-, 1,2,4- and 1,2,5-oxadiazolyl, azepinyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-, 1,2,4- and 1,2,3-triazinyl, 1,2,4-, 1,3,2-, 1,3,6- and 1,2,6-oxazinyl, oxepinyl, thiepinyl, 1,2,4-triazolonyl and 1,2,4-diazepinyl. The heteroaryl group of the present invention may be substituted by one or more identical or different groups.

[0061] According to the present invention, the substituent =O (oxo) can replace two hydrogen atoms of a methylene (CH2) group or the lone pair of electrons of a phosphorus atom having only sulfur, nitrogen, and substituents other than hydrogen. For example, the group C2-alkyl becomes, for example, -COCH3 by substitution with =O (oxo), while thietan-3-yl of a heterocyclic ring becomes 1-oxothietan-3-yl by substitution with one =O (oxo) group or 1,1-dioxothietan-3-yl by substitution with two =O (oxo) groups.

[0062] According to the present invention, the substituent =S (thiono) can replace two hydrogen atoms of a methylene (CH2) group. For example, the group C2-alkyl becomes, for example, -CSCH3 by substitution with =S (thiono).

[0063] As used herein, the expression "optionally substituted" means that the optionally substituted group is either substituted with a further substituent or not substituted with a further substituent.

[0064] 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, and heteroaryl group is substituted, and it is, for example, a substituent, such as one substituent or a plurality of substituents, preferably 1, 2, 3, 4, 5, 6, or 7 substituents, being amino, hydroxyl, halogen, nitro, cyano, isocyano, mercapto, isothiocyanato, C1-C4 carboxyl, carbonamide, SF5, aminosulfonyl, C1-C4 alkyl, C1-C4 haloalkyl, C3-C4 cycloalkyl, C2-C4 alkenyl, C5-C6 cycloalkenyl, C2-C4 alkynyl, N-mono-C1-C4 alkylamino, N,N-di-C1-C4 alkylamino, N-C1-C4 alkanoylamino, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C3-C4 cycloalkoxy, C5-C6 cycloalkenyloxy, C1-C4 alkoxycarbonyl, C2-C4 alkenyloxycarbonyl, C2-C4 alkynyloxycarbonyl, C6-,C 10 -,C 14 -aryloxycarbonyl, C1-C4 alkanoyl, C2-C4 alkenylcarbonyl, C2-C4 alkynylcarbonyl, C6-,C 10 -,C 14-arylcarbonyl, C1-C4 alkylthio, C1-C4 haloalkylthio, C3-C4 cycloalkylthio, C2-C4 alkenylthio, C5-C6 cycloalkenylthio, C2-C4 alkynylthio, C1-C4 alkylsulfinyl (including both enantiomers of the C1-C4 alkylsulfinyl group), C1-C4 haloalkylsulfinyl (including both enantiomers of the C1-C4 haloalkylsulfinyl group), C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, N-mono-C1-C4 alkylaminosulfonyl, N,N-di-C1-C4 alkylaminosulfonyl, C1-C4 alkylphosphinyl, C1-C4 alkylphosphonyl (including both enantiomers of the C1-C4 alkylphosphinyl and C1-C4 alkylphosphonyl), N-C1-C4 alkylaminocarbonyl, N,N-di-C1-C4 alkylaminocarbonyl, N-C1-C4 alkanoylaminocarbonyl, N-C1-C4 alkanoyl-N-C1-C4 alkylaminocarbonyl, C6-, C 10 -, C 14 -aryl, C6-, C 10 -, C 14 -aryloxy, benzyl, benzyloxy, benzylthio, C6-, C 10 -, C 14 -arylthio, C6-, C 10 -, C 14-aryl amino, benzyl amino, heterocycle and trialkylsilyl, substituents bonded via a double bond, such as C1-C4 alkylidene (e.g., methylidene or ethylidene), oxo group, imino group and substituted imino group, means a substituted group derived from an unsubstituted basic structure selected from the group consisting of. When two or more groups form one or more rings, these can be carbocyclic, heterocyclic, saturated, partially saturated, unsaturated, for example, including an aromatic ring, and further substituted. The substituents mentioned by way of example ("first substituent level"), when they contain a hydrocarbonaceous component, for example, each independently, by one or more of the substituents selected from halogen, hydroxyl, amino, nitro, cyano, isocyano, azide, acylamino, oxo group and imino group, may have further substitution there ("second substituent level"). The term "substituted (optionally substituted)" group preferably encompasses only one or two substituent levels.

[0065] The halogen-substituted chemical group or halogenated group (e.g., alkyl or alkoxy) of the present invention is mono- or poly-substituted with halogen up to the maximum possible number of substituents. Such a group is also referred to as a halo group (e.g., haloalkyl). In the case of poly-substitution with halogen, the halogen atoms may be the same or different, and all may be bonded to one carbon atom, or may be bonded to a plurality of carbon atoms. The halogen is particularly fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine, and more preferably fluorine. Specifically, the halogen-substituted group is monohalocycloalkyl, e.g., 1-fluorocyclopropyl, 2-fluorocyclopropyl or 1-fluorocyclobutyl, monohaloalkyl, e.g., 2-chloroethyl, 2-fluoroethyl, 1-chloroethyl, 1-fluoroethyl, chloromethyl, or fluoromethyl; perhaloalkyl, e.g., trichloromethyl or trifluoromethyl or CF2CF3, polyhaloalkyl, e.g., difluoromethyl, 2-fluoro-2-chloroethyl, dichloromethyl, 1,1,2,2-tetrafluoroethyl or 2,2,2-trifluoroethyl. Further examples of haloalkyl 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 pentafluoro-t-butyl. Preferred are haloalkyls having 1 to 4 carbon atoms and 1 to 9, preferably 1 to 5, halogen atoms selected from the same or different fluorine, chlorine and bromine. Particularly preferred are haloalkyls having 1 or 2 carbon atoms and 1 to 5 halogen atoms selected from the same or different fluorine and chlorine, especially difluoromethyl, trifluoromethyl or 2,2-difluoroethyl.Further examples of halogen-substituted compounds are haloalkoxy, such as OCF3, OCHF2, OCH2F, OCF2CF3, OCH2CF3, OCH2CHF2 and OCH2CH2Cl, haloalkylsulfanyl, 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, 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.

[0066] In the case of a group having a carbon atom, a group having 1 to 4 carbon atoms, particularly a group having 1 or 2 carbon atoms is preferred. Preferred are usually substituents from the group of halogen, for example, fluorine and chlorine, (C1-C4)alkyl, preferably methyl or ethyl, (C1-C4)haloalkyl, preferably trifluoromethyl, (C1-C4)alkoxy, preferably methoxy or ethoxy, (C1-C4)haloalkoxy, nitro and cyano. Here, particularly preferred are the substituents methyl, methoxy, fluorine and chlorine.

[0067] Substituted aminos such as mono-substituted amino or di-substituted amino mean, for example, alkyl, hydroxy, amino, alkoxy, acyl and aryl; preferably N-mono- and N,N-dialkylamino, (for example, methylamino, ethylamino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino or N,N-dibutylamino), N-mono- or N,N-dialkoxyalkylamino groups (for example N-methoxymethylamino, N-methoxyethylamino, N,N-di(methoxymethyl)amino or N,N-di(methoxyethyl)amino), N-mono- and N,N-diarylamino, for example optionally substituted anilines, acylamino, N,N-diacylamino, N-alkyl-N-arylamino, N-alkyl-N-acylamino, and further groups from the group of substituted amino groups N-substituted by one or two identical or different groups from the group of saturated N-heterocycles, where preferred is an alkyl group having 1 to 4 carbon atoms; here, aryl is preferably phenyl or substituted phenyl; for acyl, the definition further provided below applies and is preferably (C1-C4)-alkanoyl. The same applies to substituted hydroxylamino or hydrazino.

[0068] Substituted amino also includes quaternary ammonium compounds (salts) having four organic substituents on the nitrogen atom.

[0069] The phenyl which may be substituted is preferably phenyl which is unsubstituted or mono- or polysubstituted by the same or different groups from the group consisting of halogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxy-(C1-C4)alkoxy, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)haloalkoxy, (C1-C4)alkylthio, (C1-C4)haloalkylthio, (C1-C4)alkylsulfinyl (C1-C4)haloalkylsulfinyl, (C1-C4)alkylsulfonyl (C1-C4)haloalkylsulfonyl, cyano, isocyano and nitro, preferably trisubstituted phenyl, for example o-, m- and p-tolyl, dimethylphenyls, 2-, 3- and 4-chlorophenyl, 2-, 3- and 4-fluorophenyl, 2-, 3- and 4-trifluoromethyl- and 4-trichloromethylphenyl, 2,4-, 3,5-, 2,5- and 2,3-dichlorophenyl, o-, m- and p-methoxyphenyl, 4-heptafluorophenyl.

[0070] The cycloalkyl which may be substituted is preferably cycloalkyl which is unsubstituted or mono- or polysubstituted by the same or different groups from the group consisting of halogen, cyano, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxy-(C1-C4)alkoxy, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)haloalkyl and (C1-C4)haloalkoxy, particularly preferably trisubstituted cycloalkyl by the same or different groups from the group consisting of one or two (C1-C4)alkyl groups.

[0071] The compounds of the present invention can occur in preferred embodiments. The individual embodiments described herein can be combined with one another. Combinations that violate the laws of nature and would thus be excluded by a person skilled in the art based on their expertise are not included. For example, ring structures having three or more adjacent oxygen atoms are excluded.

[0072] Isomer Depending on the nature of the substituents, the compounds of formula (I) can be in the form of geometric and / or optical isomers or mixtures of the corresponding isomers in different compositions. These stereoisomers are, for example, enantiomers, diastereomers, atropisomers or geometric isomers. Accordingly, the present invention encompasses both pure stereoisomers and any mixtures of these isomers.

[0073] Methods and uses The present invention also relates to a method for controlling pest animals, which comprises allowing a compound of formula (I) to act on pest animals and / or their habitats. Such control of pest animals is preferably carried out in agriculture and forestry, as well as in material protection. Preferably, surgical treatment or therapeutic treatment methods on the human or animal body, as well as diagnostic methods carried out on the human or animal body, are excluded therefrom.

[0074] The present invention further relates to the use of the compounds of formula (I) as pesticides, in particular as crop protection agents.

[0075] In the context of the present application, the term "pesticide" always includes, in each case, the term "crop protection agent".

[0076] Compounds of formula (I) having good plant tolerance have a desirable degree of toxicity to warm-blooded animals and, when showing good environmental compatibility, are suitable for protecting plants and plant organs against biotic stress factors and abiotic stress factors, are suitable for increasing the yield, are suitable for improving the quality of the harvest, and are also suitable for controlling pests encountered in agriculture, horticulture, animal husbandry, hydroponics, in forests, in gardens and leisure facilities, in the protection of stored products and materials, and in the field of hygiene, in particular insects, arachnids, helminths, in particular nematodes and molluscs.

[0077] Within the context of this patent application, the term "hygiene" is understood to mean all means, procedures, and practices that aim to prevent diseases, particularly infectious diseases, and that serve to protect human and animal health and / or to protect the environment and / or to maintain cleanliness. According to the present invention, this particularly includes, for example, means for cleaning, disinfecting, and sterilizing textile or hard surfaces, in particular glass, wood, concrete, porcelain, ceramic, plastic surfaces, or metal surfaces, in order to keep them free of hygienic pests and / or their excrement. Preferably, in this context, surgical or therapeutic procedures that can be performed on the human or animal body, and diagnostic procedures performed on the human or animal body, are excluded from the scope of the present invention.

[0078] Accordingly, the term "hygiene sector" encompasses all areas, technical fields, and industrial applications in which these hygienic means, procedures, and practices are important in relation to hygiene, for example in kitchens, bakeries, airports, bathrooms, swimming pools, department stores, hotels, hospitals, livestock sheds, livestock farming, etc.

[0079] Therefore, the term "hygienic pest" is understood to mean one or more disease-carrying animals that are particularly problematic in the context of the hygiene sector for health reasons. Therefore, the main objective is to avoid or minimize the presence and / or exposure to hygienic pests in the hygiene sector. This can be achieved, in particular, by applying pesticides that can be used both to prevent entry and to address existing infestations. Formulations that avoid or reduce exposure to pests can also be used. Hygienic pest insects include, for example, the following organisms.

[0080] Therefore, the term "hygiene protection" encompasses all activities for maintaining and / or improving these hygienic means, procedures, and practices.

[0081] The compounds of formula (I) can preferably be used as pesticides. They are active against normally sensitive and resistant species and at all or some stages of development. The above-mentioned pests are as follows.

[0082] Pests of the phylum Arthropoda, especially of the class Arachnida, such as species of the genus Acarus, such as Acarus siro, Aceria kuko, Aceria sheldoni, species of the genus Aculops, species of the genus Aculus, such as Aculus fockeui, Aculus schlechtendali, species of the genus Amblyomma, Amphitetranychus viennensis, species of the genus Argas, species of the genus Boophilus, species of the genus Brevipalpus, such as Brevipalpus phoenicis, Bryobia graminum, Bryobia praetiosa, species of the genus Centruroides, species of the genus Chorioptes, Dermanyssus gallinae, Dermatophagoides pteronyssinus, Dermatophagoides farinae, species of the genus Dermacentor, species of the genus Eotetranychus, such as Eotetranychus hicoriae, Epitrimerus pyri, species of the genus Eutetranychus, such as Eutetranychus banksi, species of the genus Eriophyes) For example, Eriophyes pyri, Glycyphagus domesticus, Halotydeus destructor, Hemitarsonemus spp., for example, Hemitarsonemus latus (= Polyphagotarsonemus latus), Hyalomma spp., Ixodes spp., Latrodectus spp., Loxosceles spp., Neutrombicula autumnalis, Nuphersa spp., Oligonychus spp., for example, Oligonychus coffeae, Oligonychus coniferarum, Oligonychus ilicis, Oligonychus indicus, Oligonychus mangiferus, Oligonychus pratensis, Oligonychus punicae, Oligonychus yothersi, Ornithodorus spp., Ornithonyssus spp., Panonychus spp.) For example, Panonychus citri (= Metatetranychus citri), Panonychus ulmi (= Metatetranychus ulmi), Phyllocoptruta oleivora, Platytetranychus multidigituli, Polyphagotarsonemus latus, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Scorpio maurus, Steneotarsonemus spp., Steneotarsonemus spinki, Tarsonemus spp., for example, Tarsonemus confusus, Tarsonemus pallidus, Tetranychus spp., for example, Tetranychus canadensis, Tetranychus cinnabarinus, Tetranychus turkestani, Tetranychus urticae, Trombicula alfreddugesi, Vaejovis spp., Vasates lycopersici;. Of the class Chilopoda, for example, Geophilus spp., Scutigera spp.; Springtails (Collembola), for example, Onychiurus armatus; Sminthurus viridis; Millipedes (Diplopoda), for example, Blaniulus guttulatus; Insects (Insecta), for example, of the order Blattodea, for example, Blatta orientalis, Blattella asahinai, Blattella germanica, Leucophaea maderae, Loboptera decipiens, Neostylopyga rhombifolia, Panchlora spp., Parcoblatta spp., Periplaneta spp., for example, Periplaneta americana, Periplaneta australasiae, Pycnoscelus surinamensis, Supella longipalpa; 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.) For example, Bruchus pisorum, Bruchus rufimanus, Cassida spp., Cerotoma trifurcata, Ceutorrhynchus spp., for example, Ceutorrhynchus assimilis, Ceutorrhynchus quadridens, Ceutorrhynchus rapae, Chaetocnema spp., for example, Chaetocnema confinis, Chaetocnema denticulata, Chaetocnema ectypa, Cleonus mendicus, Conoderus spp., Cosmopolites spp., for example, Cosmopolites sordidus, Costelytra zealandica, Ctenicera spp., Curculio spp., for example, Curculio caryae, Curculio caryatrypes, Curculio obtusus, Curculio sayi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptorhynchus lapathi, Cryptorhynchus mangiferae, Cylindrocopturus spp.) Cylindrocopturus adspersus, Cylindrocopturus furnissi, Dendroctonus spp., such as Dendroctonus ponderosae, Dermestes spp., Diabrotica spp., such as 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., such as Epilachna borealis, Epilachna varivestis, Epitrix spp., such as 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., for example, Hypothenemus hampei, Hypothenemus obscurus, Hypothenemus pubescens, Lachnosterna consanguinea, Lasioderma serricorne, Latheticus oryzae, Lathridius spp., Lema spp., Leptinotarsa decemlineata, Leucoptera spp., for example, Leucoptera coffeella, Limonius ectypus, Lissorhoptrus oryzophilus, Listronotus(=Hyperodes) spp., Lixus spp., Luperodes spp., Luperomorpha xanthodera, Lyctus spp., Megacyllene spp.) For example, Megacyllene robiniae, Megascelis spp., Melanotus spp., such as Melanotus longulus oregonensis, Meligethes aeneus, Melolontha spp., such as Melolontha melolontha, Migdolus spp., Monochamus spp., Naupactus xanthographus, Necrobia spp., Neogalerucella spp., Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorhynchus spp., such as Otiorhynchus cribricollis, Otiorhynchus ligustici, Otiorhynchus ovatus, Otiorhynchus rugosostriarus, Otiorhynchus sulcatus, Oulema spp., such as Oulema melanopus, Oulema oryzae, Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., Phyllophaga helleri, Phyllotreta spp.) For example, Phyllotreta armoraciae, Phyllotreta pusilla, Phyllotreta ramosa, Phyllotreta striolata, Popillia japonica, Premnotrypes spp., Prostephanus truncatus, Psylliodes spp., for example, Psylliodes affinis, Psylliodes chrysoceph. Psylliodes chrysocephala, Psylliodes punctulata, Ptinus spp., Rhizobius ventralis, Rhizopertha dominica, Rhynchophorus spp., Rhynchophorus ferrugineus, Rhynchophorus palmarum, Scolytus spp., such as Scolytus multistriatus, Sinoxylon perforans, Sitophilus spp., such as Sitophilus granarius, Sitophilus linearis, Sitophilus oryzae, Sitophilus zeamais, Sphenophorus spp., Stegobium paniceum, Sternechus spp., such as Sternechus paludatus, Symphyletes spp., Tanymecus spp., such as Tanymecus dilaticollis, Tanymecus indicus, Tanymecus palliatus, Tenebrio molitor, Tenebrioides mauretanicus, Tribolium spp.) For example, Tribolium audax, Tribolium castaneum, Tribolium confusum, Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrus spp., for example, Zabrus tenebrioides;. Of the order Dermaptera, for example Anisolabis maritime, Forficula auricularia, Labidura riparia; Diptera, such as species of the genus Aedes, e.g., Aedes aegypti, Aedes albopictus, Aedes sticticus, Aedes vexans, species of the genus Agromyza, e.g., Agromyza frontella, Agromyza parvicornis, species of the genus Anastrepha, species of the genus Anopheles, e.g., Anopheles quadrimaculatus, Anopheles gambiae, species of the genus Asphondylia, species of the genus Bactrocera, e.g., Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera oleae, Bibio hortulanus, Calliphora erythrocephala, Calliphora vicina, Ceratitis capitata, species of the genus Chironomus, species of the genus Chrysomya, species of the genus Chrysops, Chrysozona pluvialis, species of the genus Cochliomya, species of the genus Contarinia) For example, Contarinia johnsoni, Contarinia nasturtii, Contarinia pyrivora, Contarinia schulzi, Contarinia sorghicola, Contarinia tritici, Cordylobia anthropophaga, Cricotopus sylvestris, Culex spp., for example, Culex pipiens, Culex quinquefasciatus, Culicoides spp., Culiseta spp., Cuterebra spp., Dacus oleae, Dasineura spp., for example, Dasineura brassicae, Delia spp., for example, Delia antiqua, Delia coarctata, Delia florilega, Delia platura, Delia radicum, Dermatobia hominis, Drosophila spp., for example, Drosphila melanogaster, Drosophila suzukii, Echinocnemus spp., Euleia heraclei, Fannia spp., Gasterophilus spp., Glossina spp., Haematopota spp., Hydrellia spp.)、Hydrellia griseola, Hylemya spp., Hippobosca spp., Hypoderma spp., Liriomyza spp., for example, Liriomyza brassicae, Liriomyza huidobrensis, Liriomyza sativae, Lucilia spp., for example, Lucilia cuprina, Lutzomyia spp., Mansonia spp., Musca spp., for example, Musca domestica, Musca domestica vicina, Oestrus spp., Oscinella frit, Paratanytarsus spp., Paralauterborniella subcincta, Pegomya or Pegomyia spp., for example, Pegomyia betae, Pegomya hyoscyami, Pegomya rubivora, Phlebotomus spp., Phorbia spp., Phormia spp., Piophila casei, Platyparea poeciloptera, Prodiplosis spp., Psila rosae, Rhagoletis spp.) For example, Rhagoletis cingulata, Rhagoletis completa, Rhagoletis fausta, Rhagoletis indifferens, Rhagoletis mendax, Rhagoletis pomonella, Sarcophaga spp., Simulium spp., for example, Simulium meridionale, Stomoxys spp., Tabanus spp., Tetanops spp., Tipula spp., for example, Tipula paludosa, Tipula simplex, Toxotrypana curvicauda;. 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.) For example, 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., for example, Aspidiotus nerii, Atanus spp., Aulacorthum solani, Bemisia tabaci, Blastopsylla occidentalis, Boreioglycaspis melaleucae, Brachycaudus helichrysi, Brachycolus spp., Brevicoryne brassicae, Cacopsylla spp., for example, Cacopsylla pyricola, Calligypona marginata, Capulinia spp.)、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., for example, Coccus hesperidum, Coccus longulus, Coccus pseudomagnoliarum, Coccus viridis, Cryptomyzus ribis, Cryptoneossa spp., Ctenarytaina spp., Dalbulus spp., Dialeurodes chittendeni, Dialeurodes citri, Diaphorina citri, Diaspis spp., Diuraphis spp., Doralis spp., Drosicha spp., Dysaphis spp.) For example, Dysaphis apiifolia, Dysaphis plantaginea, Dysaphis tulipae, Dysmicoccus spp., Empoasca spp., such as Empoasca abrupta, Empoasca fabae, Empoasca maligna, Empoasca solana, Empoasca stevensi, Eriosoma spp., such as 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., such as Icerya purchasi, Idiocerus spp., Idioscopus spp.) Laodelphax striatellus, Lecanium spp., such as Lecanium corni (= Parthenolecanium corni), Lepidosaphes spp., such as Lepidosaphes ulmi, Lipaphis erysimi, Lopholeucaspis japonica, Lycorma delicatula, Macrosiphum spp., such as Macrosiphum euphorbiae, Macrosiphum lilii, Macrosiphum rosae, Macrosteles facifrons, Mahanarva spp., Melanaphis sacchari, Metcalfiella spp., Metcalfa pruinosa, Metopolophium dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus spp., such as Myzus ascalonicus, Myzus cerasi, Myzus ligustri, Myzus ornatus, Myzus persicae, Myzus nicotianae, Nasonovia ribisnigri, Neomaskellia spp., Nephotettix spp.) For example, Nephotettix cincticeps, Nephotettix nigropictus, Nettigoniclla spectra, Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Oxya chinensis, Pachypsylla spp., Parabemisia myricae, Paratrioza spp., for example, Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., for example, Pemphigus bursarius, Pemphigus populivenae, Peregrinus maidis, Perkinsiella spp., Phenacoccus spp., for example, Phenacocc. us madeirensis), Phloeomyzus passerinii, Phorodon humuli, Phylloxera spp., for example, Phylloxera devastatrix, Phylloxera notabilis, Pinnaspis aspidistrae, Planococcus spp., for example, Planococcus citri, Prosopidopsylla flava, Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus spp., for example, Pseudococcus calceolariae, Pseudococcus comstocki, Pseudococcus longispinus, Pseudococcus maritimus, Pseudococcus viburni, Psyllopsis spp., Psylla spp., for example, Psylla buxi, Psylla mali, Psylla pyri, Pteromalus spp., Pulvinaria spp., Pyrilla spp., Quadraspidiotus spp.) For example, Quadraspidiotus juglansregiae, Quadraspidiotus ostreaeformis, Quadraspidiotus perniciosus, Quesada gigas, Rastrococcus spp., Rhopalosiphum spp., such as Rhopalosiphum maidis, Rhopalosiphum oxyacanthae, Rhopalosiphum padi, Rhopalosiphum rufiabdominale, Saissetia spp., such as 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., such as Toxoptera aurantii, Toxoptera citricidus, Trialeurodes vaporariorum, Trioza spp., such as Trioza diospyri, Typhlocyba spp., Unaspis spp., Viteus vitifolii, Zygina spp.;. Of the suborder Heteroptera, for example, species of the genus Aelia, Anasa tristis, species of the genus Antestiopsis, species of the genus Boisea, species of the genus Blissus, species of the genus Calocoris, Campylomma livida, species of the genus Cavelerius, species of the genus Cimex, for example, Cimex adjunctus, Cimex hemipterus, Cimex lectularius, Cimex pilosellus, species of the genus Collaria, Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, species of the genus Dysdercus, species of the genus Euschistus, for example, Euschistus heros, Euschistus servus, Euschistus tristigmus, Euschistus variolarius, species of the genus Eurydema, species of the genus Eurygaster, Halyomorpha halys, species of the genus Heliopeltis, Horcias nobilellus, species of the genus Leptocorisa)、Leptocorisa varicornis, Leptoglossus occidentalis, Leptoglossus phyllopus, Lygocoris spp., for example, Lygocoris pabulinus, Lygus spp., for example, Lygus elisus, Lygus hesperus, Lygus lineolaris, Macropes excavatus, Megacopta cribraria, Miridae, Monalonion atratum, Nezara spp., for example, Nezara viridula, Nysius spp., Oebalus spp., Pentomidae, Piesma quadrata, Piezodorus spp., for example, Piezodorus guildinii, Psallus spp., Pseudacysta persea, Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophora spp., Stephanitis nashi, Tibraca spp., Triatoma spp.;. Hymenoptera, such as Acromyrmex spp., Athalia spp., such as Athalia rosae, Atta spp., Camponotus spp., Dolichovespula spp., Diprion spp., such as Diprion similis, Hoplocampa spp., such as Hoplocampa cookei, Hoplocampa testudinea, Lasius spp., Linepithema humile, Monommium pharaonis, Paratrechina spp., Paravespula spp., Plagiolepis spp., Sirex spp., such as Sirex noctilio, Solenopsis invicta, Tapinoma spp., Technomyrmex albipes, Urocerus spp., Vespa spp., such as Vespa crabro, Wasmannia auropunctata, Xeris spp.; Isopoda, such as Armadillidium vulgare, Oniscus asellus, Porcellio scaber; Of the order Isoptera, such as species of the genus Coptotermes, such as Coptotermes formosanus, Cornitermes cumulans, species of the genus Cryptotermes, species of the genus Incisitermes, species of the genus Kalotermes, Microtermes obesi, species of the genus Nasutitermes, species of the genus Odontotermes, species of the genus Porotermes, species of the genus Reticulitermes, such as Reticulitermes flavipes, Reticulitermes hesperus; Lepidoptera, such as Achroia grisella, Acronicta major, Adoxophyes spp., such as Adoxophyes orana, Aedia leucomelas, Agrotis spp., such as Agrotis segetum, Agrotis ipsilon, Alabama spp., such as Alabama argillacea, Amyelois transitella, Anarsia spp., Anticarsia spp., such as 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.) For example, 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., for example, Cydia nigricana, Cydia pomonella, Dalaca noctuides, Diaphania spp., Diparopsis spp., Diatraea saccharalis, Dioryctria spp., for example Dioryctria zimmermani, Earias spp., Ecdytolopha aurantium, Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp., for example, Ephestia elutella, Ephestia kuehniella, Epinotia spp., Epiphyas postvittana, Erannis spp.) Erschoviella musculana, Etiella spp., Eudocima spp., Eulia spp., Eupoecilia ambiguella, Euproctis spp., for example, Euproctis chrysorrhoea, Euxoa spp., Feltia spp., Galleria mellonella, Gracillaria spp., Grapholitha spp., for example, Grapholita molesta, Grapholita prunivora, Hedylepta spp., Helicoverpa spp., for example, Helicoverpa armigera, Helicoverpa zea, Heliothis spp., for example, Heliothis virescens, Hepialus spp., for example Hepialus humuli, Hofmannophila pseudospretella, Homoeosoma spp., Homona spp., Hyponomeuta padella, Kakivoria flavofasciata, Lampides spp., Laphygma spp., Laspeyresia molesta, Leucinodes orbonalis, Leucoptera spp.) For example, Leucoptera coffeella, Lithocolletis spp., such as Lithocolletis blancardella, Lithophane antennata, Lobesia spp., such as Lobesia botrana, Loxagrotis albicosta, Lymantria spp., such as Lymantria dispar, Lyonetia spp., such as 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., such as Ostrinia nubilalis, Panolis flammea, Parnara spp., Pectinophora spp., such as Pectinophora gossypiella, Perileucoptera spp., Phthorimaea spp.) For example, Phthorimaea operculella, Phyllocnistis citrella, Phyllonorycter spp., such as Phyllonorycter blancardella, Phyllonorycter crataegella, Pieris spp., such as Pieris rapae, Platynota stultana, Plodia interpunctella, Plusia spp., Plutella xylostella (= Plutella maculipennis), Podesia spp., such as Podesia syringae, Prays spp., Prodenia spp., Protoparce spp., Pseudaletia spp., such as Pseudaletia unipuncta, Pseudoplusia includens, Pyrausta nubilalis, Rachiplusia nu, Schoenobius spp., such as Schoenobius bipunctifer, Scirpophaga spp., such as Scirpophaga innotata, Scotia segetum, Sesamia spp., such as Sesamia inferens, Sparganothis spp., Spodoptera spp.) For example, Spodoptera eradiana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera praefica, Stathmopoda spp., Stenoma spp., Stomopteryx subsecivella, Synanthedon spp., Tecia solanivora, Thaumetopoea spp., Thermesia gemmatalis, Tinea cloacella, Tinea pellionella, T. Tineola bisselliella, Tortrix spp., Trichophaga tapetzella, Trichoplusia spp., for example, Trichoplusia ni, Tryporyza incertulas, Tuta absoluta, Virachola spp.; Of the order Orthoptera or Saltatoria, for example, Acheta domesticus, Dichroplus spp., Gryllotalpa spp., for example, Gryllotalpa gryllotalpa, Hieroglyphus spp., Locusta spp., for example, Locusta migratoria, Melanoplus spp., for example, Melanoplus devastator, Paratlanticus ussuriensis, Schistocerca gregaria; Of the order Phthiraptera, for example, Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Phylloxera vastatrix, Phthirus pubis, Trichodectes spp.; Of the order Psocoptera, for example, Lepinotus spp., Liposcelis spp.; Of the order Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp., for example, Ctenocephalides canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans, Xenopsylla cheopis; Thrips of the order Thysanoptera, such as Anaphothrips obscurus, Baliothrips biformis, Chaetanaphothrips leeuweni, Drepanothrips reuteri, Enneothrips flavens, Frankliniella spp., such as 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., such as Thrips palmi, Thrips tabaci; Zygentoma (=Thysanura) such as Ctenolepisma spp., Lepisma saccharina, Lepismodes inquilinus, Thermobia domestica; Pests of Symphyla, such as species of Scutigerella, such as Scutigerella immaculata; Pests of the phylum Mollusca, such as those of the class Bivalvia, such as species of Dreissena; and further, Those of the class Gastropoda, such as species of Arion, such as Arion ater rufus, Biomphalaria spp., Bulinus spp., Deroceras spp., such as Deroceras laeve, Galba spp., Lymnaea spp., Oncomelania spp., Pomacea spp., Succinea spp.; Plant pests of the phylum Nematoda, i.e., plant parasitic nematodes, in particular species of the genus Aglenchus, such as Aglenchus agricola, species of the genus Anguina, such as Anguina tritici, species of the genus Aphelenchoides, such as Aphelenchoides arachidis, Aphelenchoides fragariae, species of the genus Belonolaimus, such as Belonolaimus gracilis, Belonolaimus longicaudatus, Belonolaimus nortoni, species of the genus Bursaphelenchus, such as Bursaphelenchus cocophilus, Bursaphelenchus eremus, Bursaphelenchus xylophilus, species of the genus Cacopaurus, such as Cacopaurus pestis, species of the genus Criconemella, such as Criconemella curvata, Criconemella onoensis, Criconemella ornata, Criconemella rusium, Criconemella xenoplax (= Mesocriconema xenoplax), species of the genus Criconemoides) For example, Criconemoides ferniae, Criconemoides onoense, Criconemoides ornatum, Ditylenchus spp., such as Ditylenchus dipsaci, Dolichodorus spp., Globodera spp., such as Globodera pallida, Globodera rostochiensis, Helicotylenchus spp., such as Helicotylenchus dihystera, Hemicriconemoides spp., Hemicycliophora spp., Heterodera spp., such as Heterodera avenae, Heterodera glycines, Heterodera schachtii, Hirschmaniella spp., Hoplolaimus spp., Longidorus spp., such as Longidorus africanus, Meloidogyne spp., such as Meloidogyne chitwoodi, Meloidogyne fallax, Meloidogyne hapla, Meloidogyne incognita, Meloinema spp., Nacobbus spp., Neotylenchus spp., Paralongidorus spp.) Paraphelenchus spp., Paratrichodorus spp., for example, Paratrichodorus minor, Paratylenchus spp., Pratylenchus spp., for example, Pratylenchus penetrans, Pseudohalenchus spp., Psilenchus spp., Punctodera spp., Quinisulcius spp., Radopholus spp., for example, Radopholus citrophilus, Radopholus similis, Rotylenchulus spp., Rotylenchus spp., Scutellonema spp., Subanguina spp., Trichodorus spp., for example, Trichodorus obtusus, Trichodorus primitivus, Tylenchorhynchus spp., for example, Tylenchorhynchus annulatus, Tylenchulus spp., for example, Tylenchulus semipenetrans, Xiphinema spp., for example, Xiphinema index.

[0083] The compounds of formula (I) can optionally also be used as herbicides, phytotoxicity reducing agents, growth regulators or agents for improving plant characteristics at specific concentrations or specific application rates, or as microbicides or gametocides, for example as fungicides, antimycotics, bactericides or virucides (which also includes agents against viroids), or as agents against MLO (mycoplasma-like organisms) and RLO (rickettsia-like organisms). Where appropriate, they can also be used as intermediates or precursors for the synthesis of other active compounds.

[0084] Formulations / Use forms The present invention further relates to formulations, in particular formulations for controlling unwanted pests. The formulations can be applied to the pests and / or their habitats.

[0085] The formulations of the present invention can be provided to the end user in "ready-to-use" use forms, i.e., the formulations can be applied directly to plants or seeds by means of a suitable device such as a spraying device or a spreading device. Alternatively, the formulations can be provided to the end user in the form of concentrates which preferably have to be diluted with water before use. Thus, unless otherwise stated, the expression "formulation" means such a concentrate, while the expression "use form" means the "ready-to-use" solution for the end user, i.e., usually the final use form as such a diluted formulation.

[0086] 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 as disclosed herein.

[0087] The formulations contain at least one compound of the present invention and at least one agriculturally suitable auxiliary, for example a carrier and / or a surfactant.

[0088] The carrier is usually an inert solid or liquid natural or synthetic organic or inorganic substance. The carrier usually improves, for example, the application of the compound to plants, plant parts or seeds. Examples of suitable solid carriers include ammonium salts, especially ammonium sulfates, ammonium phosphates and ammonium nitrates, natural rock powders such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite and diatomaceous earth, silica gel and synthetic rock powders such as pulverized silica, alumina and silicates, but are not limited thereto. Examples of solid carriers that are usually useful for producing granules include crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, synthetic granules of inorganic and organic powders, and granules of organic materials such as paper, sawdust, coconut shells, corn cobs and tobacco stems, but are not limited thereto. Examples of suitable liquid carriers include, but are not limited to, organic solvents and combinations thereof.Examples of suitable solvents include, for example, aromatic and non-aromatic hydrocarbons (e.g., cyclohexane, paraffins, alkylbenzenes, xylene, toluene, tetrahydronaphthalene, alkylnaphthalenes, chlorinated aromatic or chlorinated aliphatic hydrocarbons, e.g., chlorobenzenes, chloroethylenes or methylene chloride), alcohols and polyhydric alcohols (which may be substituted, etherified and / or esterified; e.g., ethanol, propanol, butanol, benzyl alcohol, cyclohexanol or glycol), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, acetophenone or cyclohexanone), esters (including fats and oils) and (poly)ethers, unsubstituted and substituted amines, amides (e.g., dimethylformamide or / fatty acid amides) and their esters, lactams (e.g., N-alkylpyrrolidones, especially N-methylpyrrolidone) and lactones, sulfones and sulfoxides (e.g., dimethyl sulfoxide), oils of plant or animal origin, nitriles (alkyl nitriles such as acetonitrile, propionitrile, butyronitrile, etc., or aromatic nitriles such as benzonitrile), and polar and non-polar organic chemical liquids from the group of carbonic esters (cyclic carbonic esters such as ethylene carbonate, propylene carbonate, butylene carbonate, or dialkyl carbonic esters 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 a gas under normal temperature and pressure, such as an aerosol propellant like a halogenated hydrocarbon, butane, propane, nitrogen and carbon dioxide.

[0089] Preferred solid carriers are selected from clay, talc and silica.

[0090] Preferred liquid carriers are selected from water, fatty acid amide and its ester, aromatic and non-aromatic hydrocarbons, lactam, lactone, carbonic ester, ketone, (poly)ether.

[0091] The amount of the carrier is typically in the range of 1 to 99.99% by weight of the formulation, preferably 5 to 99.9%, more preferably 10 to 99.5% by weight, and most preferably 20 to 99% by weight.

[0092] The liquid carrier is typically present in the range of 20 to 90% by weight of the formulation, for example 30 to 80% by weight.

[0093] The solid carrier is typically present in the range of 0 to 50% by weight of the formulation, preferably 5 to 45% by weight, for example 10 to 30% by weight.

[0094] When the formulation contains two or more carriers, the ranges outlined refer to the total amount of the carriers.

[0095] 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 promoter and any mixture thereof. Examples of suitable surfactants include salts of polyacrylic acid, ethoxylated poly(α-substituted) acrylate derivatives, salts of lignosulfonic acid (e.g., sodium lignosulfonate), salts of phenolsulfonic acid or naphthalenesulfonic acid, polycondensates of ethylene oxide and / or propylene oxide with or without alcohol, fatty acids or aliphatic amines (e.g., polyoxyethylene fatty acid esters such as ethoxylated castor oil, polyoxyethylene fatty alcohol ethers such as alkylaryl polyglycol ethers), substituted phenols (preferably alkylphenols or arylphenols), salts of sulfosuccinic acid esters, taurine derivatives (preferably alkyl taurates), phosphate esters of polyethoxylated alcohols or phenols, fatty esters of polyhydric alcohols (such as fatty acid esters of glycerol, sorbitol or sucrose), sulfates (such as alkyl sulfates and alkyl ether sulfates), sulfonates (e.g., alkyl sulfonates, aryl sulfonates and alkylbenzene sulfonates), sulfonated polymers of naphthalene / formaldehyde, phosphate esters, protein hydrolysates, lignosulfite waste liquor and methyl cellulose, including but not limited to these. The reference to salts in this paragraph preferably refers to the respective alkali salts, alkaline earth salts, and ammonium salts.

[0096] Preferred surfactants are selected from ethoxylated poly(α-substituted) acrylate derivatives, polycondensates of alcohol with ethylene oxide and / or propylene oxide, polyoxyethylene fatty acid esters, alkylbenzene sulfonates, sulfonated polymers of naphthalene / formaldehyde, polyoxyethylene fatty acid esters such as ethoxylated castor oil, sodium lignosulfonate and arylphenol ethoxylate.

[0097] The amount of surfactant is typically in the range of 5 to 40% by weight, for example 10 to 20% by weight, of the formulation.

[0098] Further examples of suitable auxiliaries include water repellents, desiccants, binders (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 cephalins and lecithins and synthetic phospholipids, polyvinylpyrrolidone and tyrosin), thickeners and secondary thickeners (cellulose ethers, acrylic acid derivatives, xanthan gum, modified clays, such as products available under the name Bentone, and finely divided silica), stabilizers (e.g. low temperature stabilizers, preservatives (such as dichlorophen, benzyl alcohol hemiformal, 1,2-benzisothiazolin-3-one, 2-methyl-4-isothiazolin-3-one), antioxidants, light stabilizers, especially UV stabilizers, or other agents which improve chemical and / or physical stability), dyes or pigments (such as inorganic pigments, such as iron oxide, titanium oxide and Prussian blue; organic dyes, such as alizarin, azo and metal phthalocyanine dyes), defoamers (such as silicone defoamers and magnesium stearate), antifreeze agents, spreading agents, gibberellins and processing aids, mineral and vegetable oils, fragrances, waxes, nutrients (such as micronutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc), protective colloids, thixotropic substances, penetrants, sequestering agents and complexing agents.

[0099] The choice of auxiliaries is determined by the intended application form of the compounds of the invention and / or the physical properties of the compounds. Furthermore, the auxiliaries can be selected to provide the formulation with specific properties (technical, physical and / or physiological properties) or the use forms manufactured therefrom. By choosing the auxiliaries, the formulation can be customized for specific needs.

[0100] 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 / mites / nematodes on cultivated plants or in the protection of materials and that causes little damage to the plants being treated. Such amounts can vary widely and are determined by various factors such as the insect / mite / nematode species to be controlled, the cultivated plant or material being treated, the climatic conditions, and the specific compound of the present invention being used. Generally, the formulation according to the present invention contains from 0.01 to 99% by weight, preferably from 0.05 to 98% by weight, more preferably from 0.1 to 95% by weight, even more preferably from 0.5 to 90% by weight, and most preferably from 1 to 80% by weight of the compound of the present invention. One formulation can contain two or more compounds of the present invention. In such cases, the ranges outlined refer to the total amount of the compounds of the present invention.

[0101] The formulations of the present invention can be any conventional formulation type such as solutions (e.g., aqueous solutions), emulsions, water- and oil-based suspensions, powders (e.g., wettable powders, soluble powders), dusts, pastes, granules (e.g., soluble granules, spreading granules), suspoemulsion formulations, natural or synthetic articles impregnated with the compounds of the present invention, fertilizers, and microencapsulation in polymeric substances. The compounds of the present invention can exist in a suspended form, an emulsified form or a dissolved form. Examples of particularly preferred 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 (CS, ZC, etc.), pastes, troches, 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), insecticides (e.g., LN), and gel formulations (e.g., GW, GF) for the treatment of plant propagation materials such as seeds. These and other formulation types are defined by the Food and Agriculture Organization of the United Nations (FAO). A summary is available in "Catalogue of pesticide formulation types and international coding system", Technical Monograph No. 2, 6th Ed. May 2008, Croplife International.

[0102] Preferably, the formulations of the present invention are in one of the following types: EC, SC, FS, SE, OD, WG, WP, CS, more preferably one of EC, SC, OD, WG, CS.

[0103] Details of the types of formulations and examples of their preparation are provided below. When two or more compounds of the present invention are present, the amounts of the compounds of the present invention as outlined refer to the total amount of the compounds of the present invention. This applies mutatis mutandis to any further components of the formulation when two or more representatives of such components, e.g., wetting agents, binders, are present.

[0104] i) Water-soluble concentrates (SL, LS) Dissolve at least one compound of the present invention in an amount of 10 - 60% by weight and a surfactant (for example, a polycondensate of ethylene oxide and / or propylene oxide and an alcohol) in an amount of 5 - 15% by weight in water and / or a water-soluble solvent (for example, an alcohol such as propylene glycol or a carbonate ester such as propylene carbonate) in such an amount that the total amount is 100% by weight. Dilute the concentrate with water before application.

[0105] ii) Dispersible concentrate (DC) Dissolve at least one compound of the present invention in an amount of 5 - 25% by weight and a surfactant and / or binder (for example, polyvinylpyrrolidone) in an amount of 1 - 10% by weight in an organic solvent (for example, cyclohexanone) in such an amount that the total amount is 100% by weight. Dilute with water to obtain a dispersion.

[0106] iii) Emulsifiable concentrate (EC) Dissolve at least one compound of the present invention in an amount of 15 - 70% by weight and a surfactant (for example, a mixture of calcium dodecylbenzenesulfonate and castor oil ethoxylate) in an amount of 5 - 10% by weight in a water-insoluble organic solvent (for example, an aromatic hydrocarbon or a fatty acid amide) and, if necessary, an additional water-soluble solvent in such an amount that the total amount is 100% by weight. Dilute with water to obtain an emulsion.

[0107] iv) Emulsion (EW, EO, ES) Dissolve at least one compound of the present invention in an amount of 5 - 40% by weight and a surfactant (for example, a mixture of calcium dodecylbenzenesulfonate and castor oil ethoxylate, or a polycondensate of ethylene oxide and / or propylene oxide with or without alcohol) in an amount of 1 - 10% by weight in a water-insoluble organic solvent (for example, an aromatic hydrocarbon) in an amount of 20 - 40% by weight. Add this mixture to water in such an amount that the total amount is 100% by weight by means of an emulsifier. The resulting formulation is a homogeneous emulsion. The emulsion can be further diluted with water before application.

[0108] v) Suspension and suspension formulation v - 1) Aqueous system (SC, FS) In a suitable grinding device, such as a stirred ball mill, 20 to 60% by weight of at least one compound of the present invention is added with 2 to 10% by weight of a surfactant (e.g., sodium lignosulfonate and polyoxyethylene fatty alcohol ether), 0.1 to 2% by weight of a thickener (e.g., xanthan gum) and water, and ground to obtain a fine active substance suspension. The water is added in an amount such that the total amount is 100% by weight. By diluting with water, a stable suspension of the active substance is obtained. In the case of FS-type formulations, up to 40% by weight of a binder (e.g., polyvinyl alcohol) is added.

[0109] v-2) Oil-based (OD, OF) In a suitable grinding device, such as a stirred ball mill, 20 to 60% by weight of at least one compound of the present invention is added with 2 to 10% by weight of a surfactant (e.g., sodium lignosulfonate and polyoxyethylene fatty alcohol ether), 0.1 to 2% by weight of a thickener (e.g., modified clay, especially Bentone, or silica) and an organic carrier, and ground to obtain a fine active substance oil suspension. The organic carrier is added in an amount such that the total amount is 100% by weight. Diluting with water gives a stable dispersion of the active substance.

[0110] vi) Granular wettable powders and water-soluble granules (WG, SG) 1 to 90% by weight, preferably 20 to 80% by weight, most preferably 50 to 80% by weight of at least one compound of the present invention is added with a surfactant (e.g., sodium lignosulfonate and sodium alkylnaphthalenesulfonate) and potentially a carrier material, finely ground, and converted into a granular wettable powder or a water-soluble granule by typical technical equipment such as extrusion, spray drying, fluidized bed granulation, etc. The surfactant and the carrier material are used in amounts such that the total amount is 100% by weight. Diluting with water gives a stable dispersion or solution of the active substance.

[0111] vii) Wettable powders and water-soluble solvents (WP, SP, WS) 50 to 80% by weight of at least one compound of the present invention is added with 1 to 20% by weight of a surfactant (for example, sodium lignosulfonate, sodium alkylnaphthylsulfonate) and an amount of a solid carrier such as silica gel such that the total amount is 100% by weight, and pulverized with a rotor-stator mill. Dilute with water to obtain a stable dispersion or solution of the active substance.

[0112] viii) Gel (GW, GF) In a stirred ball mill, 5 to 25% by weight of at least one compound of the present invention is added with 3 to 10% by weight of a surfactant (for example, sodium lignosulfonate), 1 to 5% by weight of a binder (for example, carboxymethyl cellulose) and an amount of water such that the total amount is 100% by weight, and pulverized. Thereby, a fine suspension of the active substance is obtained. Dilute with water to obtain a stable suspension of the active substance.

[0113] ix) Microemulsion (ME) 5 to 20% by weight of at least one compound of the present invention is added to 5 to 30% by weight of an organic solvent mixture (for example, fatty acid dimethylamide and cyclohexanone), 10 to 25% by weight of a surfactant mixture (for example, polyoxyethylene fatty alcohol ether and arylphenol ethoxylate), and an amount of water such that the total amount is 100% by weight. By stirring this mixture for 1 hour, a thermodynamically stable microemulsion is spontaneously formed.

[0114] x) Microcapsule (CS) An oil phase containing 5 to 50% by weight of at least one compound of the present invention, 0 to 40% by weight of a water-insoluble organic solvent (e.g., aromatic hydrocarbon), and 2 to 15% by weight of an acrylic monomer (e.g., methyl methacrylate, methacrylic acid, and di- or triacrylate) is dispersed in an aqueous solution of a protective colloid (e.g., polyvinyl alcohol). Poly(meth)acrylate microcapsules are formed by radical polymerization initiated by a radical initiator. Alternatively, an oil phase containing 5 to 50% by weight of at least one compound of the present invention, 0 to 40% by weight of a water-insoluble organic solvent (e.g., aromatic hydrocarbon), and an isocyanate monomer (e.g., diphenylmethane-4,4'-diisocyanate) is dispersed in an aqueous solution of a protective colloid (e.g., polyvinyl alcohol), thereby forming polyurea microcapsules. Optionally, the addition of a polyamine (e.g., hexamethylenediamine) is also used to form polyurea microcapsules. The monomer is 1 to 10% by weight of the total amount of the CS formulation.

[0115] xi) Dustable powder (DP, DS) At least one compound of the present invention in an amount of 1 to 10% by weight is finely pulverized and thoroughly admixed with a solid carrier, such as finely pulverized kaolin, in such an amount that the total amount is 100% by weight.

[0116] xii) Granules (GR, FG) At least one compound of the present invention in an amount of 0.5 to 30% by weight is finely pulverized and combined with a solid carrier (e.g., silicate) in such an amount that the total amount is 100% by weight.

[0117] xiii) Ultra-low volume liquid (UL) At least one compound of the present invention in an amount of 1 to 50% by weight is dissolved in an organic solvent, such as aromatic hydrocarbon, in such an amount that the total amount is 100% by weight.

[0118] The formulations of types i) to xiii) may optionally further contain auxiliary agents, such as 0.1 to 1% by weight of a preservative, 0.1 to 1% by weight of an antifoaming agent, 0.1 to 1% by weight of a dye and / or pigment, and 5 to 10% by weight of an antifreeze.

[0119] mixture The compounds of formula (I) can be used, for example, in combination with one or more suitable fungicides, bactericides, acaricides, molluscicides, nematicides, insecticides, microbicides, beneficial species, herbicides, fertilizers, bird repellents, phytotonics, sterilants, agents for reducing phytotoxicity, semiochemicals and / or plant growth regulators, in order to, for example, broaden the spectrum of action, extend the duration of action, increase the rate of action, prevent repulsion, or prevent the development of resistance. Furthermore, such combinations of active compounds can improve the growth of plants and / or improve the tolerance to abiotic factors (such as high or low temperature), tolerance to waterlogging or increased salt content in water or soil. Furthermore, it is also possible to improve the flowering and fruiting performance, optimize the germination ability and root development, facilitate harvesting, increase the yield, influence ripening, improve the quality and / or nutritional value of the harvested product, increase the shelf life of the harvested product, and / or improve the processability of the harvested product.

[0120] Furthermore, the compounds of formula (I) can be present in a mixture with another active compound or semiochemical (such as an attractant and / or a bird repellent and / or a plant activator and / or a growth regulator and / or a fertilizer). Similarly, it is also possible to improve the properties of plants (such as growth, yield and quality of the harvest) using the compounds of formula (I).

[0121] In certain embodiments according to the invention, the compounds of formula (I) are present in a formulation or in a use form prepared from such a formulation, in admixture with further compounds (preferably the compounds described below).

[0122] If one of the compounds described below can exist in various tautomeric forms, those forms are also included even if not explicitly mentioned in each case. Furthermore, all named counteragents may form salts with suitable bases or acids, if possible, depending on their functional groups.

[0123] Insecticide / acaricide / nematicide The active compounds specified by their common names in this specification are known and are described, for example, in the Pesticide Manual (″The Pesticide Manual″ 16th Ed., British Crop Protection Council 2012) or can be found on the Internet (for example, at 「http: / / www.alanwood.net / pesticides」). The classification is based on the IRAC Mode of Action Classification Scheme as of the filing date of this patent application.

[0124] (1) An acetylcholinesterase (AChE) inhibitor, preferably a carbamate selected from aldicarb, aldicarb sulfoxide, benfuracarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, methomyl, methomyl, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb, XMC, and xylylcarb; or an organophosphate selected from acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, kasugamycin, chlorfenvinphos, chlorfenvinphos, chlorpyrifos-methyl, coumaphos, cyanophos, dimethoate-S-methyl, diazinon, dichlorvos / DDVP, dichlorvos, 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, quinolphos, sulfotepp, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thimet, triazophos, trichlorfon, and vamidothion.

[0125] (2) A GABA-dependent chloride channel blocker, preferably a cyclodiene organochlorine selected from chlordane and endosulfan; or a phenylpyrazole (fipronil) selected from ethiprole and fipronil.

[0126] (3) Sodium channel regulators, preferably acrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin s-cyclopentenyl isomer, 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, monofluoroethrin, permethrin, cyphenothrin [(1R)-trans isomer], prallethrin, pyrethrins (pyrethrum), resmethrin, silafluofen, tefluthrin, tetramethrin, tetramethrin [(1R) isomer], tralomethrin, and transfluthrin; or, DDT; or, pyrethroids selected from methoxychlor.

[0127] (4) Nicotinic acetylcholine receptor (nAChR) competitive regulators, preferably acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam; or, neonicotinoids selected from nicotine; or, sulfoximines selected from sulfoxaflor; or butenolides selected from flupyradifurone; or mesoionic compounds selected from triflumizopyrim.

[0128] (5) Nicotinic acetylcholine receptor (nAChR) allosteric regulators (site I), preferably spinosins selected from spinetoram and spinosad.

[0129] (6) Glutamate-dependent chloride channel (GluCl) allosteric regulators, preferably abamectins / milbemycins selected from abamectin, emamectin benzoate, lepimectin, and milbemectin.

[0130] (7) Juvenile hormone mimics, preferably juvenile hormone analogs selected from hydroprene, kinoprene, and methoprene or fenoxycarb or pyriproxyfen.

[0131] (8) Various non-specific (multi-site) inhibitors, preferably alkyl halide-based selected from methyl bromide and another alkyl halide or chloropicrin or sulfuryl fluoride or borax or tartar emetic, or methyl isocyanate generators selected from dazomet and metam.

[0132] (9) Chordotonal organ TRPV channel regulators, preferably pyridine azomethanes selected from pimetrozine and pyrifluquinazone, or pyropenes selected from afidopyropen.

[0133] (10) Mite growth inhibitors that affect CHS1, selected from clofentezine, hexythiazox, diflovidazin, and etoxazole.

[0134] (11) A microbial disruptor of the insect midgut selected from Bacillus thuringiensis subspecies israelensis, Bacillus sphaericus, Bacillus thuringiensis subspecies aizawai, Bacillus thuringiensis subspecies kurstaki, Bacillus thuringiensis subspecies tenebrionis, and a Bt plant protein selected from Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb, and Cry34 / 35Ab1.

[0135] (12) An inhibitor of mitochondrial ATP synthase, preferably an ATP disruptor selected from diafenthiuron, or an organotin compound selected from azocyclotin, cyhexatin, and fenbutatin oxide or propargite or tetradifon.

[0136] (13) An uncoupler of oxidative phosphorylation by proton gradient disruption selected from chlorfenapyr, DNOC, and sulfuryl fluoride.

[0137] (14) A nicotinic acetylcholine receptor channel blocker selected from bensultap, cartap hydrochloride, thiram, and thiosultap-sodium.

[0138] (15) An inhibitor of chitin biosynthesis that affects CHS1, preferably benzoyl ureas selected from bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, and triflumuron.

[0139] (16) An inhibitor of chitin biosynthesis selected from buprofezin, type 1.

[0140] (17) A molting disruptor selected from silafluofen (especially in the case of Diptera, i.e., two-winged flies).

[0141] (18) An ecdysone receptor agonist, preferably diacylhydrazines selected from chromafenozide, halofenozide, methoxyfenozide, and tebufenozide.

[0142] (19) An octopamine receptor agonist selected from amitraz.

[0143] (20) A mitochondrial complex III electron transport inhibitor selected from hydramethylnon, acequinocyl, fluacrypyrim, and bifenazate.

[0144] (21) A mitochondrial complex I electron transport inhibitor, preferably a METI acaricide and insecticide selected from phenazakine, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, and tolfenpyrad or rotenone (Derris).

[0145] (22) A voltage-dependent sodium channel blocker, preferably oxadiazines selected from indoxacarb, or semicarbazones selected from metaflumizone.

[0146] (23) An inhibitor of acetyl-CoA carboxylase, preferably tetronic acid derivatives and tetramic acid derivatives selected from spirodiclofen, spirotetramat, spirodiclofen, and spirotetramat.

[0147] (24) A mitochondrial complex IV electron transport inhibitor, preferably phosphides selected from aluminum phosphide, calcium phosphide, phosphine, and zinc phosphide; or cyanides selected from calcium cyanide, potassium cyanide, and sodium cyanide.

[0148] (25) An inhibitor of mitochondrial complex II electron transfer, preferably a β-ketonitrile derivative selected from cyenopyrafen and siflumetofen, or carboxyanilides selected from piflubumide.

[0149] (28) A ryanodine receptor regulator, preferably diamides selected from chlorantraniliprole, cyantraniliprole, cyclaniliprole, flubendiamide and tetraniliprole.

[0150] (29) A chordotonal organ regulator (target site undefined) selected from flonicamid.

[0151] (30) A GABA-dependent chloride channel allosteric regulator, preferably metadiamides selected from broflanilide, or isoxazoles selected from flumetramide.

[0152] (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.

[0153] (32) A nicotinic acetylcholine receptor allosteric regulator (site II) selected from GS-omega / kappa HXTX-Hv1a peptide.

[0154] (33) Acinonapil, afoxolaner, azadirachtin, bendrothiazone, benzoximate, benzpyramoxan, bromopropylate, chinomethionat, chloroprallethrin, cryolite, cyclobutriflum or cyclobutrifen (CAS1460292-16-3), cycloxaprid, cyetpyrafen, cyhalodiamide, dichloromezothiaz, dicofol, dimetridazole, ε-methofluthrin, ε-momfluorothrin, flometokine, fluaazindrine, fluenesulfone, flufenoxuron, flufenoxystrobin, flufiprole, fluhexafon, fluopyram, flupyrimin, fluralaner, fufenozide, fupenthiopheneox (CAS1472050-04-6), guazipyr, heptafluthrin, imidaclothiz, iprodione, isocycloseram, κ-bifenthrin, κ-tefluthrin, lotilaner, meperfluthrin, oxazosulfyl, Paichongding, pyridalyl, pyrifluquinazone, pyriminostrobin, sarolaner, spirobudiclofen, tetramethylfluthrin, tetrachlorantraniliprole, thigolaner, thioxazafen, thiofluoximate, thiclorpyrazoflor, iodomethane, triflupentoxide (CAS1472050-04-6); and further, preparations based on Bacillus firmus (I-1582, Votivo) and azadirachtin (BioNeem), and further, the following compounds: 1-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)sulfinyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-Triazole-5-amine (known from WO2006 / 043635) (CAS885026-50-6), 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) (CAS872999-66-1), 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]deca-3-en-2-one (known from WO2010052161) (CAS1225292-17-0), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-2-oxo-1,8-diazaspiro[4.5]deca-3-en-4-yl ethyl carbonate (known from EP2647626) (CAS-1440516-42-6), PF1364 (known from JP2010 / 018586) (CAS1204776-60-2), (3E)-3-[1-[(6-chloro-3-pyridyl)methyl]-2-pyridylidene]-1,1,1-trifluoropropan-2-one (known from WO2013 / 144213) (CAS1461743-15-6), N-[3-(benzylcarbamoyl)-4-chlorophenyl]-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide (known from WO2010 / 051926) (CAS1226889-14-0), 5-bromo-4-chloro-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloro-2-pyridyl)pyrazole-3-carboxamide (known from CN103232431) (CAS1449220-44-3), 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxide-3-thietanyl)-benzamide, 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(trans-1-oxide-3-thietanyl)-benzamide and 4-[(5S)-5-(3,5-dichlorophenyl)-4,5-Dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxide-3-thietanyl)benzamide (known from WO2013 / 050317A1) (CAS1332628-83-7), 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 WO2013 / 162715A2, WO2013 / 162716A2, US2014 / 0213448A1) (CAS1477923-37-7), 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 CN101337937A) (CAS1105672-77-2), 3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)thiomethyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide, (Liudaibenjiaxuanan, known from CN103109816A) (CAS1232543-85-9); N-[4-chloro-2-[[(1,1-dimethylethyl)amino]carbonyl]-6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-(fluoromethoxy)-1H-pyrazole-5-carboxamide (known from WO2012 / 034403A1) (CAS1268277-22-0), 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 (known from WO2011 / 085575A1) (CAS1233882-22-8), 4-[3-[2,6-dichloro-4-[(3,3-(dichloropropen-1-yloxy)phenoxy]propoxy]-2-methoxy-6-(trifluoromethyl)-pyrimidine (known from CN101337940A) (CAS 1108184-52-6); (2E)- and 2(Z)-2-[2-(4-cyanophenyl)-1-[3-(trifluoromethyl)phenyl]ethylidene]-N-[4-(difluoromethoxy)phenyl]-hydrazinecarboxamide (known from CN101715774A) (CAS 1232543-85-9); 3-(2,2-dichloroethenyl)-2,2-dimethyl-4-(1H-benzimidazol-2-yl)phenyl-cyclopropanecarboxylic acid ester (known from CN103524422A) (CAS 1542271-46-4); (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-[(trifluoromethyl)thio]phenyl]amino]carbonyl]-indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylic acid methyl ester (known from CN102391261A) (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 (known from US2014 / 0275503A1) (CAS1181213-14-8); 8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (CAS1253850-56-4), (8-anti)-8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (CAS933798-27-7), (8-syn)-8-(2-cyclopropylmethoxy-4-trifluoromethylphenoxy)-3-(6-trifluoromethylpyridazin-3-yl)-3-azabicyclo[3.2.1]octane (known from WO2007040280A1, WO2007040282A1) (CAS934001-66-8), N-[4-(aminothioxomethyl)-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide (known from CN 103265527A) (CAS1452877-50-7), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-1,8-diazaspiro[4.5]decan-2,4-dione (known from WO2014 / 187846A1) (CAS1638765-58-8), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-2-oxo-1,8-diazaspiro[4.5]deca-3-en-4-yl-ethyl carbonate (known from WO2010 / 066780A1, WO2011151146A1) (CAS1229023-00-0), N-[1-(2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-(trifluoromethyl)benzamide (known from WO2014 / 053450A1) (CAS1594624-87-9), N-[2-(2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2-(trifluoromethyl)benzamide (known from WO2014 / 053450A1) (CAS1594637-65-6), N-[1-(3,5-Difluoro-2-pyridinyl)-1H-pyrazol-3-yl]-2-(trifluoromethyl)benzamide (known from WO2014 / 053450A1) (CAS1594626-19-3).

[0155] Fungicide The active ingredients specified by the general name in this specification are known and described, for example, in the Pesticide Manual (16th Ed. British Crop Protection Council), or can be searched on the Internet (for example, www.alanwood.net / pesticides ).

[0156] All the listed fungicide mixing partners in classifications (1) to (15) can optionally form salts with suitable bases or acids, if possible by their functional groups. All the listed mixing partners in classifications (1) to (15) can include tautomers, where applicable.

[0157] 1) Inhibitors of ergosterol biosynthesis, for example, (1.001) cyproconazole, (1.002) difenoconazole, (1.003) epoxiconazole, (1.004) fenhexamid, (1.005) fenpropin, (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, (1.031) (2S)-2-(1-chlorocyclopropyl)-4-[(1R)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.(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)oxolan-2-yl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.040)1-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxolan-2-yl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.041)1-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxolan-2-yl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.042)2-[(2R,4R,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.043) 2-[(2R,4R,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.044) 2-[(2R,4S,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.045) 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) mefenoxazole, (1.056) 2-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-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)oxiran-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)oxiran-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-(allylsulfanyl)-1-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole, (1.061) 5-(allylsulfanyl)-1-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole, (1.062) 5-(allylsulfanyl)-1-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole, (1.063) N′-(2,5-dimethyl-4-{[3-(1,1,2,2-tetrafluoroethoxy)phenyl]sulfanyl}phenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.064) N′-(2,5-dimethyl-4-{[3-(2,2,2-trifluoroethoxy)phenyl]sulfanyl}phenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.065) N′-(2,5-Dimethyl-4-{[3-(2,2,3,3-tetrafluoropropoxy)phenyl]sulfanyl}phenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.066) N′-(2,5-Dimethyl-4-{[3-(pentafluoroethoxy)phenyl]sulfanyl}phenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.067) N′-(2,5-Dimethyl-4-{3-[(1,1,2,2-tetrafluoroethyl)sulfanyl]phenoxy}phenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.068) N′-(2,5-Dimethyl-4-{3-[(2,2,2-trifluoroethyl)sulfanyl]phenoxy}phenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.069) N′-(2,5-Dimethyl-4-{3-[(2,2,3,3-tetrafluoropropyl)sulfanyl]phenoxy}phenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.070) N′-(2,5-Dimethyl-4-{3-[(pentafluoroethyl)sulfanyl]phenoxy}phenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.071) N′-(2,5-Dimethyl-4-phenoxyphenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.072) N′-(4-{[3-(difluoromethoxy)phenyl]sulfanyl}-2,5-dimethylphenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.073) N′-(4-{3-[(difluoromethyl)sulfanyl]phenoxy}-2,5-dimethylphenyl)-N-ethyl-N-methylimidohydroxamic acid amide, (1.074) N′-[5-Bromo-6-(2,3-dihydro-1H-inden-2-yloxy)-2-methylpyridin-3-yl]-N-ethyl-N-methylimidohydroxamic acid amide, (1.075) N′-{4-[(4,5-Dichloro-1,3-thiazol-2-yl)oxy]-2,5-dimethylphenyl}-N-ethyl-N-methylimidohydroxamic acid amide, (1.076) N′-{5-Bromo-6-[(1R)-1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylimidohydroxamic acid amide, (1.(1.077) N′-{5-bromo-6-[(1S)-1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylimidohydroxamic acid amide, (1.078) N′-{5-bromo-6-[(cis-4-isopropylcyclohexyl)oxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylimidohydroxamic acid amide, (1.079) N′-{5-bromo-6-[(trans-4-isopropylcyclohexyl)oxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylimidohydroxamic acid amide, (1.080) N′-{5-bromo-6-[1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylimidohydroxamic acid amide. (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-fluoro-phenyl)-2-hydroxy-propyl]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.

[0158] 2) Inhibitors of the respiratory chain in Complex I or Complex II, for example, (2.001) benzovindiflupyr, (2.002) bixafen, (2.003) boscalid, (2.004) carboxin, (2.005) fluopyram, (2.006) flutolanil, (2.007) fluxapyroxad, (2.008) flutriafol, (2.009) isofetamid, (2.010) isopyrazam (anti-epimeric enantiomer 1R,4S,9S), (2.011) isopyrazam (anti-epimeric enantiomer 1S,4R,9R), (2.012) isopyrazam (anti-epimeric racemate 1RS,4SR,9SR), (2.013) isopyrazam (mixture of syn-epimeric racemate (1RS,4SR,9RS) and anti-epimeric racemate (1RS,4SR,9SR)), (2.014) isopyrazam (syn-epimeric enantiomer 1R,4S,9R), (2.015) isopyrazam (syn-epimeric enantiomer 1S,4R,9S), (2.016) isopyrazam (syn-epimeric racemate 1RS,4SR,9RS), (2.017) penthiopyrad, (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, (2.028) Imidacloprid, (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-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.040) N-[(1S,4R)-9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-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-carbothioamide, (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.(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) Pyrapropion.

[0159] 3) Inhibitors of the respiratory chain in complex III, for example, (3.001) ametoctradin, (3.002) amisulbrom, (3.003) azoxystrobin, (3.004) coumethoxystrobin, (3.005) cumoxystrobin, (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-phenylvinyl]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, (3.029) methyl {5-[3-(2,4-dimethylphenyl)-1H-pyrazol-1-yl]-2-methylbenzyl}carbamate, (3.030) methyltetraprole, (3.031) florpicoxamid.

[0160] 4) Inhibitors of mitosis and cell division, for example, (4.001) carbendazim, (4.002) diethofencarb, (4.003) ethaboxam, (4.004) fluopicolide, (4.005) penthiocarb, (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-pyrazole-5-amine, (4.013) 4-(2-bromo-4-fluorophenyl)-N-(2-bromo-6-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (4.014) 4-(2-bromo-4-fluorophenyl)-N-(2-bromophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (4.015) 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (4.016) 4-(2-bromo-4-fluorophenyl)-N-(2-chlorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (4.017) 4-(2-bromo-4-fluorophenyl)-N-(2-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (4.018) 4-(2-chloro-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (4.019) 4-(2-chloro-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (4.020) 4-(2-chloro-4-fluorophenyl)-N-(2-chlorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (4.021) 4-(2-chloro-4-fluorophenyl)-N-(2-fluorophenyl)-1,3-dimethyl-1H-pyrazole-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-pyrazole-5-amine, (4.024) N-(2-bromophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine, (4.025) N-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine.

[0161] 5) Compounds that can have multi-site effects, for example, (5.001) Bordeaux mixture, (5.002) captan, (5.003) captan, (5.004) chlorothalonil, (5.005) copper hydroxide, (5.006) copper naphthenate, (5.007) copper oxide, (5.008) basic copper chloride, (5.009) copper sulfate (2+), (5.010) dithianon, (5.011) dodine, (5.012) folpet, (5.013) maneb, (5.014) mancozeb, (5.015) metiram, (5.016) metiram zinc, (5.017) copper oxine, (5.018) propineb, (5.019) sulfur and sulfur agents, for example, calcium polysulfide, (5.020) thiuram, (5.021) dinneb, (5.022) dithiram, (5.023) 6-ethyl-5,7-dioxo-6,7-dihydro-5H-pyrrolo[3′,4′:5,6][1,4]dithieno[2,3-c][1,2]thiazole-3-carbonitrile.

[0162] 6) Compounds that can induce host defense, for example, (6.001) acibenzolar-S-methyl, (6.002) isothianyl, (6.003) probenazole, (6.004) thiazinyl.

[0163] 7) Inhibitors of the biosynthesis of amino acids and / or proteins, for example, (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.

[0164] 8) ATP production inhibitors, for example, (8.001) Silthiopham.

[0165] 9) Inhibitors of cell wall synthesis, for example, (9.001) Benalaxyl-M, (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.

[0166] 10) Inhibitors of lipid and membrane synthesis, for example, (10.001) Propamocarb, (10.002) Propamocarb hydrochloride, (10.003) Tolfenpyrad-methyl.

[0167] 11) Inhibitors of melanin biosynthesis, for example, (11.001) Tricyclazole, (11.002) 2,2,2-Trifluoroethyl {3-methyl-1-[(4-methylbenzoyl)amino]butan-2-yl}carbamate.

[0168] 12) Inhibitors of nucleic acid synthesis, for example, (12.001) Benalaxyl, (12.002) Benalaxyl-M (Kiralaxyl), (12.003) Metalaxyl, (12.004) Metalaxyl-M (Mefenoxam).

[0169] 13) Inhibitors of signal transduction, for example, (13.001) Fluazinam, (13.002) Iprodione, (13.003) Procymidone, (13.004) Proquinazid, (13.005) Quinoxyphen, (13.006) Vinclozolin.

[0170] 14) Compounds that can act as uncoupling agents, for example, (14.001) Fluazinam, (14.002) Mepyldinocap.

[0171] (15)(15.001) Abscisic acid, (15.002) Benziothiazole, (15.003) Benzoxazine, (15.004) Capsimycin, (15.005) Carboxylic, (15.006) Quinomethionate, (15.007) Kufraneb, (15.008) Ciflufenamide, (15.009) Simoxanil, (15.010) Cyprosulfamide, (15.011) Flutianil, (15.012) Phosphorous acid aluminum salt, (15.013) Phosphorous acid calcium salt, (15.014) Phosphorous acid sodium salt, (15.015) Methyl isothiocyanate, (15.016) Metrafenone, (15.017) Mildiomycin, (15.018) Natamycin, (15.019) Nickel dimethyldithiocarbamate, (15.020) Nitrotal-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) Tebufenozide, (15.029) Techlofthalam, (15.030) Tolfenpyrad, (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) Diphenamidone, (15.(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) Chinopharmine, (15.048) 4-Amino-5-fluoropyrimidin-2-ol (tautomer: 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-sulfonohydrazide, (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) But-3-yn-1-yl {6-[({[(Z)-(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]pyridin-2-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}carbamic acid tert-butyl, (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-methylimidohydroxyformamide), (15.065) (N′-(2-chloro-5-methyl-4-phenoxyphenyl)-N-ethyl-N-methylimidohydroxyformamide), (15.(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-carbonimidoyl]-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-benzamide, (15.084) N-[(Z)-N-methoxy-C-methyl-carbonimidoyl]-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]-benzenecarbothioamide, (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-trifluoro-propanamide, (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.A further fungicide selected from the group consisting of N-{2,3-difluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl}butanamide.

[0172] Biopesticide as a mixed component The compound of formula (I) can be combined with a biopesticide.

[0173] Biopesticides include, in particular, bacteria, fungi, yeasts, plant extracts and products formed by microorganisms (for example, proteins or secondary metabolites).

[0174] Biopesticides include bacteria, for example, spore-forming bacteria, bacteria that colonize roots and bacteria that act as biological insecticides, fungicides or nematicides.

[0175] Examples of such bacteria that are used or can be used as biopesticides are the following: Bacillus amyloliquefaciens strain FZB42 (DSM 231179), or Bacillus cereus, in particular, Bacillus cereus strain CNCM I-1562, or Bacillus firmus strain I-1582 (deposit number CNCM I-1582), or Bacillus pumilus, in particular, strain GB34 (deposit number ATCC 700814) and strain QST2808 (deposit number NRRL B-30087), or Bacillus subtilis, in particular, strain GB03 (deposit number ATCC SD-1397), or Bacillus subtilis strain QST713 (deposit number NRRL B-21661), or Bacillus subtilis strain OST 30002 (deposit number NRRL B-50421), Bacillus thuringiensis, in particular, Bacillus thuringiensis subspecies israelensis (serotype H-14) strain AM65-52 (deposit 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 No. ATCC SD-5834), Streptomyces microflavus strain AQ6121 (= QRD 31.013, NRRL B-50550), Streptomyces galbus strain AQ 6047 (Accession No. NRRL 30232).

[0176] Examples of fungi and yeasts that are used or can be used as biopesticides are as follows. Beauveria bassiana, in particular strain ATCC 74040, Coniothyrium minitans, in particular strain CON / M / 91-8 (deposit number DSM-9660), Lecanicillium spp., in particular strain HRO LEC 12, Lecanicillium lecanii (formerly known as Verticillium lecanii), in particular strain KV01, Metarhizium anisopliae, in particular strain F52 (DSM3884 / ATCC 90448), Metschnikowia fructicola, in particular strain NRRL Y-30752, Paecilomyces fumosoroseus (currently: Isaria fumosorosea), in particular strain IFPC 200613 or strain Apopka 97 (deposit number ATCC 20874), Paecilomyces lilacinus, in particular Paecilomyces lilacinus strain 251 (AGAL 89 / 030550), Talaromyces flavus, in particular strain V117b, Trichoderma atroviride, in particular strain SC1 (deposit number CBS 122089), Trichoderma harzianum, in particular Trichoderma harzianum rifai T39 (deposit number CNCM I-952).

[0177] Examples of viruses that are used or can be used as biopesticides are as follows: Apple codling moth (Adoxophyes orana) granulosis virus (GV), codling moth (Cydia pomonella) granulosis virus (GV), cotton bollworm (Helicoverpa armigera) nuclear polyhedrosis virus (NPV), beet armyworm (Spodoptera exigua) mNPV, fall armyworm (Spodoptera frugiperda) mNPV, African cotton leafworm (Spodoptera littoralis) NPV.

[0178] Bacteria and fungi that are added as "inoculum sources" to plants or plant parts or plant organs and that enhance plant growth and plant health by virtue of their specific properties are also included. Examples that can be cited are as follows. Species of the genus Agrobacterium, Azorhizobium caulinodans, species of the genus Azospirillum, species of the genus Azotobacter, species of the genus Bradyrhizobium, species of the genus Burkholderia, in particular Burkholderia cepacia (formerly known as Pseudomonas cepacia), species of the genus Gigaspora or Gigaspora monosporum, species of the genus Glomus, species of the genus Laccaria, Lactobacillus buchneri, species of the genus Paraglomus, Pisolithus tinctorus, species of the genus Pseudomonas, species of the genus Rhizobium, in particular Rhizobium trifolii, species of the genus Rhizopogon, species of the genus Scleroderma, species of the genus Suillus, Streptomyces spp.

[0179] Examples of products formed by plant extracts and microorganisms (which include proteins and secondary metabolites) that are used or can be used as biopesticides are as follows: Garlic (Allium sativum), Wormwood (Artemisia absinthium), Azadirachtin, Biokeeper WP, Cassia nigricans, Celastrus angulatus, Chenopodium anthelminticum, Chitin, Armour-Zen, Male Fern (Dryopteris filix-mas), Horsetail (Equisetum arvense), Fortune Aza, Fungastop, Heads Up (Chenopodium quinoa saponin extract), Pyrethrum / Pyrethrins, Quassia amara, Quercus, Quillaja, Regalia, (Requiem (trademark) Insecticide), Rotenone, Ryania / Ryanodine, Comfrey (Symphytum officinale), Tansy (Tanacetum vulgare), Thymol, Triact 70, TriCon, Nasturtium (Tropaeulum majus), Stinging Nettle (Urtica dioica), Veratrin, Mistletoe (Viscum album), Brassicaceae extract, in particular, rapeseed powder or mustard powder, and biopesticide / acaricide active substances obtained from olive oil, in particular, for example, unsaturated fats / carboxylic acids having a carbon chain length C 16 -C 20 having.

[0180] Phytotoxicity reducing agent as a mixed component The compound of formula (I) can be combined with phytotoxicity reducing agents, for example, benoxacor, cloquintocet (-mexyl), cimetrinil, cyprosulfamide, dichloramide, fenchlorazole (-ethyl), fenclorim, flurazole, flutriafol, furilazole, isoxadifen (-ethyl), mefenpyr (-diethyl), phthalic 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).

[0181] Plants and parts of plants According to the present invention, all plants and plant parts can be treated. Here, plants include all plants and plant parts such as desirable and undesirable wild plants or crop plants (including naturally occurring crop plants), for example, cereals (wheat, rice, triticale, barley, rye, oats), maize, soybeans, potatoes, sugar beets, sugarcane, tomatoes, peppers, cucumbers, melons, carrots, watermelons, onions, lettuce, spinach, leeks, kidney beans, plants of the genus Brassica (Brassica oleracea) (e.g., cabbages) and other vegetable species, cotton, tobacco, rapeseed, and furthermore, fruit plants (fruits include apples, pears, citrus fruits, and grapes), etc. Crop plants can be plants obtained by conventional breeding methods and optimization methods, or plants obtained by biotechnology methods and genetic engineering methods, or plants obtained by a combination of these methods. Such crop plants include transgenic plants, and also plant varieties that can be protected by variety property rights or plant varieties that cannot be protected. Plants should be understood to mean all growth stages, for example, from seeds, seedlings, young plants (immature plants) to mature plants. Plant parts should be understood to mean all parts and organs of the above-ground and underground parts of plants such as shoots, leaves, flowers, and roots, and examples include leaves, needles, stems, trunks, flowers, fruiting bodies, fruits, and seeds, and furthermore, tubers, roots, and rhizomes, etc. Plant parts also include harvested plants or harvested plant parts, as well as vegetative propagation material and generative propagation material, for example, seedlings, tubers, rhizomes, cuttings, and seeds, etc.

[0182] The treatment according to the invention of plants and plant parts with the compounds of formula (I) can be carried out directly by customary treatment methods, for example by dipping, spraying, vaporizing, fogging, scattering, coating, injecting, etc., or by allowing the compounds to act on the surroundings, habitat or storage space of the plants and plant parts, and in the case of propagation material, in particular seeds, also by applying one or more coatings.

[0183] As already stated above, according to the invention all plants and parts thereof can be treated. In a preferred embodiment, wild plant species and plant varieties, or plant species and plant varieties obtained by customary methods of plant breeding such as crossing or protoplast fusion, and parts thereof are treated. In a further particularly preferred embodiment, transgenic plants and plant varieties (genetically modified organisms) obtained by genetic engineering methods in combination with customary methods where appropriate and parts thereof are treated. The terms "parts" or "parts of plants" or "plant parts" have already been explained above. The invention is particularly preferably used for treating individual commercially available customary varieties or plants of customary varieties in use. A plant variety should be understood to mean a plant having new properties ("traits") obtained by customary breeding or mutagenesis or recombinant DNA techniques. They can be varieties, variants, biotypes or genotypes.

[0184] Transgenic plants, seed treatment and integration events According to the present invention, the compounds of formula (I) can advantageously be used for treating transgenic plants, plant cultivars or plant parts which have received genetic material conferring advantageous and / or useful traits (characteristics) to these plants, plant cultivars or plant parts. Thus, the present invention is considered to be combinable with one or more recombinant traits or transgenic events, or combinations thereof. For the purposes of the present application, a transgenic event is created by inserting a specific recombinant DNA molecule at a specific location (locus) within the chromosome of the plant genome. By the insertion, a new DNA sequence called an "event" is created, characterized by the inserted recombinant DNA molecule and some amount of genomic DNA flanking / bordering both ends of the inserted DNA. Such traits or transgenic events include, but are not limited to, disease organism resistance, water use efficiency, yield performance, drought tolerance, seed quality, improved nutritional quality, hybrid seed production, and herbicide tolerance, and the traits are measured with respect to plants lacking such traits or transgenic events. Specific examples of such advantageous and / or useful traits (characteristics) are better plant growth, vigor, stress tolerance, self-supportability, lodging tolerance, nutrient uptake, plant nutrients, and / or yield, in particular improved growth, increased tolerance to high or low temperatures, improved tolerance to drought or water or soil salinity levels, improved flowering performance, ease of harvesting, accelerated ripening, increased yield, improved quality and / or nutritional value of the harvested product, improved shelf life and / or processability of the harvested product, and increased resistance or tolerance to animal and microbial disease organisms such as insects, arachnids, nematodes, mites, slugs and snails.

[0185] Among the DNA sequences encoding proteins that confer resistance or tolerance characteristics against such animal and microbial pathogens, particularly insects, the genetic material from Bacillus thuringiensis encoding Bt proteins, which are widely described in the literature and known to those skilled in the art, is particularly mentioned. Proteins extracted from bacteria such as Photorhabdus (WO97 / 17432 and WO98 / 08932) are mentioned. In particular, CrylA, CryIAb, CryIAc, CryIIA, CryIIIA, CryIIIB2, Cry9cCry2Ab, Cry3Bb and CryIF proteins or their toxic fragments, as well as their hybrids or combinations, particularly CryIF proteins or hybrids derived from CryIF proteins (e.g., hybrid CryIA-CryIF proteins or their toxic fragments), CryIA-type proteins or their toxic fragments, preferably CryIAc proteins or hybrids derived from CryIAc proteins (e.g., hybrid CryIAb-CryIAc proteins) or CryIAb or Bt2 proteins or their toxic fragments, Cry2Ae, Cry2Af or Cry2Ag proteins or their toxic fragments, CryIA.105 proteins or their toxic fragments, VIP3Aa19 proteins, VIP3Aa20 proteins, VIP3A proteins produced in the COT202 or COT203 cotton events, VIP3Aa proteins or their toxic fragments described in Estruch et al., (1996), Proc Natl Acad Sci USA. 28;93(11):5389-94, Cry proteins described in WO2001 / 47952, insecticidal proteins from the genus Xenorhabdus, Serratia (particularly from S. entomophila) or Photorhabdus (described in WO98 / 50427), e.g., Bt Cry or VIP proteins such as the Tc-protein from Photorhabdus described in WO98 / 08932 are mentioned.Also included herein are variants or mutants of any of the above-described sequences, particularly any of the sequences of their toxic fragments, that differ by several amino acids (1 to 10, preferably 1 to 5), or any of these proteins that are fused to a transport peptide, such as a plastid transport peptide, or another protein or peptide.

[0186] Another and particularly emphasized example of such a characteristic is the conferred resistance to one or more herbicides, such as imidazolinones, sulfonylureas, glyphosate or phosphinothricin. Among the DNA sequences encoding proteins that confer resistance to specific herbicides in transformed plant cells and plants, in particular, the bar or PAT genes described in WO2009 / 152359 that confer resistance to glyphosate-based herbicides, or the Streptomyces coelicolor gene described in WO2009 / 152359 that confers resistance to glufosinate-based herbicides, genes encoding suitable EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) that confer resistance to herbicides targeting EPSPS, particularly herbicides such as glyphosate and its salts, genes encoding glyphosate-n-acetyltransferase, or genes encoding glyphosate oxidoreductase. Further suitable herbicide resistance traits include at least one ALS (acetolactate synthase) inhibitor (e.g., WO2007 / 024782), mutated Arabidopsis ALS / AHAS genes (e.g., U.S. Patent No. 6,855,533), genes encoding 2,4-D-monooxygenase that confers resistance to 2,4-D (2,4-dichlorophenoxyacetic acid), and genes encoding dicamba monooxygenase that confers resistance to dicamba (3,6-dichloro-2-methoxybenzoic acid), etc.

[0187] A further particularly emphasized example of such properties is, for example, an increase in resistance to phytopathogenic fungi, bacteria and / or viruses by systemic acquired resistance (SAR), systemins, phytoalexins, elicitors, and resistance genes and correspondingly expressed proteins and toxins.

[0188] Particularly useful transgenic events in transgenic plants or plant varieties that can be preferably processed according to the present invention include event 531 / PV-GHBK04 (cotton, insect control, described in WO2002 / 040677), event 1143-14A (cotton, insect control, not deposited, described in WO2006 / 128569); event 1143-51B (cotton, insect control, not deposited, described in WO2006 / 128570); event 1445 (cotton, herbicide tolerance, not deposited, described in US-A2002-120964 or WO2002 / 034946); event 17053 (rice, herbicide tolerance, deposited as PTA-9843, described in WO2010 / 117737); event 17314 (rice, herbicide tolerance, deposited as PTA-9844, described in WO2010 / 117735); event 281-24-236 (cotton, insect control - herbicide tolerance, deposited as PTA-6233, described in WO2005 / 103266 or US-A2005-216969); event 3006-210-23 (cotton, insect control - herbicide tolerance, deposited as PTA-6233, described in US-A2007-143876 or WO2005 / 103266); event 3272 (maize, quality trait, deposited as PTA-9972, described in WO2006 / 098952 or US-A2006-230473); event 33391 (wheat, herbicide tolerance, deposited as PTA-2347, described in WO2002 / 027004), event 40416 (maize, insect control - herbicide tolerance, deposited as ATCC PTA-11508, described in WO11 / 075593); event 43A47 (maize, insect control - herbicide tolerance, deposited as ATCC PTA-11509, described in WO2011 / 075595); event 5307 (maize, insect control, deposited as ATCC PTA-9561, described in WO2010 / 077816); event ASR-368 (bentgrass, herbicide tolerance, deposited as ATCC PTA-4816, described in US-A2006-162007 or WO2004 / 053062); event B16 (maize, herbicide tolerance, not deposited, described in US-A2003-126634);Event BPS-CV127-9 (soybean, herbicide tolerance, deposited as NCIMB No. 41603, described in WO2010 / 080829); Event BLR1 (rape, restoration of male sterility, deposited as NCIMB 41193, described in WO2005 / 074671), Event CE43-67B (cotton, insect control, deposited as DSMACC2724US-A2009-217423 or WO2006 / 128573, described therein); Event CE44-69D (cotton, insect control, not deposited, described in US-A2010-0024077); Event CE44-69D (cotton, insect control, not deposited, described in WO2006 / 128571); Event CE46-02A (cotton, insect control, not deposited, described in WO2006 / 128572); Event COT102 (cotton, insect control, not deposited, described in US-A2006-130175 or WO2004 / 039986); Event COT202 (cotton, insect control, not deposited, described in US-A2007-067868 or WO2005 / 054479); Event COT203 (cotton, insect control, not deposited, described in WO2005 / 054480); Event DAS21606-3 / 1606 (soybean, herbicide tolerance, deposited as PTA-11028, described in WO2012 / 033794), Event DAS40278 (maize, herbicide tolerance, deposited as ATCCPTA-10244, described in WO2011 / 022469); Event DAS-44406-6 / pDAB8264.44.06.1 (soybean, herbicide tolerance, deposited as PTA-11336, described in WO2012 / 075426), Event DAS-14536-7 / pDAB8291.45.36.2 (soybean, herbicide tolerance, deposited as PTA-11335, described in WO2012 / 075429), Event DAS-59122-7 (maize, insect control - herbicide tolerance, deposited as ATCCPTA11384, described in US-A2006-070139); Event DAS-59132 (maize, insect control - herbicide tolerance, not deposited, described in WO2009 / 100188); Event DAS68416 (soybean, herbicide tolerance, deposited as ATCCPTA-10442, described in WO2011 / 066384 or WO2011 / 066360);Event DP-098140-6 (maize, herbicide tolerance, deposited as ATCC PTA-8296, described in US-A2009-137395 or WO08 / 112019); Event DP-305423-1 (soybean, quality trait, not deposited, described in US-A2008-312082 or WO2008 / 054747); Event DP-32138-1 (maize, hybridization system, deposited as ATCC PTA-9158, described in US-A2009-0210970 or WO2009 / 103049); Event DP-356043-5 (soybean, herbicide tolerance, deposited as ATCC PTA-8287, described in US-A2010-0184079 or WO2008 / 002872); Event EE-I (eggplant, insect control, not deposited, described in WO07 / 091277); Event Fil 17 (maize, herbicide tolerance, deposited as ATCC 209031, described in US-A2006-059581 or WO98 / 044140); Event FG72 (soybean, herbicide tolerance, deposited as PTA-11041, described in WO2011 / 063413), Event GA21 (maize, herbicide tolerance, deposited as ATCC 209033, described in US-A2005-086719 or WO98 / 044140); Event GG25 (maize, herbicide tolerance, deposited as ATCC 209032, described in US-A2005-188434 or WO98 / 044140); Event GHB119 (cotton, insect control - herbicide tolerance, deposited as ATCC PTA-8398, described in WO2008 / 151780); Event GHB614 (cotton, herbicide tolerance, deposited as ATCC PTA-6878, described in US-A2010-050282 or W02007 / 017186); Event GJ11 (maize, herbicide tolerance, deposited as ATCC 209030, described in US-A2005-188434 or WO98 / 044140); Event GMRZ13 (sugar beet, virus resistance, deposited as NCIMB-41601, described in WO2010 / 076212); Event H7-l (sugar beet, herbicide tolerance, deposited as NCIMB41158 or NCIMB41159, described in US-A2004-172669 or WO2004 / 074492);Event JOPLIN1 (wheat, disease tolerance, not deposited, described in US-A2008-064032); Event LL27 (soybean, herbicide tolerance, deposited as NCIMB41658, described in WO2006 / 108674 or US-A2008-320616); Event LL55 (soybean, herbicide tolerance, deposited as NCIMB41660, described in WO2006 / 108675 or US-A2008-196127); Event LL Cotton25 (cotton, herbicide tolerance, deposited as ATCC PTA-3343, described in WO2003 / 013224 or US-A2003-097687); Event LLRICE06 (rice, herbicide tolerance, deposited as ATCC 203353, described in US6,468,747 or WO2000 / 026345); Event LL Rice62 (rice, herbicide tolerance, deposited as ATCC 203352, described in WO2000 / 026345), Event LL Rice601 (rice, herbicide tolerance, deposited as ATCC PTA-2600, described in US-A2008-2289060 or WO2000 / 026356); Event LY038 (maize, quality trait, deposited as ATCC PTA-5623, described in US-A2007-028322 or WO2005 / 061720); Event MIR162 (maize, insect control, deposited as PTA-8166, described in US-A2009-300784 or WO2007 / 142840); Event MIR604 (maize, insect control, not deposited, described in US-A2008-167456 or WO2005 / 103301); Event MON15985 (cotton, insect control, deposited as ATCC PTA-2516, described in US-A2004-250317 or WO2002 / 100163); Event MON810 (maize, insect control, not deposited, described in US-A2002-102582); Event MON863 (maize, insect control, deposited as ATCC PTA-2605, described in WO2004 / 011601 or US-A2006-095986); Event MON87427 (maize, pollination control, deposited as ATCC PTA-7899, described in WO2011 / 062904);Event MON87460 (maize, stress tolerance, deposited as ATCC PTA - 8910, described in WO2009 / 111263 or US - A2011 - 0138504); Event MON87701 (soybean, insect control, deposited as ATCC PTA - 8194, described in US - A2009 - 130071 or WO2009 / 064652); Event MON87705 (soybean, quality trait - herbicide tolerance, deposited as ATCC PTA - 9241, described in US - A2010 - 0080887 or WO2010 / 037016); Event MON87708 (soybean, herbicide tolerance, deposited as ATCC PTA - 9670, described in WO2011 / 034704); Event MON87712 (soybean, yield, deposited as PTA - 10296, described in WO2012 / 051199), Event MON87754 (soybean, quality trait, deposited as ATCC PTA - 9385, described in WO2010 / 024976); Event MON87769 (soybean, quality trait, deposited as ATCC PTA - 8911, described in US - A2011 - 0067141 or WO2009 / 102873); Event MON88017 (maize, insect control - herbicide tolerance, deposited as ATCC PTA - 5582, described in US - A2008 - 028482 or WO2005 / 059103); Event MON88913 (cotton, herbicide tolerance, deposited as ATCC PTA - 4854, described in WO2004 / 072235 or US - A2006 - 059590); Event MON88302 (rape, herbicide tolerance, deposited as PTA - 10955, described in WO2011 / 153186), Event MON88701 (cotton, herbicide tolerance, deposited as PTA - 11754, described in WO2012 / 134808), Event MON89034 (maize, insect control, deposited as ATCC PTA - 7455, described in WO07 / 140256 or US - A2008 - 260932); Event MON89788 (soybean, herbicide tolerance, deposited as ATCC PTA - 6708, described in US - A2006 - 282915 or WO2006 / 130436); Event MS11 (rape, pollination control - herbicide tolerance, deposited as ATCC PTA - 850 or PTA - 2485, described in WO2001 / 031042);Event MS8 (rape, pollination control - herbicide tolerance, deposited as ATCC PTA - 730, described in WO2001 / 041558 or US - A2003 - 188347); Event NK603 (maize, herbicide tolerance, deposited as ATCC PTA - 2478, described in US - A2007 - 292854); Event PE - 7 (rice, insect control, not deposited, described in WO2008 / 114282); Event RF3 (rape, pollination control - herbicide tolerance, deposited as ATCC PTA - 730, described in WO2001 / 041558 or US - A2003 - 188347); Event RT73 (rape, herbicide tolerance, not deposited, described in WO2002 / 036831 or US - A2008 - 070260); Event SYHT0H2 / SYN - 000H2 - 5 (soybean, herbicide tolerance, PTA - 112; Deposited as 26, described in WO2012 / 082548); event T227-1 (sugar beet, herbicide tolerance, not deposited, described in WO2002 / 44407 or US-A2009-265817); event T25 (maize, herbicide tolerance, not deposited, described in US-A2001-029014 or WO2001 / 051654); event T304-40 (cotton, insect control - herbicide tolerance, deposited as ATCC PTA-8171, described in US-A2010-077501 or WO2008 / 122406); event T342-142 (cotton, insect control, not deposited, described in WO2006 / 128568); event TC1507 (maize, insect control - herbicide tolerance, not deposited, described in US-A2005-039226 or WO2004 / 099447); event VIP1034 (maize, insect control - herbicide tolerance, deposited as ATCC PTA-3925, described in WO2003 / 052073), event 32316 (maize, insect control - herbicide tolerance, deposited as PTA-11507, described in WO2011 / 084632), event 4114 (maize, insect control - herbicide tolerance, deposited as PTA-11506, described in W02011 / 084621), event EE-GM3 / FG72 (soybean, herbicide tolerance, ATCC deposit number PTA-11041) which may be cumulative with event EE-GM1 / LL27 or event EE-GM2 / LL55 (WO2011 / 063413A2), event DAS-68416-4 (soybean, herbicide tolerance, ATCC deposit number PTA-10442, WO2011 / 066360A1), event DAS-68416-4 (soybean, herbicide tolerance, ATCC deposit number PTA-10442, WO2011 / 066384A1), event DP-040416-8 (maize, insect control, ATCC deposit number PTA-11508, WO2011 / 075593A1), event DP-043A47-3 (maize, insect control, ATCC deposit number PTA-11509, WO2011 / 075595A1), event DP-004114-3 (maize, insect control, ATCC deposit number PTA-11506, WO2011 / 084621A1), event DP-032316-8 (maize, insect control, ATCC deposit number PTA-11507,WO2011 / 084632A1), event MON-88302-9 (rape, herbicide tolerance, ATCC Deposit No. PTA-10955, WO2011 / 153186A1), event DAS-21606-3 (soybean, herbicide tolerance, ATCC Deposit No. PTA-11028, WO2012 / 033794A2), event MON-87712-4 (soybean, quality trait, ATCC Deposit No. PTA-10296, WO2012 / 051199A2), event DAS-44406-6 (soybean, cumulative herbicide tolerance, ATCC Deposit No. PTA-11336, WO2012 / 075426A1), event DAS-14536-7 (soybean, cumulative herbicide tolerance, ATCC Deposit No. PTA-11335, WO2012 / 075429A1), event SYN-000H2-5 (soybean, herbicide tolerance, ATCC Deposit No. PTA-11226, WO2012 / 082548A2), event DP-061061-7 (rape, herbicide tolerance, deposit number not available, WO2012071039A1), event DP-073496-4 (rape, herbicide tolerance, deposit number not available, US2012131692), event 8264.44.06.1 (soybean, cumulative herbicide tolerance, deposit number PTA-11336, WO2012075426A2), event 8291.45.36.2 (soybean, cumulative herbicide tolerance, deposit number PTA-11335, WO2012075429A2), event SYHT0H2 (soybean, ATCC Deposit No. PTA-11226, WO2012 / 082548A2), event MON88701 (cotton, ATCC Deposit No. PTA-11754, WO2012 / 134808A1), event KK179-2 (alfalfa, ATCC Deposit No. PTA-11833, WO2013 / 003558A1), event pDAB8264.42.32.1 (soybean, cumulative herbicide tolerance, ATCC Deposit No. PTA-11993, WO2013 / 010094A1), event MZDT09Y (maize, ATCC Deposit No. PTA-13025, WO2013 / 012775A1), etc.

[0189] Furthermore, a list of such transgenic events is provided by the Animal and Plant Health Inspection Service (APHIS) of the United States Department of Agriculture (USDA).from aphis.usda.gov Websites on the World Wide Web can be found at For the present application, it is relevant what the status of such a list was at the filing date of the present application.

[0190] Genes / events conferring the desired traits of interest may also be present in combination with each other in transgenic plants. Examples of transgenic plants that can be mentioned are important crop plants such as cereals (wheat, rice, triticale, barley, rye, oats), maize, soybean, potato, sugarcane, cotton, tomato, pea and other types of vegetables, tobacco, rape, and also fruit plants (including fruit apples, pears, citrus fruits, grapes), with particular emphasis on maize, soybean, wheat, rice, potato, cotton, sugarcane, tobacco and rape. Particular emphasis is placed on traits that enhance the resistance of plants to insects, spiders, nematodes and slugs and snails and the resistance of plants to one or more herbicides.

[0191] Commercially available examples of such plants, plant parts or plant seeds that can be preferably treated according to the present invention include those sold or distributed under the trade names of GENUITY®, DROUGHTGARD®, SMARTSTAX®, RIB COMPLETE®, ROUNDUP READY®, VT DOUBLE PRO®, VT TRIPLEPRO®, BOLLGARD II®, ROUNDUP READY 2 YIELD®, YIELDGARD®, ROUNDUP READY® 2 XTEN DTM , INTACTA RR2PRO®, VISTIVE GOLD®, and / or plant seeds sold or distributed under the trade name XTENDFLEX®, etc.

[0192] Crop protection - type of treatment The treatment of plants and plant parts with the compounds of formula (I) is carried out using conventional treatment methods, for example, by dipping, spraying, atomizing, irrigation, vaporization, dusting, smoking, scattering, foaming, coating, spreading-on, injection, drenching, drip irrigation, etc., and in the case of propagation material, especially in the case of seeds, further as a powder for dry seed treatment, as a liquid formulation for liquid seed treatment, as an aqueous solvent for slurry treatment, by coating, coating with one or more coatings, etc., directly or by acting on the surroundings, habitat or storage space of the plants and plant parts. Furthermore, it is also possible to apply the compounds of formula (I) by the ultra-low volume method, or to inject the application form or the compounds of formula (I) itself into the soil.

[0193] A preferred direct treatment of plants is foliar application, i.e., applying the compounds of formula (I) to the foliage, in which case the treatment frequency and application rate should be adapted according to the level of pest occurrence.

[0194] In the case of systemic active compounds, the compounds of formula (I) also reach the plants via the root system. Thus, the plants are treated by acting on the habitat of the plants with the compounds of formula (I). This can be done, for example, by drenching, or by mixing with the soil or nutrient solution [i.e., impregnating the liquid form of the compounds of formula (I) into the growth site of the plants (e.g., soil, or hydroponic system)], or by soil application [i.e., introducing the compounds of formula (I) according to the invention in solid form (e.g., in granular form) into the growth site of the plants], or by drip application (often also referred to as "chemical solution irrigation"), i.e., by liquid application of the compounds of formula (I) according to the invention from a surface or subsurface drip line over a specific period together with various amounts of water at a defined location near the plants. In the case of paddy crops, this can also be done by metering the compounds of formula (I) in solid application form (e.g., as granules) and supplying them to the flooded paddy field.

[0195] Digital technology The compounds of the present invention can be used in combination with models embedded in computer programs, for example, for site-specific crop management, satellite farming, precision farming or precision agriculture. Such models use data from various sources such as soil, climate, crops (e.g., type, growth stage, plant health), weeds (e.g., type, growth stage), diseases, pests, nutrients, water, moisture, biomass, satellite data, yield, etc. with the aim of optimizing profitability, sustainability and environmental protection, and assist in site-specific management of agricultural sites. In particular, such models can help optimize agricultural decisions, control the accuracy of pesticide application, and record the operations performed.

[0196] As an example, the compounds of the present invention can be applied to crop plants according to appropriate application methods when the model models the development of pests and calculates that a threshold for applying the compound to the crop plants has been reached.

[0197] Commercially available systems including agronomic models include, for example, FieldScriptsTM from The Climate Corporation, XarvioTM from BASF, and AGLogicTM from John Deere.

[0198] The compounds of the present invention can also be used in combination with smart spraying devices such as spot spraying devices or precision spraying devices attached to or housed within agricultural vehicles such as unmanned aerial vehicles (UAVs) such as tractors, robots, helicopters, airplanes, drones, etc. Such devices typically include an input sensor (e.g., a camera, etc.) and a processing unit configured to analyze the input data and provide a decision based on the analysis of the input data to apply the compounds of the present invention to crop plants (weeds respectively) in an individual and accurate manner. To use such a smart spray device, it is usually necessary to localize the recorded data, a position system (e.g., a GPS receiver) for guiding or controlling the agricultural vehicle; a geographic information system (GIS) for representing information on an understandable map, and an appropriate agricultural vehicle for performing the necessary farming operations such as spraying.

[0199] In one example, the disease organisms can be detected from the images acquired by the camera. In one example, the pests can be identified and / or classified based on the image. Such identification and / or classification can utilize image processing algorithms. Such image processing algorithms can utilize machine learning algorithms such as trained neutral networks, decision trees, etc., and artificial intelligence algorithms can be utilized. In this way, the compounds described herein can be applied only when necessary.

[0200] Seed treatment The control of pests by treating plant seeds has been known for a long time and has been continuously improved. However, seed treatment is associated with a series of problems that cannot necessarily be solved satisfactorily. Thus, it is desirable to develop a method for protecting seeds and germinating plants such that additional application of pesticides during storage, after sowing or after germination of the plants is unnecessary or at least significantly reduced. Furthermore, it is also desirable to optimize the amount of the active compound used such that the seeds and germinating plants are optimally protected from attack by pests without causing damage to the plants themselves by the active compound used. In particular, in the method of treating seeds, the endogenous insecticidal or nematicidal properties of pest-resistant transgenic plants or pest-tolerant transgenic plants should also be taken into account in order to achieve optimal protection of the seeds and germinating plants using the least amount of pesticide.

[0201] Accordingly, the present invention also relates in particular to a method for protecting seeds and germinating plants from attack by phytopathogenic organisms, wherein the method comprises treating the seeds with one of the compounds of formula (I). The method according to the invention for protecting seeds and germinating plants from attack by phytopathogenic organisms further comprises methods in which the seeds are treated simultaneously or successively in one operation with a compound of formula (I) and a mixing component. It further comprises methods in which the seeds are treated at different times with a compound of formula (I) and a mixing component.

[0202] The present invention also relates to the use of a compound of formula (I) for treating seeds in order to protect the seeds and the plants growing from said seeds against phytopathogenic animals.

[0203] Furthermore, the present invention also relates to seeds treated with a compound of formula (I) according to the invention so as to provide protection from diseased animals. The present invention further relates to seeds simultaneously treated with a compound of formula (I) and a mixing component. The present invention further relates to seeds treated at different times with a compound of formula (I) and a mixing component. In the case of seeds treated at different times with a compound of formula (I) and a mixing component, the individual substances may be present in different layers on the surface of the seeds. Here, the layer containing the compound of formula (I) and the mixing component can optionally be separated by an intermediate layer. The present invention also further relates to seeds on which a compound of formula (I) and a mixing component are applied as components of a coating or as an additional one or more layers added to the coating.

[0204] The present invention further relates to seeds subjected to a film coating process in order to prevent abrasion of the seeds by dust after being treated with a compound of formula (I).

[0205] One of the advantages obtained with the systemic compound of formula (I) is that by treating the seeds, not only the seeds themselves but also the plants obtained from those seeds are protected from diseased animals after germination. In this way, the labor of directly treating the crop at the time of sowing or shortly after sowing can be saved.

[0206] It should be considered that by treating the seeds with a compound of formula (I), the germination and emergence of the treated seeds can be enhanced.

[0207] Similarly, it is considered advantageous that the compound of formula (I) can be used, in particular, for transgenic seeds.

[0208] Furthermore, the compound of formula (I) can be used in combination with a composition or compound of signal transduction technology, as a result of which colonization by symbiotic organisms (e.g., rhizobia, mycorrhizal fungi and / or endophytic bacteria or fungi) is improved and / or nitrogen fixation is optimized.

[0209] The compounds of formula (I) are suitable for protecting the seeds of all plant varieties used in agriculture, in greenhouses, in forests or in horticulture. In particular, these take the form of seeds of cereals (for example, wheat, barley, rye, oats and millet), maize, cotton, soybeans, rice, potatoes, sunflowers, coffee, tobacco, canola, rapeseed, beet (for example, sugar beet and fodder beet), peanuts, vegetables (for example, tomatoes, cucumbers, green beans, brassicas, onions and lettuce), fruit plants, lawns and ornamental plants. It is particularly important to treat the seeds of cereals (for example, wheat, barley, rye and millet), maize, soybeans, cotton, canola, rapeseed, vegetables and rice.

[0210] As already described above, the treatment of transgenic seeds with the compounds of formula (I) is also particularly important. These take the form of seeds of plants that basically contain at least one heterologous gene that controls the expression of a polypeptide having in particular insecticidal and / or nematicidal properties. These heterologous genes in transgenic seeds can be derived from microorganisms such as Bacillus species, Rhizobium species, Pseudomonas species, Serratia species, Trichoderma species, Clavibacter species, Glomus species or Gliocladium species. The present invention is particularly suitable for treating transgenic seeds containing at least one heterologous gene derived from a Bacillus sp. It is particularly preferably a heterologous gene derived from Bacillus thuringiensis.

[0211] In connection with the present invention, the compounds of formula (I) are applied to seeds. Preferably, the seeds are treated in a state that is sufficiently stable to avoid damage during the treatment. Generally, the seeds can be treated at any time between harvesting and sowing. The seeds commonly used are separated from the plants and have the ear axis, husk, petiole, outer skin, hairs or pulp removed. For example, seeds that have been harvested, had impurities removed, and dried to a water content that allows storage can be used. Alternatively, seeds that have been treated, for example, with water after drying and then dried again (e.g., priming) can also be used. In the case of rice seeds, for example, it is also possible to use seeds that have been immersed in water up to a certain stage of the rice embryo (the "pigeon breast stage"), thereby stimulating germination and resulting in more uniform emergence.

[0212] When treating seeds, care must generally be taken to select the amount of the compound of formula (I) and / or the amount of further additives applied to the seeds such that the germination of the seeds is not adversely affected or the plants resulting from the seeds are not damaged. This must be ensured especially in the case of active compounds that may exhibit phytotoxic effects at certain application rates.

[0213] Generally, the compounds of formula (I) are applied to seeds in suitable formulations. Suitable formulations and processes for treating seeds are known to those skilled in the art.

[0214] The compounds of formula (I) can be converted into conventional seed dressing formulations, such as solutions, emulsions, suspensions, powders, foams, slurries or other coating compositions for seeds, and can further be converted into ULV formulations.

[0215] These formulations are produced 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, second thickeners, adhesives, gibberellins, etc. in known methods, and further mixing with water.

[0216] The colorants that can be incorporated into the seed coating formulations that can be used according to the present invention are all the colorants customary for such purposes. Pigments that are not very soluble in water or dyes that are soluble in water can be used. Examples thereof include colorants known under the names "Rhodamin B", "C.I.Pigment Red 112" and "C.I.Solvent Red 1".

[0217] The useful wetting agents that can be incorporated into the seed coating formulations that can be used according to the present invention are all substances customary for promoting wetting and for the formulation of agrochemical active compounds. Preferably, alkylnaphthalenesulfonates such as diisopropyl or diisobutylnaphthalenesulfonate are used.

[0218] The useful dispersants and / or emulsifiers that can be incorporated into the seed coating formulations that can be used according to the present invention are all nonionic, anionic and cationic dispersants conventionally used in the formulation of agrochemical active ingredients. Preferably, nonionic or anionic dispersants or mixtures of nonionic or anionic dispersants are used. Suitable nonionic dispersants are, in particular, ethylene oxide / propylene oxide block polymers, alkylphenol polyglycol ethers and tristyrylphenol polyglycol ethers, and their phosphorylated or sulfated derivatives. Suitable anionic dispersants are, in particular, lignosulfonates, polyacrylates and arylsulfonate / formaldehyde condensates.

[0219] The defoamers that can be incorporated into the seed coating formulations that can be used according to the present invention are all foam-suppressing substances conventionally used in the formulation of agrochemical active ingredients. Preferably, silicone defoamers and magnesium stearate are used.

[0220] The preservatives that can be incorporated into the seed coating formulations that can be used according to the present invention are all substances that can be used for this purpose in pesticidal compositions. Examples include dichlorophene and benzyl alcohol hemi formal.

[0221] The secondary thickeners that can be incorporated into the seed coating formulations that can be used according to the present invention are all substances that can be used for this purpose in pesticidal compositions. Cellulose derivatives, acrylic acid derivatives, xanthan, modified clays and micronized silica are preferred.

[0222] The adhesives that can be incorporated into the seed coating formulations that can be used according to the present invention are all customary binders that can be used in seed coating products. Polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and tylose can be mentioned as preferred.

[0223] The gibberellins that can be incorporated into the seed coating formulations that can be used according to the present invention are preferably gibberellin A1, gibberellin A3 (= gibberellic acid), gibberellin A4 and gibberellin A7, and gibberellic acid is particularly preferably used. Gibberellins are known (see R. Wegler "Chemie der Pflanzenschutz- and Schadlingsbekampfungsmittel" vol. 2, Springer Verlag, 1970, pp. 401-412).

[0224] The seed coating formulations that can be used according to the present invention can be used directly to treat a wide range of different types of seeds, or can be used after being diluted with water in advance. For example, a concentrate or a preparation obtainable from the concentrate by dilution with water can be used to coat the seeds of cereals such as wheat, barley, rye, oats and triticale, and also, further, to coat the seeds of maize, rice, rapeseed, pea, broad bean, cotton, sunflower, soybean and beet, or can be used to coat the seeds of a wide range of different vegetables. The seed coating formulations that can be used according to the present invention or their diluted forms of use can also be used to coat the seeds of transgenic plants.

[0225] When treating seeds with the seed coating formulations that can be used according to the present invention or the forms of use prepared from the seed coating formulations by adding water, all mixing devices that can be customarily used for seed coating are useful. Specifically, the procedure in seed coating is to put the seeds into a mixer operated batchwise or continuously, add the desired specific amount of the seed coating formulation as it is or after diluting it with water in advance, and mix everything until the formulation is homogeneously distributed on the surface of the seeds. If appropriate, a drying step is subsequently carried out.

[0226] The application rate of the seed coating formulations that can be used according to the present invention can be varied within a relatively wide range. It depends on the specific content of the compound of formula (I) in the formulation and on the seeds. The application rate of the compound of formula (I) is generally from 0.001 to 50 g per kg of seeds, preferably from 0.01 to 15 g per kg of seeds.

[0227] Animal health In the field of animal health, i.e. in the field of veterinary medicine, the compounds of formula (I) are active against animal parasites, in particular against ectoparasites or endoparasites. The term "endoparasite" in particular encompasses helminths and protozoa (e.g. coccidia). Ectoparasites are typically and preferably arthropods, in particular insects or mites.

[0228] In the field of veterinary medicine, the compounds of formula (I) have a favorable toxicity in warm-blooded animals and are suitable for controlling parasites occurring in farm animals, breeding animals, zoo animals, laboratory animals, experimental animals and domestic animals in animal breeding and livestock farming.

[0229] Examples of agricultural livestock include mammals such as sheep, goats, horses, donkeys, camels, pigs, rabbits, reindeer, roe deer, and in particular cattle and pigs; or poultry such as turkeys, ducks, geese, and in particular chickens; or fish or crustacean animals such as fish and crustacean animals in aquaculture; or optionally insects such as bees.

[0230] Examples of domestic animals include mammals such as hamsters, chinchillas, rats, mice, chinchillas, ferrets, or in particular dogs, cats, cage birds, reptiles, amphibians, or aquarium fish.

[0231] According to a particular embodiment, the compounds of formula (I) are administered to mammals.

[0232] According to another particular embodiment, the compounds of formula (I) are administered to birds, i.e. cage birds, or in particular poultry.

[0233] By using the compounds of formula (I) to control animal parasites, it is intended to reduce or prevent diseases, mortality cases and productivity losses (in the case of meat, milk, wool, leather, eggs, honey, etc.), as a result, a more economical and simpler livestock industry becomes possible, and better animal health can be achieved.

[0234] As used herein in the field of animal health, the terms "control" or "controlling" mean that the compounds of formula (I) are effective in reducing the incidence of individual parasites in animals infected with the parasites to a non-harmful level. More specifically, as used herein, "control" means that the compounds of formula (I) are effective in killing individual parasites, inhibiting their growth, or inhibiting their proliferation.

[0235] Examples of arthropods include, but are not limited to, the following.

[0236] Of the order Anoplurida, such as species of the genus Haematopinus, Linognathus, Pediculus, Phtirus, and Solenopotes; Of the order Mallophagida and the suborders Amblycerina and Ischnocerina, such as species of the genus Bovicola, Damalina, Felicola; Lepikentron, Menopon, Trichodectes, Trimenopon, Trinoton, Werneckiella; Of the order Diptera and the suborders Nematocerina and Brachycerina, for example, species of the genus Aedes, Anopheles, Atylotus, Braula, Calliphora, Chrysomyia, Chrysops, Culex, Culicoides, Eusimulium, Fannia, Gasterophilus, Glossina, Haematobia, Haematopota, Hippobosca, Hybomitra, Hydrotaea, Hypoderma, Lipoptena, Lucilia, Lutzomyia, Melophagus, Morellia, Musca, Odagmia, Oestrus, Philipomyia, Phlebotomus, Rhinoestrus, Sarcophaga, Simulium, Stomoxys, Tabanus, Tipula, Wilhelmia, Wohlfahrtia; Of the order Siphonapterida, for example, species of the genus Ceratophyllus, Ctenocephalides, Pulex, Tunga, Xenopsylla; Of the order Heteropterida, for example, species of the genus Cimex, Panstrongylus, Rhodnius, Triatoma; and harmful and sanitary pests of the order Blattarida.

[0237] Furthermore, among the arthropods, but not limited to, the following mites can be mentioned as examples. Acari (Acarina) and Metastigmata, for example, Argasidae such as Argas spp., Ornithodorus spp., Otobius spp.; Ixodidae such as Amblyomma spp., Dermacentor spp., Haemaphysalis spp., Hyalomma spp., Ixodes spp., Rhipicephalus (Boophilus) spp., Rhipicephalus spp. (former genus of multi-host ticks); Mesostigmata such as Dermanyssus spp., Ornithonyssus spp., Pneumonyssus spp., Raillietia spp., Sternostoma spp., Tropilaelaps spp., Varroa spp.; Actinedida (Prostigmata) such as Acarapis spp., Cheyletiella spp., Demodex spp., Listrophorus spp., Myobia spp., Neotrombicula spp., Ornithocheyletia spp., Psorergates spp., Trombicula spp.; and 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..

[0238] Examples of parasitic protozoa include, but are not limited to, the following. Subphylum Mastigophora (Flagellata), for example: Metamonada: of the order Diplomonadida, for example, Giardia spp., Spironucleus spp.; Parabasala: of the order Trichomonadida, for example, Histomonas spp., Pentatrichomonas spp., Tetratrichomonas spp., Trichomonas spp., Tritrichomonas spp; Euglenozoa: of the order Trypanosomatida, for example, Leishmania spp., Trypanosoma spp.; Sarcomastigophora (Rhizopoda), for example, Entamoebidae, for example, Entamoeba spp., Centramoebidae, for example, Acanthamoeba sp., Euamoebidae, for example, Hartmanella sp.; Alveolata, for example, Apicomplexa (Sporozoa), for example, Cryptosporidium spp.; of Eimeriida, for example, Besnoitia spp., Cystoisospora spp., Eimeria spp., Hammondia spp., Isospora spp., Neospora spp., Sarcocystis spp., Toxoplasma spp.; of Adeleida, for example, Hepatozoon spp., Klossiella spp.; of Haemosporida, for example, Leucocytozoon spp., Plasmodium spp.; of Piroplasmida, for example, Babesia spp., Ciliophora spp., Echinozoon spp., Theileria spp.; of Vesibuliferida, for example, Balantidium spp., Buxtonella spp.; Microspora, for example, species of the genus Encephalitozoon, Enterocytozoon, Globidium, Nosema, and, further, for example, species of the genus Myxozoa.

[0239] Pathogenic helminths for humans or animals include, for example, Acanthocephala, nematodes, Pentastomida, and Platyhelminthes [for example, Monogenea, Cestodes, and Trematodes].

[0240] Examples of helminths include, but are not limited to, the following. Class Monogenea: for example, species of the genus Dactylogyrus, Gyrodactylus, Microbothrium, Polystoma, Troglocephalus; Cestodes: of the order Pseudophyllidea, for example, species of the genus Bothridium, Diphyllobothrium, Diplogonoporus, Ichthyobothrium, Ligula, Schistocephalus, Spirometra; Of the order Cyclophyllida, for example: species of 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., Paranoplocephala spp., Raillietina spp., Stilesia spp., Taenia spp., Thysaniezia spp., Thysanosoma spp.; Trematodes: of the subclass Digenea, for example: 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., Eurytrema spp., Fasciola spp., Fasciolides spp., Fasciolopsis spp., Fischoederius spp., Gastrothylacus spp., Gigantobilharzia spp., Gigantocotyle 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.;. Nematodes: of the order Trichinellida, for example: Capillaria spp., Eucoleus spp., Paracapillaria spp., Trichinella spp., Trichomosoides spp., Trichuris spp.; of the order Tylenchida, for example: Micronema spp., Parastrongyloides spp., Strongyloides spp.; Order Rhabditina, for example: 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 spp., Parafilaroides spp., Parelaphostrongylus spp., Pneumocaulus spp., Pneumostrongylus spp., Poteriostomum spp., Protostrongylus spp., Spicocaulus spp., Stephanurus spp., Strongylus spp., Syngamus spp., Teladorsagia spp., Trichonema spp., Trichostrongylus spp., Triodontophorus spp., Troglostrongylus spp., Uncinaria spp.;. Order Spirurida, for example: species of 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.;. Phylum Acanthocephala: of the order Oligacanthorhynchida, for example: Macracanthorhynchus spp., Prosthenorchis spp.; of the order Moniliformida, for example: Moniliformis spp.; of the order Polymorphida, for example: Filicollis spp.; of the order Echinorhynchida, for example, Acanthocephalus spp., Echinorhynchus spp., Leptorhynchoides spp.; Phylum Pentastoma: of the order Porocephalida, for example, Linguatula spp.

[0241] In the field of veterinary medicine and in the livestock industry, the administration of the compounds of formula (I) is carried out by methods generally known in the art, for example, in the form of suitable preparations, enterally, parenterally, transdermally or nasally. The administration can be carried out prophylactically, metaphylactically or therapeutically.

[0242] Accordingly, one embodiment of the present invention refers to a compound of formula (I) for use as a drug.

[0243] Another aspect refers to a compound of formula (I) for use as an anti-endoparasitic agent.

[0244] Another specific embodiment refers to a compound of formula (I) for use as an anthelmintic agent, in particular for use as a nematicide, a trematodicide, an acanthocephalicide, or a pentastomicide.

[0245] Another specific embodiment refers to a compound of formula (I) for use as an antiprotozoal agent.

[0246] Another embodiment refers to a compound of formula (I) for use as an antiparasitic agent, in particular as an acaricide or an insecticide, more specifically as an insecticide or a miticide.

[0247] A further embodiment of the present invention is an animal pharmaceutical preparation comprising an effective amount of at least one compound of formula (I) and the following: a pharmaceutically acceptable excipient (e.g., a solid diluent or a liquid diluent), a pharmaceutically acceptable adjuvant (e.g., a surfactant), in particular, a pharmaceutically acceptable excipient, and / or at least one of the pharmaceutically acceptable adjuvants commonly used in animal pharmaceutical preparations.

[0248] A related embodiment of the present invention is a method for producing an animal pharmaceutical preparation described herein, the method comprising the step of mixing at least one compound of formula (I) with a pharmaceutically acceptable excipient and / or adjuvant, in particular, a pharmaceutically acceptable excipient, and / or an adjuvant commonly used in animal pharmaceutical preparations.

[0249] Another specific embodiment of the present invention is an animal pharmaceutical preparation selected from the group consisting of ectoparasiticide pharmaceutical preparations and endoparasiticide pharmaceutical preparations according to the above embodiments, in particular, an animal pharmaceutical preparation selected from the group consisting of anthelmintic pharmaceutical preparations, antiprotozoal pharmaceutical preparations, and acaricide pharmaceutical preparations, and even more specifically, an animal pharmaceutical preparation selected from the group consisting of nematicide pharmaceutical preparations, trematodicide pharmaceutical preparations, acanthocephalicide pharmaceutical preparations, pentastomicide pharmaceutical preparations, insecticide pharmaceutical preparations, and miticide pharmaceutical preparations, and methods for producing the same.

[0250] Another aspect is a method for treating a parasitic infection, particularly an infection by a parasite selected from the group of ectoparasites and endoparasites described herein, the method comprising applying an effective amount of a compound of formula (I) in an animal in need of such treatment, particularly a non-human animal.

[0251] Another aspect is a method for treating a parasitic infection, particularly an infection by a parasite selected from the group of ectoparasites and endoparasites described above, the method comprising applying an animal pharmaceutical formulation as defined herein in an animal in need of such treatment, particularly a non-human animal.

[0252] Another aspect refers to the use of a compound of formula (I) in the treatment of parasitic infections in animals (particularly non-human animals), particularly infections by parasites selected from the group of ectoparasites and endoparasites described above.

[0253] In the context of animal health or veterinary medicine, the term "treatment" encompasses prophylactic treatment, post-infection protective treatment or therapeutic treatment.

[0254] In certain embodiments, there is provided a mixture of at least one compound of formula (I) with another active compound, particularly an endoparasiticide and an ectoparasiticide, in the field of veterinary medicine.

[0255] In the field of animal health, a "mixture" not only means that two (or more) different active ingredients are formulated into a joint formulation and thereby applied together, but also refers to a product containing separate formulations for each active compound. Thus, when using more than two active compounds, it is possible to formulate all the active compounds into a joint formulation or to formulate all the active compounds into separate formulations; furthermore, a mixed form is also possible in which some of the active compounds are formulated together and some of the active compounds are formulated separately. In the case of separate formulations, the plurality of active compounds can be applied separately or can be applied continuously.

[0256] The active compounds identified herein by their "common names" are known and can be found, for example, in the "Pesticide Manual" (see above) or can be searched for on the Internet (e.g., " http: / / www.alanwood.net / pesticides ").

[0257] Exemplary active ingredients selected from the group of said killing external parasite drugs as a mixing partner include insecticides and acaricides described in detail above, but are not limited thereto. Regarding further active ingredients that can be used, they are listed below according to the above classification based on the current "IRAC Mode of Action Classification Scheme": (1) acetylcholinesterase (AChE) inhibitors; (2) GABA-dependent chloride channel blockers; (3) sodium channel modulators; (4) nicotinic acetylcholine receptor (nAChR) competitive modulators; (5) nicotinic acetylcholine receptor (nAChR) allosteric modulators; (6) glutamate-dependent chloride channel (GluCl) allosteric modulators; (7) juvenile hormone mimics; (8) various non-specific (multi-site) inhibitors; (9) chordotonal organ modulators; (10) mite growth inhibitors; (12) inhibitors of mitochondrial ATP synthase, for example, ATP disruptors; (13) uncouplers of oxidative phosphorylation by disrupting the proton gradient; (14) nicotinic acetylcholine receptor channel blockers; (15) inhibitors of chitin biosynthesis (type 0); (16) inhibitors of chitin biosynthesis (type 1); (17) molting disruptors (especially in Diptera, i.e., flies); (18) ecdysone 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) inhibitors of acetyl-CoA carboxylase; (28) ryanodine receptor modulators; (30) GABA-dependent chloride channel allosteric regulators.

[0258] Active compounds whose mechanism of action is unknown or non-specific, such as, fentrifanil, phenoxacrim, cycloprene, chlorobenzilate, chlordimeform, flubenzimine, diclranil, amidoflumet, quinomethionate, triarathene, chlorothiazoben, tetrasul, potassium oleate, petroleum, methoxadiazone, gossypol, flutenzin, bromopropylate, cryolite; Another type of compound, such as, butacarb, dimetan, chloethocarb, phosphocarb, pirimiphos (-ethyl), parathion (-ethyl), methacrifos, isopropyl o-salicylate, trichlorfon, tigolaner, sulprofos, propaphos, sebufos, pyridathion, protocate, dichlofenthion, dimethon-S-methyl sulfone, isazofos, cyanofenphos, dialifos, carbophenothion, autathiphos, aromufenvinphos (-methyl), azinphos (-ethyl), chlorpyrifos (-ethyl), phosmet, iodofenphos, dioxabenzofos, formothion, honphos, flupyrazofos, fensulphothion, ethirimfos; Organochlorine compounds, such as, camphechlor, lindane, heptachlor; or, phenylpyrazole-based, such as, acetoprole, pyrafluprole, pyriprole, vaniliprole, thiacloprid; or, isoxazoline-based, such as, sarolaner, afoxolaner, lotilaner, fluralaner; Pyrethroid-based, such as, (cis-, trans-) metofluthrin, profuthrin, flufenprox, flubrocythrinate, fubfenprox, fenfluthrin, protriofenbut, pyresmethrin, RU15525, terallethrin, cis-resmethrin, heptafluthrin, bioethanomethrin, biopermethrin, fenpyrethrin, cis-cyphenothrin, cis-permethrin, cyfluthrin, cyhalothrin (lambda-), crotoxyphos, or, halogenated hydrocarbon compounds (HCHs); Neonicotinoid-based, such as, nithiazine; Dicloromezotiaz, triflumezopyrim; Macrocyclic lactones, such as, nemadectin, ivermectin, latidectin, moxidectin, selamectin, eprinomectin, doramectin, emamectin benzoate; milbemycin oxime; Triphenylene, epophenanthrene, diphenolane; Biological agents, hormones, or pheromones, such as, natural products, such as, thuringiensin, codlemone, or neem components; Dinitrophenol-based, such as, dinocap, dinobuton, binapacryl; Benzoylurea-based, such as, fluazuron, penfluron; Amidine derivatives, such as, chlormebuform, simiazole, demiditraz; Beehive varroa acaricides, such as, organic acids, such as, formic acid, oxalic acid.

[0259] Exemplary active ingredients selected from the group of said endoparasite-killing drugs as a mixed partner include, but are not limited to, anthelmintic active compounds and antiprotozoal active compounds.

[0260] Said anthelmintic active compounds include, but are not limited to, the following nematocidal active compounds, trematocidal active compounds and / or cestocidal active compounds.

[0261] Types of macrocyclic lactones, such as: eprinomectin, abamectin, nemadectin, moxidectin, doramectin, selamectin, lepimectin, latidectin, milbemycin, ivermectin, emamectin, milbemycin; Benzimidazoles and probenzimidazoles, such as: oxibendazole, mebendazole, triclabendazole, thiophanate, parbendazole, oxfendazole, netobimin, fenbendazole, febantel, thiabendazole, cyclobenzendazole, cambendazole, albendazole sulfoxide, albendazole, flubendazole; Depsipeptides, preferably cyclic depsipeptides, particularly 24-membered cyclic depsipeptides, such as: emodepside, PF1022A; Tetrahydropyrimidines, such as: morantel, pyrantel, oxantel; Imidazothiazoles, such as: butamisole, levamisole, tetramisole; Aminophenylamidines, such as: amidantel, deacylated amidantel (dAMD), tribendimidine; Aminoacetonitriles, such as: monepantel; Paraherquamides, such as: paraherquamide, derquantel; Salicylanilides, such as: tribromsalan, bromoxanide, brotianide, clioxanide, closantel, niclosamide, oxyclozanide, rafoxanide; Substituted phenols, such as: nitroxynil, bithionol, disophenol, hexachlorophene, niclofolan, meniclopholan; Organophosphates, such as: trichlorfon, naphthalofos, dichlorvos / DDVP, crufomate, coumaphos, haloxon; Piperazinones / quinolines, such as: praziquantel, epsiprantel; Types of piperazines, such as: piperazine, hydroxydine; Types of tetracyclines, such as: tetracycline, chlortetracycline, doxycycline, oxytetracycline, rolitetracycline; Various other types, such as: bunamidine, niridazole, resorantel, omphalotin, oriptal, nitros canate, nitroxynil, oxamniquine, mirasan, miracil, lucanthone, hycanthone, hetolin, emetine, diethylcarbamazine, dichlorophene, diamphenethide, clonazepam, bephenium, amoscanate, chlorothr on.

[0262] Antiprotozoal active compounds include, but are not limited to, the following active compounds, among others, but are not limited thereto. Types of triazines, such as: diclazuril, ponazuril, retrazuril, toltrazuril; Types of polyether ionophores, such as: monensin, salinomycin, maduramycin, narasin; Types of macrolides, such as: milbemycin, erythromycin; Types of quinolones, such as: enrofloxacin, pradofloxacin; Types of quinine, such as: chloroquine; Types of pyrimidines, such as: pyrimethamine; Types of sulfonamides, such as: sulfachinoxaline, trimethoprim, sulfaclozine; Types of thiamines, such as: amprolium; Types of lincosamides, such as: clindamycin; Types of carbamilides, such as: imidocarb; Types of nitrofurans, such as: nifurtimox; Types of quinazoline alkaloids, such as: halofuginone; Various other types, such as: oxamniquine, paromomycin; The types of antigens from vaccines or microorganisms, such as: 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.

[0263] All the mixing partners described can form salts with suitable bases or acids, if possible, by their functional groups.

[0264] Control of vectors The compounds of formula (I) can also be used in the control of vectors. For the purposes of the present invention, a vector is an arthropod (in particular an insect or an arachnid) capable of transporting pathogens (such as viruses, worms, unicellular organisms and bacteria) from a pathogen-carrying host (plant, animal, human, etc.) to a host. The pathogen can be transported mechanically to the host (e.g., trachoma by non-biting flies), or can be transported after injection into the host (e.g., malaria parasites by mosquitoes).

[0265] Examples of vectors and the diseases or pathogens transported by vectors are as follows: 1) Mosquitoes - Anopheles: malaria, filariasis; - Culex: Japanese encephalitis, another viral disease, filariasis, transport of worms; - Aedes: Yellow fever, dengue fever, other viral diseases, filariasis; - Simulidae: Transmission of helminths (especially Onchocerca volvulus); - Psychodidae: Transmission of leishmaniasis; 2) Lice: Skin infections, epidemic typhus; 3) Fleas: Infectious diseases, spotted fever, tapeworms; 4) Flies: Sleeping sickness (trypanosomiasis); Cholera, other bacterial diseases; 5) Ticks: Acariosis, epidemic typhus, rickettsialpox, tularemia, Saint Louis encephalitis, tick-borne encephalitis (TBE), Crimean-Congo hemorrhagic fever, borreliosis; 6) Mites: Borrelioses, for example, Borrelia burgdorferi sensu lato., Borrelia duttoni, tick-borne encephalitis, Q fever (Coxiella burnetii), Babesia canis canis, ehrlichiosis.

[0266] In the context of the present invention, examples of vectors are insects capable of transporting plant viruses to plants, such as aphids, flies, leafhoppers or thrips. Other vectors capable of transporting plant viruses are mites, lice, beetles and nematodes.

[0267] In the context of the present invention, further examples of vectors are insects and arachnids capable of transporting pathogens to animals and / or humans, such as mosquitoes [in particular, mosquitoes of the genus Aedes, Anopheles mosquitoes, such as Anopheles gambiae, Anopheles arabiensis, Anopheles funestus, Anopheles dirus (malaria), and Culex mosquitoes], Psychodidid flies, such as Phlebotomus, Lutzomyia, lice, fleas, flies, mites and ticks.

[0268] If the compound of formula (I) is resistance-breaking, vector control is likewise possible.

[0269] The compound of formula (I) is suitable for use in the prevention of diseases and / or the prevention of pathogens carried by vectors. Thus, a further aspect of the present invention is the use of a compound of formula (I) for controlling vectors, for example, in agriculture, in horticulture, in gardens and leisure facilities, and further, in the protection of material substances and stored products.

[0270] Protection of industrial materials The compound of formula (I) is suitable for protecting industrial materials against attack or destruction by insects [such as insects of the orders Coleoptera, Hymenoptera, Isoptera, Lepidoptera, Psocoptera and Zygentoma].

[0271] In the context of the present invention, industrial materials are understood to mean abiotic materials, such as, preferably, plastics, adhesives, sizes, paper and cardboard, leather, wood, processed wood products and paints, etc. The present invention is particularly preferably used for protecting wood.

[0272] In a further embodiment, the compounds of formula (I) are used together with at least one further insecticide and / or at least one fungicide.

[0273] In a further embodiment, the compounds of formula (I) are present as ready-to-use pesticides, i.e. they can be applied to the material substance without further modification. Suitable further insecticides or fungicides are, in particular, those mentioned above.

[0274] Surprisingly, it has also been found that the compounds of formula (I) can be used to protect objects in contact with sea water or brackish water, in particular hulls, screens, nets, buildings, mooring facilities and signalling systems, etc. from fouling. Similarly, the compounds of formula (I) can be used as antifouling agents, either alone or in combination with other active compounds.

[0275] Control of pests in the hygiene field The compounds of formula (I) are suitable for controlling pests in the hygiene field. In particular, the present invention can be applied to control insects, arachnids, bedbugs and mites encountered in the domestic field, in the hygiene field and in the protection of stored products, in particular in enclosed spaces such as dwellings, factory corridors, offices, passenger compartments of vehicles, animal breeding facilities. To control pests, the compounds of formula (I) are used alone or in combination with other active compounds and / or adjuvants. They are preferably included in household insecticide products. The compounds of formula (I) are effective against sensitive and resistant species and are further effective against all stages of development.

[0276] These pests include, for example, pests of the order Scorpiones, Araneae, and Opiliones of the class Arachnida, pests of the classes Chilopoda and Diplopoda, pests of the order Blattodea, Coleoptera, Dermaptera, Diptera, Heteroptera, Hymenoptera, Isoptera, Lepidoptera, Phthiraptera, Psocoptera, Saltatoria or Orthoptera, Siphonaptera, and Zygentoma of the class Insecta, and pests of the order Isopoda of the class Malacostraca.

[0277] They are used, for example, in aerosol, non-pressurized spray products such as pump sprays and aerosol sprays, automatic fogging systems, foggers, foams, gels, evaporator products having cellulose or plastic evaporator tablets, liquid evaporators, gel and membrane evaporators, propeller-driven evaporators, energy-free or passive evaporation systems, moth papers, moth bags, and moth gels, or as granules or powders, incorporated into baits for spreading or used at bait stations.

[0278] Abbreviations and Symbols AcOH: acetic acid aq.: aqueous br.: broad d: doublet DABCO: 1,4-diazabicyclo[2.2.2]octane DCC: N,N′-dicyclohexylcarbodiimide DCM: dichloromethane DIPEA: N,N-Diisopropylethylamine DMF: N,N-Dimethylformamide DMSO: Dimethyl sulfoxide ee: Enantiomeric excess eq.: Equivalent ES: Electrospray ionization Et3N: Triethylamine EtOAc: Ethyl acetate h(rs): Hours HATU: 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo 4,5-b]pyridinium-3-oxide hexafluorophosphate HOBt: 1-Hydroxybenzotriazole hydrate HPLC: High-performance liquid chromatography iPrOH: Isopropanol J: Coupling constant LCMS: Liquid chromatography - mass spectrometry m / z: Mass / charge ratio M: Molarity m: Multiplet MeCN: Acetonitrile MeOH: Methanol NaH2PO4: Sodium dihydrogen phosphate NaOH: Sodium hydroxide Na2SO4: Sodium sulfate NH4Cl: Ammonium chloride NMR: Nuclear magnetic resonance q: Quartet rt: Room temperature R t : Retention time s: Singlet sat.: Saturated T: Temperature t: Triplet T3P®: Propylphosphonic anhydride THF: Tetrahydrofuran TMSOK: Potassium trimethylsilanolate wt.: Weight xantphos: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene δ: Chemical shift λ: Wavelength.

[0279] Description of Processes and Intermediates 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 previously defined, and X 1 represents OH or Cl.

[0280] Scheme 1

Chemical formula

[0281] X 1 =OH: React the triazole compound of formula (1) with the carboxylic acid of formula (2a) (X 1 =OH) to form the compound of formula (I′). For example, in a suitable solvent such as ethyl acetate or DMF, a mixture of the triazole of formula (1), the carboxylic acid of formula (2a) (X 1 =OH), a suitable coupling reagent such as T3P (registered trademark), HATU or DCC / HOBt, and a suitable base such as triethylamine or DIPEA is mixed at a temperature in the range of about 0 to 100 °C to provide the compound of formula (I′), which can then be isolated and, if necessary and desired, purified using techniques known in the art such as chromatography.

[0282] X 1 =Cl: React the triazole compound of formula (1) with the carboxylic acid chloride of formula (2b) (X 1 =Cl) to form the compound of formula (I′). For example, in a suitable solvent such as dichloromethane or THF, the triazole of formula (1), the carboxylic acid chloride of formula (2b) (X 1A mixture of a suitable base such as triethylamine or DIPEA is admixed at a temperature in the range of about 0 to 100 °C to obtain a compound of formula (I'), which is then isolated and, if necessary and desired, can be purified using techniques known in the art such as chromatography.

[0283] The thioamide of formula (I) (X = S) can be obtained, for example, by treating a compound of formula (I') with Lawesson's reagent in boiling toluene according to the method described in WO2005009435.

[0284] 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 a specific carboxylic acid of formula (2a) (X 1 = OH) is described in WO2019 / 197468.

[0285] 3-[(1,1,2,2-Tetrafluoroethyl)sulfanyl]benzoic acid: Synthesis described in J. Org. Chem. 1964, vol 29, 895-898. Separate synthesis is possible starting from 3-sulfanylbenzoic acid, which is first converted to the methyl ester with HCl / MeOH and then alkylated with 1,2-dibromo-1,1,2,2-tetrafluoroethane in DMSO at 60 °C in the presence of cesium carbonate. The resulting methyl 3-[(2-bromo-1,1,2,2-tetrafluoroethyl)sulfanyl]benzoate is de-brominated with Zn in AcOH at 50 °C. Hydrolysis of the methyl ester gives 3-[(1,1,2,2-tetrafluoroethyl)sulfanyl]benzoic acid.

[0286] The compounds of formula (1) can be prepared according to the method depicted in Scheme 2 below, where R 1 and R 3 are as previously defined and R 4 is hydrogen or C1-C3 alkyl.

[0287] Scheme 2 [Chemical]

[0288] React the amide of formula (3) with N,N-dimethylamidedimethylacetal 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 (e.g., hydrochloride) under acidic conditions to form a compound of formula (7). For example, the compound of formula (3) and N,N-dimethylamidedimethylacetal of formula (4) are reacted under reflux in a suitable solvent such as CH2Cl2 to provide a compound of formula (5). After removal of the solvent, the compound of formula (5) is reacted with a substituted hydrazine of formula (6) or a suitable salt thereof (e.g., hydrochloride) in a suitable solvent such as 1,4-dioxane, acetic acid or a mixture of such solvents at a temperature in the range of about 20 - 80 °C. The resulting compound of formula (7) is then isolated and can be purified using techniques known in the art such as chromatography, if necessary and desired.

[0289] React the carbamate of formula (7) with an acid to form the amine of formula (1). For example, the carbamate of formula (7) and a suitable acid, such as hydrogen chloride or trifluoroacetic acid, are reacted in a suitable solvent such as 1,4-dioxane, or in the case of trifluoroacetic acid without adding an additional solvent, at a temperature in the range of about 0 - 80 °C. The resulting amine of formula (1) can then be isolated as its acid salt or as the free amine after base treatment and can be purified using techniques known in the art such as chromatography, if necessary and desired.

[0290] The required amide of formula (3) and hydrazine of formula (6) or a suitable salt thereof (e.g., hydrochloride) are commercially available or can be synthesized by the methods described in this application or methods known to those skilled in the art.

[0291] For example, the hydrazine of formula (6) can be obtained as follows.

[0292] 6-Hydroxypyrimidine-4-carboxylic acid is obtained according to the methods described in J. Org. Chem. 1961, 2755; WO2010 / 20432A2; US2011 / 21500A1 or US2007 / 259860A1 and converted to 6-chloropyrimidine-4-carbonyl chloride in the same manner as in WO2010 / 20432A2. Next, the latter acid chloride functional group is converted to an amide by reaction with a suitable amine at 0 °C in a solvent such as THF. When the reaction amine is different from ammonia, only 1 equivalent of the reaction amine is used and a suitable base such as triethylamine is further used. Such types of amides are known from Chemistry of heterocyclic compounds 1972, vol8, p509. Finally, in the same manner as in Ukrainskii Khimicheskii Zhurnal 1982, 48(1), 67-69, the chloropyrimidine functional group is converted to hydrazinopyrimidine by reacting with hydrazine hydrate in a solvent as methanol at room temperature or at a maximum high temperature of 65 °C.

[0293] The compound of formula (I′) can alternatively be prepared according to the method depicted in Scheme 3 below, where R 1 , R 2 , R 3 and R 4 are as previously defined and R 5 is hydrogen or C1-C3 alkyl.

[0294] Scheme 3

Chemical formula

[0295] React the amide of formula (8) 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 (e.g., hydrochloride) under acidic conditions to form a compound of formula (I′). For example, react the compound of formula (8) and N,N-dimethylamidedimethylacetal of formula (4) under reflux in a suitable solvent such as CH2Cl2 to obtain a compound of formula (9). After removing the solvent, react the compound of formula (9) with a substituted hydrazine of formula (6) or a suitable salt thereof (e.g., hydrochloride) in a suitable solvent such as 1,4-dioxane, acetic acid or a mixture of such solvents at a temperature in the range of about 20 to 100 °C. Next, isolate the obtained compound of formula (I′) and purify it using techniques known in the art such as chromatography, if necessary and desired.

[0296] 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 methods known to those skilled in the art.

[0297] The required amide of formula (8) can be produced according to the method depicted in Scheme 4 below, where R 1 and R 2 are as described above (see also WO2017 / 192385).

[0298] Scheme 4

Chemical formula

[0299] React the aminoamide of formula (10) with the carboxylic acid of formula (2a) (X 1 = OH) to form a compound of formula (8). For example, in a suitable solvent such as ethyl acetate or DMF, the aminoamide of formula (10), carboxylic acid (2a) (X 1A mixture of a suitable coupling reagent such as =OH), T3P (registered trademark), HATU or DCC / HOBt, and a suitable base such as triethylamine or DIPEA is admixed at a temperature in the range of about 0 to 100 °C to obtain a compound of formula (8), which is then isolated and, if necessary and desired, can be purified using techniques known in the art such as chromatography.

[0300] Alternatively, the aminoamide of formula (10) is reacted with the carboxylic acid chloride of formula (2b) (X 1 =Cl) to form a compound of formula (8). For example, in a suitable solvent such as dichloromethane or THF, a mixture of the aminoamide of formula (10), the carboxylic acid chloride of formula (2b) (X 1 =Cl), and a suitable base such as triethylamine or DIPEA is admixed at a temperature in the range of about 0 to 100 °C to obtain a compound of formula (8), which is then isolated and, if necessary and desired, can be purified using techniques known in the art such as chromatography.

[0301] The compound of formula (10) is either 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 either 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) is described in WO2019 / 197468.

[0302] Scheme 5 depicts the production of alkyltriazoles and cycloalkyltriazoles containing amine (1a), where R 4 is C1-C3 alkyl or C3-C4 cycloalkyl. Z is NH2 or OC1-C6 alkyl.

[0303] Scheme 5

Chemical Formula

[0304] React N-(tert-butoxycarbonyl)-alanine (3a) with an alkylamidine (11a, Z = NH2) or an alkylimidate (11b, Z = OC1-C6 alkyl) to form an intermediate of formula (12), and then react it with a substituted hydrazine of formula (6) to form an alkyltriazole of formula (7a).

[0305] For example, in the case of (11a, Z = NH2) (compare J. Org. Chem. 2011, 76, 1177-1179), in a suitable solvent such as DMF, in the presence of a suitable coupling reagent such as HATU and a suitable base such as triethylamine or DIPEA, at a temperature in the range of 0 to 50 °C, react N-(tert-butoxycarbonyl)-alanine and the alkylamidine of formula (11a) to obtain an acylamidine intermediate of formula (12). After removing the solvent, in a suitable solvent such as acetic acid, at a temperature in the range of about 20 to 80 °C, react the intermediate of formula (12) with a substituted hydrazine of formula (6) or a suitable salt thereof (e.g., hydrochloride). Next, the obtained alkyltriazole of formula (7a) can be isolated and purified using techniques known in the art such as chromatography, if necessary and desired.

[0306] When Z = OC1-C6 alkyl, in a suitable solvent such as THF, in the presence of a suitable coupling reagent such as HATU and a suitable base such as triethylamine or DIPEA, at a temperature in the range of about 0 to 25 °C, react N-(tert-butoxycarbonyl)-alanine and the alkylimidate of formula (11b) or a suitable salt thereof to form an acylimidate intermediate of formula (12b). After adding a substituted hydrazine of formula (6) or a suitable salt thereof (e.g., hydrochloride), react the intermediate of formula (12b) at a temperature in the range of about 20 to 80 °C to obtain an alkyltriazole of formula (7a), and then it can be isolated and purified using techniques known in the art such as chromatography, if necessary and desired.

[0307] The carbamate of formula (7a) is treated with an acid according to the method described in Scheme 2 for the amine of general formula (1) to form the amine of formula (1a) or a related salt.

[0308] The required alkylamidine (11a) and alkylimidate (11b) or their suitable salts and the hydrazine of formula (6) or its suitable salt (e.g., hydrochloride) are commercially available or can be synthesized by the methods described in this application or methods known to those skilled in the art (see, for example, WO2011 / 133447 for the synthesis of methylcyclopropanecarboximidate hydrochloride).

[0309] The compound of formula (1b) in which the alkyl is C1-C3 alkyl and R 3 is as defined above can be prepared according to the method depicted in Scheme 6 below.

[0310] Scheme 6

Chemical formula

[0311] Tetrahedron: Asymmetry, 21(8), 936 - 942, 2010, 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoic acid and oxalyl chloride were used to produce 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl chloride (13), which was reacted with potassium thiocyanate (KSCN) in acetone to obtain the corresponding isocyanate intermediate (14). In the next step, it was treated with the corresponding alcohol (alkyl OH) to obtain O-alkyl [2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl]carbamothioate (15). According to the method described in Bioorganic & Medicinal Chemistry 26(2018) 3321 - 3344, the cyclized product of formula (16) was obtained by the reaction between the intermediate of formula (15) and hydrazine of formula (6) or its hydrohalide salt in ethanol. In the final step, according to the method described in WO2018 / 086605, the phthalimide protecting group was removed by reaction with hydrazine hydrate in a suitable solvent such as ethanol. Next, the obtained amine (1b) was reacted with a carboxylic acid according to the method described in Scheme 1 to form the example compound.

[0312] The compound of formula (21) can be produced according to the method depicted in Scheme 7 below, where E is H or C1 - C6 alkyl, Hal is bromine or iodine, R 22 is as described above, and G is cyclopropyl, where the cyclopropyl may be substituted by 1 - 2 substituents selected from the group of halogen, -CN, methyl or trifluoromethyl.

[0313] Scheme 7

Chemical Structure

[0314] The halogen-containing compound of formula (19) is reacted with the boronic acid of formula (20) or the corresponding boronic acid ester to form the compound of formula (21). For example, in a suitable solvent or solvent mixture such as toluene and water, a mixture of the halogen-containing compound of formula (19), the boronic acid (20), a suitable catalyst such as palladium(II) acetate combined with tricyclohexylphosphine, and a suitable base such as tripotassium phosphate is reacted at a temperature in the range of about 0 to 100 °C to obtain the compound of formula (21), which is then isolated and, if necessary and desired, can be purified using techniques known in the art such as chromatography. The compound of formula (21) in which E is C1-C6 alkyl can be converted to the compound of formula (21) in which E is H by treatment with an alkali hydroxide in a suitable solvent or a solvent mixture containing / such as tetrahydrofuran, ethanol or water at a temperature in the range of about 0 to 100 °C.

[0315] The compound of formula (23) can be prepared according to the method depicted in Scheme 8 below, where E is H or C1-C6 alkyl, Hal is iodine or bromine, Ra is C1-C3 alkyl or cyclopropyl, and R 22 is as described above.

[0316] Scheme 8 [Chemical formula]

[0317] The aryl halide of formula (20) is reacted with the sulfinate of formula (22) under copper salt catalysis to form the sulfone of formula (23).

[0318] For example, a mixture of the compound of formula (20), sodium sulfinate of formula (22), copper(I) iodide, proline and sodium hydroxide is reacted in a suitable solvent such as dimethyl sulfoxide at a temperature in the range of 40 to 140 °C (compare with WO2019 / 197468). In another approach, a mixture of the compound of formula (20), sodium sulfinate of formula (22), copper(I) iodide, trans-N,N-dimethylcyclohexane-1,2-diamine and cesium carbonate is reacted in a suitable solvent such as DMF at a temperature in the range of 40 to 140 °C.

[0319] Next, the obtained compound of formula (23) can be isolated and purified using techniques known in the art such as chromatography, if necessary and desired. By treating in a suitable solvent or solvent mixture containing / such as tetrahydrofuran, ethanol or water at a temperature in the range of about 0 to 100 °C with an alkali hydroxide, the compound of formula (23) where E is a C1-C6 alkyl can be converted to the compound of formula (23) where E is H. When E is a tert-butyl group, this 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 in the range of 0 to 40 °C.

[0320] Aryl halide (20) and the sulfinate salt of formula (22) can be commercially available or synthesized by methods known to those skilled in the art.

[0321] In another approach, the compound of formula (23a) can be prepared according to the method depicted in Scheme 9a below, where Hal is fluorine or chlorine, Ra is C1-C3 alkyl or cyclopropyl, and R 22 is as described above.

[0322] Scheme 9a

Chemical formula

[0323] React the aryl halide of formula (24) with the thiolate salt of formula (25) to form the thioether of formula (26), and then hydrolyze it to form the carboxylic acid of formula (27). In the third step, oxidize the thioether of formula (27) to the sulfone of formula (23a).

[0324] For example, a mixture of the halide of formula (24) and sodium thiosulfate of formula (25) is reacted in a suitable solvent such as N,N-dimethylformamide at a temperature in the range of -20 to 50 °C. Next, the obtained nitrile of formula (26) is diluted in a suitable solvent or solvent mixture such as isopropanol or methanol / THF at a temperature in the range of 40 to 100 °C under basic conditions using, for example, an aqueous sodium hydroxide solution, or diluted with a suitable diluent such as an inorganic diluent or water, and hydrolyzed under acidic conditions in a suitable strong acid such as sulfuric acid or hydrochloric acid at a temperature in the range of 40 to 100 °C. Next, the obtained carboxylic acid (27) is purified, if necessary and desired, using techniques known in the art such as chromatography (see also the synthesis of 3-chloro-5-(difluoromethyl)benzoic acid described in the present application for the conditions of basic hydrolysis, and US20060276536 for the conditions of acidic hydrolysis).

[0325] The thioether-containing compound of formula (27) is reacted in a suitable solvent such as dichloromethane at a temperature in the range of 0 to 50 °C with an oxidizing reagent such as 3-chloroperbenzoic acid or a combination of formic acid and hydrogen peroxide to form the sulfone of formula (23). Next, the obtained sulfone of formula (23a) is purified, if necessary and desired, using techniques known in the art such as chromatography.

[0326] The required aryl halide (24) and thioate salt of formula (25) are commercially available or can be synthesized by methods known to those skilled in the art (for example, for the synthesis of cyclopropanethiol, see WO2013 / 049250). The thioate salt can be synthesized from the corresponding thiol by deprotonation with sodium hydride in a suitable solvent such as N,N-dimethylformamide.

[0327] In yet another approach, the compound of formula (23b) can be prepared according to the method depicted in Scheme 9b below, where Hal is chlorine, bromine or iodine, Ra is C1-C3 alkyl or C1-C3 haloalkyl, and R 22is as described above.

[0328] Scheme 9b

Chem.

[0329] Dibromobenzene of formula (43) can be lithiated at a low temperature in the range of -78 to 0 °C according to the method described in WO2009148052 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 reagent (46) in the presence of a base and, in the case of CF3Hal, in the presence of a phase transfer catalyst such as 1,1′-dimethyl-[4,4′-bipyridine]-1,1′-diium dichloride.

[0330] The resulting sulfane of formula (47) can be carbonylated and then oxidized by a method known to those skilled in the art to obtain the sulfone of formula (23b).

[0331] The compound of formula (34) can be produced according to the method depicted in Scheme 10 below. R f is C1-C3 haloalkyl, and R 21 is as described above. Hal is, when R f is difluoromethyl, iodine or chlorine. When R 21 is iodine or bromine, it can be converted to an optionally substituted cyclopropyl according to the method described in Scheme 7.

[0332] Scheme 10

Chem.

[0333] For example, in the method described in Tetrahedron Letters, 2012, 53(20), 2548-2551, the aryl fluoride of formula (28) is reacted with sodium sulfite (29) to form the thiol of formula (30). Next, an alkylated condition is used, for example, with a haloalkyl iodide or difluoromethyl chloride and a suitable base, to form a haloalkyl thioether (32). In the case of trifluoromethyl iodide, for example, an additional catalyst described in WO2015035223 is used. Next, the nitrile functional group is hydrolyzed to form the carboxylic acid of formula (33). In an additional step, the thioether of formula (33) is oxidized to the sulfone of formula (34).

[0334] For example, a mixture of the aryl fluoride of formula (28) and sodium sulfite (29) is reacted at a temperature in the range of -20 to 50 °C in a suitable solvent such as N,N-dimethylformamide. Next, the obtained thiol of formula (30) is alkylated with trifluoromethyl iodide at a temperature in the range of -20 to 50 °C in a suitable solvent such as N,N-dimethylformamide, in the presence of, for example, triethylamine and 1,1′-dimethyl-4,4′-bipyridinium dichloride.

[0335] In a suitable solvent such as methanol, at a temperature in the range of 40 to 100 °C, under basic conditions using, for example, an aqueous sodium hydroxide solution, or diluted with a suitable diluent such as an inorganic diluent or water at a temperature in the range of 40 to 100 °C, under acidic conditions in a suitable strong acid such as sulfuric acid or hydrochloric acid, the obtained thioether of formula (32) is hydrolyzed. Next, the obtained carboxylic acid (33) is purified using techniques known in the art such as chromatography, as necessary and desired.

[0336] The thioether-containing compound of formula (33) is reacted with an oxidizing reagent such as 3-chloroperbenzoic acid at a temperature in the range of 0 to 50 °C in a suitable solvent such as a mixture of dichloromethane or acetic acid and hydrogen peroxide to form the sulfone of formula (34). Next, the obtained sulfone of formula (34) is purified using techniques known in the art such as chromatography, as necessary and desired.

[0337] The necessary aryl fluoride (28) is commercially available or can be synthesized by methods known to those skilled in the art.

[0338] In another approach, the acid of formula (38) containing a substituted cyclopropyl group can be prepared according to the method depicted in Scheme 11 below, where R 22 is as described above, and Z 1 is -CN or -CO2C1-C6 alkyl. Z 2 and Z 3 are independently selected from the group consisting of hydrogen, halogen, -CN, methyl, or trifluoromethyl, provided that, as a requirement, no more than a maximum of 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 a suitable ligand substitution.

[0339] Scheme 11

Chemical formula

[0340] The alkene-containing compound of formula (35) is reacted with free carbene (36a), zinc carbenoid (36c), and certain transition metal carbene complexes (36b) to obtain the cyclopropyl-containing compound of formula (37). These are then converted to the acid of formula (38) by ester cleavage (when Z 1 is -CO2C1-C6 alkyl) or by hydrolysis of the cyano group (when Z 1 is -CN). The various cyclopropanation reactions are known to those skilled in the art and are reviewed in the literature (e.g., Chem. Rev. 2017, 117, 11651-11679).

[0341] In the case of the reaction with zinc carbenoid (36c), first, Et2Zn is reacted with trifluoroacetic acid at 0 °C in a suitable solvent such as pure dichloromethane, and then CH2I2 is added to generate zinc carbenoid. When an alkene (35) is added, the pre-formed zinc carbenoid reacts with the alkene at a temperature in the range of 20 to 40 °C to form cyclopropane (see also WO2012 / 139775).

[0342] Various transition metal carbene complexes (36b) have been found to be suitable for the cyclopropanation reaction. Examples of suitable precursors for such complexes are CuBr, Pd(OAc)2, Rh(OAc)4 or iron(III)-5,10,15,20-tetraphenyl-porphyrin (Fe(TPP)Cl).

[0343] In the case of the reaction via a palladium carbene complex, a solution of an alkene (35) in a suitable solvent such as tetrahydrofuran or diethyl ether is treated with a solution of diazomethane in a suitable solvent such as diethyl ether in the presence of a suitable palladium salt such as Pd(OAc)2 at a temperature in the range of 0 °C to 20 °C (see also WO2014 / 023367). A trifluoromethyl-substituted cyclopropyl group can be obtained by reacting an alkene (35) with an iron carbene complex obtained from in-situ generated trifluoromethyldiazomethane and Fe(TPP)Cl according to the method described in Angew. Chem. Int. Ed. 2010, 49, 938 - 941.

[0344] In the case of the reaction with free carbene (36a), a solution of an alkene (35) in a suitable solvent is mixed with a carbene precursor that generates free carbene in-situ. For example, a solution of an alkene (35) in diglyme is heated at a temperature in the range of 60 to 80 °C in the presence of sodium bromo(difluoro)acetate. An alternative carbene precursor is, for example, trimethyl(trifluoromethyl)silane, which is used in combination with sodium iodide (according to the method described in WO2017 / 040742).

[0345] The final hydrolysis with the cyano group being the corresponding acid (38) can be carried out under basic or acidic conditions according to the method described in Scheme 9. The hydrolysis of the ester can be carried out according to the method described in Scheme 8.

[0346] The alkenes (35) and reagents necessary for the generation of free carbenes (36a), zinc carbenoids (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) via palladium-catalyzed coupling reactions, reference is made, for example, to WO2013 / 178362 (1-bromo-3-(1,1-dimethylethyl)-5-(1-methylethenyl)benzene) and WO2012 / 035011 (1,5-dichloro-2-fluoro-3-(3,3,3-trifluoroprop-1-en-2-yl)benzene).

[0347] The following production examples and usage examples illustrate the present invention but do not limit the present invention.

[0348] Scheme 12 depicts the production of triazole-containing amine (1b), where R 4 , R 31 and R 32 are as described above, Alk is C1-C3 alkyl, and Hal is chlorine, bromine or iodine.

[0349] In a suitable solvent such as acetic acid, at a temperature in the range of about 20 to 80 °C, the intermediate of formula (5a) or (12) is reacted with a substituted hydrazine of formula (39) or a suitable salt thereof (for example, hydrochloride). Next, the obtained 4-halogeno-pyrimidin-6-yl-triazole of formula (40) can be isolated and purified, if necessary and desired, using techniques known in the art such as chromatography.

[0350] Next, in a similar manner to the description in WO2012 / 035039, in a suitable C1-C3 alcohol such as methanol or ethanol, in the presence of a palladium catalyst such as dichlorobis(1,1'-bis(diphenylphosphino)ferrocene)palladium, 4-halo-pyrimidin-6-yl-triazole of formula (40) is pressurized with carbon monoxide. The ester of formula (41) obtained can be converted to the amide of formula (42) by the method described in the present application or a method known to those skilled in the art.

[0351] For the amine of general formula (1), the carbamate of formula (42) is treated with an acid according to the method described in Scheme 2 to form the amine of formula (1b) or a related salt.

[0352] The required amidine (5a) and imidate (12) are described in Scheme 2 and Scheme 5, and the hydrazine of formula (39) or a suitable salt thereof (e.g., hydrochloride) is commercially available or can be synthesized by the method described in the present application or a method known to those skilled in the art.

[0353] Scheme 12

Chemical formula

[0354] The compound of formula (53) can be produced according to the method depicted in Scheme 13 below. R 22 is as described above.

[0355] Scheme 13

Chemical formula

[0356] In the same manner as the method described in WO2017 / 055859, the aryl bromide of formula (49) is readily converted to the 1-hydroxy-1-methylethyl aryl compound of formula (50) using a Grignard reagent such as isopropylmagnesium chloride and acetone as an electrophile. The resulting compound (50) is carbonylated and then 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).

[0357] The compound of formula (59) can be prepared according to the method depicted in Scheme 14 below. R f is C1-C3 haloalkyl and LG is a leaving group such as chlorine, bromine, iodine or methylsulfonate.

[0358] Scheme 14

Chemical formula

[0359] Methyl 3,5-dimercaptobenzoate (57) can be readily prepared according to the known procedure described in US20020072583. R f Haloalkylation with LG is described, for example, in WO2004 / 007444 or that with CF2ClCO2Na is described in WO2020 / 002563. The resulting thioether compound (58) is oxidized by methods known to those skilled in the art and then hydrolyzed to obtain the benzoic acid of formula (59).

[0360] Preparation of Examples 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) Step 1:2N-[(2S)-1-Amino-1-oxopropan-2-yl]-3-bromo-5-(trifluoromethoxy)benzamide [Chemical formula]

[0361] 1.75 g (14.0 mmol) of L-alanine amide 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. To the mixture, 3.1 mL (5.3 mmol) of 50% T3P (cyclic propane phosphonic anhydride) in EtOAc was added. The mixture was stirred at room temperature overnight. When water was added to the reaction mixture, a white precipitate was formed. The precipitate was separated by filtration and dissolved in ethyl acetate. The solution was washed successively with dilute hydrochloric acid (10%), water, saturated aqueous NaHCO3 and brine. Evaporation of the solvent gave 1.13 g of N-[(2S)-1-amino-1-oxopropan-2-yl]-3-bromo-5-(trifluoromethoxy)benzamide. ESI mass [m / z]: 355.0 [M+H] + .

[0362] 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) [Chemical formula]

[0363] 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 CHCl was added 0.09 mL (0.67 mmol) of N,N-dimethylformamide dimethyl acetal. The solution was heated to reflux for 2 hours, after which 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-hydrazinopyrimidine-4-carbonitrile hydrochloride was added, and the mixture was stirred at 80°C for 2 hours. 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. 1 H-NMR (400 MHz, DMSO-d6): d = 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). ESI mass [m / z]:484.1[M+H] + .

[0364] 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) Step 1: 6-Hydrazinopyrimidine-4-carbonitrile [ka]

[0365] 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 hours 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 isolated by filtration, washed with water, dissolved in acetonitrile, and dried under vacuum to give 159 mg of 6-hydrazinopyrimidine-4-carbonitrile hydrochloride. The mother liquor from the filtration step was made basic with aqueous NaHCO3. This was insufficient to dissolve the small amount of solid precipitate that had formed after filtration. The entire suspension was transferred to a separatory funnel and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, and filtered. Evaporation of the solvent under reduced pressure yielded 120 mg of 6-hydrazinopyrimidine-4-carbonitrile. The resulting 6-hydrazinopyrimidine-4-carbonitrile hydrochloride and 6-hydrazinopyrimidine-4-carbonitrile were combined and used in the next step without further purification. ESI mass [m / z]:136.1[M+H] + .

[0366] Step 2: tert-Butyl {1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate [ka]

[0367] N 2A solution of 0.26 g (1.35 mmol) of (tert-butoxycarbonyl)-alanine amide in CH2Cl2 (10 mL) was added to 0.27 mL (2.0 mmol) of N,N-dimethylformamide dimethyl acetal. The solution was heated to reflux for 2 hours, and then the solvent was removed under reduced pressure. The residue was 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-hydrazinopyrimidine-4-carbonitrile and 6-hydrazinopyrimidine-4-carbonitrile hydrochloride obtained in the first step was added as a solution in a mixture of 2 mL of glacial acetic acid and 2 mL of 1,4-dioxane. The mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified by chromatography on silica (ethyl acetate / cyclohexane) to obtain 201 mg of tert-butyl {1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate. 1 H-NMR (400 MHz, DMSO-d6): 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). ESI mass [m / z]: 316.1 [M+H] + 。

[0368] Step 3: 6-[5-(1-Aminoethyl)-1H-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride

Chemical formula

[0369] To a solution of tert-butyl {1-[1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl]ethyl}carbamate 100 mg (0.31 mmol) in 1,4-dioxane (3 mL) was added 0.79 mL (3.2 mmol) of a 4M HCl solution in 1,4-dioxane, and the mixture was stirred at room temperature overnight. Next, 0.50 mL (2.0 mmol) of an additional 4M HCl solution in 1,4-dioxane was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to afford the title compound (100 mg, purity 80%), which was used in the next step without further purification. 1 1H-NMR (400 MHz, DMSO-d6): 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). ESI mass [m / z]: 216.1 [amine + H] + 。

[0370] 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)

Chem.

[0371] To a solution of 67 mg (purity 64%, 0.18 mmol) of 3-cyclopropyl-5-(trifluoromethoxy)benzoic acid in N,N-dimethylformamide (DMF) (2 mL) were 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 hour. Next, 50 mg (purity 80%, 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. Next, the reaction mixture was directly purified by reverse-phase chromatography (water / acetonitrile) to obtain 31 mg of the title compound. ESI mass [m / z]: 444.1 [M+H] + 。 1 1H-NMR (400 MHz, DMSO-d6): 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).

[0372] Synthesis of methyl 3-bromo-5-(difluoromethoxy)benzoate Step 1: Methyl 3-bromo-5-hydroxybenzoate

Chemical formula

[0373] A solution of 3-bromo-5-hydroxybenzoic acid (49.9 g, 230 mmol) in MeOH (325 mL) was cooled to 7 - 8 °C in an ice bath. Next, SOCl2 (27.4 g, 16.79 mL, 230 mmol) was added dropwise to this solution over 25 minutes. The reaction mixture was warmed to room temperature, refluxed with stirring for 3 hours, cooled to room temperature, and stirred at this temperature for an additional 48 hours. All volatiles were removed under vacuum, and the residue was dissolved in ethyl acetate (400 mL). The solution was washed with NaHCO3, brine, dried over Na2SO4, and the volatiles were removed under reduced pressure. The residue was triturated with hexane (400 mL). The precipitate was filtered, washed with hexane / diethyl ether (1:1), and dried at 110 °C to give methyl 3-bromo-5-hydroxybenzoate (50.5 g) as a dark yellow powder. 1 1H NMR (400 MHz, CDCl3) 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 instrument.

[0374] Step 2: Methyl 3-bromo-5-(difluoromethoxy)benzoate [Chemical formula]

[0375] A mixture of methyl 3-bromo-5-hydroxybenzoate (23.1 g, 100 mmol), K2CO3 (41.5 g, 300 mmol), and ClF2CCOONa (45.7 g, 300 mmol) in DMF (350 mL) was stirred at 60 - 65 °C for 2 hours. The precipitate was separated, washed with acetone, and the filtrate was concentrated under reduced pressure to remove the solvent. The residue was dissolved in diethyl ether (300 mL), and the solution was allowed to stand at room temperature for 12 hours. The resulting precipitate was filtered and washed with water. The filtrate was washed with brine (300 mL), and the organic layer was concentrated under reduced pressure to remove the solvent. The oily residue was dissolved in hexane (250 mL) and maintained at room temperature for 2 hours. The resulting precipitate was removed by filtration, and the solvent was distilled off from the filtrate under reduced pressure. The residue was vacuum distilled (3 torr), and the fraction having a boiling point of 80 - 85 °C was collected to obtain 15.75 g of methyl 3-bromo-5-(difluoromethoxy)benzoate. 1 H NMR (400 MHz, CDCl3) 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 instrument. Recorded on a Varian Gemini 2000 instrument. 19 F NMR (376 MHz, CDCl3) δ = -84.89 (d, J = 72.7 Hz). (Recorded on a Varian Gemini 2000 instrument).

[0376] Synthesis of 3-methylsulfonyl-5-(trifluoromethoxy)benzoic acid

Chemical Structure

[0377] 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 DMF (60 mL) was degassed for 30 minutes by purging with argon. 5 g (17.5 mmol) of 3-bromo-5-(trifluoromethoxy)benzoic acid, 3.58 g (35 mmol) of sodium methanesulfinate, and 3.34 g (17.5 mmol) of copper(I) iodide were added, and the mixture was further purged with argon for 5 minutes. The mixture was stirred at 120 °C overnight, cooled to room temperature, and extracted three times with dichloromethane. The aqueous layer was acidified to pH 2 with concentrated hydrochloric acid and extracted again with dichloromethane. The dichloromethane layer was washed several times with brine. The layers were separated, and the combined organic layers were dried over anhydrous Na2SO4, filtered. The solvent was removed under reduced pressure, and the residue was triturated with n-pentane, filtered, and dried to obtain 3.2 g of 3-methylsulfonyl-5-(trifluoromethoxy)benzoic acid. 1 1H NMR (DMSO-d6, 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). ESI mass [m / z]: 285.0 [M+H] + 。

[0378] Similarly, the following intermediates were prepared.

[0379] 3-(Cyclopropylsulfonyl)-5-(trifluoromethoxy)benzoic acid ESI mass [m / z]: 311.0 [M+H] + 。

[0380] 3-Chloro-5-(4-chlorophenyl)sulfonyl-benzoic acid ESI mass [m / z]: 331.0 [M+H] + 。

[0381] Synthesis of 3-(difluoromethoxy)-5-methylsulfonyl-benzoic acid Step 1:Methyl 3-(trifluoromethoxy)-5-triisopropylsilylsulfanyl-benzoate

Chem.

[0382] To a stirred solution of triisopropylsilanethiol (21.45 g, 112 mmol) in toluene (500 mL) under an argon stream, NaH (5.03 g, 122 mmol, 60% dispersion in oil) was added portionwise. The mixture was stirred until no more gas evolved. Next, methyl 3-bromo-5-(trifluoromethoxy)benzoate (CAS: 1306763-53-0) (30 g, 100 mmol), XantPhos (6.13 g, 11.2 mmol), and Pd2(dba)3 (4.85 g, 5.3 mmol) were added to the reaction mixture in that order. The mixture was stirred at 100 °C overnight, cooled to room temperature, diluted with EtOAc (500 mL), and filtered through a thin layer of silica gel. After evaporation of the solvent, crude methyl 3-(trifluoromethoxy)-5-triisopropylsilylsulfanyl-benzoate (50 g, purity 50% by LC / MS, 64 mmol, 57% yield) was obtained and used in the next step without further purification.

[0383] Step 2: Methyl 3-(difluoromethylsulfanyl)-5-(trifluoromethoxy)benzoate

Chem.

[0384] A stirred solution of crude methyl 3-(trifluoromethoxy)-5-triisopropylsilylsulfanyl-benzoate (50 g, purity 50% by LC / MS, 64 mmol) in DMF (1000 mL) was added with sodium 2-chloro-2,2-difluoroacetate (29.27 g, 192 mmol) and cesium carbonate (62.55 g, 192 mmol) under an argon stream. The mixture was stirred at 100 °C overnight, cooled to room temperature, and the solvent was distilled off under reduced pressure. The residue was dissolved in water (1000 mL) and extracted with EtOAc (5 times with 250 mL). Methyl 3-(difluoromethylsulfanyl)-5-(trifluoromethoxy)benzoate (10.5 g, 34.7 mmol, yield 54.3%) was obtained after column chromatography.

[0385] Step 3: Methyl 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoate

Chem.

[0386] To a solution of methyl 3-(difluoromethylsulfanyl)-5-(trifluoromethoxy)benzoate (10.5 g, 34.7 mmol) in dichloromethane (200 mL) was added mCPBA (16.35 g, 93.9 mmol, purity 75%) portionwise at 0 °C under an argon stream. The mixture was stirred at room temperature overnight and the solvent was distilled off under reduced pressure. Methyl 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoate (6.8 g, 20.34 mmol, 58.63%) was obtained after column chromatography on silica gel.

[0387] Step 4: 3-(Difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoic acid

Chem.

[0388] 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, LiOH monohydrate (1.146 g, 27.459 mmol) was added at 0 °C, and the mixture was stirred at room temperature overnight. THF was distilled off under reduced pressure, the aqueous layer was acidified to pH = 3, and extracted with MTBE (5 times with 10 mL). Pure 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoic acid (3 g, 9.37 mmol, 34.12% yield) was obtained as a white solid after recrystallization from 30% aqueous EtOH. 1 1H NMR (DMSO-d6, 400 MHz): δ=7.47 (t, 1H), 8.21 (s, 1H), 8.32 (s, 1H), 8.40 (s, 1H), 13.79 (s, 1H). ESI mass [m / z]: 319.0 [M+H] + 。

[0389] 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) Step 1: 2-Chloro-6-(cyanomethyl)pyridine-4-carboxylic acid

Chemical formula

[0390] n-BuLi (91.14 mL, 2 M, 183.3 mmol) was diluted with anhydrous THF (150 mL) and cooled under argon to -78 °C. A solution of anhydrous acetonitrile (11.4 mL, 218.8 mmol) in anhydrous THF (30 mL) was added dropwise, and the reaction mixture was maintained at -78 °C for 30 minutes. 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 an additional 45 minutes and then at room temperature for 1 hour. Next, the reaction mixture was quenched with saturated aqueous citric acid (200 mL) and extracted with EtOAc (3 times with 250 mL). The organic layer was washed with water (3 times with 300 mL) and then with brine solution (200 mL), dried over anhydrous Na2SO4, 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 / DCM. The resulting solid was triturated with 50% diethyl ether / n-pentane to give 4.2 g (58% yield) of 2-chloro-6-(cyanomethyl)pyridine-4-carboxylic acid as an off-white solid. 1 H NMR (400 MHz, D6-DMSO): δ = 7.87 (s, 1H), 7.82 (s, 1H), 4.27 (s, 2H). COOH was not detected. ESI mass [m / z]: 195.0 [M-H] - 。

[0391] Step 2: 2-Chloro-6-(1-cyanocyclopropyl)pyridine-4-carboxylic acid (INT-12)

Chemical Structure

[0392] To a stirred solution of 2-chloro-6-(cyanomethyl)pyridine-4-carboxylic acid (3.5 g, 17.8 mmol) in acetonitrile (50 mL) under nitrogen was added tetrabutylammonium bromide (5.74 g, 17.8 mmol). Next, 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 an additional 30 minutes. The reaction mixture was cooled to 0 °C. 7.5 mL of an aqueous NaOH solution (50%) was slowly added dropwise over 20 minutes. Next, the reaction mixture was warmed to room temperature and stirred for an additional 24 hours. The reaction mixture was concentrated under reduced pressure at room temperature. The residue was diluted with water, acidified with citric acid (pH ~5) and extracted with EtOAc (3 times with 150 mL). The combined organic layers were washed with water (3 times with 100 mL), sodium thiosulfate solution (100 mL), and then brine solution (150 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by flash silica gel chromatography using a gradient of 0% to 10% acetone / DCM. The resulting solid was washed with n-pentane to afford 2 g (50% yield) of 2-chloro-6-(1-cyanocyclopropyl)pyridine-4-carboxylic acid (INT-12) as an off-white solid. 1 H NMR (400 MHz, DMSO-d6): 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). ESI mass [m / z]: 221.0 [M-H] - 。

[0393] Step 3: tert-Butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate

Chem.

[0394] tert-Butyl N-[(1S)-2-amino-1-methyl-2-oxo-ethyl]carbamate (40.0 g, 213 mmol) was dissolved in DCM (400 mL). Dimethylformamide dimethylacetal (38.0 g, 319 mmol, 42.4 mL) was added to the mixture. The reaction mixture was stirred at 40 °C for 2 hours. The reaction mixture was concentrated under reduced pressure. tert-Butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate (50.0 g, crude) was obtained as a colorless oil and used in the next step as the crude product.

[0395] Step 4: tert-Butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (INT-3)

Chem.

[0396] tert-Butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate (36.1 g, 267 mmol) was dissolved in dioxane (400 mL). 6-Hydrazinopyrimidine-4-carbonitrile (50.0 g, 206 mmol) was dissolved in AcOH (400 mL) and added to the mixture. The reaction mixture was stirred at 20 °C for 16 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, petroleum ether / EtOAc = 50 / 1 to 0 / 1). The crude product was triturated with MTBE (750 mL) at 20 °C for 30 minutes. tert-Butyl-N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (INT-3) (8.50 g, 27.0 mmol, yield 13.1%) was obtained as a white solid.

[0397] The enantiomeric excess of INT-3 was determined via Chiralpak OD_RH (acid): e e value = 95%; R t= 9.49 points. Method: chiral HPLC; Chiralcel OD-RH column (4.6 mm × 150 mm × 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. 1 H 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 on a Bruker AVANCE III 400 MHz. ESI mass [m / z]: 260.1 [M - C4H8 + H] +

[0398] Step 5: 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile: 2,2,2-trifluoroacetic acid (INT-4)

Chemical formula

[0399] tert-Butyl-N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (2 g, 6.34 mmol) was dissolved in 20 mL of dichloromethane. Trifluoroacetic acid (3.62 g, 31.7 mmol) was added slowly, and the reaction mixture was stirred at room temperature overnight and then heated to 40 °C for 3 hours to complete the reaction. The reaction mixture was evaporated to dryness under reduced pressure and used in the next step as a crude product. ESI mass [m / z]: 216.1 [amine + H] + 。

[0400] 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)

Chemical formula

[0401] 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. Next, the reaction mixture was concentrated under reduced pressure to remove the solvent and dissolved in acetonitrile. This solution was slowly added dropwise at room temperature to another acetonitrile solution prepared as a mixture of 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile (2,2,2-trifluoroacetate) (197 mg, purity 60%, 0.36 mmol) and DIPEA (140 mg, 1.08 mmol). The reaction mixture was stirred overnight at room temperature, diluted with water and dichloromethane, the organic layer was separated, and the solvent was removed under reduced pressure. The residue was purified by HPLC means to obtain the title compound as an off-white solid (86 mg, 56% yield). 1 1H NMR: Refer to the peak list in Table 1. ESI mass [m / z]: 420.3 [M+H] + 。

[0402] 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) Step 1:Ethyl cyclopropanecarboximidate hydrochloride [Chem.]

[0403] 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 (21.0 g, 140 mmol, yield 94.2%, HCl salt) was obtained as a white solid and used in the next step without further purification.

[0404] Step 2: Ethyl (Z)-N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidate [Chem.]

[0405] tert-Butyl N-[(1S)-2-amino-1-methyl-2-oxo-ethyl]carbamate (15.1 g, 79.7 mmol) was dissolved in THF (180 mL). 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) were added. The mixture was stirred at 25 °C for 3 h. Ethyl (Z)-N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidate (22.5 g, crude) in THF was obtained as a yellow liquid and used in the next step as a solution without further workup and purification.

[0406] Step 3:tert-Butyl N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate (INT-7)

Chemical formula

[0407] To a solution of ethyl (Z)-N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidate (15.0 g, 52.8 mmol) in THF, 6-hydrazinopyrimidine-4-carbonitrile (7.13 g, 52.8 mmol) was slowly added at 0 °C. The mixture was stirred at 25 °C for 16 h. The reaction mixture was quenched with H2O (200 mL) and extracted with ethyl acetate (3 times with 50 mL). The combined organic layers were washed with brine (200 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 50 / 1 to 3 / 1) to give 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, yield 29.6%, purity 99.1%) as a white solid.

[0408] The enantiomeric excess of INT-7 was determined via Chiralcel OD_RH (acid): e e value = 92.5%; R t = 14.45 min. Method: chiral HPLC; Chiralcel OD-RH column (4.6 mm × 150 mm × 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. 11H 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 on a Bruker AVANCE III 400MHz. ESI mass [m / z]: 356.0 [M+H] + .

[0409] 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)

Chemical formula

[0410] 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 at room temperature overnight. The 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.

[0411] 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile hydrochloride (INT-8) ESI mass [m / z]: 256.2 [amine + H] + .

[0412] 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-11) ESI mass [m / z]: 274.2 [amine + H] + .

[0413] 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) [ka]

[0414] 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 minutes. 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, extracted with DCM, the DCM layer was separated, washed with brine, concentrated under reduced pressure, and purified by preparative HPLC chromatography to obtain 11 mg (yield 6.5%) 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 (yield 54.2%) 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).

[0415] 3-bromo-N-[(1S)-1-[2-(6-cyanopyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]-5-(trifluoro-methoxy)benzamide (I-15) 1 1H NMR: Refer to the peak list in Table 1. ESI mass [m / z]: 524.1 [M+H] + 。

[0416] 6-[5-[(1S)-1-[[3-bromo-5-(trifluoromethoxy)benzoyl]amino]ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (I-13) 1 1H NMR: Refer to the peak list in Table 1. ESI mass [m / z]: 542.1 [M+H] + 。

[0417] Synthesis of Intermediate 6-Hydrazinopyrimidine-4-carboxamide / (6-Hydrazono-1,6-dihydropyrimidine-4-carboxamide) Step 1: 6-Chloropyrimidine-4-carbonyl chloride [Chemical formula]

[0418] Oxalyl chloride (26.0 mL, 297.0 mmol) was added dropwise over 1 hour to a mixture of 6-hydroxypyrimidine-4-carboxylic acid (13.86 g, 9.98 mmol) and DMF (0.13 mmol, 0.01 mL) in ethyl acetate (80 mL). The mixture was heated under reflux for 3 hours. Volatiles were removed 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).

[0419] Step 2: 6-Chloropyrimidine-4-carboxamide [Chemical formula]

[0420] 6-Chloropyrimidine-4-carbonyl chloride (11.03 g, 62.32 mmol) in THF (50 mL) was added within 10 minutes to aqueous ammonia (33%, 20 mL, 341 mmol) in a mixture of THF / ice water (0.3 L) under ice / water cooling, and the mixture was stirred for 1 hour. The mixture was acidified with aqueous HCl, and the organic solvents were removed under reduced pressure. The resulting precipitate was filtered, washed with water and dried to give 7.6 g (76% of theory, corrected for purity). ESI mass [m / z]: 158.1 [M+H] + . 1 H NMR (400 MHz, D6-DMSO): δ = 8.1 (m, 2H), 8.45 (br, 1H), 9.2 (s, 1H).

[0421] Step 3: 6-Hydrazinopyrimidine-4-carboxamide / (6-Hydrazono-1,6-dihydropyrimidine-4-carboxamide)

Chem.

[0422] 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 distilled off under reduced pressure. Aqueous HCl solution and aqueous K2CO3 solution were added until the pH reached 8. The resulting precipitate was filtered, washed with water and dried to give 7.03 g (95% of theory, corrected for purity). ESI mass [m / z]: 154.1 [M+H] + 。 1 H NMR (400 MHz, D6-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).

[0423] Synthesis of 6-[5-[(1S)-1-[(3,5-Dibromobenzoyl)amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (I-34) Step 1: 3,5-Dibromo-N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]benzamide

Chem.

[0424] 0.5 g (1.4 mmol) of N-[(2S)-1-amino-1-oxopropan-2-yl]-3,5-dibromobenzamide and 3 mL (22.6 mmol) of DMF-DMA in 40 mL of THF were stirred in a water bath of a rotary evaporator at a bath temperature of 65 °C for 10 minutes, and the solvent was distilled off under reduced pressure to obtain 0.61 g, which was used directly in the next step.

[0425] Step 2: 6-[5-[(1S)-1-[(3,5-Dibromobenzoyl)amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (I-34)

Chemical formula

[0426] 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-hydrazinopyrimidine-4-carboxamide were stirred in 60 mL of AcOH at 85 °C for 0.5 hour. The mixture was concentrated under reduced pressure, and aqueous K2CO3 solution, aqueous NaCl solution and EtOAc were added. The aqueous layer was extracted three times with THF / EtOAc. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. Crystallization of the residue from MeOH (including heating with activated carbon and hot filtration) gave 0.24 g (32%).

[0427] Refer to Table 1 for the analytical data.

[0428] Synthesis of 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-9) Step 1: tert-Butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate

Chemical formula

[0429] 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 dimethylacetal (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, R f = 0.67) indicated that the starting material had been consumed. The solution of the crude product (193 g, calculated) in dioxane was used in the next step without further purification.

[0430] Step 2: tert-Butyl N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate

Chemical formula

[0431] A reaction mixture of tert-butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate (193 g, 793 mmol, 1.00 eq) was dissolved in AcOH (1900 mL) and added dropwise to a mixture of (6-chloropyrimidin-4-yl)hydrazine (126 g, 873 mmol, 1.10 eq). The reaction mixture was stirred at 25 °C for 16 h. TLC (petroleum ether:ethyl acetate = 3:1, R f = 0.22) indicated that the starting material had been completely consumed. The reaction mixture was concentrated under reduced pressure. 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 (160 g, 493 mmol, 62.1% yield) was obtained as a white solid.

[0432] Step 3:Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate [ka]

[0433] 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 equiv.) in MeOH (1.50 L) under nitrogen, triethylamine (49.9 g, 493 mmol, 68.6 mL, 2.00 equiv.) and Pd(dppf)Cl (18.0 g, 24.6 mmol, 0.100 equiv.) were added. The suspension was degassed under reduced pressure and purged with CO (carbon monoxide) several times. The mixture was stirred at 40 °C under CO (246 mmol, 1.00 equiv.) (50.0 psi) for 16 h. TLC (petroleum ether:ethyl acetate = 1:1, R f =0.27), which indicated that the starting material had been consumed. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. 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 (80.0 g, 230 mmol, 46.6% yield) was obtained as a white solid. 1 H NMR (DMSO-d6) 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).

[0434] Step 4: tert-Butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate [Chemical formula]

[0435] Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate (40.0 g, 115 mmol, 1.00 equivalent) was dissolved in THF (240 mL) and MeOH (80.0 mL). NH4OH (96.6 g, 689 mmol, 106 mL, purity 25.0%, 6.00 equivalents) was added to the mixture. The reaction mixture was stirred at 25 °C for 6 hours. TLC (petroleum ether:ethyl acetate = 3:1, R f = 0.1) indicated that the raw material had been completely consumed. The reaction mixture was concentrated. The crude product was triturated with MTBE (300 mL) at 25 °C for 30 minutes. tert-Butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (64.0 g, 189 mmol, yield 82.1%, purity 98.2%) was obtained as a white solid. 1 H NMR (DMSO-d6) 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).

[0436] Step 5: 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-9) [Chemical formula]

[0437] 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, 4M HCl / dioxane (7.5 mL) was added, and the mixture was stirred at 50 °C for 7 hours and then at room temperature for an additional 4 days. The mixture was concentrated in vacuo to afford 1.02 g of the crude product (INT-9). ESI mass [m / z]: 234.2 [amine + H] + 。 1 H NMR (DMSO-d6) δ = 9.36 (s, 1H), 8.78 (s, 2H, NH2), 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).

[0438] Synthesis of 3-(trifluoromethoxy)-5-(trifluoromethylsulfonyl)benzoic acid (INT-13) Step 1: 3-Bromo-5-(trifluoromethoxy)benzenethiol

Chemical Structure

[0439] To a stirred solution of 1,3-dibromo-5-(trifluoromethoxy)benzene (48.9 g, 153 mmol) in pure diethyl ether (430 mL) was added dropwise a 2.5 M n-BuLi / hexane solution (77 mL, 191 mmol) at -65 °C. The reaction mixture was stirred at -65 °C for 50 minutes. Next, powdered sulfur (7.11 g, 222 mmol) was added portionwise at -65 °C. The reaction mixture was stirred at -65 °C for 1.5 hours. Next, 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 times with 300 mL). The combined diethyl ether layers were washed in order 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 subjected to vacuum distillation at a pressure of 13 mmHg. A colorless fraction at 94 - 98 °C was collected. Yield 27.7 g (66%). 1 1H-NMR (400 MHz, CDCl3): 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 19F-NMR (376 MHz, CDCl3): δ = -57.80。 1 1H and 19 19F NMR spectra were recorded on a Varian Gemini 2000 instrument.

[0440] Step 2: 1-Bromo-3-(trifluoromethoxy)-5-(trifluoromethylsulfanyl)benzene

Chemical formula

[0441] To a solution of degassed 3-bromo-5-(trifluoromethoxy)benzenethiol (17.75 g, 65 mmol) in DMF (175 mL) was added triethylamine (27.2 mL, 195 mmol) under argon. The stirred mixture was cooled to 0 °C and trifluoroiodomethane was bubbled in until the weight increased by 38 g. Next, 1,1′-dimethyl-[4,4′-bipyridin]-1,1′-diium 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 with water and brine in that order, and the solution was dried over sodium sulfate. The solvent was removed under reduced pressure to give a dark brown oil. The oil was subjected to vacuum distillation at a pressure of 20 mmHg. A colorless fraction boiling at 87 - 89 °C was collected. Yield 23.4 g (83%). 1 1H-NMR (400 MHz, CDCl3): δ = 7.76 (t, J = 1.6 Hz, 1H), 7.54 - 7.51 (m, 1H), 7.49 - 7.47 (m, 1H). 19 19F-NMR (376 MHz, CDCl3): δ = -41.92, -58.01. 1 1H and 19 19F NMR spectra were recorded on a Varian Gemini 2000 instrument.

[0442] Step 3: 3-(Trifluoromethoxy)-5-(trifluoromethylsulfanyl)benzoic acid

Chem.

[0443] A stirred mixture of 1-bromo-3-(trifluoromethoxy)-5-(trifluoromethylsulfanyl)benzene (5.12 g, 15 mmol), powdered potassium carbonate (10.4, 75 mmol), palladium(II) acetate (168 mg, 0.75 mmol), and Xantphos (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 times with 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 column chromatography (Combiflash) on silica gel. Yield 3 g (65%). 1 1H-NMR (400 MHz, DMSO-d6): 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 19F-NMR (376 MHz, DMSO-d6): δ = -44.12, -59.52. 1 H and 19 19F NMR spectra were recorded on a Varian Gemini 2000 instrument.

[0444] Step 4: 3-(Trifluoromethoxy)-5-(trifluoromethylsulfonyl)benzoic acid (INT-13)

Chem.

[0445] To a stirred solution of TFA (0.3 mL) in acetic anhydride (50 mL) at 0 °C, an aqueous hydrogen peroxide solution (40%, 20 mL, 100 mmol) was added dropwise over 1.5 h. 3-(Trifluoromethoxy)-5-(trifluoromethylsulfanyl)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 at room temperature overnight. The reaction mixture was diluted with deionized water to a volume of 250 mL. The mixture was cooled to 0 °C to precipitate a white solid. The precipitate was filtered, washed successively with water and hexane, and dried in vacuo. Yield 3.2 g (95%). ESI mass [m / z]: 337.0 [M-H] - 。 1 H NMR (400 MHz, DMSO-d6): δ = 14.37 (bs, 1H, COOH), 8.48 (s, 1H), 8.46 (s, 1H), 8.42 (s, 1H).

[0446] Synthesis of 3-bromo-5-(2,2-dichlorocyclopropyl)benzoic acid (INT-14) Step 1: 3-bromo-5-(2,2-dichlorocyclopropyl)benzonitrile

Chemical formula

[0447] 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) at room temperature, powdered potassium hydroxide (15 g, 260 mmol) was added portionwise within 30 min. 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 blackish oil. The oil was purified by Combiflash chromatography to give 4.55 g (60%). 11H-NMR (400 MHz, CDCl3): 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 Gemini 2000.

[0448] Step 2: 3-Bromo-5-(2,2-dichlorocyclopropyl)benzoic acid (INT-14) [Chemical formula]

[0449] 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) at 0 °C. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with water to a volume of 300 mL, and the resulting emulsion was extracted with diethyl ether (twice with 75 mL). The organic layer was separated, washed with brine, and dried over sodium sulfate. The solvent was removed under reduced pressure to give a yellowish 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 hours. The reaction mixture was diluted with water to a volume of 100 mL. The isopropanol was removed under reduced pressure. The remaining aqueous fraction was washed with diethyl ether (twice with 40 mL). Next, an aqueous solution of concentrated HCl in deionized water (20 mL) was added to the aqueous fraction to precipitate a white solid. The precipitate was filtered, washed successively with water and hexane, and dried in a dryer at 65 °C to give the title compound, 3.2 g (69%). ESI mass [m / z]: 311.0 [M+H] + . 11H-NMR (400 MHz, DMSO-d6): 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 Gemini 2000.

[0450] Synthesis of 3-Bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid (INT-15) 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

Chemical formula

[0451] To a solution of 1,2-dibromo-1,1,2,2-tetrafluoroethane (18.0 g, 77.9 mmol, 1.0 equivalent) in DMSO (100 mL) were added Cs2CO3 (38.1 g, 116 mmol, 1.5 equivalents) and methyl 3-bromo-5-hydroxybenzoate (commercial product, 40.4 g, 155 mmol, 2.0 equivalents), and the mixture was stirred at 60 °C for 12 hours. To the reaction mixture was added H2O (200 mL), and the mixture was extracted with ethyl acetate (3 times with 150 mL). The organic layer was dried and concentrated to obtain a mixture of products (22.0 g, 1:1) as a yellow oil.

[0452] Step 2: Methyl 3-bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoate

Chemical formula

[0453] To a solution of the mixture from the previous step (22.0 g, 53.6 mmol, 1.0 eq) in AcOH (100 mL), Zn (10.5 g, 161 mmol, 3.0 eq) was added at 50 °C, and the mixture was stirred at 50 °C for 12 h. The reaction mixture was filtered and concentrated under reduced pressure to obtain a residue (16.5 g, crude) as a pale yellow liquid.

[0454] Step 3: 3-Bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid (INT-15)

Chemical formula

[0455] 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), LiOH·H2O (2.0 M, 49.8 mL, 2.0 eq) was added, and the mixture was stirred at 25 °C for 2 h. The reaction solution was concentrated under reduced pressure to obtain a residue, which was diluted with water (50 mL), adjusted to pH = 4 with 2 M KHSO4 solution, extracted with DCM (2 times with 30 mL), the combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to obtain (10.0 g, 31.5 mmol, 63.3) as a white solid. ESI mass [m / z]: 314.9 [M-H] - 。 1 1H-NMR: (400 MHz CDCl3): 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).

[0456] Synthesis of 6-(5-{(1S)-1-[3-chloro-5-(1,1,2,2-tetrafluoroethoxy)benzamide]ethyl}-1H-1,2,4-triazol-1-yl)pyrimidine-4-carboxamide (I-113) 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

Chem.

[0457] In a thick-walled reaction tube equipped with a pressure relief valve, 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 at 60 °C for 3 days. The mixture was concentrated under reduced pressure to remove the solvent. The residue was dissolved in aqueous citric acid / ethyl acetate, and the aqueous layer was extracted 3 times with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated 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 a low-purity fraction containing 3-chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)benzoic acid and 3-chloro-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid, which was used directly in the subsequent step.

[0458] Step 2: 6-(5-{ (1S)-1-[3-chloro-5-(1,1,2,2-tetrafluoroethoxy)benzamide]ethyl}-1H-1,2,4-triazol-1-yl)pyrimidine-4-carboxamide (I-113)

Chem.

[0459] 3-Chloro-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid (0.19 g, 0.45 mmol), HATU (0.34 g, 0.89 mmol), 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) were each stirred in 1.5 mL of DMF for 1 hour. The two solutions were combined and stirred at room temperature for 16 hours. Purification of the reaction mixture by chromatography (RP18, water / ACN containing 0.1% HCOOH) gave 92 mg (42% of theory). Refer to Table 1 for the analytical data.

[0460] Synthesis of 6-(5-{(1S)-1-[3-chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)benzamide]ethyl}-1H-1,2,4-triazol-1-yl)pyrimidine-4-carboxamide (I-114)

Chemical formula

[0461] 3-Chloro-5-(1,1,2,2-tetrafluoro-2-iodoethoxy)benzoic acid (0.18 g, 0.45 mmol from the above procedure), HATU (0.34 g, 0.89 mmol), 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) were each stirred in 1.5 mL of DMF for 1 hour. The two solutions were combined and stirred at room temperature for 16 hours. Purification of the reaction mixture by chromatography (RP18, water / ACN containing 0.1% HCOOH) gave 106 mg (39% of theory). Refer to Table 1 for the analytical data.

[0462] Synthesis of 3-(1-fluoro-1-methylethyl)-5-(trifluoromethoxy)benzoic acid (INT-16) Step 1: 2-[3-Bromo-5-(trifluoromethoxy)phenyl]propan-2-ol

Chem.

[0463] To a solution of 1,3-dibromo-5-(trifluoromethoxy)benzene (20 g, 62.4 mmol) in THF (160 mL) was added dropwise i-PrMgCl (1.9 M solution in THF, 36 mL, 73.2 mmol) at -5 °C under argon. The mixture was stirred at the same temperature for 45 minutes, and then acetone (9 g, 156 mmol) was added dropwise. The reaction mixture was stirred for an additional 30 minutes, MTBE (200 mL) was added, and then 10% citric acid (200 mL) was added. The organic layer was separated, washed with brine (3 times with 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.

[0464] Step 2: Methyl 3-(1-hydroxy-1-methyl-ethyl)-5-(trifluoromethoxy)benzoate

Chem.

[0465] A solution of 2-[3-bromo-5-(trifluoromethoxy)phenyl]propan-2-ol (10.14 g, 33.91 mmol) in MeOH (110 mL) was added with Et3N (6.833 g, 67.82 mmol) and Pd(dppf)Cl2 (2.47 g, 3.391 mmol). The mixture was stirred at 130 °C for 48 h under a CO pressure of 10 Torr, diluted with EtOAc (600 mL), filtered through a celite layer, and concentrated under reduced pressure. The residue was dissolved in EtOAc (300 mL) and washed with water (2 × 200 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give methyl 3-(1-hydroxy-1-methyl-ethyl)-5-(trifluoromethoxy)benzoate (8.96 g, 32.21 mmol, 95% yield).

[0466] Step 3: Methyl 3-(1-fluoro-1-methyl-ethyl)-5-(trifluoromethoxy)benzoate

Chem.

[0467] To a solution of methyl 3-(1-hydroxy-1-methyl-ethyl)-5-(trifluoromethoxy)benzoate (8.96 g, 32.21 mmol) in dichloromethane (100 mL) was added dropwise Morph-DAST (6.2 g, 35.435 mmol) at -60 °C. The mixture was stirred at room temperature overnight and poured into an aqueous sodium bicarbonate solution. 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.

[0468] Step 4: 3-(1-Fluoro-1-methyl-ethyl)-5-(trifluoromethoxy)benzoic acid (INT-16)

Chem.

[0469] To a stirred solution of 3-(1-fluoro-1-methyl-ethyl)-5-(trifluoromethoxy)benzoate (3.8 g, 13.56 mmol) in a THF (40 mL) / H2O (12.5 mL) mixture at 0 °C was added LiOH·monohydrate (0.766 g, 18.306 mmol), and the mixture was stirred at room temperature overnight. THF was distilled off under reduced pressure, the water was acidified to pH = 4.5, and extracted with MTBE (2×25 mL). After recrystallization from 30% aqueous EtOH, pure 3-(1-fluoro-1-methyl-ethyl)-5-(trifluoromethoxy)benzoic acid (3.17 g, 11.9 mmol, 87.76% yield) was obtained as a yellow solid. ESI mass [m / zneg]: 265.1 [M-H] + 。 1 1H-NMR (400 MHz, DMSO-d6): 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.

[0470] Separate synthesis of 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-11) Step 1: tert-Butyl N-[(1S)-2-chloro-1-methyl-2-oxo-ethyl]carbamate

Chemical formula

[0471] To a solution of (2S)-2-(tert-butoxycarbonylamino)propanoic acid (90.0 g, 476 mmol, 1.00 equiv) in DCM (900 mL) was added Et3N (44.7 g, 442 mmol, 61.6 mL, 0.930 equiv). Trimethylacetyl chloride (57.4 g, 476 mmol, 58.5 mL, 1.00 equiv) was added dropwise at 0 °C. After the 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) was obtained as a colorless liquid and used in the next step.

[0472] Step 2: Ethyl (Z)-N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidate

Chem.

[0473] To a solution of tert-butyl N-[(1S)-2-chloro-1-methyl-2-oxo-ethyl]carbamate (98.8 g, 476 mmol, 1.00 equiv) in DCM (900 mL) was added Et3N (116 g, 1.14 mol, 159 mL, 2.40 equiv). Next, ethyl cyclopropanecarboximidate hydrochloride (71.1 g, 476 mmol, 1.00 equiv) was added portionwise at 20 °C. After the addition, the mixture was stirred at 20 °C for 16 h. Ethyl (Z)-N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidate (135 g, crude) in DCM was obtained as a colorless liquid and used in the next step.

[0474] Step 3: tert-Butyl N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate

Chem.

[0475] To a solution of ethyl (Z)-N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]cyclopropanecarboximidate (135 g, 475 mmol, 1.00 eq) in DCM (900 mL) was added (6-chloropyrimidin-4-yl)hydrazine (68.7 g, 475 mmol, 1.00 eq) portionwise at 20 °C or below. After the addition, the mixture was stirred at 20 °C for 16 h. To the reaction mixture was added H2O (500 mL), and the separated organic layer 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). tert-Butyl N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate (48.0 g, 132 mmol, 27.7% yield in two steps) was obtained as a yellow solid.

[0476] Step 4: Methyl 6-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate (INT-17)

Chemical formula

[0477] To a solution of tert-butyl N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate (48.0 g, 132 mmol, 1.00 equiv) in MeOH (1.00 L) were added Et3N (26.6 g, 263 mmol, 36.6 mL, 2.00 equiv) and Pd(dppf)Cl2 (9.63 g, 13.2 mmol, 0.100 equiv). The suspension was degassed under reduced pressure and purged several times with CO. The mixture was stirred at 40 °C for 16 h under CO (50 psi). 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 (41.0 g, 106 mmol, 80.2% yield) was obtained as a pale yellow solid.

[0478] Step 5: tert-butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate (INT-18)

Chem.

[0479] 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). NH4OH (54.1 g, 386 mmol, 59.5 mL, purity 25%, 6.00 eq) was added dropwise at 20 °C. After the addition, the mixture was stirred at 20 °C for 5 h. The reaction mixture was concentrated. tert-Butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate (24.0 g, 60.4 mmol, yield 93.8%, purity 94%) was obtained as a pale yellow solid and used in the next step. 1 H NMR (400 MHz, CDCl3): δ 9.08 (d, J = 0.73 Hz, 1 H), 8.65 (s, 1 H), 7.79 (br s, 1 H), 5.96 - 6.07 (m, 1 H), 5.81 (br s, 1 H), 5.56 - 5.71 (m, 1 H), 2.02 - 2.12 (m, 1 H), 1.55 (d, J = 6.8 Hz, 3 H), 1.44 (s, 9 H), 0.98 - 1.11 (m, 4 H).

[0480] Step 6: 6-[5-[(1S)-1-Aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride (INT-11)

Chemical Structure

[0481] tert-Butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-5-cyclopropyl-1,2,4-triazol-3-yl]ethyl]carbamate (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 (5.54 g, 17.01 mmol, yield 79.4%, purity 95.1%) was obtained as a white solid. ESI mass [m / z]: 274.2 [amine + H] + 。 1 1H-NMR (400 MHz, DMSO-d6): 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).

[0482] Synthesis of 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N-methyl-pyrimidine-4-carboxamide hydrochloride (INT-21) 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)

Chem.

[0483] 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 equiv) in THF (45.0 mL) was added with methylamine (a solution in 2M THF, 34.7 mL, 3.00 equiv). The mixture was stirred at 20 °C for 4 hours. After the reaction was completed, 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 (8.50 g, 20.8 mmol, yield 89.9%, purity 95%) was obtained as a pale yellow solid. 1 1H NMR (400 MHz, CDCl3): 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).

[0484] Step 2: 6-[5-[(1S)-1-aminoethyl]-3-cyclopropyl-1,2,4-triazol-1-yl]-N-methyl-pyrimidine-4-carboxamide hydrochloride (INT-21)

Chemical Structure

[0485] Trimethylsilyl chloride (7.07 g, 65.0 mmol, 8.26 mL, 3.00 equivalents) was added to CF3CH2OH (84.0 mL), and the mixture was stirred for 30 minutes. tert-Butyl N-[(1S)-1-[5-cyclopropyl-2-[6-(methylcarbamoyl)pyrimidin-4-yl]-1,2,4-triazol-3-yl]ethyl]carbamate (8.40 g, 21.7 mmol, 1.00 equivalent) in CF3CH2OH (84.0 mL) was added dropwise to the above solution at 20 °C or lower. After the addition, the mixture was stirred at 20 °C for 1 hour. 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, yield 91.0%, purity 96.8%, HCl) was obtained as a pale yellow solid. 1 1H NMR (400 MHz, MeOD): δ 9.19 (d, J = 1.00 Hz, 1 H), 8.52 (d, J = 1.00 Hz, 1 H), 5.59 (...

Claims

1. A compound of the following formula (I). 【Chemical 1】 [Wherein, X is O or S; R １ is hydrogen; R ２ is selected from the following substructures Q1 and Q2, where the bond to the C═X-group is marked with #: 【Chemical Formula 2】 Here, 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, where the phenyl may be substituted by one or two substituents selected from the group consisting of halogen, -CN, methyl, trifluoromethyl or trifluoromethoxy; or cyclopropyl, where the cyclopropyl may be substituted by one or two substituents selected from the group consisting of 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 a substituent selected from -CN or the following substructure S1, where the bond to pyrimidine is marked with #: 【Chemical Formula 3】 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 may be substituted by 1 to 3 substituents selected from the group consisting of 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. X is O or S; R １ is hydrogen; R ２ is selected from the following substructures Q1 and Q2, where the bond to the C═X-group is marked with #: [Chemical Formula 4] Here, 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, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfonyl, cyclopropylsulfonyl or 4-chlorophenyl-sulfonyl; R ２２ is hydrogen, fluorine, chlorine, bromine, iodine, -CN, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, difluoromethylsulfonyl, or trifluoromethylsulfonyl; R ３ is a substituent selected from -CN or the following substructure S1, where the bond to pyrimidine is marked with #: 【Chemical Formula 5】 R ３１ is hydrogen or methyl; R ３２ is hydrogen, cyclopropyl or C １ -C ３ alkyl, where C １ -C ３ alkyl may be substituted with 1 to 3 substituents selected from the group consisting of fluorine, chlorine, -CN, cyclopropyl and methoxy; R ４ The compound according to claim 1, wherein R is hydrogen, methyl or cyclopropyl.

3. 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-fluoro-5-(trifluoromethoxy)phenyl, 3-methylsulfonylphenyl, 3-(difluoromethoxy)-5-methylsulfanylphenyl, 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, dimethylaminocarbonyl, [ethyl(methyl)amino]carbonyl, [isopropyl(methyl)amino]carbonyl or [cyclopropylmethyl(methyl)amino]carbonyl; R ４ is hydrogen, methyl or cyclopropyl, and R ４ The compound according to claim 1 or 2, wherein R is hydrogen, methyl or cyclopropyl.

4. The compound according to any one of claims 1 to 3, wherein the compound has a structure according to the following formula (I'). 【Chemical Formula 6】 [wherein, structural elements R １ , R ２ , R ３ and R ４ have the meaning provided in claim 1 or the meaning provided in claim 2 or the meaning provided in claim 3.]

5. The compound according to any one of claims 1 to 3, wherein the compound has a structure according to the following formula (I''). 【Chemical Formula 7】 [wherein, R １ is hydrogen, and the structural elements R ２ , R ３ and R ４ have the meaning provided in claim 1 or the meaning provided in claim 2 or the meaning provided in claim 3.]

6. The compound according to any one of claims 1 to 3, wherein the compound has a structure according to the following formula (I'''). 【Chemical Formula 8】 [wherein, R １ is hydrogen, and the structural elements R ２ , R ３ and R ４ have the meaning provided in claim 1 or the meaning provided in claim 2 or the meaning provided in claim 3. ]

7. A compound of the following formula (a). 【Chemical Formula 9】 [wherein, R １ , R3 and R ４ have the meaning provided in claim 1 or the meaning provided in claim 2 or the meaning provided in claim 3. ]

8. Compound 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, 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile; 2,2,2-trifluoroacetic acid, 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, 2-chloro-6-(1-cyanocyclopropyl)pyridine-4-carboxylic acid, 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide hydrochloride, 3-(trifluoromethoxy)-5-(trifluoromethylsulfonyl)benzoic acid, 3-bromo-5-(2,2-dichlorocyclopropyl)benzoic acid, and 3-bromo-5-(1,1,2,2-tetrafluoroethoxy)benzoic acid, 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, 3-(1-fluoro-1-methylethyl)-5-(trifluoromethoxy)benzoic acid, 3,5-bis(difluoromethylsulfonyl)benzoic acid, In the case of an amine, its salt, and in the case of an amine hydrochloride, the free amine.

9. A preparation comprising at least one compound of formula (I) according to any one of claims 1 to 6, in particular an agrochemical preparation.

10. The preparation according to claim 9, further comprising at least one extender and / or at least one surfactant.

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

12. A method for controlling pest organisms, in particular pest animals, characterized in that the compound of formula (I) according to any one of claims 1 to 6 or the preparation according to any one of claims 9 to 11 is allowed to act on the pest organisms and / or their habitats, except for human surgical treatment or therapeutic procedures and diagnostic methods carried out in humans.

13. The method according to claim 12, wherein the pest organisms are pest animals, including insects, arachnids or nematodes, or the pest organisms 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 pest animals, except for human surgical treatment or therapeutic procedures and diagnostic methods carried out in humans.

15. The use according to claim 14, wherein the pest animals include insects, arachnids or nematodes, or the pest animals are insects, arachnids or nematodes.

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

17. The use according to claim 14 or 15 in the field of animal health.

18. A method for protecting seeds or germinating plants from pest organisms, in particular pest animals, comprising the method step of contacting the seeds with 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.

19. Seeds obtained by the method according to Claim 18.

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