Pesticidal Active Diazine-Amide Compounds

Abstract

Formula (I) TIFF2022527548000158.tif48157 (wherein the substituents are as defined in claim 1) The compounds of formula (I) and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of these compounds can be used as insecticides.

Description

[Technical Field]

[0001] The present invention relates to pesticidally active, in particular insecticidally active, diazine-amide compounds, processes for their preparation, compositions containing these compounds and their use for controlling animal pests, including arthropods, in particular insects or representatives of the order Acarina. [Background technology]

[0002] WO2017192385 describes certain heteroaryl-1,2,4-triazole and heteroaryl-tetrazole compounds that are used to control ectoparasites in animals, including mammals and non-mammals.

[0003] Novel pesticidally active diazine amide compounds have now been discovered. Summary of the Invention [Means for solving the problem]

[0004] Thus, in a first aspect, the present invention provides a compound of formula I [ka] (In the formula, R1 is H, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonylC1-C6 alkyl, hydroxycarbonylC1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilaneC1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkylC1-C2 alkyl-, C3-C4 cycloalkylC1-C2 alkyl- (wherein the C3-C4 cycloalkyl group is substituted with 1 or 2 halogen atoms), oxetan-3-yl-CH2-, benzyl, or benzyl substituted with halogen or C1-C6 haloalkyl; A1 is N or CR 2c and; R 2c is H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, or C1-C3 haloalkoxy; R 2a is C3-C6 cycloalkyl, C3-C6 cycloalkoxy; C3-C6 cycloalkyl substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and halogen; C3-C6 cycloalkoxy substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, cyano, and halogen; C3-C6 cycloalkylC1-C4 alkyl, C3-C6 cycloalkylC1-C4 alkoxy; C1-C3 alkyl, C1-C C3-C6 cycloalkylC1-C4 alkyl substituted with 1 to 5 substituents independently selected from 3 haloalkyl, C1-C3 alkoxy, cyano, and halogen; C3-C6 cycloalkylC1-C4 alkoxy substituted with 1 to 5 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, cyano, and halogen; C1-C5 cyanoalkyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfinyl, or C1-C4 haloalkylsulfinyl; R 2b is H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylthio, C1-C3 alkoxy, C1-C3 haloalkoxy, SF5, or CN; R3 is C1-C3 alkyl or C1-C3 haloalkyl; R4 is pyridine, pyrimidine, pyrazine, pyridazine, or pyridine, pyrimidine, pyrazine, and pyridazine each substituted with one substituent selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, and hydroxy; R 5a and R 5bare each independently selected from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy; or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer, and N-oxide of a compound of formula I. DETAILED DESCRIPTION OF THE INVENTION

[0005] Compounds of formula I having at least one basic centre can, for example, form acid addition salts with strong inorganic acids, such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or hydrohalic acids; strong organic carboxylic acids, for example C1-C4 alkanecarboxylic acids which are unsubstituted or substituted, for example, by halogens, such as acetic acid; saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid; hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or for example benzoic acid; or organic sulfonic acids, for example C1-C4 alkane- or arylsulfonic acids which are unsubstituted or substituted, for example, by halogens, such as methane- or p-toluenesulfonic acid. Compounds of formula I having at least one acidic group can, for example, form salts with bases, for example inorganic salts, for example alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or organic amines, for example morpholine, piperidine, pyrrolidine, mono-, di- or tri-lower alkylamines, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or mono-, di- or trihydroxy-lower alkylamines, for example mono-, di- or triethanolamine.

[0006] In each case, the compounds of formula I according to the invention are in free form, in oxidized form as N-oxides or in salt form, for example in agriculturally usable salt form.

[0007] N-oxides are oxidized forms of tertiary amines or nitrogen-containing aromatic heterocyclic compounds, as described, for example, in the book "Heterocyclic N-oxides", A. Albini and S. Pietra, CRC Press, Boca Raton 1991.

[0008] The compounds of formula I according to the present invention also include the hydrates which may be formed during salt formation.

[0009] As used herein, "C1-C n The term "alkyl" refers to a saturated straight or branched hydrocarbon radical having 1 to n carbon atoms attached via any of the carbon atoms, such as any one of the radicals methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl.

[0010] As used herein, "C1-C nThe term "haloalkyl" refers to a straight or branched saturated alkyl radical having 1 to n carbon atoms bonded via any of the carbon atoms (as defined above), wherein some or all of the hydrogen atoms in these radicals may be replaced by fluorine, chlorine, bromine and / or iodine, i.e., for example, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, and any one of 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, and nonafluorobutyl. The term "C1-C2 fluoroalkyl" refers to a C1-C2 alkyl radical having 1, 2, 3, 4 or 5 fluorine atoms, such as any one of difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl or pentafluoroethyl.

[0011] As used herein, "C1-C nThe term "alkoxy" refers to a straight or branched saturated alkyl radical having 1 to n carbon atoms (as defined above) attached through an oxygen atom, i.e., any one of, for example, methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy, or 1,1-dimethylethoxy radicals. As used herein, "haloC1-C n The term "alkoxy" refers to a C1-C alkyl radical in which one or more hydrogen atoms on the alkyl radical are replaced by the same or different halogen atoms. n refers to an alkoxy radical (examples include trifluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy, 3,3,3-trifluoropropoxy, 4-chlorobutoxy).

[0012] As used herein, "C1-C n The term "cyanoalkyl" refers to a linear or branched saturated C1-C alkyl group having 1 to n carbon atoms. n It refers to alkyl radicals (as defined above) in which one of the hydrogen atoms in these radicals is replaced by a cyano group, for example, cyanomethyl, 2-cyanoethyl, 2-cyanopropyl, 3-cyanopropyl, 1-(cyanomethyl)-2-ethyl, 1-(methyl)-2-cyanoethyl, 4-cyanobutyl, and the like.

[0013] As used herein, "C3-C n The term "cycloalkyl" refers to a 3- to n-membered cycloalkyl group such as cyclopropane, cyclobutane, cyclopentane, and cyclohexane. n The term "cycloalkoxy" refers to a cycloalkyl group (as defined above) attached to the remainder of the molecule through an oxygen atom.

[0014] As used herein, "C3-C n Cycloalkyl C1-C nThe term "alkyl" refers to a 3- to n-membered cycloalkyl group having an alkyl radical, which is attached to the remainder of the molecule. In this case, C3 to C n The cycloalkyl C1-C2 alkyl-group is substituted, and the substituents can be on the cycloalkyl group or on the alkyl radical.

[0015] As used herein, "aminocarbonyl C1-C n The term "alkyl" refers to an alkyl radical, wherein one of the hydrogen atoms in the radical is replaced by a CONH2 group.

[0016] As used herein, "hydroxycarbonyl C1-C n The term "alkyl" refers to an alkyl radical in which one of the hydrogen atoms in the radical has been replaced by a COOH group.

[0017] As used herein, "C1-C n The term "nitroalkyl" refers to an alkyl radical in which one of the hydrogen atoms in the radical is replaced by a NO2 group.

[0018] As used herein, "C1-C n Alkylsulfanyl" or "C1-C n The term "haloalkylthio" refers to a C-C alkyl group bonded through a sulfur atom. n Similarly, as used herein, "C1-C" refers to an alkyl moiety. n The term "haloalkylsulfanyl" refers to a C1-C alkyl group bonded through a sulfur atom. n Refers to a haloalkyl moiety.

[0019] As used herein, "C1-C n The term "alkylsulfinyl" refers to a C1-C alkyl group bonded through the sulfur atom of the S(=O) group. n Similarly, as used herein, "C1-C" refers to an alkyl moiety. nThe term "haloalkylsulfinyl" refers to a C1-C alkyl group bonded through the sulfur atom of the S(=O) group. n Refers to a haloalkyl moiety.

[0020] As used herein, "C1-C n The term "alkylsulfonyl" refers to a C1-C alkyl group bonded through the sulfur atom of the S(=O)2 group. n Similarly, as used herein, "C1-C" refers to an alkyl moiety. n The term "haloalkylsulfonyl" refers to a C1-C2 alkyl group bonded through the sulfur atom of the S(=O)2 group. n Refers to a haloalkyl moiety.

[0021] As used herein, "trimethylsilane C1-C n The term "alkyl" refers to an alkyl radical, where one of the hydrogen atoms in the radical is replaced by a -Si(CH3)3 group.

[0022] As used herein, "C2-C n The term "alkenyl" refers to a straight or branched alkenyl chain having 2 to n carbon atoms and one or two double bonds, for example ethenyl, prop-1-enyl, but-2-enyl.

[0023] As used herein, "C2-C n The term "haloalkenyl" refers to a C-C alkyl group substituted with one or more halogen atoms, which may be the same or different. n Refers to the alkenyl moiety.

[0024] As used herein, "C2-C n The term "alkynyl" refers to a straight or branched alkynyl chain having 2 to n carbon atoms and one triple bond, for example, ethynyl, prop-2-ynyl, but-3-ynyl.

[0025] As used herein, "C2-C nThe term "haloalkynyl" refers to a C-C alkyl group substituted with one or more halogen atoms, which may be the same or different. n Refers to the alkynyl moiety.

[0026] Halogen is generally fluorine, chlorine, bromine or iodine. This also applies correspondingly to halogen in combination with other meanings, such as haloalkyl.

[0027] The pyridine, pyrimidine, pyrazine and pyridazine groups (unsubstituted or substituted) of R2 and R4 are each bonded to the remainder of the compound via a carbon atom in the respective ring.

[0028] As used herein, the term "control" refers to reducing the number of pests so that damage to plants or plant-derived products is reduced, eradicating pests, and / or preventing further pest damage.

[0029] As used herein, the wavy lines, for example in K-1 and O-1, represent the points of attachment / connection to the remainder of the compound.

[0030] As used herein, the term "pest" refers to insects, mites, nematodes, and mollusks found in agriculture, horticulture, forestry, and storage of plant-derived products (such as fruit, grain, and lumber); and pests associated with damage to man-made structures. The term pest encompasses all stages in the life cycle of a pest.

[0031] As used herein, the term "effective amount" refers to that amount of a compound or salt thereof that produces a desired effect in single or multiple applications.

[0032] An effective amount is readily determined by one skilled in the art by the use of known techniques and by observing results obtained under analogous circumstances. Determining an effective amount takes into account numerous factors, including, but not limited to, the type of plant or plant-derived product to which it is applied; the pest to be controlled and its life cycle; the particular compound applied; the type of application; and other relevant circumstances.

[0033] As one of ordinary skill in the art will appreciate, the compounds of Formula I contain stereogenic centers, as indicated by an asterisk in the structures below. [ka] In the formula, R1, R 2a , R 2b , R3, R4, R 5a , R 5b and A1 is as defined in the first aspect.

[0034] The present invention contemplates both the racemate and the individual enantiomers. Compounds with preferred stereochemistry are shown below.

[0035] Particularly preferred compounds of the invention have formula I'a: [ka] (In the formula, R1, R 2a , R 2b , R3, R4, R 5a , R 5b and A1 is as defined in the first aspect. and the stereoisomers, enantiomers, tautomers and N-oxides of the compounds of formula (I'a), and agrochemically acceptable salts thereof.

[0036] As used herein, the term "optionally substituted" means that the referenced group is unsubstituted or optionally substituted with specified substituents, for example, "C3-C4 cycloalkyl optionally substituted with 1 or 2 halogen atoms" means C3-C4 cycloalkyl, C3-C4 cycloalkyl substituted with 1 halogen atom, and C3-C4 cycloalkyl substituted with 2 halogen atoms.

[0037] Embodiments according to the present invention are provided as follows.

[0038] In one embodiment according to each aspect of the present invention, A1 is AN; or BC-R 2c where R 2c is hydrogen or halogen (such as Cl, F, Br and I); preferably hydrogen.

[0039] In one embodiment according to each aspect of the present invention, R 2a teeth, A. C3-C6 cycloalkyl, C3-C6 cycloalkoxy; C3-C6 cycloalkyl substituted with 1-3 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and halogen; C3-C6 cycloalkyl C1-C4 alkyl substituted with 1-5 substituents independently selected from halogen and C1-C3 haloalkyl; C1-C5 cyanoalkyl, C3-C6 cycloalkoxy, C1-C4 haloalkylsulfonyl, or C1-C4 haloalkylsulfinyl; or B. C3-C4 cycloalkyl, C3-C4 cycloalkoxy; C3-C4 cycloalkyl substituted with 1-3 substituents independently selected from C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, cyano, and halogen; C3-C4 cycloalkyl C1-C2 alkyl substituted with 1-5 substituents independently selected from halogen and C1-C3 haloalkyl; C1-C3 cyanoalkyl, C3-C4 cycloalkoxy, C1-C3 haloalkylsulfonyl, or C1-C3 haloalkylsulfinyl; or C. cyclopropyl; cyclopropyl substituted with 1 to 3 substituents independently selected from methyl, trifluoromethyl, methoxy, cyano, fluoro, and chloro; cyclopropylmethyl substituted with 1 to 5 fluoro substituents; C1-C3 cyanoalkyl, cyclopropoxy, trifluoromethylsulfonyl, or trifluoromethylsulfinyl; or D. Cyclopropyl; cyclopropyl substituted with 1 to 3 substituents independently selected from methyl, trifluoromethyl, methoxy, cyano, fluoro, and chloro; cyclopropylmethyl substituted on the methyl moiety with 1 or 2 fluoro substituents; C1-C3 cyanoalkyl, trifluoromethylsulfonyl, or trifluoromethylsulfinyl; or E. Cyclopropyl; cyclopropyl substituted with 1 to 3 substituents independently selected from trifluoromethyl, methoxy, cyano, fluoro and chloro; cyclopropylmethyl substituted on the methyl moiety with 1 or 2 fluoro substituents; C1-C3 cyanoalkyl, trifluoromethylsulfonyl.

[0040] In one embodiment according to each aspect of the present invention, R 2b teeth, A. halogen, C1-C3 haloalkyl, C1-C3 haloalkylthio, C1-C3 alkoxy, C1-C3 haloalkoxy, or CN; or B. halogen, C1-C3 haloalkyl, or C1-C3 haloalkoxy; or C. chlorine, fluorine, difluoromethyl, trifluoromethyl, difluoromethoxy or trifluoromethoxy; or D. It is difluoromethyl or trifluoromethyl.

[0041] In one embodiment according to each aspect of the invention, R1 is A. hydrogen, methyl, ethyl, n-propyl, isobutyl, cyclopropylmethyl, or HCH≡CCH2-; or B. hydrogen, methyl, or cyclopropylmethyl; or C. hydrogen; or D. methyl; or E. Cyclopropylmethyl.

[0042] In one embodiment according to each aspect of the invention, R3 is A. C1-C3 alkyl or C1-C3 haloalkyl; or B. Methyl.

[0043] In one embodiment according to each aspect of the invention, R4 is A. 2-pyridine, 2-pyrimidine, 2-pyridine substituted with one substituent selected from cyclopropyl or halogen, or 2-pyrimidine substituted with one substituent selected from cyclopropyl or halogen; or BO-1~O-8 [ka] is selected from selected from CO-1, O-3, O-4, O-5, O-6 and O-8; or DO-3, O-4, O-5, O-6, or O-8; or EO-3, O-4, O-5, or O-8; or FO-5 or O-8.

[0044] In one embodiment according to each aspect of the present invention, R 5a and R 5b are independent of each other, A. hydrogen, halogen, C1-C3 alkyl, or C1-C3 alkoxy; or B. selected from hydrogen, bromo, chloro, methyl, and methoxy; or C. It is hydrogen.

[0045] The present invention therefore relates to the substituents R, R as defined above. 2a , R 2b , R3, R4, R 5a , R 5b and A1 in all combinations / permutations thereof. Thus, for example, compounds of formula I are available in which A1 is the first embodiment (i.e., A1 is N or CR 2c where R 2c is H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, or C1-C3 haloalkoxy); R1 is of embodiment B (i.e., hydrogen, methyl, cyclopropylmethyl); R 2a is embodiment C (i.e., cyclopropyl; cyclopropyl substituted with 1 to 3 substituents independently selected from methyl, trifluoromethyl, methoxy, cyano, fluoro, and chloro; cyclopropylmethyl substituted with 1 to 5 fluoro substituents; C1-C3 cyanoalkyl, cyclopropoxy, trifluoromethylsulfonyl, or trifluoromethylsulfinyl); R 2b is embodiment B (i.e., halogen, C1-C3 haloalkyl, or C1-C3 haloalkoxy); R3 is embodiment B (i.e., methyl); R4 is embodiment B (i.e., selected from O-1 through O-8); R 5a is embodiment A (i.e., selected from hydrogen, halogen, C1-C3 alkyl, or C1-C3 alkoxy); R 5b Compounds of Formula I are available in which is embodiment C (ie, hydrogen).

[0046] In one embodiment, the compound of formula I is [ka] where R1, R3, R4, R 5a , and R 5b is as defined in the first aspect, R2 is as defined in the first aspect, A1 and the substituent R 2a and R 2b is a cyclic group containing

[0047] In one embodiment according to each aspect of the present invention, R2 (A1 and the substituent R 2a and R 2b A cyclic group containing AK-1~K-15 [ka] is selected from selected from BK-1, K-2, K-3, K-5, K-6, K-10, K-11, K-12, K-14, K-15, and K-16; or selected from CK-1, K-2, K-6, K-10, K-12, K-14, K-15, and K-16; or Selected from DK-1, K-2, K-5, K-10, K-11, K-14, K-15 and K-16; or selected from EK-1, K-2, K-5, K-6, K-10, K-14, K-15, and K-16; or selected from FK-1, K-2, K-6, K-10, K-14, K-15, and K-16; or selected from GK-5, K-10, K-14 and K-15; or selected from HK-2, K-6, K-14 and K-15; or It is selected from IK-2, K-6 and K-10.

[0048] In one embodiment according to each aspect of the invention, the compound of formula IA or I'-A has as R1 hydrogen, methyl, ethyl, n-propyl, isobutyl, cyclopropylmethyl, or HCH≡CCH2-; as R2 one of K-1 through K-16; as R3 methyl; as R4 one of O-1 through O-8; 5a and R 5bare independently selected from hydrogen, halogen, and methyl.

[0049] In one embodiment according to each aspect of the invention, the compound of formula IA or I'-A has R1 as hydrogen, methyl, or cyclopropylmethyl; R2 as one of K-1 through K-16; R3 as methyl; R4 as one of O-1 through O-8; and R 5a and R 5b are independently selected from hydrogen, halogen, and methyl.

[0050] In one embodiment according to each aspect of the invention, the compound of formula IA or I'-A has R1 as hydrogen; R2 as one of K-1 through K-16; R3 as methyl; R4 as one of O-1 through O-8; 5a and R 5b are independently selected from hydrogen, halogen, and methyl.

[0051] In one embodiment according to each aspect of the invention, the compound of formula IA or I'-A has as R1 hydrogen, methyl, or cyclopropylmethyl; as R2 one of K-1, K-2, K-3, K-5, K-6, K-10, K-11, K-12, K-14, K-15, and K-16; as R3 methyl; as R4 one of O-1 through O-8; and 5a and R 5b are independently selected from hydrogen, halogen, and methyl.

[0052] In one embodiment according to each aspect of the invention, the compound of formula IA or I'-A has as R1 hydrogen, methyl, or cyclopropylmethyl; as R2 one of K-1, K-2, K-5, K-6, K-10, K-11, K-14; K-15, and K-16; as R3 methyl; as R4 one of O-1 through O-8; and R 5a and R 5b are independently selected from hydrogen, halogen, and methyl.

[0053] In one embodiment according to each aspect of the invention, the compound of formula IA or I'-A has as R1 hydrogen, methyl, or cyclopropylmethyl; as R2 one of K-1, K-2, K-5, K-6, K-10, K-11, K-14, K-15, and K-16; as R3 methyl; as R4 one of O-1, O-3, O-4, O-5, O-6, or O-8; and 5a and R 5b are independently selected from hydrogen, halogen, and methyl.

[0054] In one embodiment according to each aspect of the invention, the compound of formula IA or I'-A has as R1 hydrogen, methyl, or cyclopropylmethyl; as R2 one of K-1, K-2, K-5, K-6, K-10, K-11, K-14, K-15, and K-16; as R3 methyl; as R4 one of O-1, O-3, O-4, O-5, O-6, or O-8; and 5a and R 5b and each having hydrogen.

[0055] In one embodiment according to each aspect of the invention, the compound of formula IA or I'-A has as R1 hydrogen, methyl, or cyclopropylmethyl; as R2 one of K-2, K-6, K-10, K-14, and K-15; as R3 methyl; as R4 one of O-3, O-4, O-5, or O-8; and 5a and R 5b and each having hydrogen.

[0056] In a second aspect, the present invention makes available a composition comprising a compound of formula I as defined in the first aspect, one or more adjuvants and diluents and optionally one or more other active ingredients.

[0057] In a third aspect, the present invention makes available a method for combating and controlling insects, acaridae, nematodes or molluscs, which comprises applying to the pest, the pest's habitat or plants susceptible to attack by the pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound as defined in the first aspect or a composition as defined in the second aspect.

[0058] In a fourth aspect, the present invention makes available a method for the protection of plant propagation material from attack by insects, mites, nematodes or mollusks, which comprises treating the propagation material or the locus in which the propagation material is planted with an effective amount of a compound of formula I as defined in the first aspect or a composition as defined in the second aspect.

[0059] In a fifth aspect, the present invention makes available plant propagation material, such as seeds, which comprises, has been treated with or has attached thereto a compound of formula I as defined in the first aspect or a composition as defined in the second aspect.

[0060] In a further aspect, the present invention provides a method of controlling parasites in or on an animal in need thereof, the method comprising administering an effective amount of a compound of formula I as defined in the first aspect. The present invention further provides a method of controlling ectoparasites on an animal in need thereof, the method comprising administering an effective amount of a compound of the first aspect. The present invention further provides a method of preventing and / or treating diseases transmitted by ectoparasites, the method comprising administering to an animal in need thereof an effective amount of a compound of formula I as defined in the first aspect.

[0061] Compounds of formula I can be prepared by those skilled in the art by following known methods. More specifically, compounds and intermediates of formula I and I'a can be prepared as described below in the schemes and examples. The specific stereogenic centers are left unspecified for the sake of brevity and are not intended to limit the teachings of the schemes in any way.

[0062] The processes for preparing the compounds of formula I according to the invention are carried out by methods known to those skilled in the art.

[0063] Compounds of Formula I [ka] is an amine of formula II [ka] (In the formula, R1, R3, R4, R 5a , and R 5b is as defined in formula I) and a carboxylic acid derivative of formula III [ka] (In the formula, R 2a , R 2b and A1 is as defined in Formula I). ​​The chemical reaction is described in more detail in Scheme 1.

[0064] Scheme 1: [ka] In Scheme 1, a compound of formula III (wherein R 2a , R 2b、and A1 are as defined in formula I) are activated to compounds of formula IIIa by methods known to those skilled in the art and described, for example, in Tetrahedron, 61(46), 10827-10852, 2005. For example, compounds in which X0 is a halogen are formed by treatment of compounds of formula III with, for example, oxalyl chloride or thionyl chloride in an inert solvent such as methylene dichloride or THF in the presence of a catalytic amount of DMF at a temperature between 20°C and 100°C, preferably 25°C. Compounds of formula II (where R1, R3, R4, R 5a , and R 5b is as defined in Formula I), optionally in the presence of a base such as triethylamine or pyridine, provides a compound of Formula I. Alternatively, a compound of Formula I can be prepared by activating IIIa (where X is X 01 or X 02

[0033] Furthermore, acids of formula III can be prepared by treating compounds of formula IIIa (wherein X is X) with dicyclohexylcarbodiimide (DCC) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in an inert solvent, such as pyridine or THF, optionally in the presence of a base, such as triethylamine, at temperatures between 50 and 180°C, to give compounds of formula IIIa (wherein X is X), as described, for example, in Synthesis 2013, 45, 1569 and Journal Prakt. Chemie 1998, 340, 581. 03 or X 04 The amines of formula II can also be activated by reaction with coupling reagents such as propanephosphonic anhydride (T3P®) or O-(7-aza-1-benzotriazolyl)-N,N,N',N'-tetramethyluronium-hexafluorophosphate (HATU), which affords the compounds of formula I. Subsequent reaction with amines of formula II affords compounds of formula I.

[0065] An intermediate of formula II (wherein R1, R3, R4, R 5a and R5 are as defined in Formula I) can be prepared according to Scheme 2. Scheme 2: [ka] In Scheme 2, a compound of formula IV (wherein X 05 is a leaving group such as chlorine, bromine, iodine, arylsulfonate, alkylsulfonate, or trifluoromethanesulfonate; R, R 5a and R 5b is as defined in Formula I) is reacted with a tin compound of Formula V (wherein R4 is as defined in Formula I) in the presence of a palladium catalyst, such as tetrakis(triphenylphosphine)palladium(0) or (1,1'bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1:1 complex), in an inert solvent such as DMF, acetonitrile, or dioxane, optionally in the presence of an additive such as potassium fluoride or cesium fluoride, or lithium chloride, and optionally in the presence of a further catalyst, such as copper(I) iodide, to give a compound of Formula VI (wherein R3, R4, R 5a and R 5b is as defined in formula I. Such Stille coupling reactions are well known to those skilled in the art and are described, for example, in J. Org. Chem., 2005, 70, 8601; J. Org. Chem., 2009, 74, 5599; Angew. Chem. Int. Ed., 2004, 43, 1132; Heterocycles 2010, 80, 1215; and J. Am. Chem. Soc. 2004, 126, 16433. The compound of formula VI may be treated with a compound of formula VII (wherein R1 is as defined in formula I) in the presence of NaBH(OAc)3 or NaBH3CN, preferably with NaBH3CN as a reducing agent, at room temperature in a suitable solvent, preferably acetic acid, to give a compound of formula II (wherein R1, R3, R4, R 5a and R 5bis as defined in Formula I). ​​Another reagent system for reductive amination uses a combination of Ti(i-OPr)4 and NaBH4 in the presence of an amine of Formula VII to give a compound of Formula II (see Synthesis 2003(14), 2206).

[0066] A compound of formula VI (wherein R3, R4, R 5a , and R 5b is as defined in formula I) can also be prepared by Suzuki reaction (Scheme 3), which can be used to prepare, for example, compounds of formula IV (where R, R 5a , and R 5b is as defined in formula I, and X 05 is a leaving group such as, for example, chlorine, bromine, iodine, arylsulfonate, alkylsulfonate, or trifluoromethanesulfonate) with a compound of formula VIII (where W can be a boron-derived functional group such as, for example, B(OH) or pinacolboronic acid ester). The reaction can be catalyzed by a palladium-based catalyst, such as tetrakis(triphenylphosphine)-palladium or (1,1'-bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1:1 complex), in the presence of a base such as sodium carbonate or cesium fluoride, in a solvent or solvent mixture such as, for example, a mixture of 1,2-dimethoxyethane and water, dioxane and water, or DMF and water, preferably under an inert atmosphere. The reaction temperature can preferentially range from room temperature to the boiling point of the reaction mixture. Such Suzuki reactions are well known to those skilled in the art and have been reported, for example, in J. Organomet. Chem. 576, 1999, 147-168, Science of Synthesis 2010, 45b, 547, Eur. J. Org. Chem. 2012, (31), 6248 and Synthesis 2017, 49, 4372.

[0067] Scheme 3: [ka] Reductive amination as already described in Scheme 2 then similarly leads to compounds of formula II. Compounds of formula IV are generally commercially available.

[0068] A compound of formula II (wherein R, R, R, R 5a , and R 5b Yet another method for the preparation of (wherein R is as defined in Formula I) is outlined in Scheme 4.

[0069] Scheme 4: [ka] For example, a compound of formula VI (where R3, R4, R 5a , and R 5b is as defined in formula I) can be reacted with a compound of formula IVa (where R, R 5a , and R 5b (wherein R is as defined in Formula I) can be prepared by an allyl sulfone coupling reaction of a compound of Formula XI (wherein R is as defined in Formula I). ​​Such a process is described, for example, in J. Am. Chem. Soc. 2018, 140, 15916.

[0070] The required intermediate of formula XI can be obtained by nucleophilic substitution with prop-2-ene-1-thiol and subsequent oxidation with m-CPBA to give a compound of formula IX (where R4 is as defined in formula I and X 06 represents a halogen or methyl sulfone). Such a transformation is well known and is reported, for example, in J. Am. Chem. Soc. 2018, 140, 15916.

[0071] In an alternative process (Scheme 5), a ketone of formula VI (where R3, R4, R 5a , and R 5b is as defined in formula I) can be reduced to an alcohol of formula XII in the usual manner (see, for example, WO 2012 / 082997, page 141), for example by reduction with NaBH4, preferably in MeOH as solvent. Subsequent activation of the alcohol of formula XII with a compound of formula XIII (wherein Y is CH3, CF3 or p-CH3-CH4) in an inert solvent, preferably methylene dichloride, and in the presence of a base, for example triethylamine, gives a compound of formula XIV (wherein X 07 Alcohols of formula XII can also be converted to alkyl halides XIV (where X is OMs, OTs or OTf) by treatment with phosphorus compounds such as P(X0)3 (where X0 is chlorine or bromine) by methods known to those skilled in the art. 07 is Cl or Br). Such general functional group transformations are described, for example, in Organische Chemie. 4. Auflage, Wiley-VCH Verlag, Weinheim 2005, p. 393 ff. and Chem Commun. 2014, 50, 5756. Finally, nucleophilic substitution of compounds of formula XIV with amines of formula VII gives compounds of formula II (where R, R, R, R 5a , and R 5b is as defined in formula I).

[0072] Scheme 5: [ka] A ketone compound of formula VI (wherein R3, R4, R 5a and R 5b is as defined in Formula I) are commercially available or can be prepared as shown in Scheme 6. Scheme 6: [ka] As shown in Scheme 6, a compound of formula XV (where R 5a , and R 5b is as defined in Formula I, Z1 is C1-C4 alkyl, and X 05 is a leaving group as defined in formula IV) can be reacted with a compound of formula V (Still reaction) or a compound of formula VIII (Suzuki-Miyaura reaction) in the presence of a palladium catalyst to give a compound of formula XVI (where R, R 5a , R 5b and Z1 are as defined in formula XV). The compound of formula XVI is then converted to a carboxylic acid by methods known in the art (see, for example, WO 2011 / 143365, page 138). Activation of the carboxylic acid (see Scheme 1) and treatment with N-methoxy-N-methylamine (according to Weinreb et al. Tet. Lett. 1981, 39, 3815) provides the Weinreb amide of formula XVII (where R4, R 5a , and R 5b are as defined in formula I). ​​Treatment of compounds of formula XVII with Grignard reagents R3MgBr, such as MeMgBr, at lower temperatures, preferably 0-25°C, gives alkyl ketones of formula VI (where R3, R4, R 5a , and R 5b is as defined in formula I).

[0073] Yet another method for preparing compounds of general formula IIa is outlined in Scheme 7.

[0074] Scheme 7: [ka] Thus, as already detailed in Scheme 5, nucleophilic substitution of a compound of formula XIV with an amine of formula VII gives a compound of formula II (where R, R, R, R5a , and R 5b is as defined in Formula I). ​​A compound of Formula II with a protecting group (e.g., R is benzyl) is hydrogenated with hydrogen in the presence of palladium (on charcoal) in a solvent such as MeOH or EtOH to give a compound of Formula IIa (where R, R, R 5a , and R 5b is as defined in formula I) is obtained (see, for example, Synlett, 2010, (18), page 2708). 5a , and R 5b is as defined in formula I) can also be converted to compounds of formula II by reaction with N'N' dimethylbarbituric acid in the presence of a Pd catalyst, preferably tetrakis(triphenylphosphine)palladium(0), in a suitable solvent, for example CH2Cl2, according to J. Org. Chem. 1993, 58, 6109, to give compounds of formula IIa.

[0075] Carboxylic acids of formula XXI, where R 2b and A1 are as defined in Formula I) are useful intermediates for the preparation of the final compounds (see Scheme 1) and can be prepared by the process shown in Scheme 8.

[0076] Scheme 8: [ka] Thus, compounds of formula IIIa, where R 2b and A1 are as defined in formula I) can be prepared by reacting a compound of formula XXI (wherein R 2band A1 are as defined in formula I, and Z1 is C1-C4 alkyl) with a suitable base such as sodium hydroxide or lithium hydroxide. Compounds of formula XXI are prepared by oxidation of compounds of formula XXa with, for example, m-CPBA or NaIO4 / RuCl3 in a solvent, preferably CHCl3 or a mixture of HO, AcCN, and CCl4. Such transformations are known to those skilled in the art and are described, for example, in J. Med. Chem. 2008, 51, 6902 or WO 2004 / 9086, pp. 24-25.

[0077] Finally, compounds of formula XXa, where R 2b and A1 are as defined in formula I and Z1 is C1-C4 alkyl) can be prepared by reacting a compound of formula XVIIIa with a suitable trifluoromethylthiolated copper reagent of formula XIX (where R 2b and A1 are as defined in formula I, and X 08 is Br or Cl) (the ligand is, for example, 1,10-phenanthroline or 4,4'-di-tert-butylbipyridine). Such processes have been described, for example, in Angew. Chem. Int. Ed. 2013, 52, 1548-1552; Angew. Chem. Int. Ed. 2011, 50, 3793; Org. Lett. 2014, 16, 1744; J. Org. Chem. 2017, 82, 11915.

[0078] Further intermediates of formula XX (wherein R 2a , R 2b and A1 is as defined in Formula I, and Z1 is C1-C4 alkyl) are commonly known or can be readily prepared by one skilled in the art. A typical example of such a synthesis of a compound of Formula XX is shown in Scheme 9.

[0079] Scheme 9: [ka] For example, a compound of formula XX can be prepared by reacting a compound of formula XVIIIb (wherein R 2b and A1 are as defined for formula I, and X 05 is chlorine, bromine, iodine, OMs, OTs or OTf) with a compound of formula XXIII, where R 2a can be prepared by reaction with (as defined in formula I). ​​Such a process has already been described, for example, in Tetrahedron Letters 2002, 43, 6987-6990.

[0080] Compounds of formula XX can also be prepared by the reaction of a compound of formula XXIV (wherein R 2b and A1 and Z1 are as defined in formula XX) with a compound of formula XXV (wherein R 2a is as defined in formula I, and X 05 is a leaving group such as bromine or iodine. Such a process has already been described, for example, in WO 12139775, page 73.

[0081] A compound of formula XXIV, where R 2band A1 and Z1 are as defined in formula I) can be reacted with a compound of formula XVIIIb (wherein R 2b and A1 and Z1 are as defined in formula XXIV, and X 05 is Cl, Br, I, OMs, OTs or OTf) with a compound of formula XXII, such as bis(pinacolato)diboron (B2pin2). Such a process has been described, for example, in Bioorg. Med. Chem. Lett. 2015, 25, 1730 and WO 12139775, p. 67.

[0082] Carboxylic acids of formula IIIb can be prepared from compounds of formula XXVIII as outlined in Scheme 8 by treatment with, for example, aqueous LiOH, NaOH or KOH in a suitable solvent which may include, for example, a THF / MeOH mixture, typically with heating at temperatures between room temperature and 100°C, preferably between 20°C and the boiling point of the reaction mixture (see Scheme 10).

[0083] A compound of formula XXVIII, where R 2b and A1 are defined in formula I, and R 2a is H, C1-C3 alkyl, C1-C3 haloalkyl, cyano or halogen, and Z1 is C1-C4 alkyl) can be prepared by treating a compound of formula XXVII, which is commercially available, or (as in Org. Lett. 2016, 18, 2471) with a compound of formula XXVI, such as (trifluoroethyl)-diphenyl-sulfonium triflate (PhS), in the presence of an Fe catalyst and a base, preferably CsF, at a temperature between 0 and 50°C, preferably 20°C, in DMA as a solvent. + CH2CF3- OTf) by methods known to those skilled in the art (see, for example, Angew. Chem. Int. Ed. 2004, 43, 1132 and Pure Appl. Chem. 1985, 57, 1771). The compound of formula XXIX is obtained as a mixture of stereoisomers, with the trans isomer being the predominant isomer.

[0084] Yet another method for preparing compounds of formula XXVIII (see Scheme 10) uses trifluoroethylamine hydrochloride / NaNO / NaOAc in the presence of an Fe catalyst; the reaction is carried out in HO; or in a mixture of CHCl and HO at room temperature (see, for example, Angew. Chem. Int. Ed. 2010, 49, 938 and Chemm. Commun. 2018, 54, 5110).

[0085] Scheme 10: [ka] Carboxylic acids of formula IIIc, where R 2b and A1 are as defined in formula I, R 2aa is H, C1-C3 alkyl, C1-C3 haloalkyl, cyano, or halogen) can be prepared in a manner quite similar to that already shown in Scheme 10.

[0086] Scheme 11: [ka] Thus, a compound of formula XXIX (where R 2b and A1 are as defined in formula I, R 2aa is H, C1-C3 alkyl, C1-C3 haloalkyl, cyano or halogen, and Z1 is C1-C4 alkyl) is NH4 + Br -The compound of formula XXVII (synthesized analogously to ACS Med. Chem. Lett. 2013, 4,514 or Tetrahedron Lett. 2001, 42, 4083) is prepared by reacting the compound of formula XXVII with (bromodifluoromethyl)-trimethylsilane in the presence of 2-bromodifluoromethyl-2- ...

[0087] Scheme 12. [ka] Carboxylic acids of formula IIId, where R 2b and A1 are as defined in formula I, R 2aa is H, C1-C3 alkyl, C1-C3 haloalkyl, cyano, or halogen) can be prepared according to Reaction Scheme 12. Thus, compounds of Formula XVIIIa (where R 2b and A1 are as defined in Formula I, Z1 is C1-C4 alkyl, and X 08 is bromine or iodine) with iPrMgCl / LiCl-complex; subsequent reaction with CuCN and the formation of cyclopropanecarbonyl chlorides of formula XXX (where R 2a is H, C1-C3 alkyl, C1-C3 haloalkyl, cyano or halogen) to give compounds of formula XXXI (analogously to WO 2006 / 067445, p. 148). After fluorination with 2,2-difluoro-1,3-dimethylimidazoline in a solvent such as 1,2-dimethoxyethane or neat (see Chem. Commun. 2002, (15), 1618), compounds of formula XXXII are obtained. Subsequent hydrolysis, for example with LiOH as previously described, gives carboxylic acids of formula IIId.

[0088] Scheme 13: [ka]

[0033] In the presence of zinc(II) fluoride (ZnF2) and a palladium(0) catalyst, such as tris(dibenzylideneacetone)di-palladium(0)-chloroform adduct (Pd2(dba)3CHCl3), with a ligand, for example, Xantphos, in an inert solvent, such as N,N-dimethylformamide (DMF), at a temperature between 100 and 180 °C, optionally under microwave heating, trimethylsilyl-acetonitrile (TMSCN) to give a compound of formula XVIIIc (where R 2b and A1 are as defined in formula I, and X 09 is a leaving group such as a halogen or sulfonate, preferably chlorine, bromine, iodine or trifluoromethanesulfonate, and Z1 is C1-C4 alkyl to give a compound of formula XXXV, where R 2b , Z1, and A1 are as defined in formula XVIIIc). Such chemical reactions are described in the literature, for example, in Org. Lett. 16(24), 6314-6317, 2014. Alternatively, the reaction of a compound of formula XVIIIc with 4-isoxazoleboronic acid or 4-isoxazoleboronic acid pinacol ester in the presence of potassium fluoride (KF) and a palladium catalyst such as bis(triphenylphosphine)palladium(II) dichloride (Pd(PPh3)2Cl2) in an inert solvent such as dimethyl sulfoxide (DMSO), optionally in a mixture with water, at a temperature of 40-150°C, optionally under microwave heating, gives a compound of formula XXXVII (where R 2b , A1 is as defined in formula I and Z1 is C1-C4 alkyl. Reaction of compounds of formula XXXVII with aqueous potassium fluoride (KF concentration of 0.5-3 M, preferably 1 M) in an inert solvent such as dimethyl sulfoxide (DMSO) or methanol at a temperature of 20-150°C, optionally under microwave heating, gives compounds of formula XXXV, where R 2b , Z1 and A1 are as defined in formula XVIIIc) to obtain. Such chemical reactions are described in the literature, for example, in J. Am. Chem. Soc. 2011, 133, 6948-6951.

[0089] A compound of formula XXXV, where R 2b and A1 are as defined in formula I and Z1 is C1-C4 alkyl) in the presence of a base such as sodium hydride, sodium carbonate, potassium carbonate K2CO3, or cesium carbonate Cs2CO3 in an inert solvent such as N,N-dimethylformamide (DMF), acetone, or acetonitrile at a temperature between 0 and 120 °C to give a compound of formula XXXIV (wherein X 10 is further treated with a leaving group such as a halogen (preferably chlorine, bromine, or iodine) to give a compound of formula XXXVI, where R 2b and A1 are as defined in Formula I above, and Z1 is C1-C4 alkyl. Alternatively, compounds of Formula XXXVI can be prepared directly from compounds of Formula XVIIIc by treatment with compounds of Formula XXXVIII in the presence of a catalyst such as Pd2(dba)3, a ligand such as BINAP, and a strong base such as lithium hexamethyldisilazane (LiHMDS), in an inert solvent such as tetrahydrofuran (THF), at temperatures between 30 and 80°C. Such chemical reactions are described, for example, in J. Am. Chem. Soc. 127(45), 15824-15832, 2005.

[0090] Yet another method for preparing compounds of formula XXXV from compounds of formula XVIIIc is shown in Scheme 13. Compounds of formula XVIIIc (where R 2b , Z1 and A1 are as defined in Formula I, Z1 is C1-C4 alkyl, and X 09 is a leaving group, such as a halogen or sulfonate, preferably chlorine, bromine, iodine or trifluoromethanesulfonate, with a reagent of formula XXXVIII, where Z2 is C1-C4 alkyl, to give a compound of formula XXXIX, where R 2b and A1 are as defined in Formula I, and Z1 and Z2 are each C1-C4 alkyl. Compounds of formula XXXIX are decarboxylated using conditions such as heating in wet DMSO, optionally in the presence of lithium chloride or sodium chloride, at temperatures between 50°C and 180°C to give compounds of formula XXXV. Similar chemical reactions are described, for example, in Synthesis 2010, No. 19, 3332-3338.

[0091] Compound of Formula I'a [ka] is an amine of formula IIb [ka] (where R1, R3, A2, R4, R5a , and R 5b is as described in formula I) and a carboxylic acid derivative of formula III (wherein A1, R 2a and R 2b can be prepared by reaction with a methyl group (described above in Formula I).

[0092] [ka] This chemistry is described in more detail in Scheme 14.

[0093] Scheme 14: [ka] A compound of formula IIIa, wherein A1, R 2a , R 2b and X0 are described in Scheme 1) can be converted to a compound of formula IIb (where R1, R3, R4, R 5a , and R 5b is treated with a compound of formula IIIa (described in formula I). ​​The formation of a compound of formula IIIa from a compound of formula III is described in Scheme 1.

[0094] The formation of compounds of formula IIb is outlined in Scheme 15. Compounds of formula IIb can be prepared by the reaction of a compound of formula IIc (where R, R, R) with a compound of formula XL (where R is as defined in formula I) in the presence of, for example, NaBH(OAc) or NaBHCN in a suitable solvent, preferably acetic acid, at room temperature, analogously to WO 2002 / 088073, p. 35. 5a , and R 5b can be prepared by treatment of (as defined in Formula I). ​​Alternatively, another reagent system for reductive amination uses a combination of Ti(i-OiPr)4 and NaBH4 (see Synthesis 2003(14), 2206).

[0095] Amines of formula IIc can be obtained by biocatalytic deracemization of amines of formula IIa. This can be carried out, for example, using lipases, such as Candida Antarctica lipase B or Pseudomonas fluorescens lipase, eventually in immobilized form (e.g., Novozym® 435), in the presence of an acyl donor, such as ethyl methoxyacetate or vinyl acetate, in a suitable solvent such as acetonitrile or methyl tert-butyl ether at temperatures between 20°C and 100°C. Such processes are described, for example, in J. Org. Chem. 2007, 72, 6918-6923 or Adv. Synth. Catal. 2007, 349, 1481-1488. The expected stereochemical outcome of such enzymatic deracemization is known to those skilled in the art and is documented in the literature, for example in J. Org. Chem. 1991, 56, 2656-2665 or J. Am. Chem. Soc. 2015, 137, 3996-4009.

[0096] Scheme 15: [ka] In an alternative process, compounds of formula IIc can be prepared by reacting XIIa (where R3, R4, R 5a , and R 5b is obtained from (as described in Formula I).

[0097] Scheme 16: [ka] Amines of formula IIc can be prepared by reacting intermediates of formula XLI (where R3, R4, R 5a , and R 5bis as described in Formula I, and Z3 is NPhth or NBoc2. Such intermediates can be obtained from alcohols of Formula XIIa by Mitsunobu reaction, which involves treating an alcohol of Formula XIIa with diisopropyl azodicarboxylate in the presence of a phosphine such as triphenylphosphine or tributylphosphine and an amine such as phthalimide or bis(tert-butoxycarbonyl)amine. The Mitsunobu reaction is known by those skilled in the art to proceed with inversion of the stereocenter, as described, for example, in Chem. Rev. 2009, 109, 2551-2651. The amine of Formula XLI can then be converted to an amine of Formula IIc by treatment with hydrazine if Z3=NPhth, or with TFA if Z3=NBoc2.

[0098] Alternatively, amines of formula IIc can be converted to azides of formula XLII (where R3, R4, R5) by treatment with triphenylphosphine and water (Staudinger reaction) or by hydrogenation using a palladium catalyst in the presence of hydrogen, for example. 5a , and R 5b is as described in formula I. Azides of formula XLII can be obtained by reduction of alcohols of formula XIIa (where R3, R4, R5) with an azide reagent such as diphenylphosphoryl azide in the presence of a base such as DBU in a solvent such as toluene or THF. 5a , and R 5b is obtained by treating the compound (I) as described in formula I. Such processes, which lead to the inversion of the stereocenter, are known by those skilled in the art and are described in the literature, for example in Adv. Synth. Catal. 2018, 360, 2157-2165.

[0099] The alcohol of formula XIIa can be prepared by reacting a ketone of formula VI (where R3, R4, R 5a , and R 5bis obtained by enantioselective reduction of (as described in formula I). ​​Such reduction can be carried out with chiral ligands such as RuCl[(R,R)-TsDPEN] (mesitylene) or RuBF4[(R,R)-TsDPEN] (p-cymene) using a catalyst, e.g., a ruthenium or rhodium catalyst, in the presence of a hydrogen donor system, e.g., HCOOH / Et3N or HCO2NH4. Such processes are described in the literature, e.g., J. Org. Chem. 2017, 82, 5607.

[0100] Alternatively, compounds of formula IIc can also be prepared as outlined in Scheme 17.

[0101] Scheme 17: [ka] Amines of formula IIc can be prepared by the reaction of an amine of formula XLIX (where R3, R4, R 5a , and R 5b Amines of formula XLIX can be prepared by deprotection of an amine of formula XLVIII (where R3 and R4 are as described in formula I and Z 5a and Z 5b are, independently of each other, R 5a , R 5b , halogen, NH2 or OH). Such functional group interconversions are known to those skilled in the art and examples of such conversions are described in the literature, for example in Eur. J. Org. Chem. 2005, 19, 4141-4153 or J. Org. Chem. 2008, 73, 7481-7485. Amines of formula XLVIII can be obtained by the reaction of diamines of formula XLVII (where Z is selected from the group consisting of aryl, halogen, NH2 or OH) in diketones of formula XLVI (where R3 and R4 are as described in formula I). 5a and Z 5b are, independently of each other, R 5a , R 5b, halogen, NH2 or OH). This condensation can be carried out in the presence of a suitable solvent such as ethanol or isopropanol, in the presence of air or an oxidizing agent such as DDQ. Diketones of formula XLVI can be formed by oxidation of hydroxyketones of formula XLIV (where R3 and R4 are as described in formula I). ​​This oxidation can involve, for example, SO3-pyridine in the presence of DMSO and a base such as triethylamine, or alternatively, in the presence of a catalyst such as TEMPO / Bu4NHSO4 in the presence of sodium hypochlorite. Examples of such oxidations can be found in the literature, for example, Synlett, 2014, 25, 596 or J. Am. Chem. Soc. 1990, 112, 5290-5313. The hydroxyketone of formula XLIV can be synthesized by cross-benzoin condensation between an aldehyde of formula XLIII (wherein R4 is as described in formula I) and an aldehyde of formula XLV (wherein R3 is as described in formula I). ​​The aldehyde of formula XLV is commercially available in chiral form, for example, Boc-L-alaninal (CAS 79069-50-4) or tert-butyl N-[(1S)-1-(cyclopropylmethyl)-2-oxo-ethyl]carbamate (CAS 881902-36-9). The cross-benzoin condensation is carried out in the usual manner by using an organic catalyst such as a triazolium salt or a thiazolium salt in the presence of a base such as potassium tert-butoxide or isopropyldiethylamine in a suitable solvent such as dichloromethane or tetrahydrofuran at a temperature between −20° C. and the boiling point of the solvent. Examples of catalysts for such transformations are described in the literature, for example in J. Am. Chem. Soc. 2014, 136, 7539-7542 or Org. Lett. 2016, 18, 4518-4521.

[0102] Alternatively, as shown in Scheme 18, compounds of formula I'a can be prepared by reacting them with chiral compounds of formula L (where A, R, R 2a , R 2b , R3, R 5a , and R 5b is defined in formula I, and X 05can be prepared from a leaving group such as, for example, chlorine, bromine or iodine.

[0103] Scheme 18: [ka] Compounds of formula I'a can be prepared by the reaction of compounds of formula L with compounds of formula V (Still reaction) or compounds of formula VIII (Suzuki-Miyaura reaction) in the presence of a palladium catalyst, as detailed in Schemes 2 and 3.

[0104] Compounds of formula L can be prepared by the reaction of amines of formula LIa (where R, R, R 5a , and R 5b is defined in formula I, and X 05 is a leaving group such as, for example, chlorine, bromine, or iodine) and a compound of formula IIIa (wherein A1, R 2a , R 2b and X0 can be prepared by coupling of X0 and X0 as described in Scheme 1. Under the same conditions, when R1 = H, compounds of formula L can be obtained directly from compounds of formula LI (where R1, R3, R5a, and R5b are defined in formula I, and X05 is a leaving group such as, for example, chlorine, bromine, or iodine).

[0105] Compounds of formula LIa can be prepared by treatment of compounds of formula LI with compounds of formula XL (where R1 is as defined in formula I) in the presence of, for example, NaBH(OAc)3 or NaBH3CN in a suitable solvent, preferably acetic acid, at room temperature, analogously to WO 2002 / 088073, page 35. Alternatively, another reagent system for reductive amination uses a combination of Ti(i-OiPr)4 and NaBH4 (see Synthesis 2003(14), 2206).

[0106] Amines of formula LI can be prepared, for example, by a deracemization procedure involving selective acylation of one enantiomer. Such an example is described in more detail in Scheme 19.

[0107] Scheme 19: [ka] The amine of formula LI is an amine of formula LIb, where R, R 5a , and R 5b is depicted in Scheme 1, and X 05 is a leaving group such as bromine, chlorine, iodine, mesylate, tosylate, or triflate. This can be carried out, for example, using a lipase, such as Candida Antarctica lipase B or Pseudomonas fluorescens lipase, eventually in immobilized form (e.g., Novozym® 435), in the presence of an acyl donor, such as ethyl methoxyacetate or vinyl acetate, in a suitable solvent such as acetonitrile or methyl tert-butyl ether at temperatures between 20°C and 100°C. Such processes are described, for example, in J. Org. Chem. 2007, 72, 6918-6923 or Adv. Synth. Catal. 2007, 349, 1481-1488. The expected stereochemical outcome of such enzymatic deracemization is known to those skilled in the art and is documented in the literature, for example in J. Org. Chem. 1991, 56, 2656-2665 or J. Am. Chem. Soc. 2015, 137, 3996-4009.

[0108] Alternatively, resolution of amines of Formula LIb can be achieved using a chiral auxiliary, as described in Scheme 20.

[0109] Scheme 20 [ka] Amines of formula LI can be converted to intermediates of formula LII (where R3, R 5a , and R 5b is depicted in Scheme 1, and X 05 is a leaving group such as bromine, chlorine, iodine, mesylate, tosylate, or triflate, and X 11 * is a chiral auxiliary). Amines of formula LII can be prepared by the conversion of chiral compounds of formula LIII (where X is as described in Scheme 1 and X is a chiral auxiliary) with amines of formula LIb according to the conditions detailed in Scheme 1. 11 * is a chiral moiety of known chirality). Chiral auxiliaries of formula LIII can be derived, for example, from mandelic acid or (1R)-menthyl chloroformate. Examples of such deracemization processes have been reported in the literature, for example, in J. Org. Chem. 2007, 72, 485-493.

[0110] Alternatively, amines of formula LI can be formed as described in Scheme 21.

[0111] Scheme 21: [ka] The amine of formula LI can be prepared by reacting an intermediate of formula LIV (where R3, R 5a , and R 5b is as described in formula I, and X 05 is a leaving group as described in Scheme 3, and Z3 is NPhth or NBoc2. Such intermediates can be obtained by the Mitsunobu reaction from alcohols of formula IVa (where R3, R 5a , and R 5b is as described in formula I, and X 05is a leaving group as described in Scheme 3), and involves treating an alcohol of formula IVa with diisopropyl azodicarboxylate in the presence of a phosphine such as triphenylphosphine or tributylphosphine and an amine such as phthalimide or bis(tert-butoxycarbonyl)amine. The Mitsunobu reaction is known by those skilled in the art to proceed with the inversion of the stereocenter, as described, for example, in Chem. Rev. 2009, 109, 2551-2651. The amine of formula LIV can then be converted to an amine of formula LI by treatment with hydrazine if Z3=NPhth or with TFA if Z3=NBoc2.

[0112] Alternatively, amines of formula LI can be converted to azides of formula LV (where R, R) by treatment with triphenylphosphine and water (Staudinger reaction) or by hydrogenation using, for example, a palladium catalyst in the presence of hydrogen. 5a , and R 5b is as described in formula I, and X 05 is a leaving group as described in Scheme 3). Azides of formula LV can be obtained by treatment of alcohols of formula IVa with an azide reagent such as diphenylphosphoryl azide in the presence of a base such as DBU in a solvent such as toluene or THF. Such processes, which lead to the inversion of the stereocenter, are known by those skilled in the art and are described in the literature, for example in Adv. Synth. Catal. 2018, 360, 2157-2165.

[0113] The alcohol of formula IVa can be prepared by reacting a ketone of formula IV (where R3, R 5a , and R 5b is as described in formula I, and X 05is the leaving group described in Scheme 3) can be obtained by enantioselective reduction of RuCl[(R,R)-TsDPEN] (mesitylene) or RuBF4[(R,R)-TsDPEN] (p-cymene) with a chiral ligand such as RuCl[(R,R)-TsDPEN] (mesitylene) or RuBF4[(R,R)-TsDPEN] (p-cymene), using a catalyst such as a ruthenium or rhodium catalyst, in the presence of a hydrogen donor system such as HCOOH / Et3N or HCO2NH4. Such processes are described in the literature, for example in J. Org. Chem. 2017, 82, 5607.

[0114] Depending on the method or reaction conditions, the reactants can be reacted in the presence of a base. Examples of suitable bases are alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamides, alkylenediamides, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxide and carbocyclic amines. Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

[0115] The reactants can be reacted with each other as they are, i.e., without the addition of a solvent or diluent. However, in most cases, it is advantageous to add an inert solvent or diluent or a mixture thereof. When the reaction is carried out in the presence of a base, the base used in excess, such as triethylamine, pyridine, N-methylmorpholine, or N,N-diethylaniline, can also serve as the solvent or diluent.

[0116] The reaction is advantageously carried out in the temperature range of about -80°C to about +140°C, preferably about -30°C to about +100°C, and in many cases in the range of ambient temperature to about +80°C.

[0117] Depending on the respective suitable reaction conditions and the choice of starting materials, it is possible, for example, to simply replace one substituent with another substituent according to the invention in one reaction step, or multiple substituents can be replaced with other substituents according to the invention in the same reaction step.

[0118] Salts of compounds of formula I can be prepared in a manner known per se: thus, for example, acid addition salts of compounds of formula I can be obtained by treatment with a suitable acid or with a suitable ion exchange reagent, and base salts can be obtained by treatment with a suitable base or with a suitable ion exchange reagent.

[0119] Salts of compounds of formula I can be converted in a customary manner into acid addition salts of the free compounds I, for example by treatment with suitable basic compounds or suitable ion exchange reagents, and into salts with bases, for example by treatment with suitable acids or suitable ion exchange reagents.

[0120] Salts of compounds of formula I may be converted into other salts, such as acid addition salts, of compounds of formula I in a manner known per se, for example by treating the inorganic acid salt, such as the hydrochloride, with a suitable metal salt, such as the sodium, barium or silver salt of the acid, for example silver acetate, in a suitable solvent in which the inorganic salt that forms silver chloride is insoluble and therefore precipitates from the reaction mixture.

[0121] Depending on the procedure or reaction conditions, compounds of formula I having salt-forming properties may be obtained in free form or in salt form.

[0122] The compounds of formula I and, where appropriate, their tautomers, in each free or salt form, can exist in the form of pure isomers, such as enantiomers and / or diastereomers, or as isomeric mixtures, such as enantiomeric mixtures, such as racemates, diastereomeric mixtures or racemic mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms occurring in the molecule and / or depending on the configuration of non-aromatic double bonds occurring in the molecule; the invention relates to the pure isomers and also to all possible isomeric mixtures, and is to be understood in this sense above and below, respectively, even if details of the stereochemistry are not specifically stated in each case.

[0123] Diastereomeric or racemic mixtures of compounds of formula I, in free or salt form, obtained depending on which starting materials and procedures are selected, can be separated in known manner into pure diastereomers or racemates on the basis of the physical chemical differences of the components, for example, by fractional crystallization, distillation, and / or chromatography.

[0124] Enantiomeric mixtures, such as racemates, obtained in a similar manner can be resolved into their optical antipodes by known methods, for example by recrystallization from optically active solvents, by chromatography on chiral adsorbents, for example by high-performance liquid chromatography (HPLC) on acetylcellulose using suitable microorganisms, by cleavage with specific immobilized enzymes via the formation of inclusion compounds, for example with chiral crown ethers, in which only one enantiomer is complexed, or by conversion to diastereomeric salts, for example by reacting the basic final product racemate with an optically active acid, such as a carboxylic acid, for example camphoric acid, tartaric acid or malic acid, or a sulfonic acid, for example camphorsulfonic acid, and separating the diastereomeric mixtures thus obtained, for example by fractional crystallization based on their different solubilities, to give diastereomers from which the desired enantiomer can be released by the action of a suitable substance, for example a basic substance.

[0125] Pure diastereomers or enantiomers can be obtained according to the present invention not only by separating the appropriate isomeric mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, e.g. by carrying out the process according to the present invention using stereochemically characterized starting materials.

[0126] The N-oxides can be prepared by reacting the compounds of formula I with a suitable oxidizing agent, such as the H2O2 / urea adduct, in the presence of an acid anhydride, such as trifluoroacetic anhydride. Such oxidations are known from the literature, for example, J. Med. Chem., 32(12), 2561-73, 1989 or WO 2000 / 15615.

[0127] When the individual components have different biological activities, it may be advantageous to isolate or synthesize the respective more biologically active isomer, e.g., enantiomer or diastereomer, or mixture of isomers, e.g., mixture of enantiomers or diastereomers.

[0128] The compounds of formula I and, where appropriate, their tautomers, may also be obtained in free or salt form, optionally in the form of hydrates, and / or contain other solvents, such as solvents that may have been used for the crystallization of compounds present in solid form.

[0129] The compounds of formula I according to the following Tables A-1 to A-21 can be prepared according to the above method. The following examples are intended to illustrate the present invention and to show preferred compounds of formula I in the form of compounds of formula Iaa. [ka]

[0130] Table A-1 provides 16 compounds A-1.001 to A-1.016 of formula Iaa, where R1 is H, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z. For example, A-1.002 is [ka] is.

[0131] [Table 1-1] [Table 1-2]

[0132] Table A-2 provides 16 compounds of formula Iaa, A-2.001 to A-2.016, where R1 is H, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0133] Table A-3 provides 16 compounds of formula Iaa, A-3.001 to A-3.016, where R1 is H, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0134] Table A-4 provides 16 compounds of formula Iaa, A-4.001 to A-4.016, where R1 is H, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0135] Table A-5 provides 16 compounds A-5.001 to A-5.016 of formula Iaa, where R1 is H, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0136] Table A-6 provides 16 compounds of formula Iaa, A-6.001 to A-6.016, where R1 is H, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0137] Table A-7 provides 16 compounds of formula Iaa, A-7.001 to A-7.016, where R1 is H, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0138] Table A-8 provides 16 compounds of formula Iaa, A-8.001 to A-8.016, where R1 is CH3, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0139] Table A-9 provides 16 compounds of formula Iaa, A-9.001 to A-9.016, where R1 is CH3, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0140] Table A-10 provides 16 compounds of formula Iaa, A-10.001 to A-10.016, where R1 is CH3, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0141] Table A-11 provides 16 compounds of formula Iaa, A-11.001 to A-11.016, where R1 is CH3, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0142] Table A-12 provides 16 compounds of formula Iaa, A-12.001 to A-12.016, where R1 is CH3, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0143] Table A-13 provides 16 compounds of formula Iaa, A-13.001 to A-13.016, where R1 is CH3, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0144] Table A-14 provides 16 compounds of formula Iaa, A-14.001 to A-14.016, where R1 is CH3, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0145] Table A-15 provides 16 compounds of formula Iaa, A-15.001 to A-15.016, where R1 is CH2Cyp, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0146] Table A-16 provides sixteen compounds of formula Iaa, A-16.001 to A-16.016, where R1 is CH2Cyp, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0147] Table A-17 provides 16 compounds of formula Iaa, A-17.001 to A-17.016, where R1 is CH2Cyp, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0148] Table A-18 provides 16 compounds of formula Iaa, A-18.001 to A-18.016, where R1 is CH2Cyp, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0149] Table A-19 provides 16 compounds of formula Iaa, A-19.001 to A-19.016, where R1 is CH2Cyp, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0150] Table A-20 provides 16 compounds of formula Iaa, A-20.001 to A-20.016, where R1 is CH2Cyp, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0151] Table A-21 provides 16 compounds of formula Iaa, A-21.001 to A-21.016, where R1 is CH2Cyp, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0152] The compounds of formula I according to the following Tables B-1 to B-21 can be prepared according to the above method. The following examples are intended to illustrate the present invention and to show preferred compounds of formula I in the form of compounds of formula Iab. [ka]

[0153] Table B-1 provides 16 compounds B-1.001 to B-1.016 of formula Iab, where R1 is H, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0154] Table B-2 provides 16 compounds B-2.001 to B-2.016 of formula Iab, where R1 is H, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0155] Table B-3 provides 16 compounds B-3.001 to B-3.016 of formula Iab, where R1 is H, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0156] Table B-4 provides 16 compounds B-4.001 to B-4.016 of formula Iab, where R1 is H, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0157] Table B-5 provides 16 compounds B-5.001 to B-5.016 of formula Iab, where R1 is H, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0158] Table B-6 provides 16 compounds B-6.001 to B-6.016 of formula Iab, where R1 is H, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0159] Table B-7 provides 16 compounds B-7.001 to B-7.016 of formula Iab, where R1 is H, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0160] Table B-8 provides 16 compounds B-8.001 to B-8.016 of formula Iab, where R1 is CH3, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0161] Table B-9 provides 16 compounds B-9.001 to B-9.016 of formula Iab, where R1 is CH3, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0162] Table B-10 provides 16 compounds B-10.001 to B-10.016 of formula Iab, where R1 is CH3, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0163] Table B-11 provides 16 compounds of formula Iab, B-11.001 to B-11.016, where R1 is CH3, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0164] Table B-12 provides 16 compounds of formula Iab, B-12.001 to B-12.016, where R1 is CH3, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0165] Table B-13 provides 16 compounds of formula Iab, B-13.001 to B-13.016, where R1 is CH3, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0166] Table B-14 provides 16 compounds of formula Iab, B-14.001 to B-14.016, where R1 is CH3, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0167] Table B-15 provides 16 compounds B-15.001 to B-15.016 of formula Iab, where R1 is CH2Cyp, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0168] Table B-16 provides sixteen compounds of formula Iab, B-16.001 to B-16.016, where R1 is CH2Cyp, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0169] Table B-17 provides 16 compounds B-17.001 to B-17.016 of formula Iab, where R1 is CH2Cyp, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0170] Table B-18 provides 16 compounds B-18.001 to B-18.016 of formula Iab, where R1 is CH2Cyp, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0171] Table B-19 provides 16 compounds B-19.001 to B-19.016 of formula Iab, where R1 is CH2Cyp, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0172] Table B-20 provides 16 compounds B-20.001 to B-20.016 of formula Iab, where R1 is CH2Cyp, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0173] Table B-21 provides 16 compounds B-21.001 to B-21.016 of formula Iab, where R1 is CH2Cyp, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0174] The compounds of formula I according to the following Tables C-1 to C-21 can be prepared according to the above method. The following examples are intended to illustrate the present invention and to show preferred compounds of formula I in the form of compounds of formula Iac. [ka]

[0175] Table C-1 provides 16 compounds C-1.001 to C-1.016 of formula Iac, where R1 is H, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0176] Table C-2 provides 16 compounds C-2.001 to C-2.016 of formula Iac, where R1 is H, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0177] Table C-3 provides 16 compounds C-3.001 to C-3.016 of formula Iac, where R1 is H, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0178] Table C-4 provides 16 compounds C-4.001 to C-4.016 of formula Iac, where R1 is H, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0179] Table C-5 provides 16 compounds C-5.001 to C-5.016 of formula Iac, where R1 is H, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0180] Table C-6 provides 16 compounds C-6.001 to C-6.016 of formula Iac, where R1 is H, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0181] Table C-7 provides 16 compounds C-7.001 to C-7.016 of formula Iac, where R1 is H, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0182] Table C-8 provides 16 compounds C-8.001 to C-8.016 of formula Iac, where R1 is CH3, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0183] Table C-9 provides 16 compounds C-9.001 to C-9.016 of formula Iac, where R1 is CH3, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0184] Table C-10 provides 16 compounds of formula Iac, C-10.001 to C-10.016, where R1 is CH3, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0185] Table C-11 provides 16 compounds of formula Iac, C-11.001 to C-11.016, where R1 is CH3, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0186] Table C-12 provides 16 compounds of formula Iac, C-12.001 to C-12.016, where R1 is CH3, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0187] Table C-13 provides 16 compounds of formula Iac, C-13.001 to C-13.016, where R1 is CH3, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0188] Table C-14 provides 16 compounds of formula Iac, C-14.001 to C-14.016, where R1 is CH3, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0189] Table C-15 provides 16 compounds of formula Iac, C-15.001 to C-15.016, where R1 is CH2Cyp, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0190] Table C-16 provides 16 compounds of formula Iac, C-16.001 to C-16.016, where R1 is CH2Cyp, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0191] Table C-17 provides 16 compounds of formula Iac, C-17.001 to C-17.016, where R1 is CH2Cyp, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0192] Table C-18 provides 16 compounds of formula Iac, C-18.001 to C-18.016, where R1 is CH2Cyp, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0193] Table C-19 provides 16 compounds of formula Iac, C-19.001 to C-19.016, where R1 is CH2Cyp, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0194] Table C-20 provides 16 compounds of formula Iac, C-20.001 to C-20.016, where R1 is CH2Cyp, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0195] Table C-21 provides 16 compounds of formula Iac, C-21.001 to C-21.016, where R1 is CH2Cyp, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0196] The compounds of formula I according to the following Tables D-1 to D-21 can be prepared according to the above method. The following examples are intended to illustrate the present invention and to show preferred compounds of formula I in the form of compounds of formula Iad. [ka]

[0197] Table D-1 provides 16 compounds D-1.001 to D-1.016 of formula Iad, where R1 is H, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0198] Table D-2 provides 16 compounds D-2.001 to D-2.016 of formula Iad, where R1 is H, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0199] Table D-3 provides 16 compounds D-3.001 to D-3.016 of formula Iad, where R1 is H, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0200] Table D-4 provides 16 compounds D-4.001 to D-4.016 of formula Iad, where R1 is H, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0201] Table D-5 provides 16 compounds D-5.001 to D-5.016 of formula Iad, where R1 is H, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0202] Table D-6 provides 16 compounds D-6.001 to D-6.016 of formula Iad, where R1 is H, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0203] Table D-7 provides 16 compounds D-7.001 to D-7.016 of formula Iad, where R1 is H, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0204] Table D-8 provides 16 compounds D-8.001 to D-8.016 of formula Iad, where R1 is CH3, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0205] Table D-9 provides 16 compounds D-9.001 to D-9.016 of formula Iad, where R1 is CH3, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0206] Table D-10 provides 16 compounds D-10.001 to D-10.016 of formula Iad, where R1 is CH3, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0207] Table D-11 provides 16 compounds of formula Iad, D-11.001 to D-11.016, where R1 is CH3, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0208] Table D-12 provides 16 compounds of formula Iad, D-12.001 to D-12.016, where R1 is CH3, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0209] Table D-13 provides 16 compounds of formula Iad, D-13.001 to D-13.016, where R1 is CH3, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0210] Table D-14 provides 16 compounds of formula Iad, D-14.001 to D-14.016, where R1 is CH3, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0211] Table D-15 provides 16 compounds D-15.001 to D-15.016 of formula Iad, where R1 is CH2Cyp, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0212] Table D-16 provides 16 compounds D-16.001 to D-16.016 of formula Iad, where R1 is CH2Cyp, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0213] Table D-17 provides 16 compounds D-17.001 to D-17.016 of formula Iad, where R1 is CH2Cyp, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0214] Table D-18 provides 16 compounds of formula Iad, D-18.001 to D-18.016, where R1 is CH2Cyp, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0215] Table D-19 provides 16 compounds D-19.001 to D-19.016 of formula Iad, where R1 is CH2Cyp, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0216] Table D-20 provides 16 compounds D-20.001 to D-20.016 of formula Iad, where R1 is CH2Cyp, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0217] Table D-21 provides 16 compounds D-21.001 to D-21.016 of formula Iad, where R1 is CH2Cyp, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0218] The compounds of formula I according to the following Tables E-1 to E-21 can be prepared according to the above method. The following examples are intended to illustrate the present invention and to show preferred compounds of formula I in the form of compounds of formula Iae. [ka]

[0219] Table E-1 provides 16 compounds E-1.001 to E-1.016 of formula Iae, where R1 is H, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0220] Table E-2 provides 16 compounds E-2.001 to E-2.016 of formula Iae, where R1 is H, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0221] Table E-3 provides 16 compounds E-3.001 to E-3.016 of formula Iae, where R1 is H, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0222] Table E-4 provides 16 compounds E-4.001 to E-4.016 of formula Iae, where R1 is H, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0223] Table E-5 provides 16 compounds E-5.001 to E-5.016 of formula Iae, where R1 is H, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0224] Table E-6 provides 16 compounds E-6.001 to E-6.016 of formula Iae, where R1 is H, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0225] Table E-7 provides 16 compounds E-7.001 to E-7.016 of formula Iae, where R1 is H, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0226] Table E-8 provides 16 compounds E-8.001 to E-8.016 of formula Iae, where R1 is CH3, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0227] Table E-9 provides 16 compounds E-9.001 to E-9.016 of formula Iae, where R1 is CH3, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0228] Table E-10 provides 16 compounds of formula Iae, E-10.001 to E-10.016, where R1 is CH3, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0229] Table E-11 provides 16 compounds of formula Iae, E-11.001 to E-11.016, where R1 is CH3, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0230] Table E-12 provides 16 compounds of formula Iae, E-12.001 to E-12.016, where R1 is CH3, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0231] Table E-13 provides 16 compounds of formula Iae, E-13.001 to E-13.016, where R1 is CH3, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0232] Table E-14 provides 16 compounds of formula Iae, E-14.001 to E-14.016, where R1 is CH3, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0233] Table E-15 provides 16 compounds E-15.001 to E-15.016 of formula Iae, where R1 is CH2Cyp, R4 is (5-bromopyrimidin-2-yl), and R2 is as defined in Table Z.

[0234] Table E-16 provides sixteen compounds of formula Iae, E-16.001 to E-16.016, where R1 is CH2Cyp, R4 is (5-fluoropyrimidin-2-yl), and R2 is as defined in Table Z.

[0235] Table E-17 provides 16 compounds E-17.001 to E-17.016 of formula Iae, where R1 is CH2Cyp, R4 is pyrimidin-2-yl, and R2 is as defined in Table Z.

[0236] Table E-18 provides 16 compounds of formula Iae, E-18.001 to E-18.016, where R1 is CH2Cyp, R4 is (5-cyclopropylpyrimidin-2-yl), and R2 is as defined in Table Z.

[0237] Table E-19 provides 16 compounds E-19.001 to E-19.016 of formula Iae, where R1 is CH2Cyp, R4 is (5-bromo-2-pyridyl), and R2 is as defined in Table Z.

[0238] Table E-20 provides 16 compounds E-20.001 to E-20.016 of formula Iae, where R1 is CH2Cyp, R4 is (5-fluoro-2-pyridyl), and R2 is as defined in Table Z.

[0239] Table E-21 provides 16 compounds E-21.001 to E-21.016 of formula Iae, where R1 is CH2Cyp, R4 is 2-pyridyl, and R2 is as defined in Table Z.

[0240] Certain intermediate compounds of the amines of formula IIaa-IIae are also available, some of which are novel. Stereocenters are indicated by asterisks in the structures below; therefore, the present invention makes available both the racemate and the individual enantiomers. [ka]

[0241] Particular examples of compounds of Formulae IIaa-IIae are when R1 and R4 are as defined for the compounds in Tables A-1 to A-21.

[0242] Compounds of formula III, IIIa, VI, XII, XLI, XLII, XLIV, XLVI, XLVIII, XLIX, LI, LIA, L, LIV, IV, IVa, LV, XX, XXa, XVIIIa, XVIIIb, XVIIIc, XXI, XXVII, XXVIII, XXIX, XXXI, XXXII, XXXV, XXXVI, XXXVII; and XXXIX are also available, where, where applicable, substituents R1, R2 (R 2a , R 2b and A1), R3, R 5a , R 5b and R4 are as defined in any one of the compounds in Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21, and E-1 to E-21. Particularly preferred enantiomers of the compounds of Formulae III, IIIa, VI, XII, XLI, XLII, XLIV, XLVI, XLVIII, XLIX, LI, LIA, L, LIV, IV, IVa, LV, XX, XXa, XVIIIa, XVIIIb, XVIIIc, XXI, XXVII, XXVIII, XXIX, XXXI, XXXII, XXXV, XXXVI, XXXVII; and XXXIX are enantiomers having the same spatial configuration at the stereocenter shown in Formula I'a or I'-A, as applicable.

[0243] The present invention also makes available: Compounds of formula II, where R1, R3, R4, R 5a , and R 5b are as defined for Formula I; therefore, R, R, R, R for compounds of Formula I 5a , and R 5b Preferred embodiments of the formula II are similarly defined as R, R, R, R for compounds of formula II. 5a , and R 5b is a preferred embodiment of compounds of formula IIaa, IIab, IIac, IIad and IIae, wherein R1 is as defined for formula I and R4 is as defined for formula I; thus, preferred embodiments of R1 and R4 for compounds of formula I are likewise preferred embodiments of R1 and R4 for any one of the compounds of formula IIaa, IIab, IIac, IIad and IIae; Compounds of formula III, where A1, R 2a and R 2b are as defined for Formula I; therefore, A1, R for compounds of Formula I 2a and R 2b Preferred embodiments of the formula III are also exemplified by A, R 2a and R 2b is a preferred embodiment of Compounds of formula IIIa, where A1, R 2a and R 2b is as defined for formula I, and X is a halogen (such as chlorine or bromine) or X 01 ~X 04 (as defined in Scheme 1); therefore, A1, R for compounds of formula I 2a and R 2b Preferred embodiments of the formula IIIa are also preferred in the context of A1, R 2a and R 2b is a preferred embodiment of A compound of formula VI, wherein R3, R4, R 5a , and R 5b are as defined for Formula I; therefore, R, R, R for compounds of Formula I 5a , and R 5b Preferred embodiments of the formula VI are similarly defined as R3, R4, R 5a , and R 5b is a preferred embodiment of A compound of formula XII, where R3, R4, R 5a , and R 5b are as defined for Formula I; therefore, R, R, R for compounds of Formula I 5a, and R 5b Preferred embodiments of the formula XII are similarly defined as R3, R4, R 5a , and R 5b is a preferred embodiment of A compound of formula XLI, where R3, R 4a , R 5a , and R 5b are as defined for formula I, and Z3 is NPhth or NBoc2; therefore, R3, R4, R 5a , and R 5b Preferred embodiments of the formula XLI are similarly defined as R3, R4, R 5a , and R 5b is a preferred embodiment of A compound of formula XLIII, wherein R3, R4, R 5a , and R 5b are as defined for Formula I; therefore, R, R, R for compounds of Formula I 5a , and R 5b Preferred embodiments of the formula XLIII are similarly defined as R, R 4a R 5a , and R 5b is a preferred embodiment of compounds of formula XLIV, wherein R3 and R4 are as defined for formula I; thus, preferred embodiments of R3 and R4 for compounds of formula I are likewise preferred embodiments of R3 and R4 for compounds of formula XLIV; compounds of formula XLVI, wherein R3 and R4 are as defined for formula I; thus, preferred embodiments of R3 and R4 for compounds of formula I are likewise preferred embodiments of R3 and R4 for compounds of formula XLVI; a compound of formula XLVIII, wherein R3 and R4 are as defined for formula I, and Z 5a and Z 5b are, independently of each other, R 5a , R 5b , halogen, NH2, and OH; thus, R3 and R4 for compounds of formula I4a are similarly preferred embodiments of R3 and R4 for compounds of formula XLVIII; A compound of formula XLIX, where R3, R4, R 5a , and R 5b are as defined for Formula I; therefore, R, R, R for compounds of Formula I 5a , and R 5b Preferred embodiments of the formula XLIX are similarly defined as R3, R4, R 5a , and R 5b is a preferred embodiment of A compound of formula LI, where R3, R 5a , and R 5b is as defined for formula I, and X 05 is a leaving group such as bromine, chlorine, iodine, mesylate, tosylate, or triflate; thus, R, R for compounds of formula I 5a , and R 5b Preferred embodiments of the formula LI are similarly defined as R, R 5a , and R 5b is a preferred embodiment of A compound of formula LIa, where R1, R3, R 5a , and R 5b is as defined for formula I, and X 05 is a leaving group such as bromine, chlorine, iodine, mesylate, tosylate, or triflate; thus, R, R, R for compounds of formula I 5a , and R 5b Preferred embodiments of the formula LIa are similarly defined as R, R, R for compounds of formula LIa. 5a , and R 5b is a preferred embodiment of A compound of formula L, where A1, R 2a , R 2b , R1, R3, R 5a and R 5b is as defined for formula I, and X 05 is a leaving group such as bromine, chlorine, iodine, mesylate, tosylate, or triflate; therefore, A, R for compounds of formula I2a , R 2b , R1, R3, R 5a and R 5b Preferred embodiments of the formula are similarly represented by A1, R for compounds of formula L. 2a R 2b , R1, R3, R 5a and R 5b is a preferred embodiment of A compound of formula LIV, where R3, R 5a and R 5b is as defined for formula I, Z3 is NPhth or NBoc2, and X 05 is a leaving group such as, for example, chlorine, bromine, iodine, arylsulfonate, alkylsulfonate, or trifluoromethanesulfonate; thus, R, R for compounds of formula I 5a and R 5b Preferred embodiments of the formula LIV are also preferred in the R, R 5a and R 5b is a preferred embodiment of Compounds of formula IV or IVa, where R3, R 5a and R 5b is as defined for formula I, and X 05 is a leaving group such as, for example, chlorine, bromine, or iodine; thus, R, R for compounds of formula I 5a and R 5b and R3, R4 for compounds of formula IV or IVa, respectively. 5a and R 5b is a preferred embodiment of A compound of formula LV, where R3, R 5a and R 5b is as defined for formula I, and X 05 is a leaving group such as, for example, chlorine, bromine, iodine, arylsulfonate, alkylsulfonate, or trifluoromethanesulfonate; thus, R, R for compounds of formula I 5a and R 5b Preferred embodiments of the formula LV are also preferred in the R, R 5a and R 5bis a preferred embodiment of A compound of formula XX, where R 2a , R 2b and A1 are as defined for formula I, and Z1 is a C1-C4 alkyl group, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2a , R 2b and A1 are similarly preferred embodiments of R for compounds of formula XX 2a , R 2b and a preferred embodiment of A1; A compound of formula XXa, where R 2b and A1 are as defined for formula I, and Z1 is a C1-C4 alkyl group, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2b and A1 are similarly preferred embodiments of R for compounds of formula XXa 2b and a preferred embodiment of A1; Compounds of formula XXVIIIa, in which A1 and R 2b is as defined for formula I, Z1 is a C1-C4 alkyl group, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl, and X 08 is chlorine or bromine; therefore, A and R for compounds of formula I 2b A preferred embodiment of the formula XXVIIIa is similarly defined as A and R for the compound of formula XXVIIIa. 2b is a preferred embodiment of Compounds of formula XXVIIIb, in which A1 and R 2b is as defined for formula I, Z1 is a C1-C4 alkyl group, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl, and X 05 is a leaving group such as, for example, chlorine, bromine, iodine, arylsulfonate, alkylsulfonate, or trifluoromethanesulfonate; thus, A and R for compounds of formula I2b A preferred embodiment of the formula XXVIIIb is also 2b is a preferred embodiment of Compounds of formula XXVIIIc, in which A1 and R 2b are as defined for formula I, and Z and X 09 are independently selected from C1-C4 alkyl groups, e.g., methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl, and are chlorine or bromine; thus, A1 and R for compounds of formula I 2b A preferred embodiment of the formula XXVIIIc is also a compound of the formula XXVIIIc. 2b is a preferred embodiment of Compounds of formula XXI, wherein A1 and R 2b is as defined for formula I, and Z1 is a C1-C4 alkyl group, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; therefore, A1 and R for compounds of formula I 2b Preferred embodiments of the formula XXI are also preferred in the context of A and R 2b is a preferred embodiment of Compounds of formula XXVII, where R 2b and A1 are as defined for Formula I, and R 2aa is H, C1-C3 alkyl, C1-C3 haloalkyl, cyano, or halogen, and Z1 is a C1-C4 alkyl group, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2b and A1 are similarly preferred embodiments of R for compounds of formula XXVII 2b and a preferred embodiment of A1; Compounds of formula XXVIII, where R 2b and A1 are as defined for Formula I, and R 2aais H, C1-C3 alkyl, C1-C3 haloalkyl, cyano, or halogen, and Z1 is a C1-C4 alkyl group, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2b and A1 are similarly preferred embodiments of R for compounds of formula XXVIII 2b and a preferred embodiment of A1; Compounds of formula XXIX, R 2b and A1 are as defined for Formula I, and R 2aa is H, C1-C3 alkyl, C1-C3 haloalkyl, cyano, or halogen, and Z1 is a C1-C4 alkyl group, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2b and A1 are similarly preferred embodiments of R for compounds of formula XXIX 2b and a preferred embodiment of A1; Compounds of formula XXXI, R 2b and A1 are as defined for Formula I, and R 2aa is H, C1-C3 alkyl, C1-C3 haloalkyl, cyano, or halogen, and Z1 is a C1-C4 alkyl group, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2b and A1 are similarly preferred embodiments of R for compounds of formula XXXI 2b and a preferred embodiment of A1; Compounds of formula XXXII, R 2b and A1 are as defined for Formula I, and R 2aa is H, C1-C3 alkyl, C1-C3 haloalkyl, cyano, or halogen, and Z1 is a C1-C4 alkyl group, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2b and A1 are similarly preferred embodiments of R for compounds of formula XXXII2b and a preferred embodiment of A1; A compound of formula XXXV, where R 2b and A1 are as defined for formula I, and Z1 is a C1-C4 alkyl group, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2b and A1 are similarly preferred embodiments of R for compounds of formula XXXV 2b and a preferred embodiment of A1; Compounds of formula XXXVI, R 2b and A1 are as defined for formula I, and Z1 is a C1-C4 alkyl group, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2b and A1 are similarly preferred embodiments of R for compounds of formula XXXVI 2b and a preferred embodiment of A1; Compounds of formula XXXVII, R 2b and A1 are as defined for formula I, and Z1 is a C1-C4 alkyl group, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R 2b and A1 are similarly preferred embodiments of R for compounds of formula XXXVII 2b and A1 are preferred embodiments; and A compound of formula XXXIX, wherein R 2b and A1 are as defined for formula I, and Z1 and Z2 are independently selected from C1-C4 alkyl groups, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl, or n-butyl; thus, R for compounds of formula I 2b and A1 are similarly preferred embodiments of R for compounds of formula XXXIX 2b and A1 are preferred embodiments.

[0244] The compounds of formula I according to the present invention are preventively and / or therapeutically useful active ingredients in the field of pest control, even at low application rates, which have a very favorable biocidal spectrum and are well tolerated by warm-blooded animal species, fish, and plants.The active ingredients according to the present invention act not only against normally susceptible animal pests, such as insects or representatives of the order Acarina, but also against all or individual developmental stages of resistant animal pests.The insecticidal or acaricidal activity of the active ingredients according to the present invention can be manifested directly, i.e., immediately or only after some time has passed, as destruction of pests, for example, during molting, or indirectly, for example, as reduced egg production and / or hatching rate.

[0245] Examples of the above animal pests are: From the order Acarina, for example: Acalitus spp., Aculus spp., Acaricalus spp., Aceria spp., Acarus siro, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp., Calipitrimerus spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides spp., Eotetranychus spp. spp., Eriophyes spp., Hemitarsonemus spp., Hyalomma spp., Ixodes spp., Olygonychus spp., Ornithodoros spp., Polyphagotarsone latus, Panonychus spp., Phyllocoptruta oleivora, Phytonemus spp., Polyphagotarsonemus spp., Psoroptes spp., Rhipicephalus spp.), Rhizoglyphus spp., Sarcoptes spp., Steneotarsonemus spp., Tarsonemus spp. and Tetranychus spp.; From the order Anoplura, for example: Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.; From the order Coleoptera, for example: Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp., Astylus atromaculatus, Ataenius spp., Atomaria linearis, Chaetocnema tibialis, Cerotoma spp., Conoderus spp., Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp.), Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus spp., Heteronychus arator, Hypothenemus hampei, Lagria vilosa, Leptinotarsa ​​decemLineata, Lissorhoptrus spp., Liogenys spp., Maecolaspis spp., Maladera castanea, Megascelis spp. spp., Melighetes aeneus, Melolontha spp., Myochrous armatus, Orycaephilus spp., Otiorhynchus spp., Phyllophaga spp., Phlyctinus spp., Popillia spp.), Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp., Scarabaeidae, Sitophilus spp., Sitotroga spp., Somaticus spp., Sphenophorus spp., Sternechus subsignatus, Tenebrio spp., Tribolium spp. and Trogoderma spp.;. From the order Diptera, for example: Aedes spp., Anopheles spp., Antherigona soccata, Bactrocea oleae, Bibio hortulanus, Bradysia spp., Calliphora erythrocephala, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Delia spp., Drosophila melanogaster, Fannia spp. spp.), Gastrophilus spp., Geomyza tripunctata, Glossina spp., Hypoderma spp., Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp., Orseolia spp., Oscinella frit, Pegomyia hyoscyami, Phorbia spp. spp.), Rhagoletis spp., Rivelia quadrifasciata, Scatella spp., Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp. and Tipula spp.; From the order Hemiptera, for example: Acanthocoris scabrator, Acrosternum spp., Adelphocoris lineolatus, Aleurodes spp., Amblypelta nitida, Bathycoelia thalassina, Blissus spp., Cimex spp., Clavigrella tomentosicollis, Creontiades spp., Distantiella theobroma, Dichelops furcatus, Dysdercus spp., Edessa spp., Euchistus spp., Eurydema pulchrum, Eurygaster spp., Halyomorpha halys, Horcias nobilellus, Leptocorisa spp., Lygus spp., Margarodes spp., Murgantia histrionic, Neomegalotomus spp., Nesidiocoris tenuis, Nezara spp., Nysius simulans, Oebalus insularis insularis, Piesma spp., Piezodorus spp., Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophara spp.), Thyanta spp., Triatoma spp., Vatiga illudens;. Acyrthosium pisum, Adalges spp., Agalliana ensigera, Agonoscena targionii, Aleurodicus spp., Aleurocanthus spp., Aleurolobus barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiella spp. spp.), Aphididae, Aphis spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli, Bemisia spp., Brachycaudus spp., Brevicoryne brassicae, Cacopsylla spp., Cavariella aegopodii Scop., Ceroplaster spp.), Chrysomphalus aonidium, Chrysomphalus dictyospermi, Cicadella spp., Cofana spectra, Cryptomyzus spp., Cicadulina spp., Coccus hesperidum, Dalbulus maidis, Dialeurodes spp., Diaphorina citri, Diuraphis noxia, Dysaphis spp., Empoasca spp., Eriosoma larigerum, Erythroneura spp., Gascardia spp., Glycaspis brimblecombei, Hyadaphis pseudobrassicae, Hyalopterus spp., Hyperomyzus pallidus, Idioscopus clypealis, Jacobiasca lybica, Laodelphax spp., Lecanium corni, Lepidosaphes spp., Lopaphis erysimi, Lyogenys maidis, Macrosiphum spp., Mahanarva spp., Metcalfa pruinosa, Metopolophium dirhodum, Myndus crudus, Myzus spp.), Neotoxoptera spp., Nephotettix spp., Nilaparvata spp., Nippolachnus piri Mats, Odonaspis ruthae, Oregma lanigera Zehnter, Bayberry whitefly (Parabemisia myricae), Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., Corn planthopper (Peregrinus maidis), Perkinsiella spp., Hop wart aphid (Phorodon humuli, Phylloxera spp., Planococcus spp., Pseudaulacaspis spp., Pseudococcus spp., Pseudatomoscelis seriatus, Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Quesada gigas, Recilia dorsalis, Rhopalosiphum spp., Saissetia spp., Scaphoideus spp. spp.), Schizaphis spp., Sitobion spp.), Sogatella furcifera, Spisstilus festinus, Tarophagus Proserpina, Toxoptera spp., Trialeurodes spp., Tridiscus sporoboli, Trionymus spp., Trioza erytreae, Unaspis citri, Zygina flammigera, Zyginidia scutellaris; From the order Hymenoptera, for example: Acromyrmex ants, Arge spp., Atta spp., Cephus spp., Diprion spp., Diprionidae, Gilpinia polytoma, Hoplocampa spp., Lasius spp., Monomorium pharaonis ants, Neodiprion spp., Pogonomyrmex spp., Slenopsis invicta, Solenopsis spp. and Vespa spp.; From the order Isoptera, for example: Coptotermes spp., Corniternes cumulans, Incisitermes spp., Macrotermes spp., Mastotermes spp., Microtermes spp., Reticulitermes spp.; Solenopsis geminate From the order Lepidoptera, for example: Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyresthia spp., Argyrotaenia spp., Autographa spp., Bucculatrix thurberiella, Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo spp., Choristoneura spp., Chrysoteuchia topiaria, Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleophora spp., Colias lesbia, Cosmophila flava, Crambus spp., Crocidolomia binotalis, Cryptophlebia leucotreta, Cydalima perspectalis perspectalis, Cydia spp., Diaphania perspectalis, Diatraea spp., Diparopsis castanea, Earias spp.), Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp., Epinotia spp., Estigmene acrea, Etiella zinckinella, Eucosma spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia jaculiferia, Grapholita spp., Hedya nubiferana, Heliothis spp. spp.), Hellula undalis, Herpetogramma spp., Hyphantria cunea, Keiferia lycopersicella, Lasmopalpus lignosellus, Leucoptera scitella, Lithocollethis spp., Lobesia botrana, Loxostege bifidalis, Lymantria spp., Lyonetia spp., Malacosoma spp., Mamestra brassicae, Manduca sexta, Mythimna spp., Noctua spp., Operophtera spp., Orniodes indica, Ostrinia nubilalis, Pammene spp., Pandemis spp.), pine sawyer moth (Panolis flammea), Papaipema nebris, pink bollworm (Pectinophora gossypiela), coffee leafminer (Perileucoptera coffeella), Pseudaletia unipuncta, potato tuber moth (Phthorimaea operculella), cabbage white butterfly (Pieris rapae), Pieris spp., diamondback moth (Plutella xylostella), Prays spp., Pseudoplusia spp., Rachiplusia nu, Richia albicosta, Scirpophaga spp., Sesamia spp.), Sparganothis spp., Spodoptera spp., Sylepta derogate, Synanthedon spp., Thaumetopoea spp., Tortrix spp., Trichoplusia ni, Tuta absoluta and Yponomeuta spp.;. From the order Mallophaga, for example: Damalinea spp. and Trichodectes spp.; From the order Orthoptera, for example: Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp., Scapteriscus spp. and Schistocerca spp.; From the order Psocoptera, for example: Liposcelis spp.; From the order Siphonaptera, for example: Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla cheopis; From the order Thysanoptera, for example: Calliothrips phaseoli, Frankliniella spp., Heliothrips spp., Hercinothrips spp., Parthenothrips spp., Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., Thrips spp.; From the order Thysanura, for example, Lepisma saccharina.

[0246] In a further aspect, the present invention also relates to plant parasitic nematodes (endoparasitic, semi-endoparasitic and ectoparasitic nematodes), in particular the root-knot nematode Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other Meloidogyne species; cyst-forming nematodes Globodera rostochiensis and other Globodera species; wheat cyst nematode Heterodera avenae, soybean cyst nematode Heterodera glycines, sugar beet cyst nematode Heterodera schachtii, clover cyst nematode Heterodera trifolii and other cyst nematodes (Heterodera species); seed gall nematodes, Anguina species; stem and peel nematodes, Aphelenchoides species; sting nematodes, Belonolaimus longicaudatus and other Belonolaimus species; pine wood nematode, Bursaphelenchus xylophilus and other Bursaphelenchus species; ring nematodes, Criconema species, Criconemella species, Criconemoides species, Mesocriconema species; stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci and other Ditylenchus species; fire nematodes, Dolichodorus species;Screw nematodes, Heliocotylenchus multicinctus and other Helicotylenchus species; Sheath and sheathoid nematodes, Hemicycliophora species and Hemicriconemoides species; Hirshmanniella species; Spear nematodes, Hoploaimus species; False root-knot nematodes, Nacobbus species; Tylenchidae, Longidorus elongatus elongatus and other Longidorus species; pin nematodes, Pratylenchus species; root-lesion nematodes, Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi and other Pratylenchus species; root-lesion nematodes, Radopholus similis and other Radopholus species; false nematodes, Rotylenchus robustus, Rotylenchus reniformis and other Rotylenchus species; Scutellonema species; Trichodorus primitivus and other Trichodorus species, Paratrichodorus species;Plant-parasitic nematodes such as the claytonid nematode, Tylenchorhynchus claytoni, Tylenchorhynchus dubius, and other Tylenchorhynchus species; the burrowing nematode, Tylenchulus species; the giant sting nematode, Xiphinema species; and plant-parasitic nematodes such as Subanguina species, Hypsoperine species, Macroposthonia species, Melinius species, Punctodera species, and Quinisulcius species. The present invention may also relate to a method for preventing damage to plants and parts thereof by other plant-parasitic nematode species, such as Pseudomonas spp.;

[0247] The compounds of the present invention may also have activity against mollusks, such as, for example, species of the family Ampullariidae; Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus); Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C. rufus); Nemoralis); Ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H. itala, H. obvia); Helicidae (Helicigona albustrum) arbustorum); Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Monoa These include the genera Lymnaea; Milax (M. gagates, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides.

[0248] The active ingredients according to the invention can be used to control, i.e. suppress or destroy, pests of the above-mentioned types occurring in particular on plants, in particular on useful plants and ornamental plants in agriculture, horticulture and forestry, or on organs such as the fruits, flowers, leaves, stems, tubers or roots of such plants, in some cases even plant organs formed at a later time remaining protected from these pests.

[0249] Suitable target crops are, in particular, cereals such as wheat, barley, rye, oats, rice, maize or sorghum; beets such as sugar beet or fodder beet; fruits, such as pome fruits, stone fruits or soft fruits, for example apples, pears, plums, peaches, almonds, cherries or berries, for example strawberries, raspberries or blackberries; legumes, such as beans, lentils, peas or soybeans; rapeseed, mustard, poppy, olive, sunflower, palm, castor, cocoa or groundnut. citrus fruits such as oranges, lemons, grapefruits or tangerines; vegetables such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes or peppers; plants of the Lauraceae family such as avocado, cinnamon or camphor; and also tobacco, tree nuts, coffee, eggplant, sugarcane, tea, pepper, grapes, hops, plantains and latex plants.

[0250] The compositions and / or methods of the present invention may be used on any ornamental and / or vegetable crop, including flowers, shrubs, broadleaf trees and evergreen trees.

[0251] For example, the present invention relates to the use of the following ornamental species: Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g., B. elatior, B. semperflorens, B. tubereux), Bougainvillea spp., Brachycome spp. spp.), Brassica spp. (ornamental), Calceolaria spp., Capsicum annuum, Catharanthus roseus, Canna spp., Centaurea spp., Chrysanthemum spp., Cineraria spp. (C. maritime), Coreopsis spp., Crassula coccinea, Cuphea ignea, Dahlia spp., Delphinium spp., Bleeding hearts spectabilis, Dorotheantus spp., Lisianthus (Eustoma grandiflorum), Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerbera spp., Globetrotter (Gomphrena globosa), Heliotropium spp., Helianthus spp., Hibiscus spp.), Hortensia spp., Hydrangea spp., Hypoestes phyllostachya, Impatiens spp. (I. Walleriana), Iresines spp., Kalanchoe spp., Lantana camara, Lavatera trimestris, Leonotis leonurus, Lilium spp., Mesembryanthemum spp., Mimulus spp., Monarda spp. spp.), Nemesia spp., Tagetes spp., Dianthus spp. (carnations), Canna spp., Oxalis spp., Bellis spp., Pelargonium spp. (ivy geranium (P. peltatum), P. Zonale), Viola spp. (pansies), Petunia spp., Phlox spp., Plecthranthus spp., Poinsettia spp. spp.), Parthenocissus spp. (American Creeper (P. quinquefolia), Ivy (P. tricuspidata)), Primula spp., Ranunculus spp., Rhododendron spp., Rosa spp. (roses), Rudbeckia spp., Saintpaulia spp., Salvia spp.), Scaevola aemola, Schizanthus wisetonensis, Sedum spp., Solanum spp., Surfinia spp., Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp., and other bedding plants.

[0252] For example, the present invention relates to the use of the following vegetable species: Allium spp. (garlic (A. sativum), onion (A. cepa), shallot (A. oschaninii), leek (A. porrum), scallion (A. ascalonicum), green onion (A. fistulosum)), chervil (Anthriscus cerefolium), celery (Apium graveolus), asparagus (Asparagus officinalis), beet (Beta vulgarus), Brassica spp. (B. oleracea, Chinese cabbage (B. pekinensis), turnip (B. rapa)), chili pepper (Capsicum annuum), chickpea (Cicer arietinum), endive (Cichorium endivia), Cichorum spp. spp.) (chicory (C. intybus), endive (C. endivia)), watermelon (Citrillus lanatus), Cucumis spp. (saffron (C. sativus), melon (C. melo)), Cucurbita spp. (Cucurbita pepo, Cucurbita maxima), Cyanara spp. (artichoke (C. scolymus), cardoon (C. cardunculus)), carrot (Daucus carota), fennel (Foeniculum vulgare), Hypericum spp., lettuce (Lactuca sativa), tomato spp. spp.) (tomato (L. esculentum), tomato (L. lycopersicum)), mint species (Mentha spp.), basil (Ocimum basilicum), parsley (Petroselinum crispum), Phaseolus species (Phaseolus spp.) (P. vulgaris, runner bean (P.The present invention may be used in any of the following plants: pea (Pisum sativum), radish (Raphanus sativus), rhubarb (Rheum rhaponticum), rosemary (Rosemarinus spp.), salvia (Salvia spp.), yellow rosemary (Scorzonera hispanica), eggplant (Solanum melongena), spinach (Spinacea oleracea), Valerianella spp. (V. locusta, V. eriocarpa), and broad bean (Vicia faba).

[0253] Preferred ornamental species include Saintpaulia, Begonia, Dahlia, Gerbera, Hydrangea, Vervain, Rosa, Kalanchoe, Poinsettia, Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Salvia, Hydrangea, Rosemary, Sage, St. John's Wort, Mint, Bell Pepper, Tomato, and Cucumber.

[0254] The active ingredients according to the invention are particularly suitable for controlling Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetables, corn, rice and soybean crops. The active ingredients according to the invention are particularly suitable for controlling Mamestra (preferably on vegetables), codling moth (Cydia pomonella) (preferably on apple), Empoasca (preferably on vegetables and vineyards), Leptinotarsa ​​(preferably on potato) and Chilo supressalis (preferably on rice).

[0255] The compounds of formula I are particularly suitable for controlling: 1. Hemiptera pests, such as one or more of the following: seed whitefly (Bemisia tabaci), bean aphid (Aphis craccivora), green peach aphid (Myzus persicae), Rhopalosiphum padi, brown planthopper (Nilaparvata lugens) and Euschistus heros (preferably on vegetables, soybeans and sugarcane) 2. Lepidoptera pests, such as one or more of the species Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includes, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includesns and Tuta absoluta (preferably on vegetables and corn). 3. Thysanoptera pests such as Thripidae, for example, one or more species of Thrips tabaci and Frankliniella occidentalis (preferably on vegetables), and 4. Soil pests (such as those of the Coleoptera order), such as the species Diabrotica balteata, Agriotes spp. and Leptinotarsa ​​decemlineata (preferably in vegetables and corn)

[0256] The term "crop plant" should also be understood to include crop plants that have been transformed by the use of recombinant DNA techniques so as to be capable of synthesizing one or more selectively acting toxins, such as those known to be derived from toxin-producing bacteria, particularly bacteria of the genus Bacillus.

[0257] Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or δ-endotoxins, such as Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, insecticidal proteins from Bacillus thuringiensis or plant insecticidal proteins (Vip), such as Vip1, Vip2, Vip3 or Vip3A; or bacterial-colonizing nematodes, such as Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus, etc. insecticidal proteins of Azotoxins; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and neurotoxins specific to other insects; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectin, barley lectin or snowdrop lectin; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin and papain inhibitors; ricin, corn-RIP, abrin, rufin, saporin ribosome-inactivating proteins (RIPs) such as erythrin or bryodin; steroid metabolic enzymes such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers such as blockers of sodium channels or calcium channels, juvenile hormone esterase, diuretic hormone receptor, stilbene synthase, bibenzyl synthase, chitinase and glucanase.

[0258] In the context of the present invention, delta-endotoxins are understood to mean, for example, Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C, or plant insecticidal proteins (Vip), such as Vip1, Vip2, Vip3, or Vip3A, and also specifically hybrid toxins, truncated toxins, and modified toxins. Hybrid toxins are produced recombinantly by combining different domains of these proteins (see, for example, WO 02 / 15701). Truncated toxins, such as truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the native toxin are replaced. In such amino acid substitutions, preferably a non-naturally occurring protease recognition sequence is inserted into the toxin, for example, in the case of Cry3A055, a cathepsin-G recognition sequence is inserted into the Cry3A toxin (see WO 03 / 018810).

[0259] Examples of such toxins or transgenic plants capable of synthesizing such toxins are disclosed, for example, in EP 0 374 753, WO 93 / 07278, WO 95 / 34656, EP 0 427 529, EP 451 878 and WO 03 / 052073.

[0260] Methods for the preparation of such transgenic plants are generally known to those skilled in the art and are described, for example, in the publications mentioned above. Deoxyribonucleic acids of the CryI type and their preparation are known, for example, from WO 95 / 34656, EP 0 367 474, EP 0 401 979 and WO 90 / 13651.

[0261] The toxins contained in the transgenic plants confer resistance to pests found in a range of insect taxa, but are particularly common in beetles (Coleoptera), two-winged insects (Diptera), and moths (Lepidoptera).

[0262] Transgenic plants containing one or more genes encoding insecticide resistance and expressing one or more toxins are known, and some of them are commercially available. Examples of such plants include YieldGard® (a corn variety expressing the Cry1Ab toxin); YieldGard Rootworm® (a corn variety expressing the Cry3Bb1 toxin); YieldGard Plus® (a corn variety expressing the Cry1Ab and Cry3Bb1 toxins); Starlink® (a corn variety expressing the Cry9C toxin); Herculex I® (a corn variety expressing the Cry1Fa2 toxin and the enzyme phosphinothricin N-acetyltransferase (PAT) for tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (a cotton variety expressing the Cry1Ac toxin); Bollgard I® (a cotton variety expressing the Cry1Ac toxin); Bollgard II® (a cotton variety expressing Cry1Ac and Cry2Ab toxins); VipCot® (a cotton variety expressing Vip3A and Cry1Ab toxins); NewLeaf® (a potato variety expressing Cry3A toxin); NatureGard®, Agrisure® GT Advantage (GA21 glyphosate tolerance trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait), and Protecta®.

[0263] Further examples of such transgenic crops are: 1. Bt11 maize, registration number C / FR / 96 / 05 / 10, manufactured by Syngenta Seeds SAS (Chemin de l'Hobit 27, F-31 790 St. Sauveur, France). This genetically modified maize is resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) through the transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also genetically expresses the enzyme PAT to confer tolerance to the herbicide glufosinate ammonium.

[0264] 2. Bt176 maize, registration number C / FR / 96 / 05 / 10, manufactured by Syngenta Seeds SAS (Chemin de l'Hobit 27, F-31 790 St. Sauveur, France). This genetically modified maize is resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) through transgenic expression of the Cry1Ab toxin. Bt176 maize also genetically expresses the enzyme PAT to confer tolerance to the herbicide glufosinate ammonium.

[0265] 3. MIR604 maize, registration number C / FR / 96 / 05 / 10, manufactured by Syngenta Seeds SAS (Chemin de l'Hobit 27, F-31 790 St. Sauveur, France). This maize has been made insect-resistant by transgenic expression of a modified Cry3A toxin. The toxin is Cry3A055, modified by the insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03 / 018810.

[0266] 4. MON 863 maize, registration number C / DE / 02 / 9, manufactured by Monsanto Europe SA (270-272 Avenue de Tervuren, B-1150 Brussels, Belgium). MON 863 expresses the Cry3Bb1 toxin and confers resistance to certain Coleoptera insects.

[0267] 5. IPC 531 cotton, registration number C / ES / 96 / 02, manufactured by Monsanto Europe SA (270-272 Avenue de Tervuren, B-1150 Brussels, Belgium).

[0268] 6. 1507 Maize, registration number C / NL / 00 / 10, manufactured by Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium. Genetically modified maize for expression of the protein Cry1F for resistance to certain Lepidoptera insects and the protein PAT for resistance to the herbicide glufosinate ammonium.

[0269] 7. NK603 x MON 810 maize, registration number C / GB / 02 / M3 / 03, manufactured by Monsanto Europe SA (270-272 Avenue de Tervuren, B-1150 Brussels, Belgium). This maize consists of a conventionally bred hybrid maize variety by crossing the genetically modified varieties NK603 and MON 810. NK603 x MON 810 maize also genetically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which confers resistance to the herbicide Roundup® (containing glyphosate), and the Cry1Ab toxin, obtained from Bacillus thuringiensis subsp. kurstaki, which confers resistance to certain Lepidoptera, including the European corn borer.

[0270] Transgenic crops of insect-resistant plants are also described in the BATS (Zentrum für Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, (http: / / bats.ch).

[0271] The term "crop plant" should also be understood to include crop plants that have been transformed by the use of recombinant DNA technology so as to be able to synthesize antipathogenic substances with selective action, such as, for example, so-called "pathogenicity-related proteins" (PRPs, see, for example, EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesizing such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95 / 33818 and EP-A-0 353 191. Methods for producing such transgenic plants are generally known to those skilled in the art and are described, for example, in the above-mentioned publications.

[0272] Crops can also be improved to increase resistance to fungal (e.g., Fusarium, anthracnose, or Phytophthora), bacterial (e.g., Pseudomonas), or viral (e.g., potato leaf curl virus, tomato spotted wilt virus, cucumber mosaic virus) pathogens.

[0273] Crops also include those that have a high resistance to nematodes, such as the soybean cyst nematode.

[0274] Crops that are tolerant to abiotic stress include those that have increased tolerance to drought, high salinity, high temperature, low temperature, frost, or light due to, for example, expression of NF-YB or other proteins known in the art.

[0275] Antipathogenic substances that can be expressed by such transgenic plants include, for example, ion channel blockers, such as blockers of sodium or calcium channels, e.g., viral KP1, KP4 or KP6 toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases; so-called "pathogenesis-related proteins" (PRPs; see, for example, EP 0 392 225); antipathogenic substances produced by microorganisms, such as peptide or heterocyclic antibiotics (see, for example, WO 95 / 33818) or proteins or polypeptide factors involved in plant pathogen defense (the so-called "plant disease resistance genes" described in WO 03 / 000906).

[0276] Further fields of use of the compositions according to the invention are the protection of stored goods and storage rooms and of raw materials (such as wood and textiles), floor coverings and buildings, and in the hygiene sector, in particular the protection of humans, domestic animals and productive livestock from pests of the above-mentioned types.

[0277] The present invention provides compounds of the first aspect for use in therapy. The present invention provides compounds of the first aspect for use in controlling parasites in or on animals. The present invention further provides compounds of the first aspect for use in controlling ectoparasites on animals. The present invention further provides compounds of the first aspect for use in the prevention and / or treatment of diseases transmitted by ectoparasites.

[0278] The present invention provides the use of a compound of the first aspect for the manufacture of a medicament for controlling parasites in or on an animal. The present invention further provides the use of a compound of the first aspect for the manufacture of a medicament for controlling ectoparasites on an animal. The present invention further provides the use of a compound of the first aspect for the manufacture of a medicament for preventing and / or treating diseases transmitted by ectoparasites.

[0279] The present invention provides the use of a compound of the first aspect in the control of parasites in or on an animal. The present invention further provides the use of a compound of the first aspect in the control of ectoparasites on an animal.

[0280] When used in reference to parasites in or on animals, the term "control" refers to the reduction of pest or parasite numbers, the eradication of pests or parasites, and / or the prevention of further pest or parasite infestation.

[0281] The term "treating" when used in reference to parasites in or on an animal refers to suppressing, slowing, arresting or reversing the progression or severity of an existing condition or disease.

[0282] When used in reference to parasites in or on an animal, the term "prevent" refers to the avoidance of symptoms or disease developing in the animal.

[0283] When used in reference to parasites in or on animals, the term "animal" can refer to mammals and non-mammals such as birds or fish. In the case of mammals, this can be a human or non-human mammal. Non-human mammals include, but are not limited to, livestock animals and companion animals. Livestock animals include, but are not limited to, cattle, camelids, pigs, sheep, goats, and horses. Companion animals include, but are not limited to, dogs, cats, and rabbits.

[0284] A "parasite" is a pest that lives in or on a host animal and benefits from nutrients provided at the expense of the host animal. An "endoparasite" is a parasite that lives inside the body of a host animal. An "ectoparasite" is a parasite that lives on a host animal. Ectoparasites include, but are not limited to, mites, insects, and crustaceans (e.g., sea lice). The subclass Acari (or Acarina) includes ticks and mites. Ticks include, but are not limited to, members of the following genera: Rhipicaphalus, such as Rhipicaphalus (Boophilus) microplus and Rhipicephalus sanguineus; Amblyomma; Dermacentor; Haemaphysalis; Hyalomma; Ixodes; Rhipicentor; Margaropus; Argas; Otobius; and Ornithodoros. Mites include, but are not limited to, members of the following genera: Chorioptes, such as Chorioptes bovis; Psoroptes, such as Psoroptes ovis; Cheyletiella; Dermanyssus, such as Dermanyssus gallinae; Ortnithonyssus; Demodex, such as Demodex canis; Sarcoptes, such as Sarcoptes scabiei; and Psorergates.Insects include, but are not limited to, members of the following orders: Siphonaptera, Diptera, Chelonia, Lepidoptera, Coleoptera, and Homoptera. Members of the Siphonaptera order include, but are not limited to, the cat flea (Ctenocephalides felis) and the dog flea (Ctenocephatides canis). Members of the order Diptera include, but are not limited to, Musca species; bot flies, such as Gasterophilus intestinalis and Oestrus ovis; stable flies; horse flies, such as Haematopota species and Tabunus species; haematobia, such as Haematobia irritans; Stomoxys; Lucilia; midges; and mosquitoes. Members of the order Chestnuti include, but are not limited to, sucking and biting lice, such as Bovicola ovis and Bovicola bovis.

[0285] When used in connection with parasites in or on animals, the term "effective amount" refers to the amount or dosage of a compound of the present invention or a salt thereof that, upon administration to the animal in one or more doses, produces the desired effect in or on the animal. An effective amount can be readily determined by the attending diagnostician, as one skilled in the art, by using known techniques and observing results obtained under analogous circumstances. In determining an effective amount, the attending diagnostician will take into account numerous factors, including, but not limited to, the species of mammal; its size, age, and general health; the parasite and level of infestation to be controlled; the particular disease or disorder involved; the extent or complications or severity of the disease or disorder; the individual's response; the particular compound administered; the mode of administration; the bioavailability characteristics of the administered preparation; the selected dosage regimen; the use of concomitant medications; and other relevant circumstances.

[0286] The compounds of the present invention can be administered to animals by any route that has the desired effect, including, but not limited to, topical, oral, parenteral, and subcutaneous administration. Topical administration is preferred. Formulations suitable for topical administration include, for example, solutions, emulsions, and suspensions, and can be in the form of pour-ons, spots, spray-ons, spray-laces, or dips. Alternatively, the compounds of the present invention can be administered by ear tag or collar.

[0287] Salt forms of the compounds of the present invention include both pharmaceutically and veterinarily acceptable salts, which may differ from agrochemically acceptable salts. Pharmaceutically and veterinarily acceptable salts and the general methodology for preparing them are well known in the art. See, for example, Gould, PL, "Salt selection for basic drugs," International Journal of Pharmaceutics, 33:201-217 (1986); Bastin, RJ, et al., "Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities," Organic Process Research and Development, 4:427-435 (2000); and Berge, SM, et al., "Pharmaceutical Salts," Journal of Pharmaceutical Sciences, 66:1-19 (1977). Those skilled in the art of synthesis will understand that the compounds of the present invention can be easily converted to salts such as hydrochlorides and isolated as such salts using techniques and conditions well known to those skilled in the art. Additionally, those skilled in the art of synthesis will recognize that compounds of the present invention can be readily converted from a corresponding salt to the corresponding free base, and isolated as such a salt.

[0288] The present invention also provides methods for controlling pests (such as mosquitoes and other disease vectors; see also http: / / www.who.int / malaria / vector_control / irs / en / ). In one embodiment, the method for controlling pests comprises applying a composition of the present invention to the target pest, its habitat, or a surface or substrate by brushing, rolling, spraying, painting, or dipping. By way of example, IRS (indoor residual spray) application of surfaces such as walls, ceilings, or floors is contemplated by the method of the present invention. In another embodiment, it is contemplated to apply such compositions to substrates such as nonwoven or woven materials in the form of (or in a form that can be used to manufacture) netting, clothing, bedding, curtains, and tents.

[0289] In one embodiment, a method for controlling such pests comprises applying a pesticidally effective amount of a composition of the present invention to a target pest, its habitat, or a surface or substrate to provide effective, residual pest control activity to the surface or substrate. Such application may be by brushing, rolling, spraying, painting, or dipping the pesticidal composition of the present invention. For example, IRS application to surfaces such as walls, ceilings, or floors is contemplated by the method of the present invention to provide effective, residual pest control activity to the surface. In another embodiment, the application of such compositions for residual pest control on substrates such as fabric materials in the form of (or in the form that can be used to manufacture) netting, clothing, bedding, curtains, and tents is contemplated.

[0290] The substrates to be treated, including nonwovens, fabrics, or nets, can be made of natural fibers such as cotton, raffia, jute, flax, sisal, hemp, or wool, or synthetic fibers such as polyamide, polyester, polypropylene, or polyacrylonitrile. Polyesters are particularly suitable. Methods for treating textiles are known, for example, from WO 2008 / 151984, WO 2003 / 034823, U.S. Pat. No. 5,631,072, WO 2005 / 64072, WO 2006 / 128870, EP 1 724 392, WO 2005 113 886, or WO 2007 / 090739.

[0291] A further field of use for the compositions according to the invention is that of trunk injection / trunk treatment of all ornamental trees and all kinds of fruit and nut-bearing trees.

[0292] In the field of trunk injection / trunk treatment, the compounds according to the invention are particularly suitable against wood-boring insects of the above-mentioned orders Lepidoptera and Coleoptera, in particular the woodborers listed in Tables A and B below.

[0293] [Table 2]

[0294] [Table 3-1] [Table 3-2]

[0295] The present invention may be used to control any insect pest that may be present in turfgrass, including, for example, beetles, caterpillars, fire ants, ground pearls, millipedes, pill bugs, mites, mole crickets, scale insects, mealybugs, mites, boxworms, southern chinch bugs, and grubs. The present invention may also be used to control insect pests in various stages of their life cycle, including eggs, larvae, nymphs, and adults.

[0296] In particular, the present invention relates to the treatment of grubs (Cyclocephala spp. (e.g., masked chafer, C. lurida), Rhizotrogus spp. (e.g., European chafer, R. majalis), Cotinus spp. (e.g., blue swallowtail, C. nitida), Popillia spp. (e.g., Japanese beetle, P. japonica), Phyllophaga spp. (e.g., May / June beetle), Ataenius spp., and the like). spp. (e.g., Black turfgrass ataenius, A. spretulus), Maladera spp. (e.g., red-veined scarab beetle, M. castanea) and Tomarus spp.), cotton bollworms (Margarodes spp.), mole crickets (tawny, southern and brachypterous; Scapteriscus spp., Gryllotalpa africana) and leatherjackets (European crane fly, Tipula The compounds may be used to control insect pests that feed on the roots of turfgrass, including Pseudomonas spp.

[0297] The present invention may also be used to control straw-dwelling insect pests of turfgrass, including cutworms (such as Spodoptera frugiperda and the common armyworm (Pseudaletia unipuncta)), cutworms, weevils (such as Sphenophorus spp., S. venatus verstitus, and S. parvulus) and sod webworms (such as Crambus spp. and the tropical sod webworm, Herpetogramma phaeopteralis).

[0298] The present invention may also be used to control insect pests that live on the ground and feed on turfgrass leaves, including the lesser stink bug (such as the southern kinkbag, Blissus insularis), bermudagrass mite (Eriophyes cynodoniensis), rhodesgrass mealybug (Antonina graminis), two-lined spittlebug (Propsapia bicincta), leafhoppers, cutworms (Noctuidae), and greengrass aphids.

[0299] The present invention may also be used to control other pests of turfgrass, such as the red fire ant (Solenopsis invicta), which creates ant mounds in turfgrass.

[0300] In the hygiene field, the compositions according to the invention are effective against ectoparasites such as hard ticks, soft ticks, scabies mites, chiggers, flies (stable flies and licking flies), parasitic fly larvae, lice, pubic lice, biting lice and fleas.

[0301] Examples of such parasites are: Among the Anoplurida, the genera Haematopinus, Linognathus, Pediculus, Phtirus, and Solenopotes are included.

[0302] From the order Mallophagida, the genera Trimenopon, Menopon, Trinoton, Bovicola, Werneckiella, Lepikentron, Damalina, Trichodectes and Felicola.

[0303] Among the order Diptera and its suborders Nematocerina and Brachycerina, for example, the genera Aedes, Anopheles, Culex, Simulium, Eusimulium, Phlebotomus, Lutzomyia, Culicoides, Chrysops, Hybomitra, Atylotus, Tabanus, Haematopota, spp.), Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp.), sheep flies (Oestrus spp.), cow flies (Hypoderma spp.), bot flies (Gasterophilus spp.), hood flies (Hippobosca spp.), deer flies (Lipoptena spp.) and sheep hood flies (Melophagus spp.).

[0304] Among the Siphonapterida, for example, the human flea genus (Pulex spp.), the dog flea genus (Ctenocephalides spp.), the mouse flea genus (Xenopsylla spp.), and the long flea genus (Ceratophyllus spp.).

[0305] From the order Heteropterida, for example, Cimex spp., Triatoma spp., Rhodnius spp., and Panstrongylus spp.

[0306] From the order Blattaria, for example, the Asian cockroach (Blatta orientalis), the American cockroach (Periplaneta americana), the German cockroach (Blattela germanica) and the genus Supella.

[0307] Among the subclass Acaria (Acarida) and the suborder Metastigmata and Mesostigmata, for example, the genera Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp. spp.), Pneumonyssus spp., Sternostoma spp. and Varroa spp.

[0308] From the orders Actinedida (Prostigmata) and Acaridida (Astigmata), for example, the genera Acarapis, Cheyletiella, Ornithocheyletia, Myobia, Psorergates, Demodex, Trombicula, Listrophorus, Acarus, Tyrophagus, Caloglyphus, Hypodectes spp.), Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.

[0309] The compositions according to the invention are also suitable for protecting against insect infestation in materials such as wood, textiles, plastics, adhesives, glues, paints, paper and cardboard, leather, floor coverings and building materials.

[0310] The compositions according to the invention can be used, for example, against the following pests: European house borer (Hylotrupes bajulus), Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, pine wood beetle (Ernobius mollis), longhorn beetle (Priobium carpini), flat-headed beetle (Lyctus brunneus), African flat-headed beetle (Lyctus africanus), American flat-headed beetle (Lyctus planicollis), oak flat-headed beetle (Lyctus beetles such as Xyleborus species, Tryptodendron species, Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon species and Dinoderus minutus, as well as beetles such as Sirex juvencus, Urocerus gigas, Urocerus gigas Hymenopteran insects such as Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola, and Urocerus augur, as well asindicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucifugus, Mastotermes darwiniensis, Zootermopsis nevadensis and Coptotermes formosanus, as well as silverfish such as Lepisma saccharina. The compounds of formula I and I'a or salts thereof are particularly suitable for controlling one or more pests selected from the families: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae and Heteroderidae. In a preferred embodiment of each aspect, compound TX (wherein the abbreviation "TX" means "one compound selected from the compounds defined in Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21, E-1 to E-21 and Table P") controls one or more pests selected from the families: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae and Heteroderidae.

[0311] The compounds of formula I and I'a or salts thereof are effective against pests of the genera Spodoptera spp., Plutella spp., Frankliniella spp., Thrips spp., Euschistus spp., Cydia spp., Nilaparvata spp., Myzus spp., Aphis spp., Diabrotica spp., Rhopalosiphum spp., Pseudoplusia spp. and Chilo spp. spp. In a preferred embodiment of each aspect, the compound TX (here, the abbreviation "TX" means "one compound selected from the compounds defined in Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21, E-1 to E-21 and Table P") is selected from the genera: Spodoptera spp., Plutella spp., Frankliniella spp., Thrips spp., Euschistus spp., Cydia spp., Nilaparvata spp., Myzus spp., Aphis spp., Diabrotica spp. The present invention relates to the control of one or more pests selected from the group consisting of Rhopalosiphum spp, Pseudoplusia spp and Chilo spp.

[0312] The compounds of formula I and I'a or salts thereof are particularly suitable for controlling one or more of Spodoptera littoralis, diamondback moth (Plutella xylostella), western flower thrips (Frankliniella occidentalis), onion thrips (Thrips tabaci), Euschistus heros, codling moth (Cydia pomonella), brown planthopper (Nilaparvata lugens), green peach aphid (Myzus persicae), Chrysodeixis includens, bean aphid (Aphis craccivora), Diabrotica balteata, Rhopalosiphum padi and rice stem borer (Chilo suppressalis).

[0313] In a preferred embodiment of each aspect, compound TX (wherein the abbreviation "TX" means "one compound selected from the compounds defined in Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21, E-1 to E-21 and Table P") is effective against Egyptian armyworm (Spodoptera littoralis), diamondback moth (Plutella xylostella), western flower thrips (Frankliniella occidentalis), onion thrips (Thrips tabaci), Euschistus heros, codling moth (Cydia pomonella), brown planthopper (Nilaparvata lugens), green peach aphid (Myzus persicae), Chrysodeixis includens, bean aphid (Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo suppressalis such as Egyptian armyworm (Spodoptera littoralis) + TX, diamondback moth (Plutella xylostella) + TX; western flower thrips (Frankliniella occidentalis) + TX, onion thrips (Thrips tabaci) + TX, Euschistus heros + TX, codling moth (Cydia pomonella) + TX, brown planthopper (Nilaparvata lugens) + TX, green peach aphid (Myzus persicae) + TX, Chrysodeixis includens + TX, bean aphid (Aphis craccivora + TX, Diabrotica balteata + TX, Rhopalosiphum Padi + TX and Chilo suppressalis + TX are controlled.

[0314] In one embodiment of each aspect, one compound selected from the compounds defined in Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21, E-1 to E-21 and Table P is used to control Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Codling moth, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Bean aphid, Aphis spp., in cotton, vegetable, corn, cereal, rice and soybean crops. craccivora, Diabrotica balteata, Rhopalosiphum Padia and Chilo suppressalis.

[0315] In one embodiment, one compound selected from the compounds defined in Tables A-1 to A-21, B-1 to B-21, C-1 to C-21, D-1 to D-21, E-1 to E-21 and Table P is suitable for controlling Mamestra (preferably in vegetables), codling moth (Cydia pomonella) (preferably in apple), Empoasca (preferably in vegetables, vineyards), Leptinotarsa ​​(preferably in potato) and Chilo supressalis (preferably in rice).

[0316] The compounds of the present invention may have any number of benefits, including, inter alia, advantageous levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients (e.g., high biological activity, advantageous spectrum of activity, high safety profile (e.g., improved physicochemical properties or high biodegradability against above- and below-ground non-target organisms such as fish, birds and bees)). In particular, it has surprisingly been found that certain compounds of formula (I) may exhibit advantageous safety profiles, especially against non-target arthropods, such as pollinators such as honeybees, solitary bees and bumblebees, most particularly the European honeybee (Apis mellifera).

[0317] Although the compounds of the present invention can be used as pesticides in their native form, they are generally formulated into compositions using formulation aids such as carriers, solvents, and surfactants in various ways. The formulations can be in various physical forms, such as dustable powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, oil-based flowables, aqueous dispersions, oil-based dispersions, suspoemulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (containing water or a water-miscible organic solvent as a carrier), impregnated polymer films, or other forms known from, for example, the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can be used directly or diluted before use. Dilution can be carried out, for example, with water, liquid fertilizers, trace elements, biological materials, oils, or solvents.

[0318] The formulations can be prepared by mixing the active ingredient with formulation aids to obtain a composition in the form of, for example, finely divided solids, granules, solutions, dispersions, or emulsions. The active ingredient can also be formulated with other adjuvants, such as finely divided solids, mineral oil, vegetable or animal oil, modified vegetable or animal oil, organic solvent, water, surfactant, or combinations thereof.

[0319] The active ingredient can also be contained in extremely fine microcapsules. Microcapsules contain the active ingredient in a porous carrier, allowing the active ingredient to be released into the environment in controlled amounts (e.g., sustained release). Microcapsules typically have diameters of 0.1 to 500 microns. They contain the active ingredient in an amount of about 25 to 95% by weight of the capsule. The active ingredient can be in the form of a bulk solid, fine particles in a solid or liquid dispersion, or a suitable solution. The encapsulating membrane can comprise, for example, natural or synthetic rubber, cellulose, styrene / butadiene copolymer, polyacrylonitrile, polyacrylate, polyester, polyamide, polyurea, polyurethane, or chemically modified polymers, and starch xanthate, or other polymers known to those skilled in the art. Alternatively, extremely fine microcapsules can be formed containing the active ingredient in the form of fine particles in a base solid matrix, but the microcapsules themselves are not encapsulated.

[0320] The formulation auxiliaries suitable for preparing the compositions according to the invention are known per se. Liquid carriers include water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietic acid, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-Trichloroethane, 2-heptanone, α-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropyl benzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate Examples of suitable solvents include ethanol, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol and high molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, and N-methyl-2-pyrrolidone.

[0321] Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kiesl lager, limestone, calcium carbonate, bentonite, calcium montmorillonite, cotton hulls, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin, and similar materials.

[0322] Many surface-active substances can be used advantageously in both solid and liquid formulations, especially in formulations that can be diluted with a carrier before use. The surface-active substances can be anionic, cationic, nonionic, or polymeric, and they can be used as emulsifying agents, wetting agents, or suspending agents, or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates such as calcium dodecylbenzenesulfonate; alkylphenol / alkylene oxide adducts such as nonylphenol ethoxylate; alcohol / alkylene oxide adducts such as tridecyl alcohol ethoxylate; soaps such as sodium stearate; salts of alkylnaphthalenesulfonates such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinates such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters such as sorbitol oleate; quaternary amines such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkyl phosphate esters; and further substances described, for example, in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood, New Jersey (1981).

[0323] Additional adjuvants that may be used in the pest control formulations include crystallization inhibitors, viscosity modifiers, suspending agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, antifoaming agents, complexing agents, neutralizing or pH adjusting and buffering agents, corrosion inhibitors, fragrances, wetting agents, uptake enhancers, trace elements, plasticizers, glidants, lubricants, dispersants, thickeners, antifreeze agents, fungicides and liquid and solid fertilizers.

[0324] The compositions of the present invention may contain additives including vegetable or animal oils, mineral oils, alkyl esters of such oils, or mixtures of such oils and oil derivatives. The amount of oil additive in the compositions of the present invention is generally 0.01 to 10% based on the mixture to be applied. For example, the oil additive can be added to the spray tank at the desired concentration after the spray mixture has been prepared. Preferred oil additives include mineral oils or vegetable oils such as rapeseed oil, olive oil, or sunflower oil, emulsified vegetable oils, alkyl esters of vegetable oils such as methyl derivatives, or animal oils such as fish oil or beef tallow. Preferred oil additives are C8 to C 22 Alkyl esters of fatty acids, especially C 12 ~C 18 Methyl derivatives of fatty acids, including, for example, the methyl esters of lauric acid, palmitic acid, and oleic acid (methyl laurate, methyl palmitate, and methyl oleate, respectively). Many oil derivatives are listed in the Compendium of Herbicide Adjuvants, 10 th Edition, Southern Illinois University, 2010.

[0325] The compositions of the present invention generally comprise 0.1 to 99% by weight, especially 0.1 to 95% by weight, of the compounds of the present invention and 1 to 99.9% by weight of formulation aids, which preferably include 0 to 25% by weight of surfactants. Although commercial products may preferably be formulated as concentrates, end users will typically utilize diluted formulations.

[0326] The application rates vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pests to be controlled, the prevailing weather conditions and other factors which depend on the method, time of application and the target crop. As a general guideline, the compounds may be applied in amounts of 1 to 2000 l / ha, especially 10 to 1000 l / ha.

[0327] A preferred formulation may have the following composition (by weight): Emulsifiable concentrate: Active ingredient: 1-95%, preferably 60-90% Surface active agent: 1 to 30%, preferably 5 to 20% Liquid carrier: 1 to 80%, preferably 1 to 35%

[0328] Powder: Active ingredient: 0.1 to 10%, preferably 0.1 to 5% Solid carrier: 99.9 to 90%, preferably 99.9 to 99%

[0329] Suspension concentrate: Active ingredient: 5-75%, preferably 10-50% Water: 94-24%, preferably 88-30% Surface active agent: 1 to 40%, preferably 2 to 30%

[0330] Wettable powder: Active ingredient: 0.5 to 90%, preferably 1 to 80% Surface active agent: 0.5 to 20%, preferably 1 to 15% Solid carrier: 5 to 95%, preferably 15 to 90%

[0331] Granules: Active ingredient: 0.1 to 30%, preferably 0.1 to 15% Solid carrier: 99.5 to 70%, preferably 97 to 85%

[0332] The following examples further illustrate, but do not limit, the present invention.

[0333] [Table 4]

[0334] The complex is thoroughly mixed with the adjuvant and the mixture is thoroughly ground in a suitable mill to obtain a wettable powder that can be diluted with water to obtain a suspension of the desired concentration.

[0335] [Table 5]

[0336] The complex is thoroughly mixed with the adjuvant and the mixture is thoroughly ground in a suitable mill to obtain a powder that can be used directly as a seed treatment.

[0337] [Table 6]

[0338] Emulsions of any required dilution that can be used for plant protection are available from this concentrate by dilution with water.

[0339] [Table 7]

[0340] Ready-to-use dusts are obtained by mixing the complex with a carrier and grinding the mixture in a suitable mill. Such powders can also be used as dry seed dressings.

[0341] [Table 8]

[0342] The compound is mixed and ground with the adjuvant, the mixture is moistened with water, the mixture is extruded and then dried in a stream of air.

[0343] [Table 9]

[0344] In a mixer, the finely ground composite is applied uniformly to kaolin moistened with polyethylene glycol, resulting in coated, dust-free granules.

[0345] [Table 10]

[0346] The finely ground composite is thoroughly mixed with adjuvants to give a suspension concentrate which can be diluted with water to give a suspension of any desired dilution, and such dilutions can be used to treat and protect living plants and plant propagation material against microbial infestation by spraying, pouring or dipping.

[0347] [Table 11]

[0348] The finely ground composite is thoroughly mixed with adjuvants to give a suspension concentrate which can be diluted with water to give a suspension of any desired dilution, and such dilutions can be used to treat and protect living plants and plant propagation material against microbial infestation by spraying, pouring or dipping.

[0349] slow-release capsule suspension 28 parts of the composite are mixed with 2 parts aromatic solvent and 7 parts toluene diisocyanate / polymethylene-polyphenylisocyanate (8:1) mixture. This mixture is emulsified in a mixture of 1.2 parts polyvinyl alcohol, 0.05 parts defoamer, and 51.6 parts water until the desired particle size is achieved. A mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts water is added to this emulsion. The mixture is stirred until the polymerization reaction is complete. The resulting capsule suspension is stabilized by adding 0.25 parts thickener and 3 parts dispersant. The capsule suspension formulation contains 28% active ingredient. The diameter of the medium-sized capsules is 8 to 15 microns. The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for this purpose.

[0350] Formulation types include emulsion concentrates (EC), suspension concentrates (SC), suspoemulsions (SE), capsule suspensions (CS), water dispersible granules (WG), emulsifiable granules (EG), emulsions, water-in-oil (EO), emulsions, oil-in-water (EW), microemulsions (ME), oil dispersions (OD), oil-miscible flowables (OF), oil-miscible liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), technical concentrates (TK), dispersible concentrates (DC), wettable powders (WP), soluble granules (SG) or any technically preferred formulation in combination with agriculturally acceptable adjuvants. [Example]

[0351] Preparation example: LCMS method: Method 1: Spectra were recorded on a Waters mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) equipped with an electrospray source (polarity: positive and negative ions, capillary: 3.00 kV, cone range: 30 V, extractor: 2.00 V, source temperature: 150 °C, desolvation temperature: 350 °C, cone gas flow: 50 l / h, desolvation gas flow: 650 l / h, mass range: 100-900 Da) and a Waters Acquity UPLC: binary pump, heated column compartment, diode-array detector, and ELSD detector. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm; Temperature: 60 °C; DAD wavelength range (nm): 210–500; Solvent gradient: A = water + 5% MeOH + 0.05% HCOOH, B = acetonitrile + 0.05% HCOOH; Gradient: 10–100% B in 1.2 min; Flow (ml / min) 0.85.

[0352] Method 2: Spectra were recorded on a Waters mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) equipped with an electrospray source (polarity: positive and negative ions), capillary: 3.00 kV, cone range: 30 V, extractor: 2.00 V, source temperature: 150 °C, desolvation temperature: 350 °C, cone gas flow: 50 l / h, desolvation gas flow: 650 l / h, mass range: 100-900 Da) and a Waters Acquity UPLC: binary pump, heated column compartment, diode-array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm; Temperature: 60 °C; DAD wavelength range (nm): 210–500; Solvent gradient: A = water + 5% MeOH + 0.05% HCOOH, B = acetonitrile + 0.05% HCOOH; Gradient: 10–100% B in 2.7 min; Flow (ml / min) 0.85

[0353] Method 3: Spectra were recorded on an Agilent mass spectrometer (single quadrupole) equipped with multimode electrospray and APCI (polarity: positive and negative ions), capillary voltage: 4.00 kV, corona current: 4.0 μA, charging voltage: 2.00 kV, nitrogen gas flow: 9.0 L / min, nebulizer pressure: 40 psig, mass range: 100–1000 m / z), drying gas temperature: 250 °C, vaporizer temperature: 200 °C. Spectra were recorded on an Agilent LCMS system with a quaternary pump, heated column compartment, and variable wavelength detector. Column: Eclipse XDB C18, 5.0 μm, 150 × 4.6 mm, column temperature: ambient, wavelength (nm): 220 nm. Solvents: A = 0.05% TFA in water, B = 0.05% TFA in acetonitrile. Gradient: Time / %B: 0 / 5, 0.5 / 5, 3.5 / 90, 5 / 90, 5.1 / 5, 7 / 5; Flow rate: 1.0 ml / min

[0354] Method 4: Spectra were recorded on a Waters mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) equipped with an electrospray source (polarity: positive and negative ions, capillary: 3.00 kV, cone range: 41 V, extractor: 2.00 V, source temperature: 150 °C, desolvation temperature: 5000 °C, cone gas flow: 50 l / h, desolvation gas flow: 1000 l / h, mass range: 110-800 Da) and a Waters Acquity UPLC: binary pump, heated column compartment, diode-array detector, and ELSD detector. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm; Temperature: 40 °C; PDA wavelength range (nm): 200–400; Solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH; Gradient: 10–100% B in 1.3 min; Flow (ml / min) 0.6

[0355] Chiral SFC Method 1: Spectra were analyzed using a PDA Detector Waters Acquity UPC 2 Waters SFC (Waters Acquity UPC) 2 Column: Daicel SFC CHIRALPAK® IC (3 μm, 0.3 cm × 10 cm, 40°C; Mobile phase: A: CO₂ B: MeOH Isocratic: 10% B in 2.0 min; ABPR: 1800 psi; Flow rate: 2.0 ml / min; Detection: 220 nm; Sample concentration: 1 mg / mL in ACN; Injection volume: 1 μL

[0356] Chiral SFC Method 2: Spectra were analyzed using a PDA Detector Waters Acquity UPC 2 Waters SFC (Waters Acquity UPC) 2Column: Daicel SFC CHIRALPAK® IG (3 μm, 0.3 cm × 10 cm, 40°C; Mobile phase: A: CO₂ B: MeOH Isocratic: 15% B in 4.8 min; ABPR: 1800 psi; Flow rate: 2.0 ml / min; Detection: 270 nm; Sample concentration: 1 mg / mL in ACN / MeOH (1:1); Injection volume: 1 μL

[0357] Preparation of methyl 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylate (intermediate I1) [ka] Sulfuric acid (2.46 mL, 44.3 mmol, 1.00 equiv.) was added dropwise to a solution of 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylic acid (CAS 796090-23-8, 10.0 g, 44.3 mmol) in methanol (266 mL) at room temperature. The reaction mixture was heated to 65° C. and stirred overnight. After cooling to room temperature, the reaction mixture was poured into saturated aqueous sodium bicarbonate solution, and the aqueous phase was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and evaporated to give the desired product (10.2 g, 42.70 mmol), which was used without further purification. 1 H NMR (400 MHz, chloroform-d) δ ppm: 4.04 (s, 3H) 8.11 (s, 1H) 8.17 (d, J = 1.10 Hz, 1H).

[0358] Preparation of methyl 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylate (intermediate I2) and 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid (intermediate I3) [ka] Cyclopropylboronic acid (1.43 g, 16.7 mmol, 2.00 equiv.) and sodium bicarbonate (2.10 g, 25.1 mmol, 3.00 equiv.) were added to a solution of methyl 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylate (Intermediate I1, prepared as described above) (2.00 g, 8.35 mmol) in 1,4-dioxane (20.9 mL) and water (8.35 mL), and the resulting suspension was flushed with argon for 10 min. [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.322 g, 0.417 mmol, 0.05 equiv.) was added, and the resulting suspension was stirred at 100 °C under argon for 1 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and evaporated to give a first crude material which, after purification by flash chromatography on silica gel (ethyl acetate in cyclohexane), gave the desired intermediate I2 (0.706 g, 2.88 mmol). 1 H NMR (400 MHz, chloroform-d) δ ppm: 1.04-1.23 (m, 4H), 2.14-2.28 (m, 1H), 4.00 (s, 3H), 7.88 (s, 1H), 7.95 (d, J = 1.47 Hz, 1H). LC-MS (method 1): retention time 1.12 min, m / z 246[M+H] + .

[0359] After acidification to pH 1, the aqueous layer was extracted twice again with ethyl acetate, and the combined organic phases were dried over sodium sulfate, filtered, and evaporated to give a second crude material which, after purification by flash chromatography on silica gel (methanol in dichloromethane), gave intermediate I3 (0.166 g, 0.718 mmol). 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm: 0.94-1.03 (m, 2H), 1.06-1.15 (m, 2H), 2.37-2.46 (m, 1H), 7.88 (d, J = 1.10 Hz, 1H), 8.05 (d, J = 0.73 Hz, 1H), 13.89-14.33 (m, 1H). LC-MS (method 1): retention time 0.94 min, m / z 232[M+H] + .

[0360] Preparation of 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid (intermediate I3) [ka] Lithium hydroxide monohydrate (0.147 g, 3.43 mmol, 1.20 equiv.) was added to a solution of methyl 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylate (Intermediate I2, prepared as described above) in a 3:1 tetrahydrofuran / water mixture (24.5 mL). After stirring at room temperature for 2 hours, the reaction mixture was concentrated, and the remaining aqueous phase was acidified to pH 1 by the addition of 1 M aqueous hydrochloric acid (3.43 mL). The aqueous layer was extracted three times with ethyl acetate, and the combined organic phases were dried over sodium sulfate, filtered, and concentrated to give 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid. 1 H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm: 0.96-1.02 (m, 2H), 1.07-1.15 (m, 2H), 2.40 (tt, J = 8.12 Hz, J = 4.72 Hz, 1H), 7.88 (d, J = 1.10 Hz, 1H), 8.04 (s, 1H), 13.90-14.36 (m, 1H). LC-MS (method 1): retention time 0.94 min, m / z 232[M+H] + .

[0361] Preparation of methyl 3-cyclopropyl-5-(trifluoromethyl)benzoate (intermediate I4) [ka] A solution of propargyl bromide in toluene (80 wt%, 0.89 g, 0.67 mL) was added to a white suspension of 9-BBN dimer (3.0 g, 12 mmol) in 26 mL of dry tetrahydrofuran under argon to give a pale yellow solution. The mixture was refluxed for 2 hours and then cooled to room temperature. A pre-degassed 4 M aqueous solution of sodium hydroxide (4.4 mL, 18 mmol) was added to give a cloudy, colorless solution. The resulting mixture was stirred at room temperature under argon for 1 hour. The resulting very pale yellow solution was then added to a pre-degassed pale yellow solution of methyl 3-bromo-5-(trifluoromethyl)benzoate (187331-46-0, 1.5 g, 5.2 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.26 mmol) in 52 mL of dry tetrahydrofuran to give a pale yellow solution. The resulting mixture was stirred at reflux for 19 hours. The mixture was cooled to room temperature, diluted with ethyl acetate, quenched with water (+ a few drops of brine), and the aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, washed once with brine, dried over sodium sulfate, filtered, and evaporated under reduced pressure at 60 °C. The crude product was purified by chromatography on silica gel to give methyl 3-cyclopropyl-5-(trifluoromethyl)benzoate as a colorless liquid. 1 H NMR (400MHz, chloroform-d)δ ppm:0.76-0.85(m,2H)1.06-1.15(m,2H)2.03(tt,J1=8.39Hz,J2=5.00Hz,1H)3.96(s,3H)7.52(s,1H)7.91(s,1H)8.08(d,J=0.73Hz,1H). 19 F NMR (377 MHz, chloroform-d) δ ppm: −62.75 (s, 3F).

[0362] Preparation of 3-cyclopropyl-5-(trifluoromethyl)benzoic acid (intermediate I5) [ka] Methyl 3-cyclopropyl-5-(trifluoromethyl)benzoate (7.00 g, 28.7 mmol) was dissolved in tetrahydrofuran (57.3 mL) and water (28.7 mL). Lithium hydroxide (1.21 g, 28.7 mmol) was then added, and the resulting pale yellow, cloudy solution was stirred at room temperature for 4 hours. The reaction mixture was diluted with ethyl acetate and water. The organic phase was washed twice with water. The combined aqueous layers were acidified with 1 N aqueous hydrochloric acid to a pH of 1-2 and extracted three times with ethyl acetate. The combined organic layers were washed once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure at 60 °C to give 3-cyclopropyl-5-(trifluoromethyl)benzoic acid, which was used without further purification. 1 H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm: 0.79-0.85 (m, 2H), 1.03-1.10 (m, 2H), 2.12-2.22 (m, 1H), 7.70 (s, 1H), 7.88 (s, 1H), 7.93 (s, 1H), 13.47 (br s, 1H). LC-MS (method 1): retention time 0.99 min, m / z 229[MH] - .

[0363] Preparation of methyl 3-(trifluoromethyl)-5-vinyl-benzoate (intermediate I6) [ka] Under argon, in a three-necked flask, methyl 3-bromo-5-(trifluoromethyl)benzoate (CAS: 187331-46-0, 20 g, 69.24 mmol) was dissolved in toluene (312 mL). Next, tributyl(vinyl)tin (25.56 mL, 83.09 mmol) was added, and the resulting solution was degassed with argon for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.816543 g, 0.69 mmol) was added, and the resulting mixture was stirred at 110 °C for 2 hours. After cooling at room temperature, the mixture was diluted with ethyl acetate (100 mL), filtered through a pad of Celite, washed with ethyl acetate, and the filtrate was concentrated under reduced pressure. The crude product was purified by chromatography on silica gel to give methyl 3-(trifluoromethyl)-5-vinylbenzoate. 1 H NMR (400 MHz, chloroform-d) δ ppm: 3.98 (s, 3H), 5.47 (d, J = 11.00 Hz, 1H), 5.93 (d, J = 17.61 Hz, 1H), 6.79 (dd, J = 17.42 Hz, J = 10.82 Hz, 1H), 7.82 (s, 1H), 8.19 (s, 1H), 8.24-8.29 (m, 1H).

[0364] Preparation of diphenyl(2,2,2-trifluoroethyl)sulfonium trifluoromethanesulfonate [ka] Diphenyl sulfide (36.43 mL, 211.1 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (6.207 mL, 42.22 mmol) were mixed in an autoclave. The mixture was stirred at room temperature for 2 minutes, then the autoclave was closed and heated at 150°C for 20 hours. The reaction was cooled at room temperature, and a white precipitate formed. 75 mL of diethyl ether was added, and the white solid was then filtered. It was washed four times with 30 mL of diethyl ether and then dried under reduced pressure to give diphenyl(2,2,2-trifluoroethyl)sulfonium trifluoromethanesulfonate. 1H NMR (400MHz, chloroform-d) δ ppm:5.78(d,J=8.80Hz, 2H)7.89(d,J=8.07Hz, 4H)7.93-8.00(m,2H)8.37(dd,J1=8.62Hz, J2=1.28Hz, 4H). 19 F NMR (377 MHz, chloroform-d) δ ppm: -78.91 (s, 3F) -61.26 (s, 3F).

[0365] Preparation of methyl 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoate (Intermediate I7) [ka] Under argon, 3-(trifluoromethyl)-5-vinylbenzoate (1.9 g, 8.3 mmol) and cesium fluoride (1.5 g, 9.9 mmol) were dissolved in dimethylacetamide (33 mL) in a vial to give a colorless solution, which was degassed under argon for 20 minutes. 5,10,15,20-tetraphenyl-21H,23H-porphineiron(III) chloride (0.31 g, 0.41 mmol) was added. The reaction became a green suspension, and diphenyl(2,2,2-trifluoroethyl)sulfonium trifluoromethanesulfonate (3.8 g, 9.1 mmol) was also added portionwise. The reaction was stirred overnight at room temperature. The resulting mixture was diluted with dichloromethane, and then water was added. The organic layer was washed four times with water, dried over sodium sulfate, filtered, and concentrated under reduced pressure at 160 mbar and 40°C. The crude product was purified by chromatography on silica gel to give methyl 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoate. 1 H NMR (400 MHz, chloroform-d) δ ppm: 1.25-1.34 (m, 1H), 1.48-1.55 (m, 1H), 1.88-2.00 (m, 1H), 2.46-2.53 (m, 1H), 3.98 (s, 3H), 7.60 (s, 1H), 7.98 (s, 1H), 8.19 (s, 1H).

[0366] Preparation of 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoic acid (I8) [ka] 3-(Trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoate (1.43 g, 3.80 mmol) was dissolved in tetrahydrofuran (11.4 mL) and water (7.60 mL). Lithium hydroxide monohydrate (0.322 g, 7.60 mmol) was added, and the resulting mixture was stirred at room temperature for 3 hours and 30 minutes. The reaction mixture was cooled to 0°C, and then it was acidified with 2 M hydrochloric acid solution. The aqueous layer was extracted twice with ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoic acid. 1 H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 1.40-1.47 (m, 2H) 2.53-2.60 (m, 1H) 2.72 (td, J1 = 7.70 Hz, J2 = 4.77 Hz, 1H) 7.87 (s, 1H) 8.02 (s, 1H) 8.05-8.08 (m, 1H) 13.54 (br s, 1H). LC-MS (method 1): retention time 1.04 min, m / z 297[MH] - .

[0367] Preparation of methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfanyl)benzoate (Intermediate I9) [ka] (2,2'-Bipyridine)(trifluoromethanethiolato)copper (CAS 1413732-47-4) (3.9 g, 12 mmol, 2.0 equiv.) was added to a solution of methyl 3-iodo-5-(trifluoromethyl)benzoate (2.0 g, 6.1 mmol) in acetonitrile (18 mL) under argon. The reaction mixture was heated to 90 °C and stirred overnight. After cooling to room temperature, the reaction mixture was filtered through a pad of Celite and concentrated. The crude material was purified by two flash chromatography runs on silica gel (ethyl acetate in cyclohexane) to give the desired product as a yellow gum (1.5 g, 4.9 mmol). 1 H NMR (400 MHz, chloroform-d) δ ppm: 4.02 (s, 3H), 8.11 (s, 1H), 8.44 (s, 1H), 8.53 (s, 1H). LC-MS (method 1): retention time 1.21 min, m / z 279[M-MeO+H] + .

[0368] Preparation of methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoate (intermediate I10) [ka] 3-Chloroperbenzoic acid (2.3 g, 11 mmol, 2.1 equiv.) was added portionwise to a cooled solution of methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfanyl)benzoate (intermediate I13 prepared as above) (1.8 g, 5.3 mmol) in dichloromethane (16 mL) at 0 °C. After stirring at room temperature for 1 h, additional 3-chloroperbenzoic acid (2.3 g, 11 mmol, 2.1 equiv.) was added and the reaction mixture was stirred overnight. The precipitate formed was filtered. The filtrate was washed with a 10% aqueous solution of sodium thiosulfate and saturated NaHCO3 solution. The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel to give methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoate. 1H NMR (400 MHz, chloroform) δ ppm 4.07 (s, 3H) 8.43-8.51 (m, 1H) 8.70-8.80 (m, 1H) 8.84-8.91 (m, 1H). 19 F NMR (377 MHz, chloroform-d) δ ppm: -77.49 (s, 3F) -62.96 (s, 3F)

[0369] Preparation of 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoic acid (I11) [ka] Methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoate (1.8 g, 5.4 mmol) was charged to a flask and dissolved in tetrahydrofuran (16 mL) and water (11 mL). To this mixture, lithium hydroxide monohydrate (0.26 g, 11 mmol) was added, and the reaction was stirred at room temperature for 1 hour. The reaction mixture was acidified with 1 M hydrochloric acid, and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and then concentrated to give 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoic acid, which was used without further purification. 1 H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm: 8.68 (s, 2H) 8.71-8.76 (m, 1H) 13.33-15.22 (m, 1H).

[0370] Preparation of methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (intermediate I12) [ka] Methyl 3-iodo-5-(trifluoromethyl)benzoate (10 g, 28.78 mmol) was taken up in tetrahydrofuran (115 mL) under argon. The resulting light brown solution was cooled to −78 °C using a dry ice / acetone bath. Turbo Grignard 1.3 M in tetrahydrofuran solution (31 mL, 40.29 mmol) was added dropwise via syringe over 20 min, directly giving a dark solution while maintaining the temperature below −65 °C. The resulting mixture was stirred at −78 °C for 15 min. Cuprous cyanide (3.125 g, 34.5 mmol) and anhydrous lithium chloride (1.479 g, 34.5 mmol) were added simultaneously in one portion, giving a dark suspension. The resulting mixture was again stirred at −78 °C for 15 min. Cyclopropanecarbonyl chloride (5.340 mL, 57.5 mmol) was finally added dropwise over 5 minutes (the temperature reached a maximum of −68° C.). The resulting mixture was stirred at −78° C. for 1 hour, warmed to room temperature, and stirred for 30 minutes to give a brown suspension. The reaction mixture was cooled to −78° C. and slowly quenched with 20 ml of methanol. The resulting mixture was allowed to reach room temperature, and the resulting suspension was filtered through Celite. Saturated aqueous ammonium chloride solution and ethyl acetate were added to the filtrate. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure at 40° C. The crude material was purified by chromatography on silica gel to give methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate. 1 H NMR (400MHz, chloroform-d)δ ppm:1.16-1.22(m,2H)1.35(quin, J=3.76Hz, 2H)2.74(tt,J1=7.84Hz, J2=4.4 5Hz, 1H)4.02(s,3H)8.45(d,J=0.73Hz,1H)8.51(d,J=0.73Hz,1H)8.86(s,1H).

[0371] Preparation of methyl 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoate (intermediate I13) [ka] Methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (5.5 g, 20 mmol) was taken up in 2,2-difluoro-1,3-dimethyl-imidazolidine (36 mL, 280 mmol) under argon to give a pale yellow solution. The resulting mixture was stirred at 110 °C for 5 hours to give a light brown solution. The reaction mixture was cooled to room temperature and added dropwise to 1.0 L of vigorously stirred saturated aqueous sodium bicarbonate solution at 0 °C (the temperature was maintained below 10 °C). The resulting mixture (pH 8-9) was then extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure at 50 °C. The crude material was purified by chromatography on silica gel to give methyl 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoate. 1 H NMR (400 MHz, chloroform-d) δ ppm: 0.73-0.79 (m, 2H), 0.82-0.89 (m, 2H), 1.47-1.60 (m, 1H), 8.00 (d, J = 0.73 Hz, 1H), 8.39 (s, 1H), 8.42 (s, 1H). 19 F NMR (377 MHz, chloroform-d) δ ppm: −98.40 (s, 3F) −62.81 (s, 2F).

[0372] Preparation of 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (I14) [ka] Methyl 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoate (4.45 g, 15.1 mmol) was taken up in tetrahydrofuran (30.3 mL) and water (15.1 mL). Lithium hydroxide monohydrate (0.833 g, 19.7 mmol) was added, and the resulting colorless, cloudy solution was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate and water. The organic phase was washed twice with water. The combined aqueous layers were acidified with 1 N aqueous hydrochloric acid to pH 1-2 and extracted three times with ethyl acetate. The combined organic layers were washed once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure at 60 °C to give 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid, which was used without further purification. 1 H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm: 0.62-0.84 (m, 4H), 1.65-1.97 (m, 1H), 7.93-8.23 (m, 1H), 8.23-8.51 (m, 2H), 13.24-14.48 (m, 1H). LC-MS (method 1): retention time 1.03 min, m / z 279[MH] - .

[0373] Preparation of methyl 2-(1-cyano-2-ethoxy-2-oxo-ethyl)-6-(trifluoromethyl)pyridine-4-carboxylate (intermediate I15) [ka] Methyl 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylate (1.05 g, 4.40 mmol) was dissolved in dimethyl sulfoxide (13.2 mL). Ethyl 2-cyanoacetate (0.702 mL, 6.60 mmol), potassium carbonate (1.535 g, 11.00 mmol), and tetrabutylammonium bromide (0.145 g, 0.440 mmol) were then added sequentially at room temperature. The resulting suspension was stirred at 90°C for 1 hour and then allowed to stir at room temperature overnight. The reaction mixture was diluted with 50 mL of water and 100 mL of ethyl acetate, cooled to 0-10°C, and slowly quenched with 1 N hydrochloric acid via a dropping funnel until the pH reached 3. The aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure at 50°C. The crude material was purified by chromatography on silica gel with ethyl acetate in cyclohexane to give methyl 2-(1-cyano-2-ethoxy-2-oxo-ethyl)-6-(trifluoromethyl)pyridine-4-carboxylate. 1 H NMR (400 MHz, chloroform-d) δ ppm: 1.36-1.43 (m, 3H), 4.01 (s, 3H), 4.34 (q, J = 7.58 Hz, 2H), 7.34 (s, 1H), 8.06 (s, 1H), 14.46-14.67 (m, 1H). LC-MS (method 1): retention time 1.01 min, m / z 317[M+H] + .

[0374] Preparation of methyl 2-(cyanomethyl)-6-(trifluoromethyl)pyridine-4-carboxylate (I16) [ka] To a solution of methyl 2-(1-cyano-2-ethoxy-2-oxo-ethyl)-6-(trifluoromethyl)pyridine-4-carboxylate (0.800 g, 2.53 mmol) in dimethyl sulfoxide (20 mL) was added sodium chloride (0.299 g, 5.06 mmol) in water (10 mL). The resulting mixture was stirred at 95° C. for 4 hours. After cooling to room temperature, the reaction mixture was diluted with water (50 mL) and ethyl acetate (3* 50 mL) The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure to give methyl 2-(cyanomethyl)-6-(trifluoromethyl)pyridine-4-carboxylate, which was used without further purification. 1 H NMR (400 MHz, chloroform-d) δ ppm: 4.05 (s, 3H) 4.13 (s, 2H) 8.24 (s, 1H) 8.26 (s, 1H). LC-MS (method 1): retention time 0.89 min, m / z 243[MH] - .

[0375] Preparation of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (I17) [ka] Methyl 2-(cyanomethyl)-6-(trifluoromethyl)pyridine-4-carboxylate (0.05 g, 0.20 mmol) was dissolved in dimethylformamide (2 mL). Sodium hydride (24 mg, 0.61 mmol) was added at room temperature, and the colorless solution turned into a deep purple suspension. After 10 minutes, 1,2-dibromoethane (0.02 mL, 0.24 mmol) was added, and the resulting suspension was stirred at room temperature for 15 minutes. The reaction mixture was quenched with saturated ammonium chloride solution at 0-5°C and diluted with ethyl acetate. The aqueous layer was acidified to pH 2-3 with 1N hydrochloric acid and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by reverse-phase chromatography to give 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid. 1 H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm: 1.76-1.83 (m, 2H), 1.96-2.03 (m, 2H), 8.07 (d, J = 1.10 Hz, 1H), 8.17 (s, 1H), 13.35-15.45 (m, 1H). LC-MS (method 1): retention time 0.89 min, m / z 255[MH]- .

[0376] Preparation of methyl 3-(cyanomethyl)-5-(trifluoromethyl)benzoate (intermediate I18) [ka] Methyl 3-bromo-5-(trifluoromethyl)benzoate (0.600 g, 2.08 mmol) was dissolved in N,N-dimethylformamide (4.2 mL). (Trimethylsilyl)acetonitrile (0.862 mL, 6.23 mmol) was added dropwise via syringe. The solution was degassed under Ar for 5 minutes. ZnF (0.130 g, 1.25 mmol), Xantphos (0.0481 g, 0.0831 mmol), and Pd(dba) (0.0384 g, 0.0415 mmol) were then added. The resulting black suspension was stirred at 100 °C for 22 hours and then cooled to room temperature. The mixture was concentrated under reduced pressure at 50 °C. The crude material was purified by chromatography on silica gel with ethyl acetate in cyclohexane to give methyl 3-(cyanomethyl)-5-(trifluoromethyl)benzoate. 1 H NMR (400MHz, chloroform-d) δ ppm: 8.30 (1H, s), 8.23 ​​(1H, s), 7.81 (1H, s), 3.99 (3H, s), 3.90 (2H, s).LC-MS (Method 1): Retention time 0.92 min, m / z 242 [MH] - .

[0377] Preparation of methyl 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoate (intermediate I19) [ka] Methyl 3-(cyanomethyl)-5-(trifluoromethyl)benzoate (2.15 g, 7.07 mmol) was dissolved in N,N-dimethylformamide (32.3 mL). Cesium carbonate (7.13 g, 21.2 mmol) was added to the stirred solution, and the mixture was stirred at room temperature for 10 minutes. 1,2-Dibromoethane (0.68 mL, 7.78 mmol) was added, and the mixture was stirred at 60° C. for 3 hours, then cooled to room temperature. Water (30 mL) was added, and the aqueous layer was extracted with ethyl acetate (60 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (silica gel, ethyl acetate in hexane) to give methyl 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoate. 1 H NMR (400 MHz, chloroform-d) δ ppm: 8.23 ​​(1H, s), 8.09 (1H, s), 7.79 (1H, s), 3.98 (3H, s), 1.84-1.92 (2H, m), 1.47-1.57 (m, 2H).

[0378] Preparation of 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoic acid (intermediate I20) [ka] Methyl 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoate (59 mg, 0.22 mmol) was dissolved in tetrahydrofuran (0.66 mL) and water (0.33 mL). Lithium hydroxide monohydrate (9.3 mg, 0.22 mmol) was added, and the mixture was stirred at room temperature for 42 hours. 1N hydrochloric acid was added until the pH was 2. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoic acid. 1H NMR (400 MHz, chloroform-d) δ ppm: 8.60-9.90 (1H, br s), 8.29 (1H, s), 8.15 (1H, s), 7.84 (1H, s), 1.84-1.93 (2H, m), 1.50-1.60 (2H, m). LC-MS (Method 1): Retention time 0.86 min, m / z 254[MH]-.

[0379] Preparation of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanol [ka] Methylmagnesium bromide (1.00 M in THF, 63.2 mL, 63.2 mmol) was added to a solution of 3-bromo-5-(trifluoromethyl)benzaldehyde (8.00 g, 31.6 mmol) in tetrahydrofuran (100 mL) at 0° C. under nitrogen. The resulting brown reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was quenched with saturated ammonium chloride solution. The aqueous layer was extracted with ethyl acetate, dried over sodium sulfate, and concentrated under reduced pressure to give 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanol as a pale yellow liquid. 1 H NMR (400MHz, DMSO-d) δ ppm:7.78-7.88(m,2H), 7.71(s,1H), 5.52(d,1H), 4.81(m,1H), 1.35(d,3H).

[0380] Preparation of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanone [ka] Pyridinium chlorochromate (5.05 g, 23.4 mmol) was added portionwise to a stirred solution of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanol (7.00 g, 15.6 mmol) in dichloromethane (150 mL) at 0° C. The resulting brown reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered through a Celite pad, and the filtrate was evaporated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (eluting with ethyl acetate in hexanes) to give 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanone as a colorless oil. 1 H NMR (400MHz, DMSO-d) δ ppm: 8.38 (1H, s), 8.26 (1H, s), 8.19 (1H, s), 2.69 (s,1H).

[0381] Preparation of 1-[3-bromo-5-(trifluoromethyl)phenyl]cyclopropanol [ka] A solution of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanone (5.00 g, 18.3 mmol) in dichloromethane (30 mL) at 0° C. was treated with triethylamine (3.84 mL, 27.5 mmol) and trimethylsilyl trifluoromethanesulfonate (6.12 g, 27.5 mmol). The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate solution (100 mL). The aqueous layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The crude silyl enol ether was dissolved in dichloromethane and cooled to 0° C. Di-iodomethane (7.37 g, 27.5 mmol) and diethylzinc (1.00 M in hexanes, 27.5 mL, 27.5 mmol) were added dropwise, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was quenched with saturated ammonium chloride solution. The aqueous layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was dissolved in methanol at 0°C, and potassium carbonate (0.254 g, 1.83 mmol) was added. The resulting pale yellow reaction mixture was stirred at 0°C for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluting with ethyl acetate in hexane) to give 1-[3-bromo-5-(trifluoromethyl)phenyl]cyclopropanol as an off-white solid. 1 H NMR (400 MHz, chloroform-d) δ ppm: 7.75 (1H, s), 7.65 (1H, s), 7.58 (1H, s), 6.30 (s, 1H), 1.15-1.25 (m, 2H), 1.05-1.15 (m, 2H).

[0382] Preparation of 1-bromo-3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzene (I50) [ka] A solution of 1-[3-bromo-5-(trifluoromethyl)phenyl]cyclopropanol (500 mg, 1.74 mmol) in tetrahydrofuran (2.0 mL) was added dropwise to a suspension of sodium hydride (60% in oil, 139 mg, 3.49 mmol) in tetrahydrofuran (2.0 mL). The mixture was stirred at 0° C. for 10 minutes. Methyl iodide (371 mg, 2.62 mmol) was added dropwise, and the resulting mixture was stirred at 0° C. for 1 hour. Saturated ammonium chloride solution was added. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (ethyl acetate in hexane gradient) to give 1-bromo-3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzene as a colorless liquid. 1 H NMR (400MHz, DMSO-d) δ ppm: 7.82(s,1H), 7.69(s,1H), 7.55(s,1H), 3.27(s,3H), 1.20-1.28(m,2H), 1.09-1.18(m,2H).

[0383] Preparation of methyl 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoate (I51) [ka] An autoclave was charged with 1-bromo-3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzene (1.50 g, 4.83 mmol), triethylamine (1.02 mL, 7.24 mmol), and methanol (30 mL). The reaction mixture was purged with argon. [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (353 mg, 0.483 mmol) was added. The autoclave was placed under a carbon monoxide atmosphere (200 psi) and heated to 100°C for 16 hours. The autoclave was cooled to room temperature and filled with argon. The reaction mixture was filtered through Celite. Water and ethyl acetate were added to the filtrate, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (gradient of ethyl acetate in hexanes) to give methyl 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoate as a pale yellow liquid. 1 H NMR (400 MHz, chloroform-d) δ ppm: 8.17 (s, 1H), 8.05 (s, 1H), 7.78 (s, 1H), 3.95 (s, 3H), 3.25 (s, 3H), 1.30 (t, 2H), 1.05 (t, 2H).

[0384] Preparation of 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid (I52) [ka] Methyl 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoate (1.00 g, 3.46 mmol) was dissolved in tetrahydrofuran (6.0 mL) and water (3.0 mL). Lithium hydroxide monohydrate (291 mg, 6.93 mmol) was added, and the mixture was stirred at room temperature for 3 hours. The mixture was concentrated, and 2 N hydrochloric acid was added at 0 °C. The formed precipitate was filtered off, washed with water, and dried to give 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid as a white solid. 1H NMR (400 MHz, chloroform-d) δ ppm: 13.4-13.7 (br.S, 1H), 8.00-8.10 (m, 2H), 7.72 (s, 1H), 3.19 (s, 3H), 1.25-1.35 (m, 2H), 1.08-1.15 (m, 2H).

[0385] Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethenone (I21) [ka] To a previously degassed solution of 1-(3-chloropyrazin-2-yl)ethanone (8.14 g, 52.0 mmol) in toluene (160 mL) was added tetrakis(triphenylphosphine)palladium(0) (4.72 g, 4.00 mmol), copper(I) iodide (0.777 g, 4.00 mmol), and tributyl(pyrimidin-2-yl)stannane (12.7 mL, 40.0 mmol). The reaction mixture was heated to reflux and stirred overnight. After cooling to room temperature, it was filtered through Celite, and the filtrate was concentrated under reduced pressure. Two purifications of the crude material by flash chromatography on silica gel (eluting first with ethyl acetate:ethanol 3:1 in chloromethane, then with ethyl acetate in cyclohexane) afforded 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone. LCMS (Method 1): Retention time 0.37 min, m / z 201[M+H + ]; 1 H-NMR (400MHz, CDCl3): δ ppm:8.89(d,J=4.77Hz,2H)8.82(d,J=2.20Hz,1H)8.68(d,J=2.20Hz,1H)7.37(t,J=4.95Hz,1H)2.76(s,3H).

[0386] Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine (I31) [ka] To a solution of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanone (0.401 g, 2.01 mmol) in a saturated solution of ammonium acetate in ethanol (32 mL) was added ammonia (7 M in methanol, 14.3 mL) and sodium cyanoborohydride (0.398 g, 6.02 mmol). The reaction mixture was heated to reflux and stirred for 16.5 hours. After cooling to room temperature, it was concentrated under reduced pressure. The resulting residue was diluted with 2 M sodium hydroxide (10 mL), and it was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. A first purification of the crude material by reverse-phase chromatography (acetonitrile eluted in water) followed by a second purification by flash chromatography on silica gel (methanol eluted in dichloromethane) afforded 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine as a yellow solid. LCMS (Method 1): Retention time 0.19 min, m / z 202[M+H + ]; 1 H-NMR (400MHz, CDCl3):δ ppm:8.97(d,J=4.77Hz, 2H), 8.68(d,J=2.20Hz, 1H), 8.64(d,J=2.57Hz, 1H), 7.41(t,J=4.95Hz, 1H), 4.64(q,J=6.60Hz, 1H), 2.13(br s,2H), 1.48(d,J=6.60Hz, 3H).

[0387] Preparation of tributyl-(5-cyclopropylpyrimidin-2-yl)stannane [ka] To a solution of 2-chloro-5-cyclopropyl-pyrimidine (90%, 2.70 g, 15.7 mmol) in toluene (40 mL) was added hexa-n-butylditin (15.9 mL, 31.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.82 g, 1.57 mmol). The reaction mixture was purged with argon for 10 minutes, heated to 100° C., and stirred for 2 hours. After cooling to room temperature, it was diluted with water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with ethyl acetate in hexanes) afforded tributyl-(5-cyclopropylpyrimidin-2-yl)stannane as a yellow oil. 1 H-NMR (400MHz, CDCl3): δ ppm: 7.3(m,2H), 1.65(m,6H), 1.35(m,16H), 0.9(m,12H).

[0388] Preparation of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanone (I23) [ka] To a solution of 1-(3-chloropyrazin-2-yl)ethanone (90%, 2.00 g, 11.5 mmol) in toluene (20 mL) was added tributyl-(5-cyclopropylpyrimidin-2-yl)stannane (6.80 g, 14.9 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.33 g, 1.15 mmol). The reaction mixture was purged with argon for 10 minutes. Copper(I) iodide (0.438 g, 2.30 mmol) was then added, and the resulting reaction mixture was heated to 100° C. and stirred for 12 hours. After cooling to room temperature, it was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with ethyl acetate in hexanes) afforded 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanone as a brown solid. 1 H-NMR (400MHz, CDCl3): δ ppm: 8.7(d,1H), 8.55(d,1H), 8.50(s,2H), 2.7(s,3H), 1.85(m,1H), 1.1(m,2H), 0.8(m,2H).

[0389] Preparation of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanamine (I32) [ka] To a solution of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanone (90%, 1.00 g, 3.75 mmol) in a saturated solution of ammonium acetate in ethanol (75 mL) was added ammonia (30% in water, 30 mL). The reaction mixture was stirred at room temperature for 10 minutes. Sodium cyanoborohydride (0.706 g, 11.2 mmol) was then added, and the reaction mixture was heated to 100° C. and stirred for 12 hours. After cooling to room temperature, it was concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (acetonitrile eluted in water) afforded 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanamine as a brown oil. 1 H-NMR (400MHz, DMSO): δ ppm 8.85(m,2H), 8.80(m,2H), 5.0(m,1H), 3.2(m,3H)2.1(m,1H), 1.15(m,2H), 1.0(m,2H).

[0390] Preparation of tert-butyl N-(6-tributylstannyl-3-pyridyl)carbamate [ka] A solution of tert-butyl N-(6-bromo-3-pyridyl)carbamate (2.50 g, 8.24 mmol) in dry tetrahydrofuran (50 mL) was cooled to −75° C., and n-butyllithium (2.50 M, 5.77 mL, 14.4 mmol) was added dropwise over 5 minutes. The reaction mixture was stirred at the same temperature for 1 hour. Next, tributyltin chloride (4.69 g, 14.4 mmol) was added to the reaction mixture, which was then stirred at room temperature for 3 hours. The reaction mixture was quenched with saturated ammonium chloride solution, and it was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by chromatography on neutral alumina afforded the desired product. 1H-NMR (400MHz, CDCl3): δ ppm: 8.5(m,1H), 7.85(br s,1H), 7.4(dd,1H), 6.5(s,1H), 1.55(m,15H), 1.35(m,6H), 1.15(m,6H), 0.9(m,9H).

[0391] Preparation of tert-butyl N-[6-(3-acetylpyrazin-2-yl)-3-pyridyl]carbamate (I28) [ka] To a solution of tert-butyl N-(6-tributylstannyl-3-pyridyl)carbamate (36.0 g, 70.8 mmol) in toluene (720 mL) was added 1-(3-chloropyrazin-2-yl)ethanone (12.3 g, 70.8 mmol) and copper(I) iodide (2.70 g, 14.2 mmol). The reaction mixture was purged with argon for 20 minutes, and tetrakis(triphenylphosphine)palladium(0) (4.09 g, 3.54 mmol) was added. The reaction mixture was stirred at 100° C. for 5 hours. After cooling at room temperature, the reaction mixture was filtered through a pad of Celite, and the filtrate was evaporated under reduced pressure. The residue was diluted with ethyl acetate, washed with water, brine, and saturated potassium fluoride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with ethyl acetate in n-hexane) afforded tert-butyl N-[6-(3-acetylpyrazin-2-yl)-3-pyridyl]carbamate. 1 H-NMR (400MHz, DMSO): δ ppm: 9.9(s,1H), 8.6-8.9(m,3H), 8.1-8.25(m,2H), 2.55(s,1H), 1.5(s,9H).

[0392] Preparation of 1-[3-(5-amino-2-pyridyl)pyrazin-2-yl]ethanone (I29) [ka] HCl in 1,4-dioxane (4.00 M, 73.0 mL, 0.292 mol) was added dropwise to a solution of tert-butyl N-[6-(3-acetylpyrazin-2-yl)-3-pyridyl]carbamate (17.0 g, 0.0487 mol) in dichloromethane (510 mL) cooled to 0 °C. The mixture was stirred for 10 minutes and then allowed to stir at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure and poured into a mixture of ice-cold water and dichloromethane. The pH was adjusted to 12 using 2 N sodium hydroxide solution. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with methanol in dichloromethane) afforded 1-[3-(5-amino-2-pyridyl)pyrazin-2-yl]ethenone as a yellow solid. LC-MS (method 3): retention time 1.41 min, m / z 215.1[M+H] +

[0393] Preparation of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanone (I25) [ka] A solution of 1-[3-(5-amino-2-pyridyl)pyrazin-2-yl]ethanone (3.00 g, 12.6 mmol) in acetonitrile (200 mL) was cooled to 0 °C. Copper(II) chloride (3.39 g, 25.2 mmol) was added, followed by dropwise addition of tert-butyl nitrite (2.17 mL, 25.2 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was quenched with saturated ammonium chloride solution, stirred for 15 minutes, and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (C18; eluting with acetonitrile in water) afforded 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanone. 1 H-NMR (400MHz, DMSO): δ ppm: 8.9(s,1H), 8.8(d,1H), 8.7(s,1H), 8.2(m,2H), 2.6(s,3H).

[0394] Preparation of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine (I35) [ka] To a solution of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanone (3.20 g, 11.0 mmol) in a saturated solution of ammonium acetate in ethanol (150 mL) was added sodium cyanoborohydride (2.04 g, 32.9 mmol) and ammonia (30% in water, 100 mL) at room temperature. The reaction mixture was stirred at 90 °C for 12 hours. After cooling to room temperature, it was concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (acetonitrile eluted in water) afforded 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine. LCMS (Method 3): Retention time 2.7 min, m / z=235[M+H + ]

[0395] Preparation of tert-butyl N-[2-(3-acetylpyrazin-2-yl)pyrimidin-5-yl]carbamate (I53) [ka] To a solution of tert-butyl N-(2-tributylstannylpyrimidin-5-yl)carbamate (600 mg, 0.867 mmol) in toluene (20 mL) was added 1-(3-chloropyrazin-2-yl)ethanone (151 mg, 0.867 mmol) and copper(I) iodide (33 mg, 0.173 mmol). The reaction mixture was purged with argon for 5 minutes, and tetrakis(triphenylphosphine)palladium(0) (50.1 mg, 0.0434 mmol) was added. The reaction was stirred at 90° C. for 3 hours. After cooling to room temperature, the reaction mixture was filtered through a pad of Celite, and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluting with ethyl acetate in n-hexane) to give tert-butyl N-[2-(3-acetylpyrazin-2-yl)pyrimidin-5-yl]carbamate as a brown gum. LCMS (Method 3): Retention time 1.04 min, m / z=216.1[M+H + ]

[0396] Preparation of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanone (I54) [ka] A solution of 1-[3-(5-aminopyrimidin-2-yl)pyrazin-2-yl]ethanone (2.80 g, 11.7 mmol) in acetonitrile (50 mL) was cooled to 0 °C. Isoamyl nitrite (2.74 g, 23.4 mmol) was added, followed by cupric bromide (5.23 g, 23.4 mmol). The reaction mixture was stirred at room temperature for 6 hours. The reaction mixture was quenched with saturated ammonium chloride solution, stirred for 15 minutes, and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with ethyl acetate in n-hexane) afforded 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanone as a brown solid. 1H-NMR (400MHz, DMSO): δ ppm: 9.15(s,2H), 8.95(m,1H), 8.88(m,1H), 2.63(s,3H). LCMS (Method 3): Retention time 3.54 min, m / z = 279 / 281 [M+H]+ (bromo pattern)

[0397] Preparation of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine (I55) [ka] To a solution of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanone (495 mg, 1.60 mmol) in aqueous ammonia (30% in water, 4.3 mL) was added a saturated solution of ammonium acetate in ethanol (10.8 mL), followed by sodium cyanoborohydride (301 mg, 4.79 mmol). The reaction mixture was stirred at 90° C. for 12 hours. After cooling to room temperature, it was concentrated under reduced pressure to give 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine. 1 H-NMR (400MHz, DMSO): δ ppm: 9.22(s,2H), 8.70-9.00(m,2H), 4.50-4.80(m,1H), 1.42(d,3H).

[0398] Preparation of 3,5-dichloro-2-pyrimidin-2-yl-pyrazine [ka] To a solution of 3,5-dichloro-2-iodo-pyrazine (0.500 g, 1.81 mmol) in dioxane (5 mL) at room temperature was added tributyl(pyrimidin-2-yl)stannane (CAS 153435-63-3, 0.671 g, 1.81 mmol), followed by tetrakis(triphenylphosphine)palladium (0.211 g, 0.181 mmol). The reaction mixture was heated to 180° C. in a microwave for 2 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to give a crude mass, which was purified by flash column chromatography on silica gel (ethyl acetate in cyclohexane) to give 3,5-dichloro-2-pyrimidin-2-yl-pyrazine as a brown solid. LC-MS (method 4): retention time 1.23 min, m / z 228[M+H + ]; 1 H NMR (400 MHz, chloroform-d) δ ppm: 8.99 (d, 2H), 8.68 (s, 1H), 7.46 (t, 1H).

[0399] Preparation of 3-chloro-5-methoxy-2-pyrimidin-2-yl-pyrazine [ka] To a solution of 3,5-dichloro-2-pyrimidin-2-yl-pyrazine (0.100 g, 0.440 mmol) in methanol (1 mL) was added sodium methoxide (0.0099 mL, 0.044 mmol) at 0° C., and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with acetic acid and water (20 mL), extracted three times with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 3-chloro-5-methoxy-2-pyrimidin-2-yl-pyrazine as a white solid. LC-MS (Method 4): Retention time 0.37 min, m / z 223[M+H + ]; 1 H NMR(400MHz, CDCl3)δ ppm:8.95(d,2H)8.29(s,1H)7.37(t,1H)4.07(s,3H)

[0400] Preparation of 3-(1-ethoxyvinyl)-5-methoxy-2-pyrimidin-2-yl-pyrazine [ka] To a solution of 3-chloro-5-methoxy-2-pyrimidin-2-yl-pyrazine (0.060 g, 0.269 mmol) in dioxane (1 mL) was added tributyl(1-ethoxyvinyl)stannane (0.140 mL, 0.404 mmol) and tetrakis(triphenylphosphine)palladium (0.013 g, 0.026 mmol) at room temperature. The reaction mixture was heated to 150 °C and stirred in a microwave for 1 hour. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and purified by flash column chromatography on silica gel (ethyl acetate in cyclohexane) to give 3-(1-ethoxyvinyl)-5-methoxy-2-pyrimidin-2-yl-pyrazine as a brown solid. LC-MS (Method 4): Retention time 1.11 min, m / z 259[M+H+].

[0401] Preparation of 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethenone (I47) [ka] To a solution of 3-(1-ethoxyvinyl)-5-methoxy-2-pyrimidin-2-yl-pyrazine (0.10 g, 0.387 mmol) in acetonitrile (1 mL) were added acetic acid (1 mL) and water (1 mL) at room temperature, and the reaction mixture was heated at 50° C. for 2 hours. The reaction mixture was quenched with water (20 mL), extracted three times with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethenone as a white solid. LC-MS (method 4): retention time 1.07 min, m / z 231[M+H + ].

[0402] Preparation of 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethanamine (I48) [ka] To a solution of 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethanone (0.060 g, 0.260 mmol) in methanol (5 mL) was added ammonium acetate (0.209 g, 2.60 mmol) at room temperature, and the reaction mixture was stirred at room temperature for 1 hour. To this reaction mixture was added sodium cyanoborohydride (0.051 g, 0.781 mmol), and the reaction mixture was heated at 50° C. for 2 hours. The reaction mixture was diluted with water (40 mL) and extracted three times with 20% methanol in chloroform. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethanamine as a brown solid. LC-MS (method 4): retention time 0.35 min, m / z 232[M+H + ].

[0403] Preparation of 1-(3-chloropyrazin-2-yl)ethanamine [ka] To a solution of 1-(3-chloropyrazin-2-yl)ethanone (0.200 g, 1.28 mmol) in methanol (4.5 mL) was added ammonium acetate (0.995 g, 12.8 mmol) and sodium cyanoborohydride (0.0591 g, 0.894 mmol) at room temperature. The resulting suspension was stirred at room temperature for 18 hours and then concentrated under reduced pressure. The crude material was purified by reverse-phase chromatography (C18 column, gradient of acetonitrile in water) to give 1-(3-chloropyrazin-2-yl)ethanamine. 1 H NMR (400MHz, CDCl3) δ ppm: 8.49(d,1H), 8.26(d,1H), 4.56(q,1H), 1.95(br s,2H), 1.44(d,3H)ppm

[0404] Preparation of (1S)-1-(3-chloropyrazin-2-yl)ethanamine (I45) [ka] To a solution of 1-(3-chloropyrazin-2-yl)ethanamine (202.2 mg, 1.20 mmol) in tert-butyl methyl ether (11 mL) was added Novozym® 435 (240 mg) followed by ethyl methoxyacetate (1.44 mL, 12.0 mmol) at room temperature. The mixture was stirred at 40° C. for 5.5 hours. The reaction mixture was diluted with dichloromethane and filtered. The filtrate was concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluting with a gradient of methanol in dichloromethane) to give (1S)-1-(3-chloropyrazin-2-yl)ethanamine. 1 H NMR(400MHz, CDCl3)δ ppm:8.49(d,1H), 8.27(d,1H), 4.56(q,1H), 1.73(br s,2H), 1.44(d,3H):[α] D 20 :-32.3°(c:1.157, CHCl3)

[0405] Preparation of (1R)-1-(3-chloropyrazin-2-yl)ethanol (I44) [ka] 1-(3-chloropyrazin-2-yl)ethanone (157 mg, 1.00 mmol) was dissolved in dichloromethane (10.0 mL), and the flask was evacuated and backfilled with argon three times. RuBF4[(R,R)-TsDPEN](p-cymene) (0.0362 g, 0.0526 mmol) was then added. A cooled solution of triethylamine (0.348 mL, 2.50 mmol) and formic acid (0.160 mL, 4.29 mmol) was added dropwise to the reaction mixture, which was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluting with a gradient of ethyl acetate in cyclohexane) to give (1R)-1-(3-chloropyrazin-2-yl)ethanol. 1 H-NMR (400MHz, CDCl3) δ ppm: 8.49(d,1H), 8.34(d,1H), 5.18(m,1H), 3.81(d,1H), 1.52(d,3H) Chiral SFC (Method 2): 1.98 min (minor enantiomer), 2.55 min (major enantiomer); ee = 85%

[0406] Preparation of (1S)-1-(3-chloropyrazin-2-yl)ethanamine (I45) [ka] (1R)-1-(3-chloropyrazin-2-yl)ethanol (87.8 mg, 0.554 mmol) was dissolved in tetrahydrofuran (1.9 mL). 1,8-diazabicyclo[5.4.0]undec-7-ene (0.10 mL, 0.66 mmol) was then added dropwise to the reaction mixture, followed by diphenylphosphine azide (0.130 mL, 0.585 mmol). The reaction mixture was stirred at room temperature for 19 hours. Tetrahydrofuran (1.4 mL) was added, followed by triphenylphosphine (179.4 mg, 0.677 mmol). The reaction mixture was stirred at room temperature for 2 hours. Water (0.15 mL) was added, and the reaction mixture was stirred at room temperature for 46 hours. The reaction mixture was concentrated to a volume of 1 mL and then diluted with dichloromethane. 1 M hydrochloric acid was added, and the aqueous layer was then washed with dichloromethane. The aqueous layer was basified to pH = 14 with 4 M sodium hydroxide solution and extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluting with a gradient of methanol in dichloromethane) to give (1S)-1-(3-chloropyrazin-2-yl)ethanamine. 1 H NMR (400MHz, CDCl3) δ ppm: 8.49(d,1H), 8.27(d,1H), 4.56(q,1H), 1.84(s,2H), 1.44(d,3H) [α] D 20 :-26.0°(c:0.960, CHCl3)

[0407] Preparation of (2R)-N-[(1S)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide [ka] To a solution of 1-(3-chloropyrazin-2-yl)ethanamine hydrochloride (700 mg, 3.61 mmol) in dichloromethane (18 mL) was added (R)-(-)-mandelic acid (610 mg, 3.97 mmol), N-ethyldiisopropylamine (1.26 mL, 7.21 mmol), 1-hydroxybenzotriazole (50.8 mg, 0.361 mmol), and N,N'-dicyclohexylcarbodiimide (844 mg, 3.97 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with saturated aqueous sodium carbonate and extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with methanol in dichloromethane) afforded (2R)-N-[(1R)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide and (2R)-N-[(1R)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide. The relative stereochemistry of (2R)-N-[(1R)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide was determined by X-ray crystallography (crystallized from acetonitrile / water). Analytical data for (2R)-N-[(1R)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide: LCMS (Method 1): Retention time 0.74 min, m / z=291[M+H + ]

[0408] Preparation of (1S)-1-(3-chloropyrazin-2-yl)ethanamine hydrochloride [ka] A solution of (2R)-N-[(1S)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide (0.93 g, 3.2 mmol) in hydrochloric acid (32% in water, 13 mL) was heated to reflux and stirred for 2 hours. After cooling to room temperature, the reaction mixture was basified with 3N sodium hydroxide, diluted, and extracted with ethyl acetate. The aqueous layer was lyophilized overnight, and the resulting solid was suspended in acetone. The suspension was filtered, and the filtrate was concentrated under reduced pressure. The resulting oil was dissolved in ethyl acetate, and 1N hydrochloric acid was added. A precipitate appeared, which was filtered and dried under reduced pressure to give the desired product. LCMS (Method 1): Retention time 0.19 min, m / z=158[M+H+].

[0409] Preparation of (1S)-1-(3-chloropyrazin-2-yl)-N-(cyclopropylmethyl)ethanamine (I46) [ka] Sodium triacetoxyborohydride (59.4 mg, 0.267 mmol) was added to a stirred solution of (1S)-1-(3-chloropyrazin-2-yl)ethanamine (30.0 mg, 0.190 mmol), cyclopropanecarboxaldehyde (15.0 mg, 0.209 mmol), and acetic acid (0.0109 mL, 0.190 mmol) in 1,2-dichloroethane (0.95 mL). The mixture was stirred at room temperature for 4 hours. Saturated aqueous sodium carbonate was added, and the aqueous layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluting with ethyl acetate in cyclohexane) to give (1S)-1-(3-chloropyrazin-2-yl)-N-(cyclopropylmethyl)ethanamine. 11H NMR(400MHz,CDCl3)δ ppm-0.03-0.10(m,2H)0.38-0.52(m,2H)0.83-1.00(m,1H)1.40(d,3H)2.07 (dd,1H)2.15-2.29(m,1H)2.53(dd,1H)4.39(q,1H)8.26(d,1H)8.51(d,1H);

[0410] Preparation of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-2-hydroxy-1-methyl-3-oxo-propyl]carbamate [ka] A solution of tert-butyl N-[(1S)-1-methyl-2-oxo-ethyl]carbamate (CAS 79069-50-4, 1.07 g, 6.18 mmol) in dichloromethane (12 mL) was prepared in a round-bottom flask. The flask was evacuated and backfilled with argon three times. Next, 2-(3-benzyl-4-methyl-thiazol-3-ium-5-yl)ethanol; bromide (0.388 g, 1.24 mmol), 5-bromopyridine-2-carbaldehyde (CAS 31181-90-5, 1.81 g, 9.27 mmol), and dichloromethane (6 mL) were added sequentially, followed by N,N-diisopropylethylamine (2.16 mL, 12.4 mmol). The reaction mixture was stirred at room temperature for 1 hour. It was quenched with saturated aqueous ammonium chloride and extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with ethyl acetate in cyclohexane) afforded tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-2-hydroxy-1-methyl-3-oxo-propyl]carbamate as an orange gum. LCMS (Method 1): Retention time 0.98 min, m / z=359-361[M+H + ](bromopattern); 1H-NMR (400MHz, CDCl3)δ ppm:1.37-1.40(m,3H)1.43-1.44(m,9H)4.34-4.69(m,2H)5.22-5.36(m,1H)7.86-8.08(m,2H)8.73(d,J=2.20Hz, 1H).

[0411] Preparation of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxo-propyl]carbamate [ka] To a solution of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-2-hydroxy-1-methyl-3-oxopropyl]carbamate (15.2 g, 42.3 mmol) in dichloromethane (100 mL) and dimethyl sulfoxide (20 mL) at 0° C. was added N,N-diisopropylethylamine (21.8 mL, 127 mmol, 3.00 equiv.) and sulfur trioxide pyridine complex (13.9 g, 84.6 mmol, 2.00 equiv.) in two portions. The reaction mixture was stirred at 0° C. for 1 hour. It was quenched with water and diluted with dichloromethane and 1N hydrochloric acid. The aqueous layer was extracted twice with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with ethyl acetate in cyclohexane) afforded tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxo-propyl]carbamate as an orange oil. 1H-NMR (400MHz, CDCl3) δ ppm:1.36-1.41(m,9H)1.45-1.48(m,3H)4.82-4.96(m,1H)5.10(br s,1H)7.91-8.00(m,1H)8.01-8.11(m,1H)8.79(d,J=1.83Hz, 1H).

[0412] Preparation of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate (I42) [ka] To a solution of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxopropyl]carbamate (2.00 g, 5.50 mmol) in ethanol (22 mL) was added ethylenediamine (1.91 mL, 28.0 mmol). The reaction mixture was stirred at room temperature in the presence of air for 60 hours. It was concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with ethyl acetate in cyclohexane) afforded tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate as a colorless gum. LCMS (Method 1): retention time 1.09 min, m / z = 379-381 [M+H+] (bromo pattern); 1 H-NMR (400MHz, CDCl3)δ ppm:1.33-1.45(m,9H)1.52-1.56(m,3H)5.65-5.83(m,2H)7.96-8.02(m,2H)8.53-8.60(m,2H)8.79(dd,J=2.20, 1.10Hz, 1H). Chiral SFC (Method 1): 1.80 min (major enantiomer), 1.11 min (minor enantiomer); ee = 92%

[0413] Preparation of tert-butyl N-[(1S)-1-[6-amino-3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate (I49) [ka] 2-Aminoacetamidine dihydrobromide (1.21 g, 4.11 mmol) was added to a mixture of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxopropyl]carbamate (500 mg, 0.894 mmol) in 2-propanol (13.4 mL). Potassium acetate (266 mg, 2.68 mmol) was added, and the mixture was stirred at room temperature for 2.5 hours. Water was added, the aqueous layer was extracted with ethyl acetate, and the organic layer was washed with brine, dried over magnesium sulfate, and concentrated. The crude mixture was purified by reverse-phase chromatography (C18 column, gradient of acetonitrile in water) to give tert-butyl N-[(1S)-1-[6-amino-3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate. LCMS (Method 1): Retention time 1.04 min, m / z=394-396[M+H + ](bromopattern); 1 H NMR(600MHz, CDCl3)δ ppm:1.45-1.47(m,12H)4.84(br s,2H)5.66-5.74(m,1H)5.89(br s,1H)7.86-7.88(m,1H)7.89(br d,1H)7.90(s,1H)8.72(s,1H).

[0414] Preparation of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethyl]carbamate and tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethyl]carbamate [ka] 1,2-Diaminopropane (16.4 mL, 190 mmol) was added in four portions over 36 hours to a mixture of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxopropyl]carbamate (1.130 g, 3.16 mmol) in ethanol (12.7 mL). Water was added, the aqueous layer was extracted with ethyl acetate, and the organic layer was washed with brine, dried over magnesium sulfate, and concentrated. The crude mixture was purified by chromatography on silica gel (gradient of ethyl acetate in cyclohexane) to give a mixture of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethyl]carbamate and tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethyl]carbamate. LCMS (method 1): retention time 1.14 and 1.15 min, m / z=393-395[M+H + ](bromopattern); 1 H NMR (600MHz, CDCl3) δ ppm (mixed): 1.45-1.47(m,24H)4.84(br s,4H)5.66-5.74(m,2H)5.89(br s,2H)7.86-7.88(m,2H)7.89(br d,2H)7.90(s,1H)8.72(s,2H).

[0415] Preparation of (1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethanamine and (1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethanamine [ka] Trifluoroacetic acid (2.00 mL, 25.2 mmol) was added in two portions to a solution of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethyl]carbamate and tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethyl]carbamate (550 mg, 1.40 mmol) in dichloromethane (9.0 mL) at 0° C. The reaction was stirred at room temperature for 28 hours. The reaction mixture was poured into saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with dichloromethane, and the organic layer was dried over magnesium sulfate and concentrated to give a mixture of (1S)-1-[3-(5-bromo-2-pyridyl)-6-methyl-pyrazin-2-yl]ethanamine and (1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethanamine as a brown oil. LCMS (Method 1): Retention time 0.54 min, m / z=293-295[M+H + ](bromopattern); 1 H NMR (400MHz, CDCl3)δ ppm:1.40-1.46(m,6H)2.55-2.62(m,6H)4.56-4.73(m,2H)7.86-8.02(m,4H)7.93-7.93(m,1H)8.34-8.48(m,2H)8.72-8.78(m,2H)

[0416] Preparation of (1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethanamine (I43) [ka] To a solution of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate (1.14 g, 3.00 mmol) in dichloromethane (27 mL) was added trifluoroacetic acid (5.40 mL, 68.0 mmol) at 0 °C. The reaction mixture was stirred at room temperature overnight. It was added dropwise to a saturated solution of sodium carbonate. The layers were separated, and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give (1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethanamine as a yellow oil. LCMS (method 1): retention time 0.54, m / z=279-281[M+H+] (bromo pattern); 1H-NMR (400MHz, CDCl3)δ ppm:1.47(d,J=6.60Hz,3H)2.09(s,2H)4.67-4.76(m,1H)7.90-7.94(m,1H)7.96-8.0 3(m,1H)8.51(d,J=2.20Hz,1H)8.60(d,J=2.57Hz,1H)8.77(dd,J=2.20,0.73Hz,1H).

[0417] Preparation of 2-(1-cyanocyclopropyl)-N-[1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethyl]-6-(trifluoromethyl)pyridine-4-carboxamide (P32) [ka] To a solution of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanamine (20.7 mg, 85.9 μmol) in N,N-dimethylformamide (1 mL) was added 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (22 mg, 85.9 μmol), N,N-diisopropylethylamine (44.9 μL, 0.258 mmol), and propanephosphonic anhydride (78.1 μL, 0.172 mmol) at 0° C. The reaction mixture was stirred at room temperature for 6 hours. It was then poured into ice water and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with ethyl acetate in hexanes) afforded 2-(1-cyanocyclopropyl)-N-[1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethyl]-6-(trifluoromethyl)pyridine-4-carboxamide as a light brown solid. 1 H-NMR (400MHz, DMSO):δ ppm:9.4(d,1H), 8.75(m,1H), 8.7(m,3H), 8.1(s,1H), 7.95(s,1H), 5.65(m,1H) ), 2.0(m,1H), 1.95(m,2H), 1.75(m,2H), 1.6(m,3H), 1.1(m,2H), 0.85(m,2H).

[0418] Preparation of N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzamide (P17) [ka] To a solution of 3-[cyano(cyclopropyl)methyl]-5-(trifluoromethyl)benzoic acid (130 mg, 0.484 mmol) in toluene (20 mL) was added dropwise thionyl chloride (0.141 mL, 1.94 mmol) at 0° C. The reaction mixture was stirred at 90° C. for 20 hours. After cooling to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added to a solution of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine (139 mg, 0.532 mmol) and triethylamine (0.272 mL, 1.94 mmol) in dichloromethane (10 mL) at 0° C. The reaction mixture was stirred at room temperature for 2 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by reverse phase chromatography (acetonitrile eluting in water) afforded N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzamide. 1H-NMR (400MHz, DMSO):δ ppm:9.25(d,1H), 8.8(m,1H), 8.75(m,1H), 8.65(m,1H), 8.15(m,1H), 8.05(s, 1H), 8(d,1H), 7.95(m,1H), 7.75(s,1H), 5.8(m,1H), 1.8(m,2H), 1.65(m,5H).

[0419] Preparation of N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide (P16) [ka] To a solution of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (130 mg, 0.482 mmol) in toluene (20 mL) was added dropwise thionyl chloride (0.141 mL, 1.94 mmol) at 0° C. The reaction mixture was stirred at 90° C. for 2 hours. After cooling to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added to a solution of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanamine (138 mg, 0.530 mmol) and triethylamine (0.271 mL, 1.93 mmol) in dichloromethane (10 mL) at 0° C. The reaction mixture was stirred at room temperature for 2 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (acetonitrile eluted in water) afforded N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide as an off-white solid. 1 H-NMR (400MHz, DMSO):δ ppm:9.55(d,1H), 8.60-8.80(m,3H), 8.12(m,1H), 8.01(m,2H), 7.95(s,1H), 5.83(m,1H), 1.92(m,2H), 1.75(m,2H), 1.67(d,3H).

[0420] Preparation of N-[1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide (P28) [ka] To a solution of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (100 mg, 0.371 mmol) in toluene (15 mL) was added dropwise thionyl chloride (0.108 mL, 1.48 mmol) at 0° C. The reaction mixture was stirred at 90° C. for 2.5 hours. After cooling to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added to a solution of 1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethanamine (108 mg, 0.371 mmol) and triethylamine (0.208 mL, 1.48 mmol) in dichloromethane (10 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (acetonitrile eluted in water) afforded N-[1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide as an off-white solid. 1 H-NMR (400MHz, DMSO):δ ppm:9.53(d,1H), 8.80-8.90(m,1H), 8.60-8.80(m,2H), 8.20-8.30(m,1H), 8.12(m ,1H), 7.97(m,2H), 5.79-5.90(m,1H), 1.93(m,2H), 1.70-1.80(m,2H), 1.65(d,3H); 19 F-NMR (377MHz, DMSO): δ ppm: -66.69.

[0421] Preparation of 3-cyclopropyl-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)-benzamide (P41) [ka] A mixture of 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid (0.10 g, 0.43 mmol, 1.0 equiv.), 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine trifluoroacetate (1.6 g, 0.52 mmol, 1.2 equiv.), and HATU (0.17 g, 1.3 mmol, 3.0 equiv.) in N,N-dimethylformamide (2.9 mL) was stirred at room temperature for 1 hour. The reaction mixture was then diluted with ethyl acetate, and the organic phase was washed with water (5 times), brine, dried over magnesium sulfate, filtered, and concentrated. The crude material was purified by chromatography on silica gel to give the title compound as an off-white solid. 1 H NMR (400MHz, chloroform-d)δ ppm:0.79(q,J=5.14Hz, 2H), 1.03-1.11(m,2H), 1.64(d,J=6.6Hz, 3H), 1.97-2.05(m,1H), 6.22-6.29(m,1H), 7.4 2(s,1H), 7.46(t,J=4.9Hz, 1H), 7.64-7.72(m,2H), 7.77(s,1H), 8.72(s,1H), 8.76(s,1H), 9.04(d,J=5.1Hz, 2H) 19 F NMR (376 MHz, chloroform-d) δ / ppm -62.58 (s, 3F) LC-MS (method 1): retention time 0.97 min, m / z 414[M+H] +

[0422] Preparation of 3-[cyclopropyl(difluoro)methyl]-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzamide (P30) [ka] To a solution of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine (50 mg, 0.22 mmol) in N,N-dimethylformamide (2 mL) was added 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (84 mg, 0.27 mmol), 1-propanephosphonic acid cyclic anhydride (0.21 g, 0.67 mmol), and N,N-diisopropylethylamine (87 mg, 0.67 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 5 hours. It was then diluted with water and extracted twice with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (acetonitrile eluted in water) afforded 3-[cyclopropyl(difluoro)methyl]-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzamide as an off-white solid. 1 H-NMR (400MHz, DMSO-d6): δ ppm: 9.3(m,1H)8.95(m,2H)8.75(m,2H)8.2(m,2H), 8.0(m,1H)7.55(m,1H)5.6(m,1H)1.8(m,1H)1.6(m,3H)0.7(m,4H).

[0423] Preparation of 3-(1-methoxycyclopropyl)-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzamide (P47) [ka] To a solution of 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid (130 mg, 0.490 mmol) in toluene (3 mL) was added dropwise thionyl chloride (0.107 mL, 1.47 mmol) at 0° C. The reaction mixture was stirred at 90° C. for 2 hours. After cooling to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (2 mL) and added to a solution of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethanamine (201 mg, 0.979 mmol) and triethylamine (0.206 mL, 1.47 mmol) in dichloromethane (2 mL) at 0° C. The reaction mixture was stirred at room temperature for 2 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by reverse phase chromatography (acetonitrile eluting in water) afforded 3-(1-methoxycyclopropyl)-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzamide as an off-white solid. 1 H-NMR (400MHz, DMSO-d6):δ ppm:9.1(m,1H)8.95(m,2H)8.77(m,1H)8.66(m,1H), 7.92(m,1H), 7.78(m,1H), 7.64(m,1H), 7.50 -7.60(m,1H), 5.55-5.65(m,1H), 3.12(s,3H), 1.61(d,3H), 1.20-1.30(m,2H), 1.00-1.13(m,2H)

[0424] Preparation of N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-cyclopropyl-5-(trifluoromethyl)benzamide (P58) [ka] To a solution of 3-cyclopropyl-5-(trifluoromethyl)benzoic acid (60 mg, 0.248 mmol) in toluene (8 mL) was added dropwise thionyl chloride (0.723 mL, 9.91 mmol) at 0° C. The reaction mixture was stirred at 90° C. for 2.5 hours. After cooling to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added to a solution of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanamine (217 mg, 0.310 mmol) and triethylamine (0.139 mL, 0.991 mmol) in dichloromethane (10 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by reverse phase chromatography (acetonitrile eluting in water) afforded N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-cyclopropyl-5-(trifluoromethyl)benzamide as an off-white solid. 1 H-NMR (400MHz, DMSO-d6):δ ppm:9.12(m,2H)9.00(m,1H)8.76(m,1H)8.68(m,1H), 7.77(m,1H), 7.58(m,2H), 5.5 2-5.61(m,1H), 2.05-2.12(m,1H), 1.60(d,3H), 0.98-1.08(m,2H), 0.75-0.82(m,2H)

[0425] Preparation of N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide (P55) [ka] To a solution of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (60 mg, 0.222 mmol) in toluene (10 mL) was added dropwise thionyl chloride (0.162 mL, 2.22 mmol) at 0° C. The reaction mixture was stirred at 90° C. for 2 hours. After cooling to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added to a solution of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanamine (78 mg, 0.222 mmol) and triethylamine (0.125 mL, 0.890 mmol) in dichloromethane (10 mL) at 0° C. The reaction mixture was stirred at room temperature for 2 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (acetonitrile eluted in water) afforded N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide as an off-white solid. 1 H-NMR (400MHz, DMSO-d6):δ ppm:9.44(m,1H)9.16(s,2H)8.80(m,1H)8.71(m,1H), 8.05(m,1H), 7.95(m ,1H), 5.55-5.65(m,1H), 1.90-2.00(m,2H), 1.70-1.80(m,2H)1.61(d,3H)

[0426] Preparation of N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide (P53) [ka] To a solution of 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (90 mg, 0.305 mmol) in toluene (10 mL) was added dropwise thionyl chloride (0.089 mL, 1.22 mmol) at 0° C. The reaction mixture was stirred at 90° C. for 2.5 hours. After cooling to room temperature, it was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (10 mL) and added to a solution of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanamine (321 mg, 0.458 mmol) and triethylamine (0.172 mL, 1.22 mmol) in dichloromethane (10 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. It was then diluted with dichloromethane and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by reverse-phase chromatography (acetonitrile eluted in water) afforded N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide as a brown solid. 1 H-NMR (400MHz, DMSO-d6):δ ppm:9.29(d,1H)9.14(s,2H)8.81(m,1H)8.70(m,1H), 8.15-8.25(m,2H), 8.00 (m,1H), 5.58-5.68(m,1H), 1.70-1.90(m,1H), 1.61(d,3H), 0.65-0.75(m,4H)

[0427] Preparation of N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide (P42) [ka] Oxalyl chloride (0.0281 mL, 0.321 mmol) was added to a solution of 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (0.0600 g, 0.214 mmol) in dichloromethane (0.65 mL) containing one drop of N,N-dimethylformamide. After 30 minutes, the reaction mixture was concentrated under reduced pressure. The crude acyl chloride was dissolved in ethyl acetate (0.86 mL), and (1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethanamine (0.0598 g, 0.214 mmol) and aqueous sodium bicarbonate (1N, 0.86 mL) were added. The mixture was stirred at room temperature for 45 minutes. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. Purification of the crude material by flash chromatography on silica gel (eluting with ethyl acetate in cyclohexane) afforded N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide. 1 H-NMR (400MHz, chloroform-d): δ ppm:0.71-0.80(m,2H)0.81-0.88(m,2H)1.47-1.61(m,1H)1.68(d,J=6.97Hz,3H)6.25-6.35(m,1H)7.83(br d,J=8.07Hz, 1H)7.93(s,1H)8.02-8.07(m,1H)8.07-8.11(m,1H)8.12(s,1H)8.18(s,1H)8.61-8.67(m,2H)8.87(dd,J=2.20, 0.73Hz, 1H); [α] D 20 :+115°(c:0.580, CHCl3)

[0428] The compounds listed in Table P were prepared by methods similar to those described for the examples above.

[0429] [Table 12-1]

Table 12-2

Table 12-3

Table 12-4

Table 12-5

Table 12-6

Table 12-7

Table 12-8

Table 12-9

Table 12-10

Table 12-11

Table 12-12

Table 12-13

Table 12-14

Table 12-15

Table 12-16

Table 12-17

Table 12-18

[0430]

Table 13-1

Table 13-2

Table 13-3

Table 13-4

Table 13-5

Table 13-6

Table 13-7

Table 13-8

Table 13-9

Table 13-10

Table 13-11

Table 13-12

Table 13-13

[0431] The activity of the composition of the present invention can be considerably broadened by adding other insecticidal, acaricidal and / or fungicidal active ingredients, and can be adapted to the general situation.The mixture of the compound of formula I with other insecticidal, acaricidal and / or fungicidal active ingredients can also have other unexpected advantages, which may be described in a broader sense as synergistic activity.For example, better tolerance by plants, reduced phytotoxicity, insects can be controlled at different stages of their development, or better behavior during their preparation, for example, during grinding or mixing, during their storage, or during their use.

[0432] Suitable additives to the active ingredients herein are, for example, exemplified by the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, urea, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations.

[0433] The following mixtures of compounds of formula I with active ingredients are preferred (the abbreviation "TX" means "one compound selected from the compounds defined in Tables A-1 to A27, B-1 to B-21, C-1 to C-21, D-1 to D-21, E-1 to E-21 and Table P"): an adjuvant selected from the group of substances consisting of petroleum (alternative name) (628) + TX; Abamectin +TX, Acequinocyl +TX, Acetamiprid +TX, Acetoprole +TX, Acrinathrin +TX, Acinonapyr +TX, Afidopiropen +TX, Afoxalanal +TX, Alanycarb +TX, Allethrin +TX, α-Cypermethrin +TX, α-Methrin +TX, Amidoflumet +TX, Aminocarb +TX, Azocyclotine +TX, Bensultap +TX, Benzochimate +TX, Benzpyrimoxane +TX, β-Cyfluthrin +TX, β-Cypermethrin +TX, Bifenazate +TX, Bifenthrin +TX, Binapacryl +T X, Bioallethrin + TX, Bioallethrin S)-Cyclopentyl Isomer + TX, Bioresmethrin + TX, Bistrifluron + TX, Brofuranilide + TX, Broflutrinate + TX, Bromophos-ethyl + TX, Buprofezin + TX, Butocarboxim + TX, Cadusafos + TX, Carbaryl + TX, Carbosulfan + TX, Cartap + TX, CAS Number: 1472050-04-6 + TX, CAS Number: 1632218-00-8 + TX, CAS Number: 1808115-49-2 + TX, CAS Number: 2032403-97-5 + TX , CAS No.: 2044701-44-0 + TX, CAS No.: 2128706-05-6 + TX, CAS No.: 2249718-27-0 + TX, chlorantraniliprole + TX, chlordane + TX, chlorfenapyr + TX, chlorprallethrin + TX, chromafenozide + TX, clenpirin + TX, cloetocarb + TX, clothianidin + TX, 2-chlorophenyl N-methylcarbamate (CPMC) + TX, cyanofenphos + TX, cyantraniliprole + TX, cyclaniliprole + TX, cyclobutrifluram + TX, cyclopropanol Lothrin + TX, cycloxapride + TX, cycloxapride + TX, cyenopyrafen + TX, cetoprafen (or ethopirafen) + TX, cyflumetofen + TX, cyfluthrin + TX, cyhalodiamide + TX, cyhalothrin + TX, cypermethrin + TX, cyphenothrin + TX, cyromazine + TX, deltamethrin + TX, diafenthiuron + TX, dialifos + TX, dibrom + TX, dichloromezothiaz + TX, diflovidazin + TX, diflubenzuron + TX, dimepropylpyridaz + TX, dinactin + TX, dinocap + TX,Dinotefuran +TX, Dioxabenzophos +TX, Emamectin +TX, Empenthrin +TX, ε-Monfluorotrin +TX, ε-Metofluthrin +TX, Esfenvalerate +TX, Ethion +TX, Ethiprole +TX, Etofenprox +TX, Etoxazole +TX, Fanfur +TX, Fenazaquin +TX, Fenfluthrin +TX, Fenitrothion +TX, Fenobucarb +TX, Fenothiocarb +TX, Fenoxycarb +TX, Fenpropathrin +TX, Fenproximate +TX, Fensulfothion +TX, Fenthion +TX, Fentin acetate +TX, Fenvalerate +TX, Fipronil +TX, Floretoquin +TX, Flonicamid +TX, Fluacrypyrim +TX, Fluazaindolizine +TX, Fluazuron +TX, Flubendiamide +TX, Flubenzimine +TX, Flucythrinate +TX, Flucycloxuron +TX, Flucythrinate +TX, Fluensulfone +TX, Flufenerim +TX, Flufenprox +TX, Flufiprole +TX, Fluhexafon +TX, Flumethrin +TX, Fluopyram +TX, Flupentio Fenox + TX, Flupyradifurone + TX, Flupirimine + TX, Fluralaner + TX, Fluvalinate + TX, Fluxamethamide + TX, Fosthiazate + TX, γ-cyhalothrin + TX, Gossiplur (trademark) + TX, Guadipyr + TX, Halofenozide + TX, Halofenozide + TX, Halofenprox + TX, Heptafluthrin + TX, Hexythiazox + TX, Hydramethylnon + TX, Imicyafos + TX, Imidacloprid + TX, Imiprothrin + TX, Indoxacarb + TX, Iodomethane + TX, Iprodione + TX, I Socycloceram +TX, Isothioate +TX, Ivermectin +TX, κ-Bifenthrin +TX, κ-Tefluthrin +TX, Lambda-Cyhalothrin +TX, Lepimectin +TX, Lufenuron +TX, Metaflumizone +TX, Metaldehyde +TX, Metam +TX, Methomyl +TX, Methoxyfenozide +TX, Metofluthrin +TX, Metolcarb +TX, Mexacarbate +TX, Milbemectin +TX, Momfluorotrin +TX, Niclosamide +TX, Nitenpyram +TX, Nithiazine +TX, Omethoate +TX, Oxamyl +TX,Oxazosphyl + TX, Parathion-ethyl + TX, Permethrin + TX, Fenothrin + TX, Phosphocarb + TX, Piperonyl butoxide + TX, Pirimicarb + TX, Pirimiphos-ethyl + TX, Polyhedrovirus + TX, Prallethrin + TX, Profenofos + TX, Profenofos + TX, Profluthrin + TX, Propargite + TX, Propetamfos + TX, Propoxur + TX, Prothiofos + TX, Protrifenbut + TX, Piflubumid + TX, Pymetrozine + TX, Pyraclofos + TX, Pyrafluprole + TX, Pyridabe phenanthrene +TX, pyridalyl +TX, pyrifluquinazone +TX, pyrimidifen +TX, pirimostrobin +TX, pyriprole +TX, pyriproxyfen +TX, resmethrin +TX, sarolaner +TX, selamectin +TX, silafluofen +TX, spinetoram +TX, spinosad +TX, spirodiclofen +TX, spiromesifen +TX, spiropydione +TX, spirotetramat +TX, sulfoxaflor +TX, tebufenozide +TX, tebufenpyrad +TX, tebupirimiphos +TX, tefluthrin +TX, temephos +TX, tetrafluthrin ... Chloraniliprole +TX, tetradifon +TX, tetramethrin +TX, tetramethylfluthrin +TX, tetranactin +TX, tetraniliprole +TX, θ-cypermethrin +TX, thiacloprid +TX, thiamethoxam +TX, thiocyclam +TX, thiodicarb +TX, thiofanox +TX, thiometon +TX, thiosultap +TX, thioxazaphen +TX, tolfenpyrad +TX, toxaphene +TX, tralomethrin +TX, transfluthrin +TX, triazamate +TX, triazophos +TX, trichlorfon + TX, trichloronate +TX, trichlorophone +TX, triflumezopyrin +TX, cyclopyrazoflor +TX, zeta-cypermethrin +TX, seaweed extract and fermented product from Melasse +TX, seaweed extract and fermented product from Melasse containing urea +TX, amino acids +TX, potassium and molybdenum and EDTA-chelated manganese +TX, seaweed extract and fermented plant product +TX, seaweed extract and fermented plant product containing plant hormones +TX, vitamins +TX, EDTA-chelated copper +TX, zinc +TX, and iron +TX, azadirachtin +TX,Bacillus aizawai + TX, Bacillus chitinosporus AQ746 (NRRL accession number B-21618) + TX, Bacillus firmus + TX, Bacillus kurstaki + TX, Bacillus mycoides AQ726 (NRRL accession number B-21664) + TX, Bacillus pumilus (NRRL accession number B-30087) + TX, Bacillus pumilus AQ717 (NRRL accession number B-21662) + TX, Bacillus species sp. AQ178 (ATCC accession number 53522) + TX, Bacillus sp. AQ175 (ATCC accession number 55608) + TX, Bacillus sp. AQ177 (ATCC accession number 55609) + TX, Bacillus subtilis unspecified + TX, Bacillus subtilis AQ153 (ATCC accession number 55614) + TX, Bacillus subtilis AQ30002 (NRRL accession number B-50421) + TX, Bacillus subtilis AQ30004 (NRRL accession number B-50455) + TX, Bacillus subtilis AQ713 (NRRL accession number B-21661) + TX, Bacillus subtilis AQ743 (NRRL accession number B-21665) + TX, Bacillus thuringiensis AQ52 (NRRL accession number B-21619) + TX, Bacillus thuringiensis BD#32 (NRRL accession number B-21530) + TX, Bacillus thuringiensis subspec. kurstaki BMP 123 + TX, Beauveria bassiana + TX, D-limonene + TX,Granulovirus +TX, Harpin +TX, Helicoverpa armigera nucleopolyhedron virus +TX, Helicoverpa zea nucleopolyhedron virus +TX, Heliothis virescens nucleopolyhedron virus +TX, Heliothis punctigera nucleopolyhedron virus +TX, Metarhizium spp. +TX, Muscodor albus 620 (NRRL accession number 30547) +TX, Muscodor roseus A3-5 (NRRL accession number 30548) +TX, Neem tree product +TX, Paecilomyces fumosoroseus fumosoroseus + TX, Paecilomyces lilacinus + TX, Pasteuria nishizawae + TX, Pasteuria penetrans + TX, Pasteuria ramosa + TX, Pasteuria thornei + TX, Pasteuria usgae + TX, P-cymene + TX, Plutella xylostella granulosis virus + TX, Plutella xylostella nucleopolyhedrovirus + TX, Polyhedrovirus + TX, Calystegia japonica + TX, QRD 420 (Terpenoid Blend) + TX, QRD 452 (Terpenoid Blend) + TX, QRD 460 (terpenoid blend) + TX, Quillaja saponaria + TX, Rhodococcus globerulus AQ719 (NRRL accession number B-21663) + TX, Spodoptera frugiperda nucleopolyhedrovirus + TX, Streptomyces galbus (NRRL accession number 30232) + TX,an insect control active agent selected from Streptomyces sp. (NRRL Accession No. B-30145) + TX, a terpenoid blend + TX, and Verticillium spp.; an algicide selected from the group of substances consisting of bethoxadin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, sibutrin [CCN] + TX, dichloron (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamide (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (1011) + TX, cyclobutrifluram + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX, an avian repellent selected from the group of substances consisting of chloralose (127) + TX, endrin (1122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745) + TX, 1-Hydroxy-1H-pyridine-2-thione (IUPAC name) (1222) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (IUPAC name) (170) + TX, copper hydroxide (IUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1105) + TX, dodicine (1112) + TX, fenaminosulf (1144) + TX, formaldehyde (404) + TX, hydrargafen (alternative name) [CCN] + TX a fungicide selected from the group of substances consisting of TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis(dimethyldithiocarbamate) (IUPAC name) (1308) + TX, nitrapyrin (580) + TX, octhilinone (590) + TX, oxolinic acid (606) + TX, oxytetracycline (611) + TX, potassium hydroxyquinoline sulfate (446) + TX, probenazole (658) + TX, streptomycin (744) + TX, streptomycin sesquisulfate (744) + TX, tecloftalam (766) + TX and thiomersal (alternative name) [CCN] + TX, Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter (alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis (alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX, Aphidoletes aphidimiza aphidimyza (alternative name) (35) + TX, Autographa californica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX, Bacillus thuringiensis Berliner (scientific name) (51) + TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51) + TX, Bacillus thuringiensis subsp. israelensis) (scientific name) (51) + TX, Bacillus thuringiensis subsp. japonensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. kurstaki (scientific name) (51) + TX, Bacillus thuringiensis subsp. tenebrionis (Bacillus thuringiensis subsp.tenebrionis (scientific name) (51) + TX, Beauveria bassiana (alternate name) (53) + TX, Beauveria brongniartii (alternate name) (54) + TX, Chrysoperla carnea (alternate name) (151) + TX, Cryptolaemus montrouzieri (red ladybird beetle) (alternate name) (178) + TX, Cydia pomonella GV (alternate name) (191) + TX, Dacnusa sibirica (alternate name) (212) + TX, Diglyphus isaea (alternate name) (254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus (alternate name) (300) + TX, Helicoverpa zea NPV (alternate name) (431) + TX, Heterorhabditis bacteriophora and H. megidis (alternate name) (433) + TX, Hippodamia convergens (alternate name) (442) + TX, Leptomastix dactylopii (alternate name) (488) + TX, Macrolophus caliginosus (alternate name) (491) + TX, Mamestra brassicae NPV (alternate name) (494) + TX, Metaphycus helvolus (alternate name) (522) + TX, Metarhizium anisopliae var. acridum (scientific name) (523) + TX, Metarhizium anisopliae var. anisopliae (scientific name) (523) + TX, Neodiprion sertifer NPV and N. leconti (N.lecontei NPV (alternate name) (575) + TX, Orius spp. (alternate name) (596) + TX, Paecilomyces fumosoroseus (alternate name) (613) + TX, Phytoseiulus persimilis (alternate name) (644) + TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741) + TX, Steinernema bibionis (alternate name) (742) + TX, Steinernema carpocapsae (alternate name) (742) + TX, Steinernema felziae feltiae (alternate name) (742) + TX, Steinernema glaseri (alternate name) (742) + TX, Steinernema riobrave (alternate name) (742) + TX, Steinernema riobravis (alternate name) (742) + TX, Steinernema scapterisci (alternate name) (742) + TX, Steinernema spp. (alternate name) (742) + TX, Trichogramma spp. (alternate name) (826) + TX, Typhlodromus occidentalis a biological agent selected from the group consisting of Verticillium lecanii (alternative name) (848) + TX, a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) and methyl bromide (537) + TX; an antisterilant selected from the group of substances consisting of Afolate [CCN] + TX, Visadyl (alternative name) [CCN] + TX, Busulfan (alternative name) [CCN] + TX, Diflubenzuron (250) + TX, Zimatif (alternative name) [CCN] + TX, Hemel [CCN] + TX, Hempa [CCN] + TX, Metepa [CCN] + TX, Methiotepa [CCN] + TX, Methyl Afolate [CCN] + TX, Morzide [CCN] + TX, Penfluron (alternative name) [CCN] + TX, Tepa [CCN] + TX, Thiohempa (alternative name) [CCN] + TX, Thiotepa (alternative name) [CCN] + TX, Tretamine (alternative name) [CCN] and Uredepa (alternative name) [CCN] + TX, (E)-Deca-5-en-1-yl acetate and (E)-dec-5-en-1-ol (IUPAC name) (222) + TX, (E)-tridec-4-en-1-yl acetate (IUPAC name) (829) + TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541) + TX, (E,Z)-tetradec-4,1 0-Dien-1-yl acetate (IUPAC name) (779) + TX, (Z)-Dodec-7-en-1-yl acetate (IUPAC name) (285) + TX, (Z)-Hexadec-11-enal (IUPAC name) (436) + TX, (Z)-Hexadec-11-en-1-yl acetate (IUPAC name) (437) + TX, (Z)-Hex Sadec-13-en-11-yn-1-yl acetate (IUPAC name) (438) + TX, (Z)-Icos-13-en-10-one (IUPAC name) (448) + TX, (Z)-tetradec-7-en-1-al (IUPAC name) (782) + TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783) + TX, ( Z)-Tetradeca-9-en-1-yl acetate (IUPAC name) (784) + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate (IUPAC name) (283) + TX, (9Z,11E)-tetradeca-9,11-dien-1-yl acetate (IUPAC name) (780) + TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate (IUPAC name) (781) + TX, 14-methyloctadec-1-ene (IUPAC name) (545) + TX, 4-methylnonan-5-ol and 4-methylnonan-5-one (IUPAC name) (544) + TX, α-multistriatin (alternative name) [CCN] + TX, Brevicomin (alternative name) [CCN] + TX, Codlerua (alternative name) [CCN] + TX, Codlemone (alternative name) (167) + TX, Curua ( (alternative name) (179) + TX, disparlure (277) + TX, dodec-8-en-1-yl acetate (IUPAC name) (286) + TX, dodec-9-en-1-yl acetate (IUPAC name) (287) + TX, dodec-8 + TX, 10-dien-1-yl acetate (IUPAC name) (284) + TX, dominicalure (alternative name) [CCN] + TX, ethyl 4-methyloctanoate (IUPAC name) (317) + TX, eugenol (alternative name) ) [CCN] + TX, Frontalin (alternate name) [CCN] + TX, Gossip Lua (alternate name) (420) + TX, Grand Lua (421) + TX, Grand Lua I (alternate name) (421) + TX, Grand Lua II (alternate name) (421) + TX, Grand Lua III (alternate name) (421) + TX, Grand Lua IV (alternate name) (421) + TX, Hexalua [CCN] + TX, Ipsdienol (alternate name) [CCN] + TX, Ipsenol (alternate name [ CCN] + TX, Japonirua (alternative name) (481) + TX, Lineatin (alternative name) [CCN] + TX, Litirua (alternative name) [CCN] + TX, Lupulua (alternative name) [CCN] + TX, Medurua [CCN] + TX, Megatomoic acid (alternative name) [CCN] + TX, Methyleugenol (alternative name) (540) + TX, Muscalua (563) + TX, Octadeca-2,13-dien-1-yl acetate (IUPAC name) (588) + TX, Octadeca-3,13-Dien-1-yl acetate (IUPAC name) (589) + TX, Olfrulure (alternative name) [CCN] + TX, Orictalure (alternative name) (317) + TX, Ostramon (alternative name) [CCN] + TX, Siglua [CCN] + TX, Soldigin (alternative name) (736) + TX, Sulcatol (alternative name) [CCN] + TX, Tetradec-11-en-1-yl acetate (IU an insect pheromone selected from the group of substances consisting of Trimedulla (PAC name) (785) + TX, Trimedulla (839) + TX, Trimedulla A (alternate name) (839) + TX, Trimedulla B1 (alternate name) (839) + TX, Trimedulla B2 (alternate name) (839) + TX, Trimedulla C (alternate name) (839) and Trunk-call (alternate name) [CCN] + TX, an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (IUPAC name) (591) + TX, butopyronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (IUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (IUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethylcarbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1137) + TX, hexamide [CCN] + TX, methoquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX, Bis(tributyltin)oxide (IUPAC name) (913) + TX, Bromoacetamide [CCN] + TX, Calcium arsenate [CCN] + TX, Cloethocarb (999) + TX, Copper acetarsenite [CCN] + TX, Copper sulfate (172) + TX, Fentin (347) + TX, Ferric phosphate (IUPAC name) (352) + TX, Metaldehyde (518) + TX, Methiocarb (530) + TX, Niclosamide (576) + TX, Niclosamide-olamine (576) + TX, Pentachloroethylene (Phenylalanine) a molluscicide selected from the group of substances consisting of: chlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, thazimcarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, triphenmorph (1454) + TX, trimethacarb (840) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, pyriprole [394730-71-3] + TX, AKD-3088 (compound code) + TX, 1,2-dibromo-3-chloropropane (IUPAC / Chemical Abstracts Name) (1045) + TX, 1,2-dichloropropane (IUPAC / Chemical Abstracts Name) (1062) + TX, 1,2-dichloropropane and 1,3-dichloropropene (IUPAC Name) (1063) + TX, 1,3-dichloropropene (233) + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC / Chemical Abstracts Name) (Plastic name) (1065) + TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980) + TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid (IUPAC name) (1286) + TX, 6-isopentenylaminopurine (alternative name) (210) + TX, abamectin (1) + TX, acetoprole [CCN] + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxicarb (863) + TX, AZ60541 (compound code) + TX, benclotiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, carbosulfan (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, cloetocarb (999) + TX, cyclobutrifluram + TX, cytokinin (alternative name) (210) + T X, Dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, Diamidaphos (1044) + TX, Diclofenthion (1051) + TX, Dicrifos (alternative name) + TX, Dimethoate (262) + TX, Doramectin (alternative name) [CCN] + TX, Emamectin (291) + TX, Emamectin Benzoate (291) + TX, Eprinomectin (alternative name) [CCN] + TX, Ethoprophos (312) + TX, Ethyl Dibromide len (316) + TX, fenamiphos (326) + TX, fenpyrad (alternative name) + TX, fensulfothion (1158) + TX, fosthiazate (408) + TX, fostietan (1196) + TX, furfural (alternative name) [CCN] + TX, GY-81 (development code) (423) + TX, heterophos [CCN] + TX, iodomethane (IUPAC name) (542) + TX, isamidophos (1230) + TX, isazophos (1231) + TX, ebe Lumectin (alternative name) [CCN] + TX, Kinetin (alternative name) (210) + TX, Mecarfone (1258) + TX, Metam (519) + TX, Metam-potassium (alternative name) (519) + TX, Metam-sodium (519) + TX, Methyl bromide (537) + TX, Methyl isothiocyanate (543) + TX, Milbemycin oxime (alternative name) [CCN] + TX, Moxidectin (alternative name) [CCN] + TX, Myrotheciumverrucaria) Composition (alternative name) (565) + TX, NC-184 (compound code) + TX, Oxamyl (602) + TX, Phorate (636) + TX, Phosphamidon (639) + TX, Phosphocarb [CCN] + TX, Cebufos (alternative name) + TX, Selamectin (alternative name) [CCN] + TX, Spinosad (737) + TX, Terbam (alternative name) + TX, Terbufos (773) + TX, Tetrachlorothiophene (IU a nematicide selected from the group of substances consisting of PAC / Chemical Abstracts Name) (1422) + TX, Thiafenox (alternative name) + TX, Thionazine (1434) + TX, Triazophos (820) + TX, Triazuron (alternative name) + TX, Xylenol [CCN] + TX, YI-5302 (compound code) and Zeatin (alternative name) (210) + TX, Fluensulfone [318290-98-1] + TX, Fluopyram + TX, a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX; a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar-S-methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alternative name) (720) + TX, 2-Isovalerylindan-1,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, α-chlorohydrin [CCN] + TX, aluminum phosphide (640) + TX, antu (880) + TX, arsenic trioxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifacoium (89) + TX, bromadiolone (91) + TX, brome Talin (92) + TX, Calcium Cyanide (444) + TX, Chloralose (127) + TX, Chlorophacinone (140) + TX, Cholecalciferol (alternative name) (850) + TX, Coumachlor (1004) + TX, Coumafuryl (1005) + TX, Coumatetralyl (175) + TX, Crimidine (1009) + TX, Difenacoum (246) + TX, Difethialone (249) + TX, Diphacinone (273) + TX, Ergocalciferol (301) + TX, Flocoumafe Fluoroacetamide (357) + TX, Fluoroacetamide (379) + TX, Flupropadiene (1183) + TX, Flupropadiene Hydrochloride (1183) + TX, γ-HCH (430) + TX, HCH (430) + TX, Hydrogen Cyanide (444) + TX, Iodomethane (IUPAC name) (542) + TX, Lindane (430) + TX, Magnesium Phosphide (IUPAC name) (640) + TX, Methyl Bromide (537) + TX, Norbormide (1318) + TX, Fosacetim (1336) + TX, Phosphido a rodenticide selected from the group of substances consisting of arsenic (IUPAC name) (640) + TX, phosphorus [CCN] + TX, pindone (1341) + TX, potassium arsenite [CCN] + TX, pyrinuron (1371) + TX, sciliroside (1390) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoroacetate (735) + TX, strychnine (745) + TX, thallium sulfate [CCN] + TX, warfarin (851) and zinc phosphide (640) + TX, a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934) + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903) + TX, farnesol and nerolidol (alternative names) (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piperotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesamolin (1394) and sulfoxide (1406) + TX, an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetate (422) + TX, methiocarb (530) + TX, pyridin-4-amine (IUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] and ziram (856) + TX, a virucidal agent selected from the group of substances consisting of Imanin (alternative name) [CCN] and Ribavirin (alternative name) [CCN] + TX, a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octilinone (590) and thiophanate-methyl (802) + TX, and 1,1-bis(4-chlorophenyl)-2-ethoxyethanol + TX, 2,4-dichlorophenylbenzenesulfonate + TX, 2-fluoro-N-methyl-N-1-cinnamaldehyde + TX, 4-chlorophenyl phenyl sulfone + TX, acetoprole + TX, aldoxicarb + TX, amidithione + TX, amidothioate + TX, amiton + TX, amiton hydrogen oxalate + TX, amitraz + TX, alamite + TX, arsenic trioxide + TX, azobenzene + TX, azotoate + TX, benomyl + TX, benoxafos + TX, benzyl benzoate Oxalate +TX, Bixafen +TX, Brofenvalerate +TX, Bromocyclen +TX, Bromophos +TX, Bromopropylate +TX, Buprofezin +TX, Butocarboxim +TX, Butoxycarboxim +TX, Butylpyridaben +TX, Calcium polysulfate +TX, Camphechlor +TX, Carbanolate +TX, Carbophenothion +TX, Cimiazole +TX, Thiomethionate +TX, Chlorbeside +TX, Chlordimeform +TX, Chlordimeform hydrochloride +TX, Chlorphenetole +TX, Chlorfenson +TX , Chlorofensulfide +TX, Chlorobenzilate +TX, Chlormebform +TX, Chlormethiuron +TX, Chloropropylate +TX, Chlorthiophos +TX, Cinerin I +TX, Cinerin II +TX, Cinerins +TX, Closantel +TX, Coumaphos +TX, Crotamiton +TX, Crotoxyphos +TX, Kufraeb +TX, Cyanthoate +TX, DCPM +TX, DDT +TX, Demefion +TX, Demefion-O +TX, Demefion-S +TX, Demeton-methyl +TX, Demeton-O +TX, Demeton-O-methyl +TX , Demeton-S+TX, Demeton-S-methyl+TX, Demeton-S-methylsulfone+TX, Dichlofluanid+TX, Dichlorvos+TX, Dicrifos+TX, Dienochlor+TX, Dimefox+TX, Zinex+TX, Zinex-diclexin+TX, Dinocap-4+TX, Dinocap-6+TX, Dinocton+TX, Dinopenton+TX, Dinosulfone+TX, Dinotervone+TX, Dioxathion+TX, Diphenylsulfone+TX, Disulfiram+TX, DNOC+TX, Dofenapine+TX, Doramectin+TX, Endothion+TX,Epirinomectin +TX, Ethoate-methyl +TX, Etrimphos +TX, Fenazaflor +TX, Fenbutatin oxide +TX, Fenothiocarb +TX, Fenpyrad +TX, Fenpyroximate +TX, Fenpyrazamine +TX, Fenson +TX, Fentrifanil +TX, Flubenzimine +TX, Flucycloxuron +TX, Fluenethyl +TX, Fluorobenside +TX, FMC 1137+TX, formetanate+TX, formetanate hydrochloride+TX, formparanate+TX, γ-HCH+TX, gliodin+TX, halfenprox+TX, hexadecylcyclopropanecarboxylate+TX, isocarbophos+TX, jasmolin I+TX, jasmolin II+TX, jodofenphos+TX, lindane+TX, malonoven+TX, mecarbam+TX, mefosfolan+TX, mesulfen+TX, methacrifos+TX, methyl bromide+TX, metolcarb+TX, mexacarbate+TX, milbemycin oxime+TX, Mipafox + TX, monocrotophos + TX, morphothion + TX, moxidectin + TX, naled + TX, 4-chloro-2-(2-chloro-2-methyl-propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one + TX, nifururizide + TX, nikkomycin + TX, nitrilacarb + TX, nitrilacarb 1:1 zinc chloride complex + TX, omethoate + TX, oxydeprophos + TX, oxydisulfoton + TX, pp'-DDT + TX, parathion + TX, permethrin + TX, fencapton + TX, phosalone + TX, phospholan + TX, phosphamidon + TX, polychloroterpenes + TX, polychloroterpenes Linactin +TX, Proclonol +TX, Promacyl +TX, Propoxur +TX, Protidathion +TX, Protoate +TX, Pyrethrin I +TX, Pyrethrin II +TX, Pyrethrin +TX, Pyridaphenthion +TX, Pirimitate +TX, Quinalphos +TX, Quinthiofos +TX, R-1492 +TX, Phosglycine +TX, Rotenone +TX, Schladan +TX, Cebufos +TX, Selamectin +TX, Sofamid +TX, SSI-121 +TX, Sulfiram +TX, Sulfuramide +TX, Sulfotep +TX, Sulfur +TX, Diflobidazin +TX, τ-Fulvalinate +TX, TEPP +TX, Thelbam +TX,Tetradifon + TX, Tetrasul + TX, Thiafenox + TX, Thiocarboxim + TX, Thiofanox + TX, Thiometon + TX, Thioquinox + TX, Thuringiensin + TX, Triamiphos + TX, Triatene + TX, Triazophos + TX, Triazuron + TX, Trifenofos + TX, Trinactin + TX, Vamidothion + TX, Vaniliprole + TX, Bethoxadin + TX, Copper dioctanoate + TX , Copper sulfate + TX, Sibutrin + TX, Dichlorn + TX, Dichlorophen + TX, Endothal + TX, Fentin + TX, Slaked lime + TX, Nabam + TX, Quinoclamine + TX, Quinoneamide + TX, Simazine + TX, Triphenyltin acetate + TX, Triphenyltin hydroxide + TX, Crufomate + TX, Piperazine + TX, Thiophanate + TX, Chloralose + TX, Fenthion + TX, Pyridin-4-amine + T X, strychnine + TX, 1-hydroxy-1H-pyridine-2-thione + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide + TX, 8-hydroxyquinoline sulfate + TX, bronopol + TX, copper hydroxide + TX, cresol + TX, dipyrithione + TX, doditin + TX, fenaminosulf + TX, formaldehyde + TX, hydralgafen + TX, kasugamycin + TX, kasugamycin hydrochloride hydrate + TX, nickel bis(dimethyldithiocarbamate) + TX, nitrapyrin + TX, octhilinone + TX, oxolinic acid + TX, oxytetracycline + TX, potassium hydroxyquinoline sulfate + TX, probenazole + TX, streptomycin + TX, streptomycin sesquisulfate + TX, tecloftalam + TX, thiomersal + TX, Adoxophyes orana GV+TX, Agrobacterium radiobacter+TX, Amblyseius spp.+TX, Anagrapha falcifera NPV+TX, Anagrafa atomus+TX, Aphelinus abdominalis+TX, Aphidius colemani+TX,Aphidoletes aphidimyza + TX, Autographa californica NPV + TX, Bacillus sphaericus Neide + TX, Beauveria brongniartii + TX, Chrysoperla carnea + TX, Cryptolaemus montrouzieri + TX, Codling moth (Cydia pomonella GV) + TX, Dacnusa sibirica + TX, Diglyphus isaea + TX, Encarsia formosa + TX, Eretmocerus eremicus + TX, Heterorhabditis bacteriophora and H. megidis + TX, Hippodamia convergens + TX, Leptomastix dactylopii + TX, Macrolophus caliginosus + TX, Mamestra brassicae NPV + TX, Metaphycus helvolus + TX, Metarhizium anisopliae var. acridum + TX, Metarhizium anisopliae var. anisopliae + TX, Neodiprion sertifer NPV and N. lecontei NPV + TX, Orius spp. + TX, Paecilomyces fumosoroseus + TX, Phytoseiulus persimilis + TX, Steinernema bibionis + TX,Steinernema carpocapsae + TX, Steinernema feltiae + TX, Steinernema glaseri + TX, Steinernema riobrave + TX, Steinernema riobravis + TX, Steinernema scapterisci + TX, Steinernema spp. + TX, Trichogramma spp. + TX, Typhlodromus occidentalis + TX, Verticillium lecanii) + TX, apholate + TX, Visadil + TX, busulfan + TX, dimatif + TX, hemel + TX, hempa + TX, metepa + TX, methiotepa + TX, methyl apholate + TX, molzide + TX, penfluron + TX, tepa + TX, thiohempa + TX, thiotepa + TX, trethamine + TX, uredepa + TX, (E)-dec-5-en-1-yl acetate and (E)-dec-5-en-1-ol + TX, (E)-Trideca-4-en-1-yl acetate + TX, (E)-6-methylhept-2-en-4-ol + TX, (E,Z)-tetradec-4,10-dien-1-yl acetate + TX, (Z)-dodec-7-en-1-yl acetate + TX, (Z)-hexadec-11-enal + TX, (Z)-hexadec-11-en-1-yl acetate + TX, (Z)-hexadec-13-en-11-yn-1-yl acetate + TX, (Z)-icosa-13-en-10-one + TX, (Z)-tetradec-7-en-1-al + TX, (Z)-tetradec-7-en-1-al + TX tradec-9-en-1-ol + TX, (Z)-tetradec-9-en-1-yl acetate + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate + TX, (9Z,11E)-tetradec-9,11-dien-1-yl acetate + TX, (9Z,12E)-tetradec-9,12-dien-1-yl acetate + TX, 14-methyloctadec-1-ene + TX, 4-methylnonan-5-ol and 4-methylnonan-5-one + TX, α-multistriatin + TX, brevicomin + TX, codrellet + TX, codlemone + TX, Querle + TX, Disparlure + TX, Dodec-8-en-1-yl acetate + TX, Dodec-9-en-1-yl acetate + TX, Dodec-8 + TX, 10-dien-1-yl acetate + TX, Dominicalure + TX, Ethyl 4-methyloctanoate + TX, Eugenol + TX, Frontalin + TX, Grandlure + TX, Grandlure I + TX, Grandlure II + TX, Grandlure III + TX, Grandlure IV + TX, Hexalure + TX, Ipsdienol + TX, Ipsenol + TX, Japonilure + TX, Lineatin + TX, Li Tolua + TX, Lupula + TX, Medula + TX, Megatomoic acid + TX, Methyleugenol + TX, Muscala + TX, Octadeca-2,13-dien-1-yl acetate + TX, Octadeca-3,13-dien-1-yl acetate + TX, Olfurala + TX, Orictala + TX, Ostramon + TX, Siglua + TX, Soldigin + TX, Sulcatol + TX, Tetradec-11-en-1-yl acetate + TX, Trimedula + TX, Trimedula A + TX, Trimedula B1 + TX, Trimedula B2 + TX, Trimedula C + TX,Trunc-call + TX, 2-(octylthio)ethanol + TX, butapyronoxyl + TX, butoxy(polypropylene glycol) + TX, dibutyl adipate + TX, dibutyl phthalate + TX, dibutyl succinate + TX, diethyl toluamide + TX, dimethylcarbate + TX, dimethyl phthalate + TX, ethyl hexanediol + TX, hexamide + TX, methoquin-butyl + TX, methyl neodecanoamide + TX, oxamate + TX, picaridin + TX, 1-dichloro- 1-Nitroethane + TX, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane + TX, 1,2-dichloropropane and 1,3-dichloropropene + TX, 1-bromo-2-chloroethane + TX, 2,2,2-trichloro-1-(3,4-dichlorophenyl)acetate + TX, 2,2-dichlorovinyl 2-ethylsulfinylethylmethylphosphate + TX, 2-(1,3-dithiolan-2-yl)phenyldimethylcarbamate + TX, 2-(2-butoxyethoxy)ethylthiocyanate + TX, 2- (4,5-Dimethyl-1,3-dioxolan-2-yl)phenylmethylcarbamate + TX, 2-(4-chloro-3,5-xylyloxy)ethanol + TX, 2-chlorovinyldiethyl phosphate + TX, 2-Imidazolidone + TX, 2-Isovalerylindan-1,3-dione + TX, 2-Methyl(prop-2-ynyl)aminophenylmethylcarbamate + TX, 2-Thiocyanatoethyl laurate + TX, 3-Bromo-1-chloroprop-1-ene + TX, 3-Methyl-1-phenylpyrazol-5-yl Dimethyl carbamate + TX, 4-methyl(prop-2-ynyl)amino-3,5-xylylmethylcarbamate + TX, 5,5-dimethyl-3-oxocyclohex-1-enyldimethylcarbamate + TX, acetione + TX, acrylonitrile + TX, aldrin + TX, allosamidin + TX, alixycarb + TX, α-ecdysone + TX, aluminum phosphide + TX, aminocarb + TX, anabasine + TX, atidathion + TX, azamethiphos + TX, Bacillus thuringiensis δ-endotoxin + TX, barium hexafluorosilicate + TX, barium polysulfide + TX, bartholin + TX,Bayer 22 / 190+TX, Bayer 22408+TX, β-cyfluthrin+TX, β-cypermethrin+TX, bioethanomethrin+TX, biopermethrin+TX, bis(2-chloroethyl)ether+TX, sodium borate+TX, bromfenvinphos+TX, bromo-DDT+TX, bufencarb+TX, butacarb+TX, butathiophos+TX, butonate+TX, calcium arsenate+TX, calcium cyanide+TX, carbon disulfide+TX, carbon tetrachloride+TX, cartap hydrochloride+TX, sevadin+TX, chlorbicyclen+TX, chlordane+TX, chlordecone+TX, chloroform+TX, chloropicrin+TX, chlorphoxim+TX, chlorprazophos+TX, cis-resmethrin+TX, cismethrin+TX, clocitrin+TX, acetoarsenous acid Copper + TX, Copper arsenate + TX, Copper oleate + TX, Cumitoate + TX, Cryolite + TX, CS708 + TX, Cyanofenphos + TX, Cyanophos + TX, Cyclethrin + TX, Sithioate + TX, d-Tetramethrin + TX, DAEP + TX, Dazomet + TX, Decarbofuran + TX, Diamidaphos + TX, Dikapton + TX, Dichlorophenthion + TX, Dicresyl + TX, Dicyclanil + TX, Dieldrin + TX, Diethyl 5-methylpyrazol-3-yl phosphate + TX, Dilol + TX, Dimefluthrin + TX, Dimethane + TX, Dimethryn + TX, Dimethylvinphos + TX, Dimethylan + TX, Dinoprop + TX, Dinosam + TX, Dinoseb + TX, Diofenolan + TX, Dioxabenzophos + TX, Dicyclophos + TX, DSP + TX, Ecdysterone + TX, EI 1642+TX, EMPC+TX, EPBP+TX, Ethaphos+TX, Ethiofencarb+TX, Ethyl formate+TX, Ethylene dibromide+TX, Dichloroethane+TX, Ethylene oxide+TX, EXD+TX, Fenchlorphos+TX, Fenetacarb+TX, Fenitrothion+TX, Fenoxacrim+TX, Fenpyrithrin+TX, Fensulfothion+TX, Fenthion-ethyl+TX, Flucofuron+TX, Fosmetilan+TX, Fospirate+TX, Fostietan+TX, Furathiocarb+TX, Frethrin+TX, Guazatine+TX, Guazatine acetate+TX, Sodium tetrathiocarbonate+TX,Halfenprox + TX, HCH + TX, HEOD + TX, Heptachlor + TX, Heterofos + TX, HHDN + TX, Hydrogen cyanide + TX, Hikincarb + TX, IPSP + TX, Isazophos + TX, Isobenzane + TX, Isodrin + TX, Isofenphos + TX, Isolane + TX, Isoprothiolane + TX, Isoxathion + TX, Juvenile hormone I + TX, Juvenile hormone II + TX, Juvenile hormone III + TX, Kereva thiamin + TX, kinoprene + TX, lead arsenate + TX, leptophos + TX, lilimphos + TX, ritidathion + TX, m-cumenylmethylcarbamate + TX, magnesium phosphide + TX, magidox + TX, mecarfone + TX, menasone + TX, mercurous chloride + TX, mesulfenphos + TX, metam + TX, metam-potassium + TX, metam-sodium + TX, methanesulfonyl fluoride + TX, metoclotophos + TX, methoprene + TX X, Methotrin + TX, Methoxychlor + TX, Methyl Isothiocyanate + TX, Methyl Chloroform + TX, Methylene Chloride + TX, Methoxadiazone + TX, Mirex + TX, Naphthalophos + TX, Naphthalene + TX, NC-170 + TX, Nicotine + TX, Nicotine Sulfate + TX, Nithiazine + TX, Nornicotine + TX, O-5-Dichloro-4-iodophenyl O-ethylethylphosphonothioate + TX, O,O -Diethyl O-4-methyl-2-oxo-2H-chromen-7-yl phosphorothioate + TX, O,O-Diethyl O-6-methyl-2-propylpyrimidin-4-yl phosphorothioate + TX, O,O,O',O'-Tetrapropyldithiopyrophosphate + TX, Oleic acid + TX, para-dichlorobenzene + TX, parathion-methyl + TX, pentachlorophenol + TX, pentachlorophenyl laurate + TX, PH 60-38+TX, Fenkapton+TX, Fosnichlor+TX, Phosphine+TX, Phoxim-methyl+TX, Pyrimetaphos+TX, Polychlorodicyclopentadiene Isomers+TX, Potassium Arsenite+TX, Potassium Thiocyanate+TX, Precocene I+TX, Precocene II+TX, Precocene III+TX, Pyrimidophos+TX, Profluthrin+TX, Promecarb+TX, Prothiofos+TX, Pyrazophos+TX, Pyresmethrin+TX, Cassia+TX, Quinalphos-methyl+TX,Quinothione +TX, Rafoxanide +TX, Resmeslin +TX, Rotenone +TX, Cadetrin +TX, Riania +TX, Ryanodine +TX, Sabadila +TX, Shladan +TX, Cebufos +TX, SI-0009 +TX, Tiapronil +TX, Sodium arsenite +TX, Sodium cyanide +TX, Sodium fluoride +TX, Sodium hexafluorosilicate +TX, Pentachlorophenoxide sodium salt +TX, Sodium selenate +TX, Sodium thiocyanate +TX, Sulcofuron +TX, Sulcofuron-sodium +TX, Sulfuryl fluoride +TX, Sulprofos +TX, Tar oil +TX, Thionazine +TX, TDE +TX, Tebupirimfos +TX, Temephos +TX , telallethrin + TX, tetrachloroethane + TX, cyclofos + TX, thiocyclam + TX, thiocyclam hydrogen oxalate + TX, thionazine + TX, thiosultap + TX, thiosultap-sodium + TX, tralomethrin + TX, transpermethrin + TX, triazamate + TX, trichlormethaphos-3 + TX, trichloronath + TX, trimethacarb + TX, tolprocarb + TX, triclopiricarb + TX, triplenone + TX, veratridine + TX, veratrine + TX, XMC + TX, zetamethrin + TX, zinc phosphide + TX, zolaprofos + TX, and meperfluthrin + TX, tetramethylfluthrin + TX, bis(tributyltin) oxide + TX, Bromoacetamide + TX, ferric phosphate + TX, niclosamide-olamine + TX, tributyltin oxide + TX, pyrimorph + TX, triphenmorph + TX, 1,2-dibromo-3-chloropropane + TX, 1,3-dichloropropene + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide + TX, 3-(4-chlorophenyl)-5-methylrhodanine + TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid + TX, 6-isopentenylaminopurine + TX, 2-fluoro-N-(3-methoxyphenyl)-9H-purin-6-amine + TX, benclothiaz + TX, cytokinin + TX, DCIP + TX, rufural + TX, isamidophos + TX, kinetin + TX, Myrothecium verrucaria verrucaria) composition +TX, tetrachlorothiophene +TX, xylenol +TX, zeatin +TX, potassium ethylxanthate +TX, acibenzolar +TX, acibenzolar-S-methyl +TX, giant knotweed (Reynoutria sachalinensis) extract +TX, α-chlorohydrin +TX, anth +TX, barium carbonate +TX, bisthiosemi +TX, brodifacoum +TX, bromadiolone +TX, bromethalin +TX, chlorophacinone +TX, cholecalciferol +TX, coumachlor +TX, coumafuryl +TX, coumatetralyl +TX, crimidine +TX, difenacoum +TX, difethialone +TX, diphacinone +TX, ergocalciferol +TX, flocoumafen +TX, fluoroacetamide +TX, flupropazine +TX, flupropazine hydrochloride +TX, norbormide +TX, fosacetim +TX, phosphorus +TX, pindone +TX, pyrinuron +TX, sciliroside +TX, sodium fluoroacetate +TX, thallium sulfate +TX, warfarin +TX, 2-(2-butoxyethoxy)ethyl piperonylate +TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone +TX, farnesol and nerolidol +TX, verbutin +TX, MGK 264 +TX, piperonyl butoxide +TX, piprotal +TX, propyl isomer +TX, S421 +TX, sesamex +TX, sesasmolin +TX, sulfoxide +TX, anthraquinone +TX,Copper naphthenate + TX, copper oxychloride + TX, dicyclopentadiene + TX, thiram + TX, zinc naphthenate + TX, ziram + TX, imanin + TX, ribavirin + TX, mercury(II) oxide + TX, thiophanate-methyl + TX, azaconazole + TX, bitertanol + TX, bromuconazole + TX, cyproconazole + TX, difenoconazole + TX, diniconazole + TX, epoxiconazole + TX, fenbuconazole + TX, fluquinconazole + TX, flusilazole + TX, flutriafol + TX, furametpyr + TX, hexaconazole azolyl + TX, imibenconazole + TX, ipconazole + TX, metconazole + TX, myclobutanil + TX, paclobutrazol + TX, pefurazoate + TX, penconazole + TX, prothioconazole + TX, pyrifenox + TX, prochloraz + TX, propiconazole + TX, pyrisoxazole + TX, simeconazole + TX, tebuconazole + TX, tetraconazole + TX, triadimefon + TX, triadimenol + TX, triflumizole + TX, triticonazole + TX, ancymidol + TX, Fenarimol + TX, Nuarimol + TX, Bupirimate + TX, Dimethirimol + TX, Ethirimol + TX, Dodemorph + TX, Fenpropizin + TX, Fenpropimorph + TX, Spiroxamine + TX, Tridemorph + TX, Cyprodinil + TX, Mepanipyrim + TX, Pyrimethanil + TX, Fenpiclonil + TX, Fludioxonil + TX, Benalaxyl + TX, Furalaxyl + TX, Metalaxyl + TX, R-Metalaxyl + TX, Ofrace + TX, Oxadixyl + TX, Carbendazim + TX, Debacarb + TX, Fuberidazole + TX, thiabendazole + TX, chlozolinate + TX, dichlozolin + TX, mycrozolin + TX, procymidone + TX, vinclozolin + TX, boscalid + TX, carboxin + TX, fenfuram + TX, flutolanil + TX, mepronil + TX, oxycarboxin + TX, penthiopyrad + TX, thifluzamide + TX, dodine + TX, iminoctadine + TX, azoxystrobin + TX, dimoxystrobin + TX, enestrobulin + TX, phenaminestrobin + TX, flufenoxystrobin + TX, fluoxastrobin + TX,Kresoxim-methyl + TX, Metominostrobin + TX, Trifloxystrobin + TX, Oryzastrobin + TX, Picoxystrobin + TX, Pyraclostrobin + TX, Pyrametstrobin + TX, Pyraoxystrobin + TX, Ferbam + TX, Mancozeb + TX, Maneb + ​​TX, Metiram + TX, Propineb + ​​TX, Zineb + ​​TX, Captafol + TX, Captan + TX, Fluorimide + TX, Folpet + TX, Tolylfluanid + TX, Bordeaux mixture + TX, Copper oxide + TX, Mancopper + TX, Copper oxalate + TX, Nitto Lothal-isopropyl + TX, Edifenphos + TX, Iprobenfos + TX, Fosdifen + TX, Turcofos-methyl + TX, Anilazine + TX, Benthiavalicarb + TX, Blasticidin-S + TX, Chloroneb + ​​TX, Chlorothalonil + TX, Cyflufenamid + TX, Cymoxanil + TX, Diclocymet + TX, Diclomedine + TX, Dicloran + TX, Diethofencarb + TX, Dimethomorph + TX, Flumorph + TX, Dithianon + TX, Ethaboxam + TX, Etridiazole + TX, Famoxadone + TX, Fena Midon +TX, Fenoxanil +TX, Ferimzone +TX, Fluazinam +TX, Fluopicolide +TX, Flusulfamide +TX, Fluxapyroxad +TX, Fenhexamid +TX, Fosetyl-aluminum +TX, Hymexazole +TX, Iprovalicarb +TX, Cyazofamid +TX, Metasulfocarb +TX, Metrafenone +TX, Pencycuron +TX, Phthalide +TX, Polyoxin +TX, Propamocarb +TX, Pyribencarb +TX, Proquinazid +TX, Pyroquilon +TX, Pyriophenone +TX, Quinoxyfen +TX, quintozene +TX, tiadinil +TX, triazoxide +TX, tricyclazole +TX, triforine +TX, validamycin +TX, valifenalate +TX, zoxamide +TX, mandipropamide +TX, isopyrazam +TX, sedaxane +TX, benzovindiflupyr +TX, pydiflumetofen +TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3',4',5'-trifluoro-biphenyl-2-yl)-amide +TX, isoflucipram +TX, isotianil +TX, dipimethitrone +TX,6-Ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithiino[1,2-c]isothiazole-3-carbonitrile + TX, 2-(difluoromethyl)-N-[3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, 4-(2,6-difluorophenyl)-6-methyl-5-phenyl-pyridazine-3-carbonitrile + TX, (R)-3-(difluoromethyl)-1-methyl -N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3-amine + TX, 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine + TX, Fluindapyr + TX, Methoxystrobin (jiaxiangjunzhi) + TX, rubenmixianan + TX, diclobenthiazox + TX, mandestrobin + TX, 3-(4,4-difluoro-3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone + TX, 2-[2-fluoro-6-[(8-fluoro-2-methyl-3-quinolyl)oxy]phenyl]propan-2-ol + TX, oxathiapiproline + TX, t-bu ethyl N-[6-[[[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate + TX, pyraziflumide + TX, inpirfluxam + TX, turolprocarb + TX, mefentrifluconazole + TX, ipfentrifluconazole + TX, 2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, N'-(2,5-dimethyl-4-phenanthroline) N'-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine + TX, [2-[3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]-3-chloro-phenyl]methanesulfonic acid + TX, but-3-yl Nyl N-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate + TX, methyl N-[[5-[4-(2,4-dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamate + TX, 3-chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine + TX, pyridaclomethyl + TX, 3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 1-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3-methyl-phenyl]-4-methyl-tetrazol-5-one + TX, 1-methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5-trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]tetrazol-5-one + TX, Aminopyrifen + TX, ametoctrazine + TX, amisulbrom + TX, penflufen + TX, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide + TX, florylpicoxamide + TX, fenpicoxamide + TX, tebufloquin + TX, ipulfenoquin + TX, quinofumelin + TX, isofetamide + TX, N-[2-[2,4-dichloro-phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX, N-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX, Benzothiostrobin + TX, Fenamacryl + TX, 5-amino-1,3,4-thiadiazole-2-thio fluopyram zinc salt (2:1) + TX, fluopyram + TX, flutianil + TX, fluopimomide + TX, pyrapropoin + TX, picarbutrazox + TX, 2-(difluoromethyl)-N-(3-ethyl-1,1-dimethyl-indan-4-yl)pyridine-3-carboxamide + TX, 2-(difluoromethyl)-N-((3R)-1,1,3-trimethylindan-4-yl)pyridine-3-carboxamide + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, Methyltetraprole + TX, 2-(difluoromethyl)-N-((3R)-1,1,3-trimethylindan-4-yl)pyridine-3-carboxamide + TX, α-(1,1-dimethylethyl)-α-[4'-(trifluoromethoxy)[1,1'-biphenyl]-4-yl]-5-pyrimidinemethanol + TX, Fluoxapiprolin + TX, Enoxastrobin + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl [[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-sulfanyl-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, trinexapac + TX, cumoxystrobin + TX, zhongshengmycin + TX, copper thiodiazole + TX, zinc thiazole + TX, amethotractin + TX, iprodione + TX;N'-[5-bromo-2-methyl-6-[(1S)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-chloro N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds can be prepared by the method described in WO 2015 / 155075); N'-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX N-isopropyl-N'-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidine + TX (this compound can be prepared by the method described in IPCOM000249876D); N-isopropyl-N'-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidine + TX, N'-[4-(1-cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds N-ethyl-N'-[5-methoxy-2-methyl-4-[2-trifluoromethyl)oxetan-2-yl]phenyl]-N-methyl-formamidine + TX, N-ethyl-N'-[5-methoxy-2-methyl-4-[2-trifluoromethyl)tetrahydrofuran-2-yl]phenyl]-N-methyl-formamidine + TX (these compounds can be prepared by the methods described in WO 2019 / 110427);N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide + TX, 8-fluoro-N-[1-[(3-fluorophenyl)methyl]- 1,3-dimethyl-butyl]quinoline-3-carboxamide + TX, N-(1-benzyl-1,3-dimethyl-butyl)-8-fluoro-quinoline-3-carboxamide + TX, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX, N-(1-benzyl-3-chloro-1-methyl-but-3 -enyl)-8-fluoro-quinoline-3-carboxamide + TX (these compounds can be prepared by the methods described in WO 2017 / 153380); 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline + TX, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline + TX, 4,4-difluoro- 3,3-dimethyl-1-(6-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline + TX, 4,4-difluoro-3,3-dimethyl-1-(7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline + TX, 1-(6-chloro-7-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline + TX (these compounds can be prepared by the method described in WO 2017 / 025510);1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline + TX, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline + TX, 6-chloro-4,4-difluoro-3,3-dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline + TX, 4,4-difluoro-1-(5-fluoro-4-methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline + TX, 3-(4,4-difluoro (6H-3,3-dimethyl-1-isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole + TX (these compounds can be prepared by the method described in WO 2016 / 156085); N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide + TX, N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide + TX; N-ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide + TX, 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea + TX, 1,3-dimethoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea + TX, 3-ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea + TX, N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl ]methyl]propanamide + TX, 4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one + TX, 5,5-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one + TX, ethyl 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxylate + TX, N,N-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-1,2,4-triazol-3-amine + TX. The compounds in this paragraph can be prepared by the methods described in WO 2017 / 055473, WO 2017 / 055469, WO 2017 / 093348 and WO 2017 / 118689; 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol + TX (this compound can be prepared by the methods described in WO 2017 / 029179); 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol + TX (this compound can be prepared by the methods described in WO 2017 / 029179);3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxypropyl]imidazole-4-carbonitrile + TX (this compound can be prepared by the method described in WO 2016 / 156290); 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluorophenyl)-2-hydroxypropyl]imidazole-4-carbonitrile + TX (this compound can be prepared by the method described in WO 2016 / 156290); (4 N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxazolidinyl]-1H,5H-[1,4]dithiino[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone + TX (this compound can be prepared by the method described in WO 2011 / 138281); ... N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX; (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide + TX (this compound can be prepared by the method described in WO 2018 / 153707); N'-(2-chloro-5-methyl-4-phenoxy-phenyl)-N- Ethyl-N-methyl-formamidine + TX; N'-[2-chloro-4-(2-fluorophenoxy)-5-methyl-phenyl]-N-ethyl-N-methyl-formamidine + TX (this compound can be prepared by the method described in WO 2016 / 202742); 2-(difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX (this compound can be prepared by the method described in WO 2014 / 095675);(5-methyl-2-pyridyl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone + TX, (3-methylisoxazol-5-yl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone + TX (these compounds can be prepared by the methods described in WO 2017 / 220485); 2-oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide + TX (this compound can be prepared by the methods described in WO 2018 / 065414); ethyl 1-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4-carboxylate + TX (this compound can be prepared by the methods described in WO 2018 / 065414). , which can be prepared by the methods described in WO 2018 / 158365; biologically active substances selected from 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide + TX, N-[(E)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX, N-[(Z)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX, N-[N-methoxy-C-methyl-carbonimidoyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX (these compounds can be prepared by the methods described in WO 2018 / 202428); Microorganisms including: Acinetobacter lwoffii + TX, Acremonium alternatum + TX + TX, Acremonium cephalosporium + TX + TX, Acremonium diospyri + TX, Acremonium obclavatum + TX, Adoxophyes orana granulovirus (AdoxGV) (Capex®) + TX, Agrobacterium radiobacter strain K84 (Galltrol-A®) + TX, Alternaria alternata + TX, Alternaria cassia + TX, cassia) + TX, Alternaria destruens (Smolder®) + TX, Ampelomyces quisqualis (AQ10®) + TX, Aspergillus flavus AF36 (AF36®) + TX, Aspergillus flavus NRRL 21882 (Aflaguard®) + TX, Aspergillus spp.) + TX, Aureobasidium pullulans + TX, Azospirillum + TX, (MicroAZ® + TX, TAZO B®) + TX, Azotobacter + TX, Azotobacter chroocuccum (Azotomeal®) + TX, Azotobacter cysts (Bionatural Blooming Blossoms®) + TX, Bacillus amyloliquefaciens + TX, Bacillus cereus + TX, Bacillus chitinosporus strain CM-1 + TX, Bacillus chitinosporus strain AQ746 + TX, Bacillus licheniformis strain HB-2 (Biostart™ Rhizoboost®) + TX, Bacillus licheniformis strain 3086 (EcoGuard® + TX, Green Releaf®) + TX, Bacillus circulans + TX, Bacillus firmus (BioSafe® + TX, BioNem-WP® + TX, VOTiVO®) + TX, Bacillus firmus strain I-1582 + TX, Bacillus macerans + TX, Bacillus marismortui + TX, Bacillus megaterium megaterium) + TX, Bacillus mycoides strain AQ726 + TX, Bacillus papillae (Milky Spore Powder®) + TX, Bacillus pumilus spp.) + TX, Bacillus pumilus strain GB34 (Yield Shield®) + TX, Bacillus pumilus strain AQ717 + TX, Bacillus pumilus strain QST 2808 (Sonata® + TX, Ballad Plus®) + TX, Bacillus spahericus (VectoLex®) + TX, Bacillus spp. + TX, Bacillus spp. strain AQ175 + TX, Bacillus spp. strain AQ177 + TX, Bacillus spp. strain AQ178 + TX, Bacillus subtilis Bacillus subtilis strain QST 713 (CEASE®+TX, Serenade®+TX, Rhapsody®)+TX, Bacillus subtilis strain QST 714 (JAZZ®)+TX, Bacillus subtilis strain AQ153+TX, Bacillus subtilis strain AQ743+TX, Bacillus subtilis strain QST3002+TX, Bacillus subtilis strain QST3004+TX, Bacillus subtilis var. amyloliquefaciens (Bacillus subtilis var.amyloliquefaciens strain FZB24 (Taegro® +TX, Rhizopro®) +TX, Bacillus thuringiensis Cry 2Ae +TX, Bacillus thuringiensis Cry1Ab +TX, Bacillus thuringiensis aizawai GC 91 (Agree®) +TX, Bacillus thuringiensis israelensis (BMP123® +TX, Aquabac® +TX, VectoBac®) +TX, Bacillus thuringiensis kurstakii kurstaki (Javelin® + TX, Deliver® + TX, CryMax® + TX, Bondide® + TX, Scutella WP® + TX, Turilav WP® + TX, Astuto® + TX, Dipel WP® + TX, Biobit® + TX, Foray®) + TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®) + TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF / 3P®) + TX, Bacillus thuringiensis strain BD#32 + TX, Bacillus thuringiensis strain BD#32 + TX, Bacillus thuringiensis strain AQ52+TX, Bacillus thuringiensis var. aizawai (XenTari®+TX, DiPel®)+TX, Bacteria spp.) (GROWMEND® +TX, GROWSWEET® +TX, Shootup®) +TX, Clavipacter michiganensis bacteriophage (AgriPhage®) +TX, Bakflor® +TX, Beauveria bassiana (Beaugenic® +TX, Brocaril WP®) +TX, Beauveria bassiana GHA (Mycotrol ES® +TX, Mycotrol O® +TX, BotaniGuard®) +TX, Beauveria brongniartii (Engerlingspilz® +TX, Schweizer Beauveria® +TX, Melocont®) +TX, Beauveria species (Beauveria spp.) + TX, Botrytis cineria + TX, Bradyrhizobium japonicum (TerraMax®) + TX, Brevibacillus brevis + TX, Bacillus thuringiensis tenebrionis (Novodor®) + TX, BtBooster + TX, Burkholderia cepacia (Deny® + TX, Intercept® + TX, Blue Circle®) + TX, Burkholderia gladii + TX, Burkholderia gladioli + TX, Burkholderia spp.) + TX, Canadian thistle fungus (CBH Canadian Bioherbicide®) + TX, Candida butyri + TX, Candida famata + TX, Candida fructus + TX, Candida glabrata + TX, Candida guilliermondii + TX, Candida melibiosica + TX, Candida oleophila strain O + TX, Candida parapsilosis + TX, Candida pelliculosa + TX, Candida pulcherrima + TX, Candida leucoffii reukaufii + TX, Candida saitoana (Bio-Coat® + TX, Biocure®) + TX, Candida sake + TX, Candida spp. + TX,. Candida tenius + TX, Cedecea dravisae + TX, Cellulomonas flavigena + TX, Chaetomium cochliodes (Nova-Cide®) + TX, Chaetomium globosum (Nova-Cide®) + TX, Chromobacterium subtsugae strain PRAA4-1T (Grandevo®) + TX, Cladosporium cladosporioides + TX, Cladosporium oxysporum + TX, Cladosporium chlorocephalum chlorocephalum + TX, Cladosporium spp. + TX, Cladosporium tenuissimum + TX, Clonostachys rosea (EndoFine®) + TX, Colletotrichum acutatum + TX, Coniothyrium minitans (Cotans WG®) + TX, Coniothyrium spp.) + TX, Cryptococcus albidus (YIELDPLUS®) + TX, Cryptococcus humicola + TX, Cryptococcus infirmo-miniatus + TX, Cryptococcus laurentii + TX, Cryptophlebia leucotreta granulovirus (Cryptex®) + TX, Cupriavidus campinensis + TX, Cydia pomonella granulovirus (CYD-X®) + TX, Cydia pomonella granulovirus granulovirus) (Madex® + TX, Madex Plus® + TX, Madex Max / Carpovirusine®) + TX, Cylindrobasidium laeve (Stumpout®) + TX, Cylindrocladium + TX, Debaryomyces hansenii + TX, Drechslera hawaiinensis + TX, Enterobacter cloacae + TX, Enterobacter iacae + TX, Entomophtora virulenta (Vektor®) + TX, Epicoccum nigrum + TX, Epicoccum purpuraense purpurascens) + TX, Epicoccum spp.) + TX, Filobasidium floriforme + TX, Fusarium acuminatum + TX, Fusarium chlamydosporum + TX, Fusarium oxysporum (Fusaclean® / Biofox C®) + TX, Fusarium proliferatum + TX, Fusarium spp. + TX, Galactomyces geotrichum + TX, Gliocladium catenulatum (Primastop® + TX, Prestop®) + TX, Gliocladium roseum roseum + TX, Gliocladium spp. (SoilGard®) + TX, Gliocladium virens (Soilgard®) + TX, Granulovirus (Granupom®) + TX, Halobacillus halophilus + TX, Halobacillus litoralis + TX, Halobacillus trueperi + TX, Halomonas spp.) + TX, Halomonas subglaciescola + TX, Halovibrio variabilis + TX, Hanseniaspora uvarum + TX, Helicoverpa armigera nuclear polyhedrosis virus (Helicovex®) + TX, Helicoverpa zea nuclear polyhedrosis virus (Gemstar®) + TX, isoflavone-formononetin (Myconate®) + TX, Kloeckera apiculata + TX, Kloeckera spp.) + TX, Lagenidium giganteum (Laginex®) + TX, Greenhouse whitefly (Lecanicillium longisporum) (Vertiblast®) + TX, Lecanicillium muscarium (Vertikil®) + TX, Gypsy moth (Lymantria dispar) nuclear polyhedrosis virus (Disparvirus®) + TX, Marinococcus halophilus + TX, Meira geulakonigii + TX, Metarhizium anisopliae (Met52®) + TX, Metarhizium anisopliae (Destruxin®) + TX, WP®) + TX, Metschnikowia fruticola (Shemer®) + TX, Metschnikowia pulcherrima + TX, Microdochium dimerum (Antibot®) + TX, Micromonospora coerulea + TX, Microsphaeropsis ochracea + TX, Muscodor albus 620 (Muscudor®) + TX, Muscodor roseus strain A3-5 + TX, Mycorrhizae spp.) (AMykor® +TX, Root Maximizer®) +TX, Myrothecium verrucaria strain AARC-0255 (DiTera®) +TX, BROS PLUS® +TX, Ophiostoma piliferum strain D97 (Sylvanex®) +TX, Paecilomyces farinosus +TX, Paecilomyces fumosoroseus (PFR-97® +TX, PreFeRal®) +TX, Paecilomyces linacinus (Biostat WP®) +TX, Paecilomyces lilacinus strain 251 (MeloCon WG®) + TX, Paenibacillus polymyxa + TX, Pantoea agglomerans (BlightBan C9-1®) + TX, Pantoea spp. + TX, Pasteuria spp. (Econem®) + TX, Pasteuria nishizawae + TX, Penicillium aurantiogriseum + TX, Penicillium billai (Jumpstart® + TX, TagTeam®) + TX, Penicillium brevicompactum + TX, Penicillium frequentans + TX, Penicillium griseofulvum + TX, Penicillium purpurogenum + TX, Penicillium spp.) + TX, Penicillium viridicatum + TX, Phlebiopsis gigantean (Rotstop®) + TX, Phosphhomeal® + TX, Phytophthora cryptogea + TX, Phytophthora palmivora (Devine®) + TX, Pichia anomala + TX, Pichia guilermondii + TX, Pichia membranaefaciens + TX, Pichia onychis + TX, Pichia stipites + TX, Pseudomonas aeruginosa aeruginosa + TX, Pseudomonas aureofaciens (Spot-Less Biofungicide®) + TX, Pseudomonas cepacia + TX, Pseudomonas chlororaphis (AtEze®) + TX, Pseudomonas corrugate + TX, Pseudomonas fluorescens strain A506 (BlightBan A506®) + TX, Pseudomonas putida + TX, Pseudomonas reactans + TX, Pseudomonas spp.) + TX, Pseudomonas syringae (Bio-Save®) + TX, Pseudomonas viridiflava + TX, Pseudomonas fluorescens (Zequanox®) + TX, Pseudozyma flo...

Claims

1. Compounds of Formula I 【Chemistry 1】 (In the formula, R1 is H, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonyl C1-C6 alkyl, hydroxycarbonyl C1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilane C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, C3-C4 cycloalkyl C1-C2 alkyl- (wherein the C3-C4 cycloalkyl group is substituted with 1 or 2 halogen atoms), oxetan-3-yl-CH 2 -, benzyl or benzyl substituted with halogen or C1-C6 haloalkyl; A1 is N or C-R2c; R2c is H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, or C1-C3 haloalkoxy; R2a is selected from the group consisting of C3-C6 cycloalkyl, C3-C6 cycloalkoxy; C3-C6 cycloalkyl substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and halogen; C3-C6 cycloalkoxy substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, cyano, and halogen; C3-C6 cycloalkyl C1-C4 alkyl, C3-C6 cycloalkyl C1-C4 alkoxy; C1-C3 alkyl, C1 C3-C6 cycloalkylC1-C4 alkyl substituted with 1-5 substituents independently selected from C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and halogen; C3-C6 cycloalkylC1-C4 alkoxy substituted with 1-5 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, cyano, and halogen; C1-C5 cyanoalkyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfinyl, or C1-C4 haloalkylsulfinyl; R2b is H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylthio, C1-C3 alkoxy, C1-C3 haloalkoxy, SF5, or CN; R3 is C1-C3 alkyl or C1-C3 haloalkyl; R4 is pyridine, pyrimidine, pyrazine, pyridazine, or pyridine, pyrimidine, pyrazine, and pyridazine each substituted with one substituent selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, and hydroxy; R5a and R5b are each independently selected from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy; or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer, and N-oxide of a compound of formula I.

2. The compound of claim 1, wherein R3 is methyl.

3. The compound according to claim 1 or claim 2, wherein A1 is N.

4. The compound according to claim 1 or claim 2, wherein A1 is C-R2c, where R2c is hydrogen or halogen.

5. The compound of claim 1 or claim 2, wherein A1 is C-R2c, where R2c is hydrogen.

6. R1 is hydrogen, methyl, ethyl, n-propyl, isobutyl, cyclopropylmethyl or CH≡CCH 2 The compound according to any one of claims 1 to 5, wherein

7. The compound according to any one of claims 1 to 6, wherein R2a is C3-C6 cycloalkyl, C3-C6 cycloalkoxy; C3-C6 cycloalkyl substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, cyano, and halogen; C3-C6 cycloalkyl substituted with 1 to 5 substituents independently selected from halogen and C1-C3 haloalkyl; C1-C4 alkyl; C1-C5 cyanoalkyl, C3-C6 cycloalkoxy, C1-C4 haloalkylsulfonyl, or C1-C4 haloalkylsulfinyl.

8. The compound of any one of claims 1 to 7, wherein R2b is halogen, C1-C3 haloalkyl, C1-C3 haloalkylthio, C1-C3 alkoxy, C1-C3 haloalkoxy, or CN.

9. The compound according to any one of claims 1 to 8, wherein R4 is 2-pyridine, 2-pyrimidine, 2-pyridine substituted with one substituent selected from cyclopropyl or halogen, and 2-pyrimidine substituted with one substituent selected from cyclopropyl or halogen.

10. The compound according to any one of claims 1 to 9, wherein R5a and R5b are independently selected from hydrogen, bromo, chloro, methyl and methoxy.

11. A composition comprising a compound according to any one of claims 1 to 10, one or more auxiliaries and diluents, and optionally one or more other active ingredients.

12. (i) a method for combating and controlling insects, acarids, nematodes or molluscs, comprising applying to the pest, the non-human habitat of the pest, or to plants susceptible to attack by the pest, an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound according to any one of claims 1 to 10 or a composition according to claim 11; or (ii) a method for the protection of plant propagation material from attack by insects, acarids, nematodes or mollusks, which comprises treating said propagation material or the locus in which said propagation material is planted with an effective amount of a compound according to any one of claims 1 to 10 or a composition according to claim 11; or (iii) A method for controlling parasites in or on a non-human animal in need thereof, comprising administering an effective amount of a compound according to any one of claims 1 to 10 or a composition according to claim 11.

13. Plant propagation material comprising, treated with or having attached thereto a compound according to any one of claims 1 to 10 or a composition according to claim 11.

14. Seeds comprising, treated with or having attached thereto a compound according to any one of claims 1 to 10 or a composition according to claim 11.

15. Compounds of Formulae IIab to IIae, except for N-[1-[3-(2-pyridyl)pyrazin-2-yl]ethyl]prop-2-en-1-amine and 1-[3-(2-pyridyl)pyrazin-2-yl]ethanamine 【Chemistry 2】 (wherein R1 is as defined in either claim 1 or 6, and R4 is as defined in claim 9).

16. Use of a compound according to any one of claims 1 to 10 or a composition according to claim 11 for the manufacture of a medicament for controlling parasites in or on an animal in need thereof.

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