Diazine-amide compounds with pesticidal activity

Abstract

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

Description

[0001] The present invention relates to pesticidally active, in particular insecticidal, diazine-amide compounds, to a process for their preparation, to compositions comprising those compounds, and to their use for controlling animal pests, including arthropods and in particular insects or representatives of the order Acarina.

[0002] WO 2017192385 describes certain heteroaryl-1,2,4-triazole and heteroaryl-tetrazolyl compounds for use in controlling ectoparasites in animals (such as mammals and non-mammals).

[0003] Novel pesticidally active diazinonamide compounds have now been found.

[0004] Therefore, the present invention relates in a first aspect to compounds having formula I

[0005]

[0006] in

[0007] R 1 It is H, C 1 -C 6 Alkyl, C 1 -C 6 Cyanoalkyl, aminocarbonyl C 1 -C 6 Alkyl, hydroxycarbonyl C 1 -C 6 Alkyl, C 1 -C 6 Nitroalkyl, trimethylsilane C 1 -C 6 Alkyl, C 1 –C 6 Haloalkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Halogenated alkenyl, C 2 -C 6 Alkynyl, C 2 -C 6 Haloalkynyl, C 3 -C 4 Cycloalkyl C 1 -C 2 Alkyl-, C 3 -C 4 Cycloalkyl C 1 -C 2 Alkyl-wherein the C 3 -C 4 Cycloalkyl is substituted by 1 or 2 halogen atoms, oxetane-3-yl-CH 2 -, benzyl or halogen or C1 -C 6 benzyl substituted with haloalkyl;

[0008] A 1 Is N or CR 2c ;

[0009] R 2c H, halogen, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, or C 1 -C 3 Haloalkoxy;

[0010] R 2a It is C 3 -C 6 Cycloalkyl, C 3 -C 6 Cycloalkoxy, substituted by one to three independently selected 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, cyano, and halogen substituted C 3 -C 6 Cycloalkyl, composed of one to three independently selected 1 -C 3 Alkyl, C 1 -C 3 C substituted with haloalkyl, cyano, and halogen 3 -C 6 Cycloalkoxy, C 3 -C 6 Cycloalkyl C 1 -C 4 Alkyl, C 3 -C 6 Cycloalkyl C 1 -C 4 Alkoxy, composed of one to five independently selected 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, cyano, and halogen substituted C 3 -C 6 Cycloalkyl C 1 -C 4 Alkyl, composed of one to five independently selected C 1-C 3 Alkyl, C 1 -C 3 C substituted with haloalkyl, cyano, and halogen 3 -C 6 Cycloalkyl C 1 -C 4 Alkoxy, C 1 -C 5 Cyanoalkyl, C 1 -C 4 Alkylsulfonyl, C 1 -C 4 Haloalkylsulfonyl, C 1 -C 4 Alkylsulfinyl, or C 1 -C 4 haloalkylsulfinyl;

[0011] R 2b H, halogen, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Halogenated alkylthio, C 1 -C 3 Alkoxy, C 1 -C 3 Halogenated alkoxy, SF 5 , or CN;

[0012] R 3 It is C 1 -C 3 Alkyl or C 1 -C 3 Haloalkyl;

[0013] R 4 is pyridine, pyrimidine, pyrazine or pyridazine, each of which is substituted by a substituent selected from C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, C 3 -C 4 Cycloalkyl, halogen, and hydroxyl;

[0014] R 5a and R 5b are independently selected from hydrogen, halogen, CN, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C3 -C 4 Cycloalkyl, C 1 -C 3 Alkoxy, and C 1 -C 3 or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer and N-oxide of the compound of formula I.

[0015] Compounds of formula I having at least one basic center can form acid addition salts, for example, with strong inorganic acids (for example mineral acids, such as perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or hydrohalic acids), strong organic carboxylic acids (for example unsubstituted or halogen-substituted C 1 -C 4 Alkanecarboxylic acids, for example acetic acid, for example saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, for example 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 unsubstituted or substituted, for example, by halogen, C 1 -C 4 The compounds of formula I having at least one acidic group can, for example, form salts with bases, for example mineral salts, for example alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts; or with ammonia or organic amines (for example morpholine, piperidine, pyrrolidine, mono-, di- or tri-lower alkylamines, for example ethylamine, diethylamine, triethylamine or dimethylpropylamine, or mono-, di- or tri-hydroxy lower alkylamines, for example monoethanolamine, diethanolamine or triethanolamine).

[0016] In each case, the compounds of formula I according to the invention are in free form, in oxidized form such as N-oxides, or in salt form (eg in the form of an agronomically usable salt).

[0017] N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen-containing heteroaromatic compounds. They are described, for example, by A. Albini and S. Pietra in 1991 in the book "Heterocyclic N-oxides", CRC Press, Boca Raton.

[0018] The compounds of formula I according to the invention also include hydrates which may be formed during salt formation.

[0019] As used herein, the term “C 1 -C n"Alkyl" refers to a saturated straight or branched hydrocarbon group having 1 to n carbon atoms, attached via any carbon atom, such as any of the following groups: 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.

[0020] As used herein, the term “C 1 -C n “Haloalkyl” refers to a straight-chain or branched saturated alkyl group (as mentioned above) having 1 to n carbon atoms, attached via any carbon atom, wherein some or all of the hydrogen atoms in these groups may be replaced by fluorine, chlorine, bromine and / or iodine, i.e., for example, any of the following: 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, 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 or nonafluorobutyl. Accordingly, the term “C 1 -C 2 "Fluoroalkyl" shall mean a C 1 -C 2 Alkyl, such as any of the following: difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl or pentafluoroethyl.

[0021] As used herein, the term “C 1 -C n"Alkoxy" refers to a straight or branched saturated alkyl group having 1 to n carbon atoms (as mentioned above), which is attached via an oxygen atom, i.e., for example, any of the following groups: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy or 1,1-dimethylethoxy. As used herein, the term "halogenated C 1 -C n "Alkoxy" refers to C 1 -C n Alkoxy wherein one or more hydrogen atoms on the alkyl group are replaced by the same or different one or more halogen atoms - examples include trifluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy, 3,3,3-trifluoropropoxy, 4-chlorobutoxy.

[0022] As used herein, the term “C 1 -C n "Cyanoalkyl" refers to a straight-chain or branched saturated C 1 -C n Alkyl (as mentioned above), wherein one of the hydrogen atoms in these groups 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, etc.

[0023] As used herein, the term “C 3 -C n The term "cycloalkyl" refers to a 3- to n-membered cycloalkyl group such as cyclopropane, cyclobutane, cyclopentane and cyclohexane.

[0024] As used herein, the term “C 3 -C n Cycloalkyl C 1 -C n "Alkyl" refers to a 3 to n-membered cycloalkyl group having an alkyl group attached to the remainder of the molecule. In this case, C 3 -C n Cycloalkyl C 1 -C 2 An alkyl-group is substituted, the one or more substituents being either on the cycloalkyl or the alkyl group.

[0025] As used herein, the term "aminocarbonyl C 1 -C n "Alkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is replaced by a CONH2 group.

[0026] As used herein, the term "hydroxycarbonyl C 1 -C n "Alkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is replaced by a COOH group.

[0027] As used herein, the term “C 1 -C n "Nitroalkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is replaced by a NO2 group.

[0028] As used herein, the term “C 1 -C n Alkylsulfanyl" or "C 1 -C n "Haloalkylthio" refers to a C 1 -C n Similarly, as used herein, the term "C 1 -C n "Haloalkylsulfanyl" refers to a C 1 -C n A haloalkyl moiety.

[0029] As used herein, the term “C 1 -C n "Alkylsulfinyl" refers to a C 1 -C n Similarly, as used herein, the term "C 1 -C n "Haloalkylsulfinyl" refers to a C 1 -C n A haloalkyl moiety.

[0030] As used herein, the term “C 1 -C n "Alkylsulfonyl" refers to a 2 The sulfur atom of the group is connected to the C 1 -C n Similarly, as used herein, the term "C 1 -C n "Haloalkylsulfonyl" refers to a 2 The sulfur atom of the group is connected to the C 1 -C n A haloalkyl moiety.

[0031] As used herein, the term "trimethylsilane C 1 -C n "Alkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is replaced by -Si(CH 3 ) 3 Group substitution.

[0032] As used herein, the term “C 2 -Cn "Alkenyl" refers to a straight or branched alkenyl chain having from two to n carbon atoms and one or two double bonds, for example vinyl, prop-1-enyl, but-2-enyl.

[0033] As used herein, the term “C 2 -C n "Haloalkenyl" refers to a C 2 -C n Alkenyl moiety.

[0034] As used herein, the term “C 2 -C n "Alkynyl" refers to a straight or branched alkynyl chain having from 2 to n carbon atoms and one triple bond, for example ethynyl, prop-2-ynyl, but-3-ynyl.

[0035] As used herein, the term “C 2 -C n "Haloalkynyl" means a C 2 -C n Alkynyl moiety.

[0036] Halogen is typically fluorine, chlorine, bromine or iodine. This also applies correspondingly to halogen in combination with other meanings, such as haloalkyl.

[0037] R 2 and R 4 The pyridine, pyrimidine, pyrazine and pyridazine groups (unsubstituted or substituted) are each attached to the remainder of the compound through a carbon atom on the corresponding ring.

[0038] As used herein, the term "control" refers to reducing the number of pests, eliminating pests, and / or preventing further pest damage, such that damage to plants or to plant-derived products is reduced.

[0039] Staggered lines as used herein, for example in K-1 and O-1, indicate the point of connection / attachment to the rest of the compound.

[0040] As used herein, the term "pest" refers to insects, mites, nematodes and molluscs found in agriculture, horticulture, forestry, storage of plant-derived products (such as fruits, grains and wood); and those pests associated with damage to man-made structures. The term pest covers all stages of the life cycle of the pest.

[0041] As used herein, the term "effective amount" refers to an amount of a compound or a salt thereof that provides the desired effect upon single or multiple administrations.

[0042] The effective amount is readily determined by one skilled in the art by using known techniques and by observing the results obtained under similar circumstances. In determining the effective amount, many factors are considered, including, but not limited to: the type of plant or derived product to be applied; the pest to be controlled and its life cycle; the specific compound being applied; the type of application; and other relevant circumstances.

[0043] As will be appreciated by one of ordinary skill in the art, compounds having Formula I contain stereocenters, which are indicated by asterisks in the following structures:

[0044]

[0045] Where R 1 , R 2a , R 2b , R 3 , R 4 , R 5a , R 5b , and A 1 is as defined in the first aspect.

[0046] The present invention contemplates both the racemates and the individual enantiomers.Compounds with preferred stereochemistry are listed below.

[0047]

[0048] Particularly preferred compounds of the present invention are compounds having formula I'a:

[0049] Where R 1 , R 2a , R 2b , R 3 , R 4 , R 5a , R 5b , and A 1 is as defined in the first aspect, and stereoisomers, enantiomers, tautomers and N-oxides of compounds of formula (I'a), and agrochemically acceptable salts thereof.

[0050] As used herein, the term "optionally substituted" means that the referenced group is unsubstituted or substituted with a specified substituent, for example, "C 3 -C 4 Cycloalkyl is optionally substituted by 1 or 2 halogen atoms" means C 3 -C 4 Cycloalkyl, C substituted by 1 halogen atom 3 -C 4 Cycloalkyl and C substituted by 2 halogen atoms 3 -C 4 Cycloalkyl.

[0051] Embodiments according to the present invention are provided as listed below.

[0052] In an embodiment of each aspect of the present invention, A 1 yes

[0053] AN; or

[0054] BC-R 2c , where R 2c is hydrogen or a halogen (such as Cl, F, Br and I); preferably hydrogen.

[0055] In an embodiment of each aspect of the present invention, R 2a yes

[0056] AC 3 -C 6 Cycloalkyl, C 3 -C 6 Cycloalkoxy, substituted by one to three independently selected 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, cyano, and halogen substituted C 3 -C 6 Cycloalkyl, substituted by one to five independently selected from halogen and C 1 -C 3 The substituents of the haloalkyl group are substituted with C 3 -C 6 Cycloalkyl C 1 -C 4 Alkyl, C 1 -C 5 Cyanoalkyl, C 3 -C 6 Cycloalkoxy, C 1 -C 4 Haloalkylsulfonyl or C 1 -C 4 haloalkylsulfinyl; or

[0057] BC 3 -C 4 Cycloalkyl, C 3 -C 4 Cycloalkoxy, substituted by one to three independently selected 1 -C 2 Alkyl, C 1 -C 2 Haloalkyl, C 1 -C 2 Alkoxy, cyano, and halogen substituted C3 -C 4 Cycloalkyl, substituted by one to five independently selected from halogen and C 1 -C 3 The substituents of the haloalkyl group are substituted with C 3 -C 4 Cycloalkyl C 1 -C 2 Alkyl, C 1 -C 3 Cyanoalkyl, C 3 -C 4 Cycloalkoxy, C 1 -C 3 Haloalkylsulfonyl or C 1 -C 3 haloalkylsulfinyl; or

[0058] C. cyclopropyl, cyclopropyl substituted by one to three substituents independently selected from methyl, trifluoromethyl, methoxy, cyano, fluorine and chlorine, cyclopropylmethyl substituted by one to five fluorine substituents, C 1 -C 3 Cyanoalkyl, cyclopropyloxy, trifluoromethylsulfonyl or trifluoromethylsulfinyl; or

[0059] D. cyclopropyl, cyclopropyl substituted by one to three substituents independently selected from methyl, trifluoromethyl, methoxy, cyano, fluorine and chlorine, cyclopropylmethyl substituted by one or two fluorine substituents on the methyl portion, C 1 -C 3 cyanoalkyl, trifluoromethylsulfonyl or trifluoromethylsulfinyl; or

[0060] E. cyclopropyl, cyclopropyl substituted by one to three substituents independently selected from trifluoromethyl, methoxy, cyano, fluorine and chlorine, cyclopropylmethyl substituted by one or two fluorine substituents on the methyl portion, C 1 -C 3 Cyanoalkyl, trifluoromethylsulfonyl.

[0061] In an embodiment of each aspect of the present invention, R 2b yes

[0062] A. Halogen, C 1 -C 3 Haloalkyl, C 1 -C 3 Halogenated alkylthio, C 1 -C 3 Alkoxy, C 1 -C 3 haloalkoxy, or CN; or

[0063] B. Halogen, C 1 -C3 Haloalkyl, or C 1 -C 3 haloalkoxy; or

[0064] C. chlorine, fluorine, difluoromethyl, trifluoromethyl, difluoromethoxy or trifluoromethoxy; or

[0065] D. Difluoromethyl or trifluoromethyl.

[0066] In an embodiment of each aspect of the present invention, R 1 yes

[0067] A. Hydrogen, methyl, ethyl, n-propyl, isobutyl, cyclopropylmethyl or HCH≡CCH 2 -;or

[0068] B. hydrogen, methyl, or cyclopropylmethyl; or

[0069] C. Hydrogen; or

[0070] D. methyl; or

[0071] E. Cyclopropylmethyl.

[0072] In an embodiment of each aspect of the present invention, R 3 yes

[0073] AC 1 -C 3 Alkyl or C 1 -C 3 haloalkyl; or

[0074] B. Methyl.

[0075] In an embodiment of each aspect of the present invention, R 4 yes

[0076] A. 2-pyridine, 2-pyrimidine, 2-pyridine substituted by a substituent selected from cyclopropyl or halogen, or 2-pyrimidine substituted by a substituent selected from cyclopropyl or halogen; or

[0077] B. Selected from O-1 to O-8

[0078]

[0079] C. is selected from O-1, O-3, O-4, O-5, O-6 and O-8; or

[0080] DO-3, O-4, O-5, O-6, or O-8; or

[0081] EO-3, O-4, O-5, or O-8; or

[0082] FO-5 or O-8.

[0083] In an embodiment of each aspect of the present invention, R 5a and R 5b Independently of each other

[0084] A. Hydrogen, halogen, C 1 -C 3 Alkyl, or C 1 -C 3 Alkoxy; or

[0085] B. is selected from hydrogen, bromine, chlorine, methyl, and methoxy; or

[0086] C. Hydrogen.

[0087] The present invention thus makes available the following compounds having the substituents R as defined above in all combinations / permutations: 1 , R 2a , R 2b , R 3 , R 4 , R 5a , R 5b , and A 1 Thus, for example, it is possible to obtain a compound of formula I in which A 1 It belongs to the first aspect (i.e. A 1 Is N or CR 2c , where R 2c H, halogen, C 1 -C 3 Alkyl, C 1 -C 3 Haloalkyl, C 1 -C 3 Alkoxy, or C 1 -C 3 Haloalkoxy); R 1 is Example B (i.e., hydrogen, methyl, cyclopropylmethyl); R 2a is Example C (i.e., cyclopropyl, cyclopropyl substituted by one to three substituents independently selected from methyl, trifluoromethyl, methoxy, cyano, fluorine and chlorine, cyclopropylmethyl substituted by one to five fluorine substituents, C 1 -C 3 cyanoalkyl, cyclopropyloxy, trifluoromethylsulfonyl or trifluoromethylsulfinyl); R 2b Example B (i.e., halogen, C 1 -C 3 Haloalkyl, or C 1 -C 3 Haloalkoxy); R 3 is Example B (i.e., methyl); R 4is Example B (i.e., selected from O-1 to O-8); and R 5a is Example A (i.e. selected from hydrogen, halogen, C 1 -C 3 Alkyl, or C 1 -C 3 alkoxy); and R 5b is Example C (ie, hydrogen).

[0088] In one embodiment, the compound having Formula I can be represented as

[0089]

[0090] Where R 1 , R 3 , R 4 , R 5a , and R 5b is as defined in the first aspect, R 2 is a compound containing A as defined in the first aspect 1 and the substituent R 2a and R 2b cyclic group.

[0091] In an embodiment of each aspect of the present invention, R 2 (Contains A 1 and the substituent R 2a and R 2b Cyclic group)

[0092] A. Selected from K-1 to K-15

[0093]

[0094]

[0095] B. selected from K-1, K-2, K-3, K-5, K-6, K-10, K-11, K-12, K-14, K-15 and K-16; or

[0096] C. selected from K-1, K-2, K-6, K-10, K-12, K-14, K-15 and K-16; or

[0097] D. selected from K-1, K-2, K-5, K-10, K-11, K-14, K-15 and K-16; or

[0098] E. selected from K-1, K-2, K-5, K-6, K-10, K-14, K-15 and K-16; or

[0099] F. is selected from K-1, K-2, K-6, K-10, K-14, K-15 and K-16; or

[0100] G. Selected from K-5, K-10, K-14 and K-15; or

[0101] H. Selected from K-2, K-6, K-14 and K-15; or

[0102] I. Selected from K-2, K-6 and K-10.

[0103] In an embodiment of each aspect of the invention, the compound of formula I has as R 1 hydrogen, methyl, ethyl, n-propyl, isobutyl, cyclopropylmethyl or HCH≡CCH 2 -; as R 2 One of K-1 to K-16; as R 3 Methyl; as R 4 One of O-1 to O-8; and R independently selected from hydrogen, halogen, methyl 5a and R 5b .

[0104] In an embodiment of each aspect of the invention, the compound of formula I has as R 1 as hydrogen, methyl, or cyclopropylmethyl; as R 2 One of K-1 to K-16; as R 3 Methyl; as R 4 One of O-1 to O-8; and R independently selected from hydrogen, halogen, methyl 5a and R 5b .

[0105] In an embodiment of each aspect of the invention, the compound of formula I has as R 1 Hydrogen; as R 2 One of K-1 to K-16; as R 3 Methyl; as R 4 One of O-1 to O-8; and R independently selected from hydrogen, halogen, methyl 5a and R 5b .

[0106] In an embodiment of each aspect of the invention, the compound of formula I has as R 1 as hydrogen, methyl, or cyclopropylmethyl; as R 2 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 R 3 Methyl; as R 4 One of O-1 to O-8 and R independently selected from hydrogen, halogen, methyl 5a and R 5b.

[0107] In an embodiment of each aspect of the invention, the compound of formula I has as R 1 as hydrogen, methyl, or cyclopropylmethyl; as R 2 One of K-1, K-2, K-5, K-6, K-10, K-11, K-14, K-15 and K-16; as R 3 Methyl; as R 4 One of O-1 to O-8; and R independently selected from hydrogen, halogen, methyl 5a and R 5b .

[0108] In an embodiment of each aspect of the invention, the compound of formula I has as R 1 as hydrogen, methyl, or cyclopropylmethyl; as R 2 One of K-1, K-2, K-5, K-6, K-10, K-11, K-14, K-15 and K-16; as R 3 Methyl; as R 4 One of O-1, O-3, O-4, O-5, O-6 or O-8; and R independently selected from hydrogen, halogen, methyl 5a and R 5b .

[0109] In an embodiment of each aspect of the invention, the compound of formula I has as R 1 as hydrogen, methyl, or cyclopropylmethyl; as R 2 One of K-1, K-2, K-5, K-6, K-10, K-11K-14, K-15 and K-16; as R 3 Methyl; as R 4 O-1, O-3, O-4, O-5, O-6 or O-8; and as R 5a and R 5b of each hydrogen.

[0110] In an embodiment of each aspect of the invention, the compound of formula I has as R 1 as hydrogen, methyl, or cyclopropylmethyl; as R 2 One of K-2, K-6 and K-10; as R 3 Methyl; as R 4 O-3, O-4, O-5, or O-8; and as an R 5a and R 5b of each hydrogen.

[0111] 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.

[0112] In a third aspect, the present invention makes available a method for combating and controlling insects, mites, nematodes or molluscs, the method comprising applying an insecticidal, acaricidal, nematicidal or molluscicidal effective amount of a compound as defined in the first aspect or a composition as defined in the second aspect to the pest, the location of the pest, or a plant susceptible to attack by the pest.

[0113] In a fourth aspect, the present invention makes available a method for protecting plant propagation material from attack by insects, mites, nematodes or molluscs, the method comprising treating the propagation material or the site where 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.

[0114] In a fifth aspect, the present invention makes it possible to obtain a plant propagation material, such as a seed, which comprises a compound of formula I as defined in the first aspect or a composition as defined in the second aspect, or is treated with or has attached thereto said compound or said composition.

[0115] In another aspect, the present invention provides a method for controlling parasites in or 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 for controlling external parasites of 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 for preventing and / or treating a disease transmitted by external parasites, the method comprising administering an effective amount of a compound of formula I as defined in the first aspect to an animal in need thereof.

[0116] Compounds of formula I can be prepared by those skilled in the art according to known methods. More specifically, compounds of formula I and I'a and intermediates thereof can be prepared as described below in the schemes and examples. For the sake of clarity, certain stereocenters are not specified and are not intended to limit the teachings of these schemes in any way.

[0117] The process according to the invention for preparing compounds of formula I is carried out by methods known to those skilled in the art.

[0118] Compounds having formula I

[0119]

[0120] It can be prepared by the reaction of: Amines having formula II

[0121]

[0122] Where R 1 , R 3 , R 4 , R 5a , and R 5b is defined as in formula I, and a carboxylic acid derivative having formula III

[0123]

[0124] Where R 2a , R 2b , and A 1 is as defined in Formula I. The chemistry is described in more detail in Scheme 1.

[0125] Scenario 1:

[0126]

[0127] In Scheme 1, a compound of formula III (wherein R 2a , R 2b and A 1 (as defined in Formula I) is activated to a compound having Formula IIIa. For example, wherein X 0 The compound which is a halogen is formed by treating a compound of formula III with, for example, oxalyl chloride or thionyl chloride in the presence of a catalytic amount of DMF in an inert solvent such as dichloromethane or THF at a temperature between 20° C. and 100° C., preferably 25° C. Optionally, the compound is treated with a compound of formula II (wherein R 1 , R 3 , R 4 , R 5a , and R 5b is as defined in formula I) to produce a compound of formula I. Alternatively, the compound of formula I can be prepared by treating a compound of formula III 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 a temperature between 50°C and 180°C to give an activated species IIIa (wherein X 0 Yes X 01 or X02 ). In addition, the acid of formula III can be activated by coupling with a coupling agent such as propanephosphonic anhydride or O-(7-aza-1-benzotriazolyl)-N,N,N',N'-tetramethyluronium-hexafluorophosphate (HATU) to provide 0 Yes X 03 or X 04 Compounds of formula IIIa are prepared as described, for example, in Synthesis 2013, 45, 1569 and Journal Prakt. Chemie 1998, 340, 581. Subsequent reaction with amines of formula II provides compounds of formula I.

[0128] An intermediate having formula II (wherein R 1 , R 3 , R 4 , R 5a and R 5 is as defined in Formula I) can be prepared according to Scheme 2:

[0129] Scenario 2:

[0130]

[0131] In Scheme 2, a compound having Formula IV (wherein X 05 is a leaving group such as chloro, bromo, iodo, arylsulfonate, alkylsulfonate or trifluoromethanesulfonate and R 3 , R 5a and R 5b is as defined in formula I) in the presence of a palladium catalyst (e.g. tetrakis(triphenylphosphine)palladium(0) or (1,1'bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1:1 complex)), in an inert solvent (e.g. DMF, acetonitrile or dioxane), optionally in the presence of an additive (e.g. potassium fluoride or cesium fluoride or lithium chloride), and optionally in the presence of another catalyst (e.g. copper iodide(I)) with a tin compound of formula V (wherein R 4 is as defined in formula I) to give a compound of formula VI (wherein R 3 , R 4 , R 5a and R 5bis as defined in formula I). ​​Such Stille coupling reactions are well known to those skilled in the art and have been 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. Compounds of formula VI may be used in the presence of compounds of formula VII (wherein R 1 is as defined in formula I) for example analogously to WO 2002 / 088073, page 35, in NaBH(OAc) 3 or NaBH 3 In the presence of CN (preferably with NaBH 3 CN as a reducing agent), in a suitable solvent (preferably acetic acid) at room temperature to form a compound of formula II (wherein R 1 , R 3 , R 4 , R 5a and R 5b is as defined in Formula I). ​​Another reagent system for reductive amination uses Ti(i-OPr) in the presence of an amine having Formula VII 4 and NaBH 4 to provide a compound of formula II (see Synthesis 2003 (14), 2206).

[0132] A compound of formula VI (wherein R 3 , R 4 , R 5a , and R 5b is as defined in Formula I) can also be prepared by a Suzuki reaction (Scheme 3), which involves, for example, reacting a compound having Formula IV (wherein R 3 , R 5a , and R 5b is as defined in Formula I and X 05 is a leaving group such as, for example, chloro, bromo, iodo, arylsulfonate, alkylsulfonate or trifluoromethanesulfonate) and a compound of formula VIII (wherein W may be a boron-derived functional group such as, for example, B(OH) 2The reaction may be carried out by a palladium-based catalyst (e.g., tetrakis(triphenylphosphine)-palladium or (1,1'-bis(diphenylphosphino)-ferrocene)dichloropalladium-dichloromethane (1:1 complex)) in the presence of a base (e.g., sodium carbonate or cesium fluoride) in a solvent or solvent mixture (e.g., a mixture of 1,2-dimethoxyethane and water, dioxane and water, or DMF and water), preferably under an inert atmosphere. The reaction temperature may preferably 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.

[0133] Scenario 3:

[0134]

[0135] Reductive amination as already described in Scheme 2 then leads to compounds of the formula II in the same way. Compounds of the formula IV are generally commercially available.

[0136] For preparing a compound having formula II (wherein R 1 , R 3 , R 4 , R 5a , and R 5b Yet another method wherein (I) is as defined in Formula I) is outlined in Scheme 4.

[0137] Solution 4:

[0138]

[0139] For example, a compound of formula VI (wherein R 3 , R 4 , R 5a , and R 5b is as defined in formula I) can be prepared by: making a compound having formula IVa (wherein R 3 , R 5a , and R 5b is as defined in formula I) and a compound of formula XI (wherein R 4(defined in Formula I) in a suitable solvent (preferably dioxane or DMF), in the presence of a Pd catalyst (preferably palladium acetate), a ligand (such as di-tert-butyl(methyl)phosphine) and a base (such as Cs 2 CO 3 ) is present, usually under heating at a temperature between 120° C. and 130° C. Such methods have been described, for example, in J. Am. Chem. Soc. [Journal of the American Chemical Society] 2018, 140, 15916.

[0140] The desired intermediate of formula XI can be prepared from an intermediate of formula IX (wherein R 4 is as defined in Formula I and X 06 Compounds containing halogen or methyl sulfone are obtained by nucleophilic substitution with propane-2-ene-1-thiol and subsequent oxidation with m-CPBA. Such transformations are well known and reported in, for example, J.Am.Chem.Soc. [Journal of the American Chemical Society] 2018, 140, 15916.

[0141] In an alternative method (Scheme 5), a ketone having formula VI (wherein R 3 , R 4 , R 5a , and R 5b is as defined in formula I) can be obtained, for example, by using NaBH 4 The reduction to the alcohol of formula XII is carried out in the usual manner (see, for example, WO 2012 / 082997, page 141), preferably in MeOH as solvent. The reaction is carried out in an inert solvent, preferably in dichloromethane, in the presence of a base, such as triethylamine, with a compound of formula XIII (wherein Y is CH 3 CF 3 or p-CH 3 -C 6 H 4 ) The subsequent activation of the alcohol of formula XII affords a compound of formula XIV (wherein X 07 is OMs, OTs or OTf). It is also possible to prepare the precipitate by methods known to those skilled in the art by using a phosphorus compound (e.g. P(X 0 ) 3 , where X 0 is chlorine or bromine) to activate the alcohol of formula XII to the alkyl halide XIV (wherein X 07is Cl or Br). Such general functional group transformations are described, for example, in Organische Chemie. 4. Auflage [Organic Chemistry 4th Edition], Wiley-VCH Verlag, Weinheim 2005, pp. 393 et ​​seq. and Chem Commun. 2014, 50, 5756. Finally, nucleophilic substitution reaction of compounds of formula XIV with amines of formula VII provides compounds of formula II (wherein R 1 , R 3 , R 4 , R 5a and R 5b is as defined in Formula I).

[0142] Solution 5:

[0143]

[0144] A ketone compound having the formula VI (wherein R 3 , R 4 , R 5a and R 5b is as defined in Formula I) is commercially available or can be prepared as shown in Scheme 6:

[0145] Solution 6:

[0146]

[0147] As shown in Scheme 6, a compound having Formula XV (wherein R 5a and R 5b is as defined in Formula I, Z 1 It is C 1 -C 4 Alkyl and X 05 is a leaving group as defined in formula IV) can be converted to a compound of formula XVI (wherein R 4 , R 5a , R 5b and Z 1is 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, p. 138). Activation of the carboxylic acid (see Scheme 1) and treatment with N-methoxy-N-methylamine (according to Weinreb et al. Tet. Lett. [Tet. Lett.] 1981, 39, 3815) yields a Weinreb amide of formula XVII (wherein R 4 , R 5a , and R 5b is as defined in formula I). 3 Treatment of a compound of formula XVII with MgBr (e.g. MeMgBr) at a relatively low temperature (preferably between 0°C and 25°C) affords an alkyl ketone of formula VI (wherein R 3 , R 4 , R 5a and R 5b is as defined in Formula I).

[0148] Yet another method for preparing compounds of general formula IIa is outlined in Scheme 7.

[0149] Solution 7:

[0150]

[0151] Thus, nucleophilic substitution reaction of a compound of formula XIV with an amine of formula VII provides a compound of formula II (wherein R 1 , R 3 , R 4 , R 5a , and R 5b is as defined in formula I), as already described in detail in Scheme 5. The protective group (e.g. R 1 is benzyl) to give a compound of formula IIa (wherein R 3 , R 4 , R 5a and R 5b is as defined in Formula I) (see, for example, Synlett [Synthesis Express], 2010, (18), p. 2708). A compound of Formula II (wherein R 1 is allyl, and R 3 , R 4 , R 5a and R 5bis as defined in formula I) can also be converted into a compound having formula IIa by the following method: according to J.Org.Chem. [Journal of Organic Chemistry] 1993, 58, 6109, in the presence of a Pd catalyst (preferably tetrakis(triphenylphosphine)-palladium(0)), in a suitable solvent (e.g. CH 2 Cl 2 ) is reacted with N'N' dimethylbarbituric acid to provide a compound having Formula IIa.

[0152] A carboxylic acid having the formula XXI (wherein R 2b and A 1 is as defined in formula I) is an intermediate useful in the preparation of final compounds (see Scheme 1) and can be prepared by the method shown in Scheme 8.

[0153] Solution 8:

[0154]

[0155] Thus, a compound of formula IIIa (wherein R 2b and A 1 is as defined in formula I) can be prepared by: making a compound of formula XXI (wherein R 2b and A 1 is as defined in Formula I and Z 1 It is C 1 -C 4 The alkyl group) is reacted with a suitable base (such as sodium hydroxide or lithium hydroxide) in a suitable solvent (such as MeOH, THF and H 2 O or a mixture thereof), the reaction is usually carried out under heating at a temperature between room temperature and reflux. The compound of formula XXI is prepared by the following method: in a solvent (preferably CH 2 Cl 2 or CHCl 3 or H 2 O, AcCN and CCl 4 mixture), for example, with m-CPBA or NaIO 4 / RuCl 3 Oxidation of the compound of formula XXa Such transformations are known to the person skilled in the art and are described, for example, in J. Med. Chem. 2008, 51, 6902 or WO 2004 / 9086, pages 24-25.

[0156] Finally, compounds of formula XXa (wherein R 2b and A 1 is as defined in Formula I and Z 1 It is C 1 -C4 alkyl) can be prepared by: making a compound having the formula XVIIIa (wherein R 2b and A 1 is as defined in Formula I and X 08 is Br or Cl) with a suitable trifluoromethylthiolate copper reagent of formula XIX (ligand is, for example, 1,10-phenanthroline or 4,4'-di-tert-butylbipyridyl), in a suitable solvent (e.g. acetonitrile or DMF), usually under heating at a temperature between 20°C and 150°C, preferably between 40°C and the boiling point of the reaction mixture. Such methods have been previously described, for example, in Angew. Chem. Int. Ed. [Applied Chemistry International Edition] 2013, 52, 1548-1552, Angew. Chem. Int. Ed. [Applied Chemistry International Edition] 2011, 50, 3793, Org. Lett. [Organic Letters] 2014, 16, 1744, J. Org. Chem. [Organic Chemistry Journal] 2017, 82, 11915.

[0157] Additional intermediates of formula XX (wherein R 2a , R 2b and A 1 is as defined in Formula I, and Z 1 It is C 1 -C 4 Alkyl) are generally known to or can be easily prepared by a person skilled in the art. A typical example of such a synthesis of compounds having formula XX is shown in Scheme 9.

[0158] Solution 9:

[0159]

[0160] For example, a compound of formula XX can be prepared by reacting a compound of formula XVIIIb (wherein R 2b and A 1 is as defined for Formula I and X 05 is chlorine, bromine, iodine, OMs, OTs or OTf) and a compound of formula XXIII (wherein R 2a is defined in Formula I) over a palladium catalyst (e.g., Pd(PPh 3 ) 4), in a suitable solvent (e.g., toluene / water, 1,4-dioxane / water), in the presence of a suitable base (e.g., sodium carbonate, potassium carbonate or cesium carbonate or tripotassium phosphate), typically at room temperature and 200° C., preferably at a temperature between 20° C. and the boiling point of the reaction mixture, optionally under microwave heating conditions. Such methods have been previously described, for example, in Tetrahedron Letters [tetrahedron express] 2002, 43, 6987–6990.

[0161] The compound of formula XX can also be prepared by reacting a compound of formula XXIV (wherein R 2b and A 1 and Z 1 is as defined in formula XX) and a compound of formula XXV (wherein R 2a is as defined in Formula I and X 05 is a leaving group, e.g., bromine or iodine) on a palladium catalyst (e.g., PdCl 2 (dppf)), in a suitable solvent (which may include, for example, toluene / water, 1,4-dioxane / water), in the presence of a suitable base (such as sodium carbonate, potassium carbonate or cesium carbonate or tripotassium phosphate), usually at room temperature and 200 ° C, preferably at a temperature between 20 ° C and the boiling point of the reaction mixture, optionally under microwave heating conditions. Such methods have been previously described, for example, in WO 12139775, page 73.

[0162] A compound of formula XXIV (wherein R 2b and A 1 and Z 1 is as defined in Formula I) can be prepared by: making a compound of Formula XVIIIb (wherein R 2b and A 1 and Z 1 is as defined in Formula XXIV and X 05 is Cl, Br, I, OMs, OTs or OTf) and a compound having formula XXII (e.g., bis(pinacolato)diboron (B2pin2)) in the presence of a palladium catalyst (e.g., PdCl 2(dppf)), in a suitable solvent (which may include, for example, toluene / water, 1,4-dioxane / water), in the presence of a suitable base (such as sodium carbonate, potassium carbonate or cesium carbonate or potassium acetate), usually between room temperature and 200 ° C, preferably at a temperature between 20 ° C and the boiling point of the reaction mixture, optionally under microwave heating conditions. Such methods have been previously described, for example, in Bioorg. Med. Chem. Lett. [Biological Organic and Medicinal Chemistry Express] 2015, 25, 1730, and WO 12139775, No. 67.

[0163] 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, THF / MeOH mixtures), 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).

[0164] The compound of formula XXVIII (wherein R 2b and A 1 is defined in Formula I and R 2a It is H, C 1 -C 3 Alkyl, C 1 -C 3 haloalkyl, cyano or halogen and Z 1 It is C 1 -C 4 alkyl) can be prepared by reacting a compound of formula XXVI (e.g. (trifluoroethyl)-diphenyl-sulfonium trifluoromethanesulfonate (Ph 2 S + CH 2 CF 3 – Compounds of formula XXVII (analogously to Org. Lett. [Organic Letters] 2016, 18, 2471) are obtained as mixtures of stereoisomers with the trans isomer being the main isomer.

[0165] Yet another method for preparing compounds of formula XXVIII (see Scheme 10) uses trifluoroethylamine hydrochloride / NaNO in the presence of an iron catalyst. 2 / NaOAc; This reaction was carried out at room temperature in H 2 O or in CH 2 Cl 2 and H 2 O, see, for example, Angew. Chem. Int. Ed. [Applied Chemistry International Edition] 2010, 49, 938 and Chemm. Commun. [Chemical Communications] 2018, 54, 5110.

[0166] Solution 10:

[0167]

[0168] A carboxylic acid having the formula IIIc (wherein R 2b and A 1 is as defined in Formula I and R 2aa It is H, C 1 -C 3 Alkyl, C 1 -C 3 The radicals (haloalkyl, cyano or halogen) can be prepared in a rather analogous manner as already shown in Scheme 10.

[0169] Solution 11:

[0170]

[0171] Thus, a compound of formula XXIX (wherein R 2b and A 1 is as defined in Formula I and R 2aa It is H, C 1 -C 3 Alkyl, C 1 -C 3 haloalkyl, cyano or halogen and Z 1 It is C 1 -C 4 The compound of formula XXVII (synthesized similarly to ACS Med. Chem. Lett. [ACS Medicinal Chemistry Express] 2013, 4, 514 or Tetrahedron Lett. [Tetrahedron Express] 2001, 42, 4083) is prepared by reacting (bromodifluoromethyl)-trimethylsilane in NH 4 + Br -The reaction is carried out in the presence of in a suitable solvent, preferably in THF or toluene, at a temperature between 70° C. and 110° C. Subsequent saponification of the ester intermediate XXIX provides compounds of formula IIIc (Scheme 11).

[0172] Solution 12.

[0173]

[0174] A carboxylic acid having the formula IIId (wherein R 2b and A 1 is as defined in Formula I and R 2aa It is H, C 1 -C 3 Alkyl, C 1 -C 3 haloalkyl, cyano or halogen) can be prepared according to Reaction Scheme 12. Thus, a compound having Formula XVIIIa (wherein R 2b and A 1 is as defined in Formula I, Z 1 It is C 1 -C 4 Alkyl and X 08 is bromine or iodine) is treated with iPrMgCl / LiCl-complex; subsequently reacted with CuCN and with cyclopropanecarbonyl chloride of formula XXX (wherein R 2a It is H, C 1 -C 3 Alkyl, C 1 -C 3 Quenching with a haloalkyl, cyano or halogen) provides compounds of formula XXXI (similar to WO 2006 / 067445, page 148). Fluorination with 2,2-difluoro-1,3-dimethylimidazoline in a solvent (e.g. in 1,2-dimethoxy-ethane) or in pure form (see Chem. Commun. 2002, (15), 1618) gives compounds of formula XXXII. Subsequent hydrolysis using, for example, LiOH as already described yields carboxylic acids of formula IIId.

[0175] Solution 13:

[0176]

[0177] In zinc(II) fluoride (ZnF 2 ) and a palladium(0) catalyst such as tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (Pd 2 (dba) 3 CHCl 3) in the presence of an inert solvent such as N,N-dimethylformamide (DMF) at a temperature between 100°C and 180°C, optionally under microwave heating, treating a compound of formula XVIIIc (wherein R 2b and A 1 is as defined in Formula I, X 09 is a leaving group, such as a halogen or a sulfonate, preferably chloro, bromo, iodo or trifluoromethanesulfonate, and Z 1 It is C 1 -C 4 alkyl) to produce a compound having the formula XXXV (wherein R 2b , Z 1 and A 1 is as defined in formula XVIIIc). Such chemical processes have been described in the literature, for example in Org. Lett. [Organic Letters], 16 (24), 6314-6317, 2014. Alternatively, a compound of formula XVIIIc is reacted 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(PPh 3 ) 2 Cl 2 )) in the presence of an inert solvent (such as dimethyl sulfoxide DMSO), optionally in a mixture with water, at a temperature between 40°C and 150°C, optionally under microwave heating to produce a compound of formula XXXVII (wherein R 2b , A 1 is as defined in Formula I and Z 1 It is C 1 -C 4 The compound of formula XXXVII is reacted with aqueous potassium fluoride (KF concentration between 0.5 and 3 M, preferably 1 M) in an inert solvent (such as dimethyl sulfoxide DMSO or methanol) at a temperature between 20°C and 150°C, optionally under microwave heating to produce a compound of formula XXXV (wherein R 2b , Z 1 and A 1 is as defined in formula XVIIIc). Such chemistry has been described in the literature, for example in J. Am. Chem. Soc. [Journal of the American Chemical Society] 2011, 133, 6948-6951.

[0178] The compound of formula XXXV (wherein R 2b and A 1 is as defined in Formula I and Z 1 It is C 1 -C 4The alkyl) can be further reacted with a base (such as sodium hydride, sodium carbonate, potassium carbonate, K 2 CO 3 , or cesium carbonate Cs 2 CO 3 ) in the presence of an inert solvent (such as N,N-dimethylformamide (DMF), acetone, or acetonitrile) at a temperature between 0°C and 120°C with a compound of formula XXXIV (wherein X 10 is a leaving group, such as a halogen (preferably chlorine, bromine or iodine) to give a compound of formula XXXVI (wherein R 2b and A 1 is as defined in Formula I above and Z 1 It is C 1 -C 4 Alternatively, the reaction can be carried out by reacting the catalyst (e.g., Pd with a ligand (e.g., BINAP) 2 (dba) 3 Compounds of formula XXXVI can be prepared directly from compounds of formula XVIIIc by treating them with compounds of formula XXXVIII in the presence of a strong base such as lithium hexamethyldisilazane (LiHMDS) in an inert solvent such as tetrahydrofuran (THF) at a temperature between 30°C and 80°C. Such chemical processes have been described, for example, in J.Am.Chem.Soc. [Journal of the American Chemical Society] 127(45), 15824-15832, 2005.

[0179] Yet another method for preparing a compound of Formula XXXV from a compound of Formula XVIIIc is shown in Scheme 13. 2b and A 1 is as defined in Formula I, Z 1 It is C 1 -C 4 Alkyl and X 09 is a leaving group, such as a halogen or sulfonate, preferably chloro, bromo, iodo or trifluoromethanesulfonate) and a reagent having the formula XXXVIII (wherein Z 2 It is C 1 -C 4 alkyl) in the presence of a base (such as sodium carbonate, potassium carbonate or cesium carbonate, or sodium hydride, sodium methoxide or sodium ethoxide, potassium tert-butoxide), optionally in the presence of palladium (for example including Pd(PPh 3 ) 2 Cl 2) or copper (e.g., including CuI) catalysis, in a suitable solvent (such as, for example, toluene, dioxane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone (NMP) or dimethyl sulfoxide (DMSO)), optionally in the presence of a phase transfer catalyst PTC (such as, for example, tetrabutylammonium bromide or triethylbenzylammonium chloride TEBAC), at a temperature between room temperature and 180 °C to carry out a reaction to produce a compound having formula XXXIX (wherein R 2b and A 1 are as defined in formula I and Z 1 and Z 2 each is C 1 -C 4 alkyl). The compound having formula XXXIX can be decarboxylated under the following conditions to obtain a compound having formula XXXV: heating in wet DMSO, optionally in the presence of lithium chloride or sodium chloride, at a temperature between 50 °C and 180 °C. Similar chemical processes have been described, for example, in Synthesis 2010, issue 19, 3332 - 3338.

[0180] The compound having formula I’a

[0181]

[0182] can be prepared by the reaction of: an amine having formula IIb

[0183]

[0184] wherein R 1 、R 3 、A 2 、R 4 、R 5a 、and R 5b are as described in formula I, with a carboxylic acid derivative having formula III, wherein A 1 、R 2a and R 2b are as described above under formula I.

[0185]

[0186] The said chemical process is described in more detail in Scheme 14.

[0187] Solution 14:

[0188]

[0189] The compound having formula IIIa (wherein A 1 、R 2a 、R2b and X 0 is described in Scheme 1) can be used with a compound having Formula IIb (wherein R 1 , R 3 , R 4 , R 5a and R 5b is described in Formula I) is treated under the conditions detailed in Scheme 1. The formation of compounds of Formula IIIa from compounds of Formula III is described in Scheme 1.

[0190] The formation of compounds of formula IIb is outlined in Scheme 15. Compounds of formula IIb can be prepared, for example, by reacting a mixture of 2-hydroxy-1-nitropropene in NaBH(OAc) 3 or NaBH 3 CN in a suitable solvent, preferably acetic acid, at room temperature, analogously to WO 2002 / 088073, page 35, with a compound of formula XL (wherein R 1 is as defined in formula I) treating a compound of formula IIc (wherein R 3 , R 4 , R 5a and R 5b is as described in Formula I). ​​Alternatively, another reagent system for reductive amination uses Ti(i-OiPr) 4 and NaBH 4 combination (see Synthesis 2003(14), 2206).

[0191] Amines of formula IIc can be obtained by biocatalytic deracemization of amines of formula IIa. This can be accomplished, for example, using a final immobilized form (e.g. 435), such as Candida Antarctica lipase B or Pseudomonas fluorescens lipase, 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 a temperature between 20° C. and 100° C. Such methods are described, for example, in J. Org. Chem. [Journal of Organic Chemistry] 2007, 72, 6918-6923 or Adv. Synth. Catal. [Advanced Synthesis and Catalysis] 2007, 349, 1481-1488. The expected stereochemical outcome of such enzymatic deracemization is known to the person 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.

[0192] Solution 15:

[0193]

[0194] In an alternative approach, compounds of formula IIc can be synthesized as described in Scheme 16 from XIIa (wherein R 3 , R 4 , R 5a and R 5b is obtained as described in formula I).

[0195] Solution 16:

[0196]

[0197] Amines of formula IIc can be prepared from intermediates of formula XLI (wherein R 3 , R 4 , R 5a , and R 5b is as described in Formula I and Z 3 Is NPhth or NBoc 2 ). Such intermediates can be obtained from alcohols of formula XIIa by the 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-butyloxycarbonyl)amine). The Mitsunobu reaction is known to those skilled in the art for inversion of stereocenters, as described, for example, in Chem. Rev. 2009, 109, 2551-2651. The reaction can then be carried out by reacting with hydrazine (if Z 3 =NPhth) or with TFA (if Z 3 =NBoc 2 ) to convert the amine of formula XLI to the amine of formula IIc.

[0198] Alternatively, the amine of formula IIc can be reduced to the azide of formula XLII (wherein R 3 , R 4 , R 5a and R 5b The azide of formula XLII can be obtained by treating an alcohol of formula XIIa (wherein R 3 , R4 , R 5a and R 5b is as described in formula I). ​​Such methods are known to those skilled in the art for inversion of stereocenters and are described in the literature, for example, in Adv. Synth. Catal. [Advanced Synthesis and Catalysis] 2018, 360, 2157-2165.

[0199] The alcohol of formula XIIa can be obtained by reacting a ketone of formula VI (wherein R 3 , R 4 , R 5a and R 5b is as described in Formula I) by enantioselective reduction. Such reduction can be obtained in a hydrogen donor system (such as, for example, HCOOH / Et 3 N or HCO 2 NH 4 ) in the presence of a catalyst (e.g., a ruthenium or rhodium catalyst with a chiral ligand such as RuCl[(R,R)-TsDPEN] (mesitylene) or RuBF 4 [(R,R)-TsDPEN](p-cymene)). Such methods are described in the literature, for example in J.Org.Chem. [Journal of Organic Chemistry] 2017, 82, 5607.

[0200] Alternatively, compounds of formula IIc can also be prepared as outlined in Scheme 17.

[0201] Solution 17:

[0202]

[0203] The amine of formula IIc can be prepared by, for example, treating an amine of formula XLIX (wherein R 3 , R 4 , R 5a and R 5b Amines of formula XLIX can be prepared from amines of formula XLVIII (wherein R 3 , R 4 is described in Formula I and Z 5 a and Z 5 b are independently selected from R 5 a. R 5 b. Halogen, NH 2Such functional group interconversions are known to those skilled in the art and examples of such transformations 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 reacting diketones of formula XLVI (wherein R 3 and R 4 The diketone of formula XLVI can be obtained by oxidizing a hydroxyketone of formula XLIV (wherein R 3 and R 4 is as described in Formula I). ​​This oxidation may involve, for example, SO in the presence of DMSO and a base (e.g., triethylamine). 3 -pyridine, or alternatively in the presence of a catalyst (such as TEMPO / Bu 4 NHSO 4 ) in the presence of sodium hypochlorite. Examples of such oxidations can be found in the literature, for example Synlett [Synthesis Express], 2014, 25, 596 or J. Am. Chem. Soc. [Journal of the American Chemical Society] 1990, 112, 5290-5313. Hydroxyl ketones of formula XLIV can be obtained by reacting aldehydes of formula XLIII (wherein R 4 is described in Formula I) and an aldehyde having Formula XLV (wherein R 3 The cross-benzoin condensation is synthesized by a cross-benzoin condensation between two chiral aldehydes (described in formula I). ​​Aldehydes of formula XLV are commercially available in chiral form, such as, 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 have been described in the literature, for example in J. Am. Chem. Soc. [Journal of the American Chemical Society] 2014, 136, 7539-7542 or Org. Lett. [Organic Letters] 2016, 18, 4518-4521.

[0204] Alternatively, the compound of formula I'a can be prepared from a chiral compound of formula L (wherein A1 , R 1 , R 2a , R 2b , R 3 , R 5a and R 5b is defined in Formula I and X 05 is a leaving group like for example chloro, bromo or iodo) as shown in Scheme 18.

[0205] Solution 18:

[0206]

[0207] Compounds of formula I'a can be prepared by reacting a compound of formula L with a compound of formula V (Stiller reaction) or a compound of formula VIII (Suzuki-Miyaura reaction) in the presence of a palladium catalyst as described in detail in Schemes 2 and 3.

[0208] The compound of formula L can be prepared by reacting an amine of formula LIa (wherein R 1 , R 3 , R 5a , and R 5b is defined in Formula I, and X 05 is a leaving group, such as, for example, chloro, bromo, iodo) and a compound having formula IIIa (wherein A 1 , R 2a , R 2b and X 0 is described in Scheme 1) under the conditions described in detail in Scheme 1. Under the same conditions, if R 1 =H, then the compound of formula L can be obtained directly from the compound of formula LI (wherein R1, R3, R5a and R5b are as defined in formula I, and X05 is a leaving group, such as, for example, chlorine, bromine, iodine).

[0209] Compounds of formula LIa can be prepared, for example, by reacting NaBH(OAc) 3 or NaBH 3 CN in a suitable solvent, preferably acetic acid, at room temperature, analogously to WO 2002 / 088073, page 35 with a compound of the formula XL (wherein R 1 is as defined in formula I) to treat a compound having formula LI. Alternatively, another reagent system for reductive amination uses Ti(OiPr) 4 and NaBH 4 combination (see Synthesis 2003(14), 2206).

[0210] Amines of formula LI can be prepared by deracemization procedures involving, for example, selective acylation of one enantiomer. Such an example is described in more detail in Scheme 19.

[0211] Solution 19:

[0212]

[0213] Amines of formula LI can be biocatalytically deracemized to amines of formula LIb (where R 3 , R 5a , and R 5b is as described in Scheme 1 and X 05 is a leaving group such as bromine, chloride, iodine, mesylate, tosylate or triflate). This can be achieved, for example, using a final immobilized form (e.g. 435), such as Candida antarctica lipase B or Pseudomonas fluorescens lipase, 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 a temperature between 20° C. and 100° C. Such methods are described, for example, in J. Org. Chem. [Journal of Organic Chemistry] 2007, 72, 6918-6923 or Adv. Synth. Catal. [Advanced Synthesis and Catalysis] 2007, 349, 1481-1488. The expected stereochemical results of such enzymatic deracemization are known to those skilled in the art and are documented in the literature, for example, in J. Org. Chem. [Journal of Organic Chemistry] 1991, 56, 2656-2665 or J. Am. Chem. Soc. [Journal of the American Chemical Society] 2015, 137, 3996-4009.

[0214] Alternatively, resolution of amines of formula LIb can be achieved using a chiral auxiliary as described in Scheme 20.

[0215] Solution 20

[0216]

[0217] Amines of formula LI can be prepared from intermediates of formula LII (wherein R 3 , R 5a , and R 5b is described in Scheme 1, X 05 is a leaving group such as bromine, chloride, iodine, mesylate, tosylate or triflate and X 11* is a chiral auxiliary). Amines of formula LII can be formed by reacting a chiral compound of formula LIII (wherein X 0 is as described in Scheme 1 and X 11 * is a chiral moiety with known chirality) is coupled with an amine of formula LIb. The chiral auxiliary of formula LIII is derived, for example, from mandelic acid or (1R)-methylchloroformate. Examples of such deracemization are reported in the literature, for example, in J.Org.Chem. [Journal of Organic Chemistry] 2007, 72, 485-493.

[0218] Alternatively, amines of formula LI can be formed as described in Scheme 21.

[0219] Solution 21:

[0220]

[0221] Amines of formula LI can be prepared from intermediates of formula LIV (wherein R 3 , R 5a , and R 5b is as described in Formula I, X 05 is a leaving group as described in Scheme 3 and Z 3 Is NPhth or NBoc 2 ). Such intermediates can be obtained from alcohols of formula IVa (wherein R 3 , R 5a , and R 5b is as described in Formula I and X 05 is a leaving group as described in Scheme 3) is obtained by the Mitsunobu reaction, which 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-butyloxycarbonyl)amine). The Mitsunobu reaction is known to those skilled in the art for inversion of stereocenters, as described, for example, in Chem. Rev. 2009, 109, 2551-2651. The reaction can then be carried out by treating with hydrazine (if Z 3 =NPhth) or with TFA (if Z 3 =NBoc 2 ) to convert the amine having formula LIV to the amine having formula LI.

[0222] Alternatively, the amine of formula LI can be reduced to an azide of formula LV (wherein R 3 , R 5a , and R 5bis 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 treating alcohols of formula IVa with an azidating agent (such as diphenylphosphoryl azide) in a solvent (such as toluene or THF) in the presence of a base (such as DBU). Such methods are known to those skilled in the art for inversion of stereocenters and are described in the literature, for example, in Adv. Synth. Catal. [Advanced Synthesis and Catalysis] 2018, 360, 2157–2165.

[0223] The alcohol of formula IVa can be prepared by reacting a ketone of formula IV (wherein R 3 , R 5a , and R 5b is as described in Formula I and X 05 is a leaving group as described in Scheme 3) by enantioselective reduction. Such reduction can be obtained in a hydrogen donor system (such as, for example, HCOOH / Et 3 N or HCO 2 NH 4 ) in the presence of a catalyst (e.g., a ruthenium or rhodium catalyst with a chiral ligand such as RuCl[(R,R)-TsDPEN] (mesitylene) or RuBF 4 [(R,R)-TsDPEN](p-cymene)). Such methods are described in the literature, for example in J.Org.Chem. [Journal of Organic Chemistry] 2017, 82, 5607.

[0224] Depending on the procedure or reaction conditions, the reactants may 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, alkylamines, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

[0225] These reactants can react with each other as is, i.e. without adding solvent or diluent. However, in most cases, it is advantageous to add an inert solvent or diluent or a mixture of these. If 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 a solvent or diluent.

[0226] These reactions are advantageously carried out in a temperature range of from about -80°C to about +140°C, preferably from about -30°C to about +100°C, and in many cases in a range between ambient temperature and about +80°C.

[0227] Depending on the reaction conditions and the starting materials chosen which are appropriate in the respective case, it is possible, for example, to replace only one substituent with another substituent according to the invention in one reaction step or to replace several substituents with further substituents according to the invention in one and the same reaction step.

[0228] 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 are obtained by treatment with a suitable acid or a suitable ion exchanger reagent, and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent.

[0229] Salts of compounds of the formula I can be converted in a customary manner into the free compounds I, acid addition salts (for example by treatment with suitable basic compounds or with suitable ion exchanger reagents) and salts with bases (for example by treatment with suitable acids or with suitable ion exchanger reagents).

[0230] Salts of compounds of formula I can be converted into other salts, acid addition salts of compounds of formula I in a manner known per se, for example into other acid addition salts, for example by treating salts of inorganic acids (such as hydrochlorides) with suitable metal salts of the acid (such as sodium, barium or silver salts, for example with silver acetate) in a suitable solvent in which the inorganic salt formed (such as silver chloride) is insoluble and therefore precipitates from the reaction mixture.

[0231] Depending on the procedure or reaction conditions, those compounds of the formula I which have salt-forming properties can be obtained in free form or in the form of salts.

[0232] Depending on the number of asymmetric carbon atoms present in the molecule, the absolute and relative configuration and / or on the configuration of non-aromatic double bonds present in the molecule, the compounds of the formula I and, where appropriate, their tautomers, in each case in free form or in salt form, may be present in the form of one of the possible isomers or as a mixture of these, for example in the form of pure isomers, such as enantiomers and / or diastereomers, or as isomer mixtures, such as enantiomeric mixtures, for example racemates, diastereomeric mixtures or racemic mixtures; the invention relates to the pure isomers and also to all possible isomer mixtures, and the above and below are to be understood as such in each case, even if stereochemical details are not explicitly mentioned in each case.

[0233] Diastereomeric mixtures or racemic mixtures of compounds of formula I in free form or in salt form, which can be obtained depending on the starting materials and procedures chosen, can be separated in a known manner into the pure diastereomers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and / or chromatography.

[0234] Enantiomeric mixtures that can be obtained in an analogous manner (such as racemates) can be resolved into the optical antipodes by known methods, for example by recrystallization from optically active solvents; by chromatography on chiral adsorbents, such as high performance liquid chromatography (HPLC) on acetylcellulose; by cleavage with specific immobilized enzymes with the aid of suitable microorganisms; by forming containing compounds, for example using chiral crown ethers, in which only one enantiomer is complexed; or by conversion into diastereomeric salts, for example by reacting the basic end product racemate with an optically active acid (such as a carboxylic acid, such as camphoric acid, tartaric acid or malic acid, or a sulfonic acid, such as camphorsulfonic acid), and separating the diastereomeric mixture that can be obtained in this way, for example by fractional crystallization based on their different solubility, thereby obtaining the diastereomers from which the desired enantiomer can be freed by the action of a suitable reagent (such as a basic reagent).

[0235] Pure diastereomers or enantiomers can be obtained according to the invention not only by separation of the appropriate isomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the methods according to the invention with starting materials having the appropriate stereochemistry.

[0236] The oxidative reaction can be carried out by reacting a compound of formula I with a suitable oxidizing agent (e.g., H 2 O 2 / urea adduct) in the presence of anhydrides (e.g. trifluoroacetic anhydride) to prepare N-oxides. Such oxidations are known from the literature, for example from J. Med. Chem. [Journal of Medicinal Chemistry], 32 (12), 2561-73, 1989 or WO 2000 / 15615.

[0237] If the individual components have different biological activities, it is advantageous to separate or synthesize the biologically more effective isomers, such as enantiomers or diastereomers or isomer mixtures, such as enantiomeric mixtures or diastereomeric mixtures, in each case.

[0238] If appropriate, the compounds of the formula I and, where appropriate, their tautomers (in each case in free form or in salt form) can also be obtained in the form of hydrates and / or include further solvents, such as those which can be used for crystallization of compounds present in solid form.

[0239] The compounds of formula I according to the following tables A-1 to A-21 can be prepared according to the methods described above. The following examples are intended to illustrate the invention and to show preferred compounds of formula I in the form of compounds of formula Iaa.

[0240]

[0241] Table A-1 16 compounds A-1.001 to A-1.016 having formula Iaa are provided, wherein R 1 Yes H, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z. For example, A-1.002 is

[0242]

[0243] Table Z : R 2 Definition of substituents:

[0244]

[0245]

[0246] Table A-2 16 compounds A-2.001 to A-2.016 having formula Iaa are provided, wherein R 1 Yes H, R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0247] Table A-316 compounds A-3.001 to A-3.016 having formula Iaa are provided, wherein R 1 Yes H, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0248] Table A-4 16 compounds A-4.001 to A-4.016 having formula Iaa are provided, wherein R 1 Yes H, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0249] Table A-5 16 compounds A-5.001 to A-5.016 having formula Iaa are provided, wherein R 1 Yes H, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0250] Table A-6 16 compounds A-6.001 to A-6.016 having formula Iaa are provided, wherein R 1 Yes H, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0251] Table A-7 16 compounds A-7.001 to A-7.016 having formula Iaa are provided, wherein R 1 Yes H, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0252] Table A-8 Provided are 16 compounds A-8.001 to A-8.016 having formula Iaa, wherein R 1 Yes CH 3 , R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0253] Table A-9 16 compounds A-9.001 to A-9.016 having formula Iaa are provided, wherein R 1 Yes CH 3 , R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0254] Table A-10 16 compounds A-10.001 to A-10.016 having formula Iaa are provided, wherein R 1 Yes CH 3 , R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0255] Table A-11 Provided are 16 compounds A-11.001 to A-11.016 having formula Iaa, wherein R 1 Yes CH 3 , R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0256] Table A-12 16 compounds A-12.001 to A-12.016 having formula Iaa are provided, wherein R 1 Yes CH 3 , R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0257] Table A-13 16 compounds A-13.001 to A-13.016 having formula Iaa are provided, wherein R 1 Yes CH 3 , R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0258] Table A-14 16 compounds A-14.001 to A-14.016 having formula Iaa are provided, wherein R 1 Yes CH 3 , R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0259] Table A-15 16 compounds A-15.001 to A-15.016 having formula Iaa are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0260] Table A-16 Provided are 16 compounds A-16.001 to A-16.016 having formula Iaa, wherein R 1Yes CH 2 Cyp, R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0261] Table A-17 Provided are 16 compounds A-17.001 to A-17.016 having formula Iaa, wherein R 1 Yes CH 2 Cyp, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0262] Table A-18 16 compounds A-18.001 to A-18.016 having formula Iaa are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0263] Table A-19 16 compounds A-19.001 to A-19.016 having formula Iaa are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0264] Table A-20 16 compounds A-20.001 to A-20.016 having formula Iaa are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0265] Table A-21 16 compounds A-21.001 to A-21.016 having formula Iaa are provided, wherein R 1 Yes CH 2 Cyp, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0266] The compounds of formula I according to the following tables B-1 to B-21 can be prepared according to the methods described above. The following examples are intended to illustrate the invention and to show preferred compounds of formula I in the form of compounds of formula Iab.

[0267]

[0268] Table B-1 16 compounds B-1.001 to B-1.016 of formula Iab are provided, wherein R 1 Yes H, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0269] Table B-2 16 compounds B-2.001 to B-2.016 of Formula Iab are provided, wherein R 1 Yes H, R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0270] Table B-3 16 compounds B-3.001 to B-3.016 of Formula Iab are provided, wherein R 1 Yes H, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0271] Table B-4 16 compounds B-4.001 to B-4.016 of Formula Iab are provided, wherein R 1 Yes H, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0272] Table B-5 16 compounds B-5.001 to B-5.016 of Formula Iab are provided, wherein R 1 Yes H, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0273] Table B-6 16 compounds B-6.001 to B-6.016 of Formula Iab are provided, wherein R 1 Yes H, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0274] Table B-7 16 compounds B-7.001 to B-7.016 of Formula Iab are provided, wherein R 1 Yes H, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0275] Table B-8 16 compounds B-8.001 to B-8.016 of Formula Iab are provided, wherein R 1 Yes CH 3 , R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0276] Table B-9 16 compounds B-9.001 to B-9.016 of Formula Iab are provided, wherein R 1 Yes CH 3 , R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0277] Table B-10 16 compounds B-10.001 to B-10.016 of Formula Iab are provided, wherein R 1 Yes CH 3 , R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0278] Table B-11 Provided are 16 compounds B-11.001 to B-11.016 having formula Iab, wherein R 1 Yes CH 3 , R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0279] Table B-12 Provided are 16 compounds B-12.001 to B-12.016 having formula Iab, wherein R 1 Yes CH 3 , R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0280] Table B-13 16 compounds B-13.001 to B-13.016 of Formula Iab are provided, wherein R 1 Yes CH 3 , R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0281] Table B-1416 compounds B-14.001 to B-14.016 of Formula Iab are provided, wherein R 1 Yes CH 3 , R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0282] Table B-15 16 compounds B-15.001 to B-15.016 of Formula Iab are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0283] Table B-16 Provided are 16 compounds B-16.001 to B-16.016 having formula Iab, wherein R 1 Yes CH 2 Cyp, R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0284] Table B-17 16 compounds B-17.001 to B-17.016 of Formula Iab are provided, wherein R 1 Yes CH 2 Cyp, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0285] Table B-18 16 compounds B-18.001 to B-18.016 of Formula Iab are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0286] Table B-19 Provided are 16 compounds B-19.001 to B-19.016 having formula Iab, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0287] Table B-20 16 compounds B-20.001 to B-20.016 of Formula Iab are provided, wherein R1 Yes CH 2 Cyp, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0288] Table B-21 16 compounds B-21.001 to B-21.016 of Formula Iab are provided, wherein R 1 Yes CH 2 Cyp, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0289] The compounds of formula I according to the following tables C-1 to C-21 can be prepared according to the methods described above. 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 lac.

[0290]

[0291] Table C-1 Provided are 16 compounds C-1.001 to C-1.016 having formula Iac, wherein R 1 Yes H, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0292] Table C-2 16 compounds C-2.001 to C-2.016 of formula Iac are provided, wherein R 1 Yes H, R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0293] Table C-3 16 compounds C-3.001 to C-3.016 of formula Iac are provided, wherein R 1 Yes H, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0294] Table C-4 16 compounds C-4.001 to C-4.016 of formula Iac are provided, wherein R 1 Yes H, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0295] Table C-516 compounds C-5.001 to C-5.016 having formula Iac are provided, wherein R 1 Yes H, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0296] Table C-6 16 compounds C-6.001 to C-6.016 of formula Iac are provided, wherein R 1 Yes H, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0297] Table C-7 16 compounds C-7.001 to C-7.016 having formula Iac are provided, wherein R 1 Yes H, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0298] Table C-8 Provided are 16 compounds C-8.001 to C-8.016 having formula lac, wherein R 1 Yes CH 3 , R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0299] Table C-9 Provided are 16 compounds C-9.001 to C-9.016 having formula Iac, wherein R 1 Yes CH 3 , R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0300] Table C-10 16 compounds C-10.001 to C-10.016 having formula Iac are provided, wherein R 1 Yes CH 3 , R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0301] Table C-11 Provided are 16 compounds C-11.001 to C-11.016 having formula Iac, wherein R 1 Yes CH 3 , R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2is as defined in Table Z.

[0302] Table C-12 Provided are 16 compounds C-12.001 to C-12.016 having formula Iac, wherein R 1 Yes CH 3 , R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0303] Table C-13 Provided are 16 compounds C-13.001 to C-13.016 having formula Iac, wherein R 1 Yes CH 3 , R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0304] Table C-14 Provided are 16 compounds C-14.001 to C-14.016 having formula Iac, wherein R 1 Yes CH 3 , R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0305] Table C-15 16 compounds C-15.001 to C-15.016 having formula Iac are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0306] Table C-16 Provided are 16 compounds C-16.001 to C-16.016 having formula Iac, wherein R 1 Yes CH 2 Cyp, R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0307] Table C-17 Provided are 16 compounds C-17.001 to C-17.016 having formula Iac, wherein R 1 Yes CH 2 Cyp, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0308] Table C-18Provided are 16 compounds C-18.001 to C-18.016 having formula Iac, wherein R 1 Yes CH 2 Cyp, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0309] Table C-19 Provided are 16 compounds C-19.001 to C-19.016 having formula Iac, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0310] Table C-20 16 compounds C-20.001 to C-20.016 of formula Iac are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0311] Table C-21 16 compounds C-21.001 to C-21.016 having formula Iac are provided, wherein R 1 Yes CH 2 Cyp, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0312] The compounds of formula I according to the following tables D-1 to D-21 can be prepared according to the methods described above. The following examples are intended to illustrate the invention and to show preferred compounds of formula I in the form of compounds of formula Iad.

[0313]

[0314] Table D-1 16 compounds D-1.001 to D-1.016 having the formula Iad are provided, wherein R 1 Yes H, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0315] Table D-2 16 compounds D-2.001 to D-2.016 of formula Iad are provided, wherein R 1 Yes H, R 4is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0316] Table D-3 16 compounds D-3.001 to D-3.016 of formula Iad are provided, wherein R 1 Yes H, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0317] Table D-4 16 compounds D-4.001 to D-4.016 of formula Iad are provided, wherein R 1 Yes H, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0318] Table D-5 16 compounds D-5.001 to D-5.016 having the formula Iad are provided, wherein R 1 Yes H, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0319] Table D-6 16 compounds D-6.001 to D-6.016 of formula Iad are provided, wherein R 1 Yes H, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0320] Table D-7 16 compounds D-7.001 to D-7.016 of formula Iad are provided, wherein R 1 Yes H, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0321] Table D-8 16 compounds D-8.001 to D-8.016 of formula Iad are provided, wherein R 1 Yes CH 3 , R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0322] Table D-9 16 compounds D-9.001 to D-9.016 of formula Iad are provided, wherein R 1 Yes CH 3 , R4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0323] Table D-10 16 compounds D-10.001 to D-10.016 having the formula Iad are provided, wherein R 1 Yes CH 3 , R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0324] Table D-11 16 compounds D-11.001 to D-11.016 having the formula Iad are provided, wherein R 1 Yes CH 3 , R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0325] Table D-12 16 compounds D-12.001 to D-12.016 of formula Iad are provided, wherein R 1 Yes CH 3 , R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0326] Table D-13 16 compounds D-13.001 to D-13.016 of formula Iad are provided, wherein R 1 Yes CH 3 , R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0327] Table D-14 16 compounds D-14.001 to D-14.016 of formula Iad are provided, wherein R 1 Yes CH 3 , R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0328] Table D-15 16 compounds D-15.001 to D-15.016 of formula Iad are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0329] Table D-16 16 compounds D-16.001 to D-16.016 of formula Iad are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0330] Table D-17 16 compounds D-17.001 to D-17.016 of formula Iad are provided, wherein R 1 Yes CH 2 Cyp, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0331] Table D-18 16 compounds D-18.001 to D-18.016 of formula Iad are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0332] Table D-19 16 compounds D-19.001 to D-19.016 of formula Iad are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0333] Table D-20 16 compounds D-20.001 to D-20.016 having formula Iad are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0334] Table D-21 16 compounds D-21.001 to D-21.016 having the formula Iad are provided, wherein R 1 Yes CH 2 Cyp, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0335] The compounds of formula I according to the following tables E-1 to E-21 can be prepared according to the methods described above. The following examples are intended to illustrate the present invention and show preferred compounds of formula I in the form of compounds of formula lae.

[0336]

[0337] Table E-1 16 compounds E-1.001 to E-1.016 having formula lae are provided, wherein R 1 Yes H, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0338] Table E-2 16 compounds E-2.001 to E-2.016 of formula lae are provided, wherein R 1 Yes H, R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0339] Table E-3 16 compounds E-3.001 to E-3.016 of formula lae are provided, wherein R 1 Yes H, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0340] Table E-4 16 compounds E-4.001 to E-4.016 of formula lae are provided, wherein R 1 Yes H, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0341] Table E-5 16 compounds E-5.001 to E-5.016 of formula lae are provided, wherein R 1 Yes H, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0342] Table E-6 16 compounds E-6.001 to E-6.016 of formula lae are provided, wherein R 1 Yes H, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0343] Table E-716 compounds E-7.001 to E-7.016 of formula lae are provided, wherein R 1 Yes H, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0344] Table E-8 16 compounds E-8.001 to E-8.016 of formula lae are provided, wherein R 1 Yes CH 3 , R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0345] Table E-9 16 compounds E-9.001 to E-9.016 of formula lae are provided, wherein R 1 Yes CH 3 , R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0346] Table E-10 16 compounds E-10.001 to E-10.016 of formula lae are provided, wherein R 1 Yes CH 3 , R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0347] Table E-11 16 compounds E-11.001 to E-11.016 of formula lae are provided, wherein R 1 Yes CH 3 , R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0348] Table E-12 16 compounds E-12.001 to E-12.016 of formula lae are provided, wherein R 1 Yes CH 3 , R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0349] Table E-13 16 compounds E-13.001 to E-13.016 of formula lae are provided, wherein R 1 Yes CH 3 , R 4is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0350] Table E-14 16 compounds E-14.001 to E-14.016 of formula lae are provided, wherein R 1 Yes CH 3 , R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0351] Table E-15 16 compounds E-15.001 to E-15.016 of formula lae are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromopyrimidin-2-yl) and R 2 is as defined in Table Z.

[0352] Table E-16 Provided are 16 compounds E-16.001 to E-16.016 of formula lae, wherein R 1 Yes CH 2 Cyp, R 4 is (5-fluoropyrimidin-2-yl) and R 2 is as defined in Table Z.

[0353] Table E-17 16 compounds E-17.001 to E-17.016 of formula lae are provided, wherein R 1 Yes CH 2 Cyp, R 4 is pyrimidin-2-yl and R 2 is as defined in Table Z.

[0354] Table E-18 16 compounds E-18.001 to E-18.016 of formula lae are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-cyclopropylpyrimidin-2-yl) and R 2 is as defined in Table Z.

[0355] Table E-19 16 compounds E-19.001 to E-19.016 of formula lae are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-bromo-2-pyridyl) and R 2 is as defined in Table Z.

[0356] Table E-20 16 compounds E-20.001 to E-20.016 of formula lae are provided, wherein R 1 Yes CH 2 Cyp, R 4 is (5-fluoro-2-pyridyl) and R 2 is as defined in Table Z.

[0357] Table E-21 16 compounds E-21.001 to E-21.016 of formula lae are provided, wherein R 1 Yes CH 2 Cyp, R 4 is 2-pyridyl and R 2 is as defined in Table Z.

[0358] It also makes available certain intermediate compounds of amines having formulae IIaa to IIae, some of which are novel. Stereocenters are indicated in the structures below with asterisks; and thus the invention makes available both racemates and individual enantiomers.

[0359]

[0360] Specific examples of compounds of Formulae IIaa to IIae are those wherein R 1 and R 4 is as defined for the compounds in Tables A-1 to A-21.

[0361] It also makes available 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, wherein, where applicable, the substituent R 1 , R 2 (corresponding to R 2a , R 2b and A 1 Ring), R 3 , R 5a , R 5b and R 4is as defined in any 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 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, where applicable, those having the same spatial arrangement at the stereocenter as depicted in formula I'a or I'-A.

[0362] The present invention also makes it possible to obtain

[0363] A compound of formula II, wherein R 1 , R 3 , R 4 , R 5a , and R 5b is as defined for formula I; thus R 1 , R 3 , R 4 , R 5a , and R 5b Preferred embodiments are also compounds of formula II where R 1 , R 3 , R 4 , R 5a , and R 5b The preferred embodiment of

[0364] Compounds of formula IIaa, IIab, IIac, IIad and IIae, wherein R 1 is as defined for Formula I and R 4 is as defined for Formula I; therefore, R of a compound having Formula I 1 and R 4 Preferred embodiments are also compounds having any of the formulae IIaa, IIab, IIac, IIad and IIae wherein R 1 and R 4 The preferred embodiment of

[0365] A compound of formula III, wherein A 1 , R 2a and R 2b is as defined for Formula I; thus, A of a compound having Formula I 1 , R 2a and R2b A preferred embodiment is also a compound of formula III wherein A 1 , R 2a and R 2b The preferred embodiment of

[0366] A compound of formula IIIa, wherein A 1 , R 2a and R 2b is as defined for Formula I and X 0 is a halogen (such as chlorine or bromine) or X 01 To X 04 (as defined in Scheme 1); therefore, A of the compound having Formula I 1 , R 2a and R 2b A preferred embodiment is also a compound of formula IIIa 1 , R 2a and R 2b The preferred embodiment of

[0367] A compound of formula VI, wherein R 3 , R 4 , R 5a and R 5b is as defined for Formula I; therefore, R of a compound having Formula I 3 , R 4 , R 5a and R 5b Preferred embodiments are also compounds of formula VI wherein R 3 , R 4 , R 5a and R 5b The preferred embodiment of

[0368] A compound of formula XII, wherein R 3 , R 4 , R 5a and R 5b is as defined for Formula I; therefore, R of a compound having Formula I 3 , R 4 , R 5a and R 5b Preferred embodiments are also compounds of formula XII where R 3 , R 4 , R 5a and R 5b The preferred embodiment of

[0369] A compound of formula XLI, wherein R 3 , R 4a , R 5a and R 5bis as defined for Formula I and Z 3 Is NPhth or NBoc 2 Therefore, the R of the compound of formula I 3 , R 4 , R 5a and R 5b Preferred embodiments are also compounds of formula XLI where R 3 , R 4 , R 5a and R 5b The preferred embodiment of

[0370] A compound of formula XLIII, wherein R 3 , R 4 , R 5a and R 5b is as defined for Formula I; therefore, R of a compound having Formula I 3 , R 4 , R 5a and R 5b Preferred embodiments are also compounds of formula XLIII where R 3 , R 4a , R 5a and R 5b The preferred embodiment of

[0371] A compound of formula XLIV, wherein R 3 and R 4 is as defined for Formula I; therefore, R of a compound having Formula I 3 and R 4 Preferred embodiments are also compounds of formula XLIV wherein R 3 and R 4 The preferred embodiment of

[0372] A compound of formula XLVI wherein R 3 and R 4 is as defined for Formula I; therefore, R of a compound having Formula I 3 and R 4 Preferred embodiments are also compounds of formula XLVI wherein R 3 and R 4 The preferred embodiment of

[0373] A compound of formula XLVIII, wherein R 3 and R 4 is as defined for Formula I, and Z 5a and Z 5b are independently selected from R 5a , R 5b , halogen, NH2 and OH; therefore, R of the compound having formula I 3 and R 4a Preferred embodiments are also compounds of formula XLVIII where R 3 and R 4 A preferred embodiment of

[0374] A compound of formula XLIX, wherein R 3 , R 4 , R 5a and R 5b is as defined for Formula I; therefore, R of a compound having Formula I 3 , R 4 , R 5a and R 5b Preferred embodiments are also compounds of formula XLIX where R 3 , R 4 , R 5a and R 5b A preferred embodiment of

[0375] A compound of formula LI, wherein R 3 , R 5a and R 5b is as defined for Formula I and X 05 is a leaving group, such as bromine, chloride, iodine, mesylate, tosylate or triflate; thus R of the compound of formula I 3 , R 5a , and R 5b Preferred embodiments are also compounds of formula LI where R 3 , R 5a , and R 5b A preferred embodiment of

[0376] A compound of formula LIa, wherein R 1 , R 3 , R 5a and R 5b is as defined for Formula I and X 05 is a leaving group, such as bromine, chloride, iodine, mesylate, tosylate or triflate; thus, R of the compound of formula I 1 , R 3 , R 5a and R 5b Preferred embodiments are also compounds of formula LIa where R 1 , R 3 , R 5a and R 5b The preferred embodiment of

[0377] A compound having the formula L, wherein A 1 , R 2a , R 2b , R 1 , R 3 , R 5a and R 5b is as defined for Formula I and X 05 is a leaving group, such as bromine, chloride, iodine, mesylate, tosylate or triflate; thus, A of the compound having formula I 1 , R 2a , R 2b , R 1 , R 3 , R 5a and R 5b A preferred embodiment is also a compound of formula L wherein A 1 , R 2a , R 2b , R 1 , R 3 , R 5a and R 5b The preferred embodiment of

[0378] A compound of formula LIV, wherein R 3 , R 5a and R 5b is as defined for Formula I, Z 3 Is NPhth or NBoc 2 And X 05 is a leaving group, such as chloro, bromo, iodo, arylsulfonate, alkylsulfonate or trifluoromethanesulfonate; thus, R of the compound of Formula I 3 , R 5a and R 5b Preferred embodiments are also compounds of formula LIV where R 3 , R 5a and R 5b The preferred embodiment of

[0379] A compound of formula IV or IVa, wherein R 3 , R 5a and R 5b is as defined for Formula I, and X 05 is a leaving group, such as chloro, bromo, iodo; therefore, R of the compound of formula I 3 , R 5a and R 5b Preferred embodiments are also compounds of formula IV or IVa where R 3 , R 5a and R 5b The preferred embodiment of

[0380] A compound of formula LV, wherein R 3 , R 5a and R 5b is as defined for Formula I, and X 05 is a leaving group, such as chloro, bromo, iodo, arylsulfonate, alkylsulfonate or trifluoromethanesulfonate; thus, R of the compound of Formula I 3 , R 5a and R 5b Preferred embodiments are also compounds of formula LV wherein R 3 , R 5a and R 5b The preferred embodiment of

[0381] A compound of formula XX, wherein R 2a , R 2b and A 1 is as defined for Formula I, and Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2a , R 2b and A 1 Preferred embodiments are also compounds of formula XX where R 2a , R 2b and A 1 The preferred embodiment of

[0382] A compound of formula XXa, wherein R 2b and A 1 is as defined for Formula I, and Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXa where R 2b and A 1 The preferred embodiment of

[0383] A compound of formula XXVIIIa wherein A 1 and R 2b is as defined for Formula I, Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl, and X 08 is chlorine or bromine; therefore, A of the compound having formula I1 and R 2b A preferred embodiment is also a compound of formula XXVIIIa wherein A 1 and R 2b The preferred embodiment of

[0384] A compound of formula XXVIIIb wherein A 1 and R 2b is as defined for Formula I, Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl, and X 05 is a leaving group, such as chloro, bromo, iodo, arylsulfonate, alkylsulfonate or trifluoromethanesulfonate; thus, A of the compound having formula I 1 and R 2b A preferred embodiment is also a compound of formula XXVIIIb wherein A 1 and R 2b The preferred embodiment of

[0385] A compound of formula XXVIIIc wherein A 1 and R 2b is as defined for Formula I, and Z 1 and X 09 Independently selected from C 1 -C 4 Alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl, is chloro or bromo; thus, A of the compound of formula I 1 and R 2b A preferred embodiment is also a compound of formula XXVIIIc wherein A 1 and R 2b The preferred embodiment of

[0386] A compound of formula XXI wherein A 1 and R 2b is as defined for Formula I, and Z 1 It is C 1 -C 4 Alkyl, for example, methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, A of the compound having formula I 1 and R 2b A preferred embodiment is also a compound of formula XXI 1 and R 2b The preferred embodiment of

[0387] A compound of formula XXVII, wherein R 2b and A 1is as defined for Formula I, R 2aa It is H, C 1 -C 3 Alkyl, C 1 -C 3 haloalkyl, cyano or halogen, and Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXVII where R 2b and A 1 The preferred embodiment of

[0388] A compound of formula XXVIII, wherein R 2b and A 1 is as defined for Formula I, R 2aa It is H, C 1 -C 3 Alkyl, C 1 -C 3 haloalkyl, cyano or halogen, and Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXVIII where R 2b and A 1 The preferred embodiment of

[0389] A compound of formula XXIX, R 2b and A 1 is as defined for Formula I, R 2aa It is H, C 1 -C 3 Alkyl, C 1 -C 3 haloalkyl, cyano or halogen, and Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXIX where R 2b and A 1 The preferred embodiment of

[0390] A compound of formula XXXI, R 2b and A 1 is as defined for Formula I, R 2aa It is H, C 1 -C 3 Alkyl, C 1 -C 3 haloalkyl, cyano or halogen, and Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXXI where R 2b and A 1 The preferred embodiment of

[0391] A compound of formula XXXII, R 2b and A 1 is as defined for Formula I, R 2aa It is H, C 1 -C 3 Alkyl, C 1 -C 3 haloalkyl, cyano or halogen, and Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXXII where R 2b and A 1 The preferred embodiment of

[0392] A compound of formula XXXV, wherein R 2b and A 1 is as defined for Formula I, and Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXXV where R 2b and A 1 The preferred embodiment of

[0393] A compound of formula XXXVI, R 2b and A 1 is as defined for Formula I, and Z1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXXVI wherein R 2b and A 1 The preferred embodiment of

[0394] A compound of formula XXXVII, R 2b and A 1 is as defined for Formula I, and Z 1 It is C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXXVII where R 2b and A 1 Preferred embodiments of; and

[0395] A compound of formula XXXIX, wherein R 2b and A 1 is as defined for Formula I, and Z 1 and Z 2 Independently selected from C 1 -C 4 alkyl, such as methyl, ethyl, isopropyl, propyl, tert-butyl, sec-butyl or n-butyl; thus, R of the compound of formula I 2b and A 1 Preferred embodiments are also compounds of formula XXXIX where R 2b and A 1 A preferred embodiment of the present invention.

[0396] The compounds of formula I according to the invention are active ingredients of preventive and / or therapeutic value in the field of pest control, even at low application rates, they have a very favorable biocidal spectrum and are well tolerated by warm-blooded species, fish and plants. These active ingredients according to the invention act on all or individual developmental stages of normally sensitive and also resistant animal pests (such as representatives of insects or Acarina). The insecticidal or acaricidal activity of the active ingredient according to the invention can be manifested directly itself, i.e., the destruction of the pest occurs immediately or only after some time has passed (e.g., during molting); or indirectly, for example, by reducing egg laying and / or hatching rates.

[0397] Examples of animal pests referred to above are:

[0398] From the order Acarina, e.g.

[0399] Acalitus spp., Aculus spp., Acaricalus spp., Aceria spp., Acarus siro, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp., Calipitrimerus spp., Chorioptes spp., Dermanyssusgallinae, Dermatophagoides spp., Eotetranychus 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.;

[0400] From the order Phthirus, e.g.

[0401] Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp., and Phylloxera spp.;

[0402] From the order Coleoptera, e.g.

[0403] Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp., Astylus atromaculatus, Ataenius spp., Atomaria linearis, Chaetocnema tibialis, Cerotomaspp., Conoderus spp., Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephalaspp., 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., Melighetes aeneus, Melolontha spp., Myochrousarmatus, Orycaephilus spp., Otiorhynchus spp., Phyllophaga spp.), Phlyctinus spp., Popillia spp., Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp., Scarabeidae, Sitophilus spp., Sitotroga spp.), Somaticus spp., Sternechus subsignatus, Tenebrio spp., Tribolium spp., and Trogoderma spp.;

[0404] From the order Diptera, e.g.

[0405] Aedes spp., Anopheles spp., Antherigonas occata., Bactrocea oleae, Bibio hortulanus, Bradysia spp., Calliphora erythrocephala, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Delia spp., Drosophilamelanogaster, Fannia 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., Rhagoletis spp., Rivelia quadrifasciata, Scatella spp., Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp.) and Tipula spp.;

[0406] From the order Hemiptera, e.g.

[0407] Acanthocoris scabrator, Acrosternum spp., Adelphocoris lineolatus, Aleurodes spp., Bathycoeliathalassina, Acanthocoris spp., Clavigralla tomentosicollis, Creontiades spp., Dichelops furcatus, Edessa spp., Euchystomus spp., Eurydema pulchrum, Horcias spp., Horcias spp. nobilellus), Lygus spp., Lygus spp., Tropical Scale spp., Murgantia histrionicus, Nesidiocoris tenuis, Nysius simulans, Nysius simulans, Nesidiocoris tenuis, Nysius simulans, Nysius simulans, Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp., Nysius spp.

[0408] Acyrthosium pisum, Adalges species, Agallina ensigera, Targuilon vein psyllid, Aleurodicus species, Aleurocanthus species, Sugarcane hole whitefly, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Citrus long-spiked leafhopper, Nephrodactylus species, Aphididae, Aphid species, Aspidiotus species, Solanum grove netless aphid, Bactericera cockerelli, Aleurodicus species, Brachycaudus species, Cabbage aphid, Cavariella species, Cavariella aegopodii Scop.), wax scale species, black brown round shield scale, orange brown round shield scale, leafhopper species, large white leafhopper (Cofana spectra), Cryptomyxodon species, leafhopper species, brown soft scale, corn yellow-winged leafhopper, naked whitefly species, citrus psyllid, wheat aphid, western round tail aphid species, small green leafhopper species, apple aphid, grape leafhopper species, Gascardia species, red eucalyptus psyllid (Glycaspis brimblecombei), vegetable constriction aphid (Hyadaphispseudobrassicae), large tail aphid species (Hyalopterus spp.), hyperomyzuspallidus species (Hyperomyzuspallidus), lemon fruit green leafhopper (Idioscopus clypealis), African leafhopper, Laodelphax species, water and soil hard scale, oyster shield scale species, radish aphid (Lopaphis erysimi), Lyogenys maidis, Aphids spp., Metcalfa pruinosa, Aphids spp., Aphids spp., Neotoxoptera sp., Nilaparvata spp., Nilaparvata spp.), pear green aphid, Odonaspis ruthae, sugarcane cotton aphid, bayberry whitefly, Caulis psyllid, spp. of shield scale, spp. of gall aphid, corn wax cicada, spp. of flat horned planthopper, spp. of warty aphid, spp. of root nodule aphid, spp. of Mosella, spp. of white scale, spp. of mealybug, spp. of cotton blind bug (Pseudatomoscelis seriatus), spp. of psyllid, spp. of cotton scale (Pulvinaria aethiopica), spp. of toothed shield scale, spp. of Quesada gigas, spp. of electric light leafhopper (Reciliadorsalis), spp. of constricted tube aphid, spp. of black helmet scale, spp. of banded leafhopper, spp. of dichotomous aphid, spp. of wheat aphid (Sitobion spp.), white-backed planthopper, Spissistilus festinus, Tarophagus Proserpina), aphid species, whitefly species, Tridiscus sporoboli, Trionymus spp., African psyllids, scutellaria spp., flame leafhoppers, Zyginidia scutellaris;.

[0409] From the order Hymenoptera, e.g.

[0410] Acromyrmex, Arge spp., Atta spp., Cephus spp., Diprion spp., Diprionidae, Gilpinia polytoma, Hoplocampa spp., Lasius spp., Monomorium pharaonis, Neodiprions spp., Pogonomyrmex spp., Fire ants, Solenopsis spp., and Vespa spp.

[0411] From the order Isoptera, e.g.

[0412] Coptotermes spp., Corniternes cumulans, Incisitermes spp., Macrotermes spp., Mastotermes spp., Microtermes spp., Reticulitermes spp.; Tropical fire ant (Solenopsis geminate)

[0413] From the order Lepidoptera, for example,

[0414] Species of the genus Long-winged Tortoise, Species of the genus Brown-banded Tortoise, Species of the genus Clearwing, Species of the genus Spodoptera, Cotton leafworm, Species of the genus Amylois, Bean armyworm, Species of the genus Yellow-winged Tortoise, Species of the genus Argyresthia, Species of the genus Banded Tortoise, Species of the genus Spodoptera, Cotton miner, Corn armyworm, Powderyngium striata, Peach fruit moth, Species of the genus Graminus, Species of the genus Colored Tortoise, Chrysoteuchia topiaria, Grape fruit moth, Species of the genus Leaffolder, Species of the genus Cloud-winged Tortoise, Species of the genus Sheath moth, Colias lesbia, Cosmophila flava), Sesamia spp., Greater Cabbage Borer, Apple Trichodina, Boxwood Moth, Trichodina spp., Boxwood Borer, Trichodina spp., Sudanese Bollworm, Spodoptera spp., South American Corn Seedling Borer (Elasmopalpus lignosellus), Sweet Potato Stem Borer, Mealworm spp., Epinotia spp., Estigmene acrea, Etiellazinckinella, Flower Trichodina spp., Ring Needle Trichodina, Yellow Tufted Moth spp., Feltia jaculiferia, Grapholita spp., Cloud Trichodina, Spodoptera spp., Cabbage Borer, Herpetogramma spp., White Moth, Tomato Borer, Lasmopalpus lignosellus, spiral leafminer, leafminer species, grape flower moth, Loxostege bifidalis, tussock moth species, miner species, Malacosoma spp., cabbage armyworm, tobacco hornworm, Mythimna spp., noctuid species, fall geometrid species, Orniodes indica, European corn borer, super-small tortoise species, brown tortoise species, small-eyed moth, stem borer, red bell moth, coffee leafminer, one-star armyworm, potato moth, cabbage butterfly, Pieris species, diamondback moth, white nest moth species, leaf moth species, mint gray moth (Rachiplusianu), western bean incense (Richia albicosta), white grain borer species (Scirpophaga spp.), Spodoptera species, Cynocephala species, Spodoptera species, Cotton leaf folder, Hymenoptera species, Heteroptera species, Cynocephala species, Trichoplusia species, Liriomyza species, and Lymantria species;

[0415] From the order Mallophaga, for example,

[0416] Damalina spp. and Trichodectes spp.;

[0417] From the order Orthoptera, for example,

[0418] Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae, Locusta spp., Neocurtilla hexadactyla, Periplaneta spp., Scapteriscus spp., and Schistocerca spp.;

[0419] From the order Psocoptera, for example,

[0420] Liposcelis spp.;

[0421] From the order Siphonaptera, for example,

[0422] Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla cheopis;

[0423] From the order of the Thysanoptera, for example,

[0424] Calliothrips phaseoli, Frankliniella spp., Heliothrips spp., Hercinothrips spp., Parthenothrips spp., Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., Thrips spp.;

[0425] From the order of the Thysanura, for example, Lepisma saccharina.

[0426] In another aspect, the present invention may also relate to a method for controlling damage to plants and parts thereof by plant parasitic nematodes (endoparasitic-, semiendoparasitic- and ectoparasitic nematodes), in particular the following plant parasitic nematodes, such as root knot nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other species of root knot nematodes; cyst-forming nematodes, Globodera rostochiensis and other species of Globodera; cereal cyst nematodes (Heterodera avenae), soybean cyst nematodes (Heteroderaglycines), beet cyst nematodes (Heterodera exigua) and other species of Globodera. schachtii), Heteroderatrifolii, and other Heterodera species; Seed gall nematodes, Anguina species; Stem and foliar nematodes, Aphelenchoides species; Sting nematodes, Belonolaimuslongicaudatus, and other Belonolaimus species; Pine nematodes, Bursaphelenchus xylophilus, and other Bursaphelenchus species; Ring nematodes, nematodes), Criconema species, Criconemella species, Criconemoides species, Mesocriconema species; Stemand bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci and other Ditylenchus species; Awl nematodes, Dolichodorus species;Spiral nematodes, Heliocotylenchus multicinctus and other species of the genus Helicotylenchus; Sheath and sheathoid nematodes, species of the genera Hemicycliophora and Hemicriconemoides; species of the genus Hirshmanniella; Lancenematodes, species of the genus Hoploaimus; false rootknot nematodes, species of the genus Nacobbus; Needle nematodes, Longidoruse longatus and other species of the genus Longidorus; Pin nematodes, species of the genus Pratylenchus; Lesion nematodes nematodes, Pratylenchus negletus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi, and other Pratylenchus species; Burrowing nematodes, Radopholus similis, and other Radopholus species; Reniform nematodes, Rotylenchus robustus, Rotylenchus reniformis, and other Rotylenchus species; Scutellonema species; Stubby root nematodes, Trichodorus primitivus and other species of the genus Trichodorus, species of the genus Paratrichodorus; Stunt nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other species of the genus Tylenchorhynchus;Citrus nematodes, Tylenchulus species; Dagger nematodes, Xiphinema species; and other plant parasitic nematode species, such as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp., and Quinisulcius spp.;

[0427] The compounds of the invention also have activity against molluscs. Examples include, for example, the family Pomacea; the family Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus); the family Bradybaenidae (Bradybaenidae, fruticum); Cepaea (C. hortensis, C. nemoralis); Ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H. itala, H. obvia); Helicigona arbustorum; Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Lymnaea; Milax (M. gagates, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides.

[0428] The active ingredients according to the invention can be used for controlling, i.e. suppressing or destroying pests of the abovementioned type, which occur in particular on plants, especially on useful and ornamental plants in agriculture, in horticulture and in forestry, or on organs of these plants, such as fruits, flowers, leaves, stems, tubers or roots, and in some cases even plant organs formed at a later point in time still remain protected against these pests.

[0429] In particular, suitable target crops are cereals, such as wheat, barley, rye, oats, rice, corn or sorghum; beets, such as sugar beets or fodder beets; fruits, such as pome, stone or soft fruit, such as apples, pears, plums, peaches, apricots, cherries or berries, such as strawberries, raspberries or blackberries; leguminous crops, such as beans, lentils, peas or soybeans; oilseed crops, such as rapeseed, mustard, poppy, olive, sunflower, coconut, castor, cocoa beans, or groundnuts; melons, such as pumpkin, cucumber, or melon; fiber plants, such as cotton, flax, hemp, or jute; citrus fruits, such as oranges, lemons, grapefruits, or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, or bell peppers; lauraceae, such as avocado, cinnamon, or camphor; and also tobacco, nuts, coffee, eggplant, sugar cane, tea, pepper, grapevines, hops, plantaginaceae, and latex plants.

[0430] The compositions and / or methods of the invention may also be used on any ornamental and / or vegetable crops, including flowers, shrubs, broadleaf trees and evergreen plants.

[0431] For example, the present invention can be used in any of the following ornamental plant species: Ageratum species, Alonsoa spp., Anemone species, Anisodontea capsenisis, Anthemis species, Antirrhinum species, Aster species, Begonia species (e.g., Rieger Begonia, Begonia sempervivum, Begonia tubéreux), Bougainvillea species, Brachycome spp., Brassica species (ornamental plants), Calceolaria species, Capsicum, Catharanthus roseus, Canna species, Centaurea species, Chrysanthemum species, Cineraria species (C. maritime), Coreopsis species, Crassula coccinea, Cupheaignea, Dahlia species, Delphinium species, Dicentra species, Dorotheantus species. spp.), Eustoma, Forsythia, Fuchsia, Geranium, Geranium, Geranium gnaphalium, Gerbera, Globe amaranth, Heliotropium, Hibiscus, Hydrangea, Hydrangea, Iris, Impatiens, Iresines, Kalanchoe, Lantana, March flower, Lion's ear, Lilium, Mesembryanthemum, Physalis, Monarda, Tagetes, Dianthus, Canna, Oxalis, Daisy, Geranium, Viola, Petunia, Nerium, Plecthranthus spp.), poinsettia, creeper (parthenocissus quinquefolia, Parthenocissus tricuspidata), primrose, ranunculus, azalea, rosa (rose), rudbeckia, African violet, salvia, Scaevola aemola, Schizanthus wisetonensis, sedum, Solanum, Surfinia spp., marigold, tobacco, verbena, zinnia, and other bedding plants.

[0432] For example, the present invention can be used with any of the following vegetable species: Allium species (garlic, onion, A.oschaninii, leek, shallot, scallion), fennel, celery (Apium graveolus), asparagus, beets (Beta vulgarus), Brassica species (brassica, Chinese cabbage, turnip), peppers, chickpeas, endive, chicory species (chicory, endive), watermelon, Cucumis species (cucumber, melon), Cucurbita species (zucchini, Indian pumpkin), Cyanara spp. (artichoke, cardoon), wild carrot, fennel, Hypericum species, lettuce, Lycopersicon species (tomato, cherry tomato), mint species, basil, parsley, Phaseolus species (bean, pea), peas, radish, edible rhubarb, Rosemary species, Sage species, black salsify (Scorzonera hispanica), eggplant, spinach, new valerian species (V. eriocarpa), and broad beans.

[0433] Preferred ornamental plant species include African violet, begonia, dahlia, gerbera, hydrangea, verbena, rose, kalanchoe, poinsettia, aster, cornflower, coreopsis, delphinium, monarda, phlox, rudbeckia, sedum, petunia, viola, impatiens, geranium, chrysanthemum, ranunculus, fuchsia, salvia, hydrangea, rosemary, sage, St. Johnswort, mint, sweet pepper, tomato and cucumber.

[0434] The active ingredients according to the invention are particularly suitable for controlling bean aphids, cucumber leaf beetles, tobacco budworm, peach aphid, diamondback moth and sea lily armyworm on cotton, vegetables, corn, rice and soybean crops. The active ingredients according to the invention are further particularly suitable for controlling cabbage armyworm (preferably on vegetables), codling moth (preferably on apples), green leafhopper (preferably on vegetables, vineyards), potato leaf beetle (Leptinotarsa) (preferably on potatoes) and striped stem borer (preferably on rice).

[0435] The compounds of formula I are particularly suitable for controlling:

[0436] 1. Pests of the order Hemiptera, for example one or more of the following species: Bemisia tabaci, Bean aphid, Green peach aphid, Rhopalosiphum padi, Nilaparvata lugens, and Euschistus heros (preferably on vegetables, soybeans, and sugar cane);

[0437] 2. Pests of the order Lepidoptera, for example one or more of the following species: Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Codling moth, Soybean looper (Chrysodeixis includes), Chilo suppressalis, Elasmopalpuslignosellus, Pseudoplusia includens, and Tomato leafminer (preferably on vegetables and corn);

[0438] 3. Pests of the order Thysanoptera, such as the family Thripidae, for example one or more of Thrips tabaci and Thrips occidentalis (preferably on vegetables); and

[0439] 4. Soil pests (e.g. of the order Coleoptera), for example species Diabrotica decemlineata, species of the genus Coleoptera and potato beetles (preferably on vegetables and maize).

[0440] The term "crops" is to be understood as also including crop plants which have been transformed by the use of recombinant DNA techniques in such a way that they are able to synthesize one or more selectively acting toxins, such as are known, for example, from toxigenic bacteria, in particular those of the genus Bacillus.

[0441] Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, such as those from Bacillus cereus or Bacillus japonicus; or insecticidal proteins from Bacillus thuringiensis, such as delta-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C, or vegetative insecticidal proteins (Vips), such as Vip1, Vip2, Vip3, or Vip3A; or insecticidal proteins of bacterial colonizing nematodes, such as certain species of Photorhabdus spp. or certain species of Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophila, or Xenorhabdus nematophila. nematophilus); toxins produced by animals, such as scorpion toxins, spider toxins, bee toxins and other insect-specific neurotoxins; toxins produced by fungi, such as streptomycin, plant lectins, such as pea lectin, barley lectin or snowdrop lectin; lectins (agglutinin); protease inhibitors, such as trypsin inhibitor, silk proteinase inhibitor, potato glycoprotein, cystatin, papain inhibitor; ribosome inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffa seed protein, saporin or bryophyllin; steroid metabolizing enzymes, such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitor, HMG-COA-reductase; ion channel blockers, such as sodium channel or calcium channel blockers; juvenile hormone esterase; diuretic hormone receptor; stilbene synthase; bibenzyl synthase; chitinase and glucanase.

[0442] In the context of the present invention, delta-endotoxins (e.g., Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C) or vegetative insecticidal proteins (Vips) (e.g., Vip1, Vip2, Vip3, or Vip3A) are understood to include, obviously, also mixed toxins, truncated toxins, and modified toxins. Mixed toxins are recombinantly produced by new combinations of different domains of those proteins (see, e.g., WO 02 / 15701). Truncated toxins, such as truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of a naturally occurring toxin are replaced. In such amino acid replacements, it is preferred that a non-naturally occurring protease recognition sequence is inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into the Cry3A toxin (see WO 03 / 018810).

[0443] Examples of such toxins or transgenic plants capable of synthesizing such toxins are disclosed in, for example, EP-A-0 374 753, WO 93 / 07278, WO 95 / 34656, EP-A-0 427 529, EP-A-451 878 and WO 03 / 052073.

[0444] Methods for preparing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95 / 34656, EP-A-0 367474, EP-A-0 401 979 and WO 90 / 13651.

[0445] The toxins included in the transgenic plants render the plants tolerant to harmful insects. Such insects can be found in any insect taxonomic group, but are particularly common among beetles (Coleoptera), two-winged insects (Diptera), and moths (Lepidoptera).

[0446] Transgenic plants comprising 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 are: (corn variety expressing Cry1Ab toxin); YieldGard (corn variety expressing Cry3Bb1 toxin); YieldGard (corn varieties expressing Cry1Ab and Cry3Bb1 toxins); (corn variety expressing Cry9C toxin); Herculex (a corn variety expressing the Cry1Fa2 toxin and the enzyme phosphinothricin N-acetyltransferase (PAT) that confers tolerance to the herbicide glufosinate-ammonium); NuCOTN (cotton variety expressing Cry1Ac toxin); Bollgard (cotton variety expressing Cry1Ac toxin); Bollgard (cotton varieties expressing Cry1Ac and Cry2Ab toxins); (cotton varieties expressing Vip3A and Cry1Ab toxins); (potato variety, expressing Cry3A toxin); GT Advantage (GA21 glyphosate tolerance trait), CB Advantage (Bt11 corn borer (CB) trait) and

[0447] Other examples of such genetically modified crops are:

[0448] 1. Bt11 corn, from Syngenta Seeds SAS, Chemin del'Hobit 27, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. Genetically modified maize, which is resistant to attack by European corn borer (Ostrinia nubilalis and Sesamia inermis) by transgenic expression of a truncated Cry1Ab toxin. Bt11 corn also transgenic expression of the PAT enzyme to obtain tolerance to the herbicide glufosinate ammonium.

[0449] 2. Bt176 corn, from Syngenta Seeds, 27 Hobbit Road, F-31 790 Saint-Sauveur, France, registration number C / FR / 96 / 05 / 10. Genetically modified maize, which is resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia inermis) by transgenic expression of the Cry1Ab toxin. Bt176 corn also transgenic expression of the enzyme PAT to obtain tolerance to the herbicide glufosinate ammonium.

[0450] 3. MIR604 corn, from Syngenta Seeds, 27 Rue Hobbitt, F-31 790 Saint-Sauveur, France, registration number C / FR / 96 / 05 / 10. Corn rendered insect resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic corn plants is described in WO 03 / 018810.

[0451] 4. MON 863 maize, from Monsanto Europe SA, 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C / DE / 02 / 9. MON 863 expresses the Cry3Bb1 toxin and is resistant to certain coleopteran insects.

[0452] 5. IPC 531 Cotton, from Monsanto Europe NV, 270-272 Avenue Tervuren, B-1150 Brussels, Belgium, registration number C / ES / 96 / 02.

[0453] 6.1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7B-1160 Brussels, Belgium, registration number C / NL / 00 / 10. Genetically modified maize expressing the protein Cry1F for resistance to certain lepidopteran insects and the protein PAT for tolerance to the herbicide glufosinate ammonium.

[0454] 7. NK603×MON 810 corn, from Monsanto Europe, 270-272 Boulevard Tervuren, B-1150 Brussels, Belgium, registration number C / GB / 02 / M3 / 03. Made from a conventionally bred hybrid corn variety by crossing the genetically modified varieties NK603 and MON 810. NK603×MON 810 corn transgenically expresses the protein CP4 EPSPS obtained from the Agrobacterium strain CP4, rendering it tolerant to herbicides (contains glyphosate), and also Cry1Ab toxin obtained from Bacillus thuringiensis subsp. kurstakia, which confers resistance to certain lepidopteran insects, including the European corn borer.

[0455] 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 )middle.

[0456] The term "crops" is to be understood as also including crop plants that have been transformed by the use of recombinant DNA technology so that they can synthesize antipathogenic substances with selective action, such as, for example, so-called "pathogenesis-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 353191. Methods for producing such transgenic plants are generally known to those skilled in the art and are described, for example, in the publications mentioned above.

[0457] Crops may also be modified to increase resistance to fungal (eg, Fusarium, Anthracnose, or Phytophthora), bacterial (eg, Pseudomonas), or viral (eg, Potato Leaf Roll Virus, Tomato Spotted Wilt Virus, Cucumber Mosaic Virus) pathogens.

[0458] Crops also include those with increased resistance to nematodes, such as Heterodera glycines.

[0459] Crops with tolerance to abiotic stress include those with increased tolerance to drought, high salt, high temperature, cold, frost or light radiation, for example through expression of NF-YB or other proteins known in the art.

[0460] Antipathogenic substances that can be expressed by such transgenic plants include, for example, ion channel blockers, such as blockers of sodium channels and calcium channels, for example viral KP1, KP4 or KP6 toxins; stilbene synthases; bibenzyl synthases; chitinases; glucanases; so-called "pathogenesis-related proteins" (PRPs; see, for example, EP-A-0 392 225); antipathogenic substances produced by microorganisms, such as peptide antibiotics or heterocyclic antibiotics (see, for example, WO 95 / 33818) or proteins or polypeptide factors that are involved in plant defense against pathogens (so-called "plant disease resistance genes", as described in WO 03 / 000906).

[0461] Further areas 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, textiles, floors or buildings, and also in the hygiene sector, in particular for the protection of humans, domestic animals and productive livestock from pests of the type mentioned.

[0462] The present invention provides a compound of the first aspect for use in therapy. The present invention provides a compound of the first aspect for use in controlling parasites in or on an animal. The present invention further provides a compound of the first aspect for use in controlling external parasites of an animal. The present invention further provides a compound of the first aspect for use in preventing and / or treating a disease transmitted by an external parasite.

[0463] The present invention provides the use of the 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 the compound of the first aspect for the manufacture of a medicament for controlling external parasites of an animal. The present invention further provides the use of the compound of the first aspect for the manufacture of a medicament for preventing and / or treating a disease transmitted by an external parasite.

[0464] The present invention provides the use of the compound of the first aspect in controlling parasites in or on an animal. The present invention further provides the use of the compound of the first aspect in controlling external parasites of an animal.

[0465] When used in the context of parasites in or on animals, the term "control" means reducing the number of pests or parasites, eliminating pests or parasites and / or preventing further infestation by pests or parasites.

[0466] The terms "treat" or "treat" when used in the context of parasites in or on an animal means to inhibit, slow, halt or reverse the progression or severity of existing symptoms or disease.

[0467] The term "prevent" when used in the context of parasites in or on animals means avoiding the development of symptoms or disease in the animal.

[0468] When used in the context of parasites in or on animals, the term "animal" may refer to mammals and non-mammals, such as birds or fish. In the case of a mammal, it can be a human or a non-human mammal. Non-human mammals include, but are not limited to, livestock animals and pets. Livestock animals include, but are not limited to, cattle, camels, pigs, sheep, goats, and horses. Pets include, but are not limited to, dogs, cats, and rabbits.

[0469] "Parasits" are harmful organisms that live in or on a host animal and benefit by obtaining nutrients at the expense of the host animal. "Endoparasites" are parasites that live inside a host animal. "Exoparasites" are parasites that live on the surface of a host animal. Exoparasites include, but are not limited to, ticks, insects, and crustaceans (e.g., sea lice). The subclass Acarina (or Acarina) includes ticks and mites. Ticks include, but are not limited to, members of the genus Rhipicaphalus, such as Rhipicaphalus microplus (Boophilus microplus) and Rhipicephalus sanguineus; Amblyomrna; Dermacentor; Haemaphysalis; Hyalomma; Ixodes; Rhipicentor; Margaropus; Argas; Otobius; and Ornithodoros. Mites include, but are not limited to, members of the following genera: Dermestes, such as Dermestes gallinae; Itch, such as Sheep; Cheyletus; Dermatosus; such as Dermatosus gallinae; Ortnithonyssus; Demodex, such as Demodex canis; Sarcoptes, such as Sarcoptes hominis; and Psora. Insects include, but are not limited to, members of the following orders: Siphonaptera, Diptera, Trichoderma, Lepidoptera, Coleoptera, and Homoptera. Members of Siphonaptera include, but are not limited to, Ctenocephatides canis and Ctenocephatides canis. Members of Diptera include, but are not limited to, species of the genus Musca; Skin flies, such as horse flies and sheep flies; Biting flies; Gadflies, such as Tabunus species and Tabunus species; Black horn flies, such as Haematobium; Stomoxys; Lucilia; Midges; and mosquitoes. Members of the order Trichoderma include, but are not limited to, blood-sucking lice and chewing lice, such as the wool lice (Bovicola Ovis) and the cattle feather lice.

[0470] When used in the context of parasites in or on an animal, the term "effective amount" refers to the amount or dosage of a compound of the invention or a salt thereof, which, when administered to an animal in a single dose or multiple doses, provides the desired effect in or on the animal. The attending diagnostician (as one skilled in the art) can readily determine the effective amount by using known techniques and by observing the results obtained in similar situations. In determining the effective amount, the attending diagnostician considers many factors, including, but not limited to: the species of mammal; its size, age, and general health; the parasites to be controlled and the degree of infestation; the specific disease or condition involved; the degree of involvement or severity of the disease or condition; individual responses; the specific compound administered; the mode of administration; the bioavailability characteristics of the administered formulation; the dosage regimen selected; the use of concomitant medications; and other relevant circumstances.

[0471] The compounds of the present invention can be given to animals by any route with the desired effect, including but not limited to topical, oral, parenteral and subcutaneous. Topical administration is preferred. Formulations suitable for topical administration include, for example, solutions, emulsions and suspensions, and can be poured, dotted, sprayed, sprayed, sprayed or dipped. In an alternative, the compounds of the present invention can be given by ear tags or collars.

[0472] The salt forms of the compounds of the present invention include both pharmaceutically acceptable salts and veterinarily acceptable salts, which may be different from agrochemically acceptable salts. Pharmaceutically and veterinarily acceptable salts and common methods 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). It will be appreciated by those skilled in the art that the compounds of the present invention are easily converted into salts using techniques and conditions known to those of ordinary skill in the art, and can be separated as salts (such as hydrochlorides). In addition, it will be appreciated by those skilled in the art that the compounds of the present invention are easily converted into corresponding free alkalis, and can be separated from corresponding salts as corresponding free alkalis.

[0473] 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 the composition of the present invention to the target pests, their loci or surfaces or substrates by painting, rolling, spraying, coating or dipping. By way of example, IRS (indoor residual spray) application of surfaces (such as wall, ceiling or floor surfaces) is contemplated by the methods of the present invention. In another embodiment, it is contemplated that such compositions are applied to substrates such as nonwoven or fabric materials in the form of netting, coverings, bedding, curtains and tents (or can be used in the manufacture of such articles).

[0474] In one embodiment, the method for controlling such harmful organisms comprises applying the composition of the present invention of pesticidal effective amount to the target harmful organisms, their place or surface or substrate, so as to provide effective retained pesticidal activity on the surface or substrate. Such application can be carried out by brushing, rolling, spraying, coating or dipping the pesticidal composition of the present invention. By way of example, the IRS application of surfaces (such as walls, ceilings or floor surfaces) is considered by the method of the present invention, so as to provide effective retained pesticidal activity on the surface. In another embodiment, it is considered to apply such compositions for the residual control of harmful organisms on substrates, and the substrate is a fabric material such as in the form of netting, coverings, bedding, curtains and tents (or can be used in the manufacture of these articles).

[0475] The substrate to be treated (including nonwovens, fabrics or nettings) can be made of natural fibers, such as cotton, raffia, jute, flax, sisal, burlap or wool, or synthetic fibers, such as polyamide, polyester, polypropylene, polyacrylonitrile, etc. Polyester is particularly suitable. Methods for textile treatment are known, for example WO 2008 / 151984, WO 2003 / 034823, US 5631072, WO 2005 / 64072, WO 2006 / 128870, EP 1724392, WO 2005113886 or WO 2007 / 090739.

[0476] A further area of ​​use of the compositions according to the invention is in the field of tree injection / trunk treatment of all ornamental trees as well as all kinds of fruit and nut trees.

[0477] In the field of tree injection / trunk treatment, the compounds according to the invention are particularly suitable for combating wood-boring insects from the orders Lepidoptera mentioned above and from the orders Coleoptera, in particular against the wood-boring insects listed in the following Tables A and B:

[0478] Table A. Examples of exotic wood-boring insects of economic importance.

[0479]

[0480] Table B. Examples of native wood-boring insects of economic importance.

[0481]

[0482]

[0483]

[0484] The present invention can also be used to control any insect pest that may be present in turfgrass, including, for example, beetles, caterpillars, fire ants, ground pearls, millipedes, woodlice, mites, mole crickets, scale insects, mealybugs, ticks, cicadas, southern wheat bugs, and grubs. The present invention can be used to control insect pests at all stages of their life cycle, including eggs, larvae, nymphs, and adults.

[0485] In particular, the present invention can be used to control insect pests that feed on the roots of turfgrass, including grubs (such as Cyclocephala spp. (e.g., labeled beetle, C. lurida), Rhizotrogus spp. (e.g., European beetle, European root-cutting gill beetle (R. majalis)), Cotinus spp. (e.g., Green June beetle, Green June flower beetle (C. nitida)), Popillia spp. (e.g., Japanese beetle, Japanese arc beetle (P. japonica)), Phyllophaga spp. (e.g., May / June beetle), Chafer spp. (e.g., Blackturfgrass ataenius, Black velvet beetle), Maladera spp. (e.g., Asiatic garden beetle (Asiatic garden beetle)), beetle, chestnut beetle) and Tomarus species), ground pearls (Margarodes spp.), mole crickets (tawny, southern, and short-winged; mole crickets (Scapteriscus spp., Gryllotalpa africana) and leatherjackets (European crane fly, Tipula spp.).

[0486] The present invention can also be used to control insect pests of turfgrass in thatched homes, including armyworms (such as fall armyworm, Spodoptera frugiperda, and common armyworm, Pseudaletia unipuncta), cutworms, weevils (Sphenophorus spp., such as S. venatus verstitus and S. parvulus), and grass borers (such as Crambus spp. and tropical grass borer, Herpetogramma phaeopteralis).

[0487] The present invention can also be used to control insect pests in turfgrass that live above ground and feed on turfgrass leaves, including wheat stink bugs (such as the southern wheat stink bug, Blissus insularis), Bermudagrass mite (Eriophyes cynodoniensis), Grass mealybug (Antonina graminis), Propsapia bicincta, leafhoppers, cutworms (Noctuidae), and Schizaphis graminis.

[0488] The present invention may also be used to control other pests in turfgrass, such as introduced red imported fire ants (Solenopsis invicta) which create nests in the lawn.

[0489] In the hygiene sector, the compositions according to the invention are effective against ectoparasites such as hard ticks, soft ticks, scabies, autumn mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas.

[0490] Examples of such parasites are:

[0491] From the order of the Pediculus: Haematopus spp., Linognathus spp., Pediculus spp., and Phtirus spp., Phidirus spp.

[0492] From the order Trichophagus: Felicola spp., Felicola spp., Felicola spp., Felicola spp., Werneckiella spp., Lepikentron spp., Felicola spp., Felicola spp. and Felicola spp.

[0493] From the order Diptera and the suborder Nematocerina and Brachycerina, for example, Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp. spp.), Musca spp., Hydrotaea spp., Biting flies spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp.) and tick species (Melophagus spp.).

[0494] From the order of the Siphonapterida, for example, Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllum spp.

[0495] From the order of the Heteropterida, for example, Cimex spp., Trypanosoma spp., Echinostoma spp., Panstrongylus spp.

[0496] From the order of the Blattarida, for example, Blatta orientalis, Periplaneta americana, Blattelagermanica and Supella spp.

[0497] The subclass Acaria (family Acarida) and the orders Meta-stigmata and Meso-stigmata, for example Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonyssus spp. spp.), Sternostoma spp., and Varroa spp.

[0498] From the order Actinedida (suborder Prostigmata) and Acaridida (suborder Astigmata), for example, Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergates spp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp. spp.), Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedress spp., Knemidocoptes spp., Cytodites spp., and Laminosioptes spp.

[0499] The compositions according to the invention are also suitable for protecting materials in the case of, for example, wood, textiles, plastics, adhesives, glues, paints, paper and card, leather, floor coverings and construction from infestation by insects.

[0500] The compositions according to the invention can be used, for example, against the following pests: beetles such as Hylotrupes bajulus, Cerambycidae, Anobium punctatum, Xestobium rufovillosum, Ernobius mollis, Dendrobium pertinex, Trypodendron lineatum, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis, Lyctus linearis, Lyctus pubescens, Lyctus thoracicus, Lepidosterna species, Xyleborus species, Dinoderus minutus, Sinoxylon anale, Heterobostrychus brunneus, Scolytidae species and Bostrychidae species; and also Hymenoptera such as Sirex noctilio, Urocerus gigas, Urocerus gigas taiganus and Urocerus augur; and termites such as Kalotermes flavicollis, Cryptotermes domesticus, Heterotermes indicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucifugus, Mastotermes darwiniensis, Archotermopsis nevadensis and Coptotermes formosanus; and moths such as Lepisma saccharina. Compounds of formula I and Ia 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, the compound TX (where the abbreviation "TX" means "a compound selected from 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, and the compounds defined in Table P") controls one or more pests selected from the families: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae and Heteroderidae.

[0501] Compounds of formula I and Ia or salts thereof are particularly suitable for controlling one or more pests selected from the genera: Spodoptera species, Plutella species, Frankliniella species, Thrips species, Euschistus species, Cydia species, Nilaparvata species, Myzus species, Aphis species, Diabrotica species, Rhopalosiphum species, Xestia species and Chilo species. In a preferred embodiment of each aspect, the compound TX (where the abbreviation "TX" means "a compound selected from 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, and the compounds defined in Table P") controls one or more pests selected from the genera: Spodoptera species, Plutella species, Frankliniella species, Thrips species, Euschistus species, Cydia species, Nilaparvata species, Myzus species, Aphis species, Diabrotica species, Rhopalosiphum species, Xestia species and Chilo species.

[0502] The compounds of formula I and I'a or their salts are particularly useful for controlling one or more of the following: Spodoptera littoralis, Plutella xylostella, western flower thrips, Thrips tabaci, American hero stink bug, codling moth, brown rice hopper, peach aphid, soybean looper, bean aphid, cucumber leaf beetle, cereal aphid, and striped stem borer.

[0503] In preferred embodiments of each aspect, compound TX (wherein the abbreviation "TX" means "a compound selected from the group consisting of 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, and E-1 to E-21, and Table P") controls one or more of: Spodoptera littoralis, diamondback moth, western flower thrips, tobacco thrips, hero American stink bug, codling moth, brown rice hopper, peach aphid, soybean looper, bean aphid, cucumber leaf beetle, cereal aphid, and striped stem borer, such as Spodoptera littoralis + TX, diamondback moth + TX; western flower thrips + TX, tobacco thrips + TX, hero American stink bug + TX, codling moth + TX, brown rice hopper + TX, peach aphid + TX, soybean looper + TX, bean aphid + TX, cucumber leaf beetle + TX, cereal aphid + TX, and striped stem borer + TX.

[0504] In one embodiment of each aspect, a 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 and E-1 to E-21, and Table P is suitable for controlling Spodoptera littoralis, Plutella xylostella, Western Flower Thrips, Thrips tabaci, American stink bug, Codling moth, Brown rice hopper, Green peach aphid, Soybean looper, Bean aphid, Cucumber leaf beetle, Grain aphid, and Chilo suppressalis on cotton, vegetables, corn, cereals, rice and soybean crops.

[0505] In one embodiment, a 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 and E-1 to E-21, and Table P is suitable for controlling Spodoptera exigua (preferably on vegetables), Codling moth (preferably on apples), Empoasca spp. (preferably on vegetables, vineyards), Diabrotica spp. (preferably on potatoes) and Chilo suppressalis (preferably on rice).

[0506] The compounds according to the invention may have any number of benefits, including, in particular, favorable levels of biological activity for protecting plants against insects or superior properties for use as agrochemical active ingredients (e.g., higher biological activity, favorable activity spectrum, increased safety (for non-target organisms above and below ground (such as fish, birds and bees)), improved physico-chemical properties, or increased biodegradability). In particular, it has been unexpectedly found that certain compounds of formula I may exhibit favorable safety relative to non-target arthropods, particularly pollinators (such as honey bees, solitary bees and bumble bees). Most particularly, relative to the Italian honey bee (Apis mellifera).

[0507] The compounds according to the invention can be used as pesticides in unmodified form, but they are usually formulated into compositions in various ways using formulation adjuvants such as carriers, solvents and surface-active substances. These formulations can be in different physical forms, for example in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent compressed tablets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, flowable oils, aqueous dispersions, oily dispersions, suspoemulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or water-miscible organic solvents as carriers), impregnated polymer films or in other forms known, for example, from Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, 1st edition, second revision (2010). Such formulations can be used directly or can be diluted before use. Dilution can be carried out with, for example, water, liquid fertilizers, micronutrients, biological organisms, oils or solvents.

[0508] These formulations can be prepared, for example, by mixing the active ingredient with a formulation adjuvant in order to obtain a composition in the form of a finely divided solid, granules, solution, dispersion or emulsion. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of plant or animal origin, modified oils of plant or animal origin, organic solvents, water, surface-active substances or combinations thereof.

[0509] These active ingredients can also be contained in very fine microcapsules. Microcapsules contain active ingredients in porous carriers. This allows the active ingredients to be released (e.g., slowly released) to the environment in controlled amounts. Microcapsules typically have a diameter of from 0.1 to 500 microns. The amount of active ingredients they contain is about 25% to 95% of the capsule weight by weight. These active ingredients can be in the form of an integral solid, in the form of fine particles in a solid or liquid dispersion, or in the form of a suitable solution. The encapsulated membrane can include, for example, natural or synthetic rubber, cellulose, styrene / butadiene copolymers, polyacrylonitrile, polyacrylate, polyester, polyamide, polyurea, polyurethane or chemically modified polymers and starch xanthate or other polymers known to those skilled in the art. Alternatively, very fine microcapsules can be formed, in which the active ingredients are contained in the form of finely dispersed particles in a solid matrix of a base material, but these microcapsules themselves are not wrapped.

[0510] Formulation adjuvants suitable for preparing the compositions according to the invention are known per se. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol rosinate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl Formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, dipropylene glycol, alkyl pyrrolidone, 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, acetic acid glyceryl, diacetic acid glyceryl, triacetin, decaglycerol Hexadecane, hexanediol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, dichloromethane, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, 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 higher molecular weight alcohols such as amyl alcohol, tetrahydrofuranol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone, etc.

[0511] Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances.

[0512] Many surface-active substances can be used advantageously in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier before use. Surface-active substances can be anionic, cationic, nonionic or polymeric and they can act 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 dodecyl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol / alkylene oxide addition products, such as ethoxylated nonylphenol; alcohol / alkylene oxide addition products, such as ethoxylated tridecanol; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; salts of dialkylsulfosuccinates, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitan oleate; quaternary ammoniums, such as dodecyltrimethylammonium 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 dialkyl phosphates; and also other substances, such as are described in: McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Company (MC Publishing Corp., Ridgewood New Jersey (1981).

[0513] Additional adjuvants that can be used in pesticidal formulations include crystallization inhibitors, viscosity modifiers, suspending agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, defoamers, complexing agents, substances and buffers that neutralize or change the pH, corrosion inhibitors, fragrances, wetting agents, absorption enhancers, micronutrients, plasticizers, glidants, lubricants, dispersants, thickeners, antifreeze agents, microbicides, and liquid and solid fertilizers.

[0514] The composition according to the invention may comprise an additive comprising an oil of plant or animal origin, a mineral oil, an alkyl ester of such an oil or a mixture of such an oil with an oil derivative. The amount of the oil additive in the composition according to the invention is generally from 0.01% to 10% based on the mixture to be applied. For example, the oil additive may be added to the spray tank in the desired concentration after the spray mixture has been prepared. Preferred oil additives include mineral oil or oil of plant origin, such as rapeseed oil, olive oil or sunflower oil; emulsified vegetable oils; alkyl esters of oils of plant origin, such as methyl derivatives; or oils of animal origin, such as fish oil or tallow. Preferred oil additives include C 8 -C 22 Alkyl esters of fatty acids, especially C 12 -C 18 Methyl derivatives of fatty acids, such as the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10th edition, Southern Illinois University, 2010.

[0515] These compositions according to the invention generally comprise from 0.1% to 99% by weight, in particular from 0.1% to 95% by weight, of a compound according to the invention and from 1% to 99.9% by weight of formulation adjuvants, preferably including from 0 to 25% by weight of surface-active substances. Whereas commercial products may preferably be formulated as concentrates, the end user will generally use dilute formulations.

[0516] The application rate varies within a wide range and depends on the nature of the soil, the application method, the crop plants, the harmful organisms to be controlled, the prevailing climatic conditions, and other factors governed by the application method, the application time and the target crop. In general, the compound can be applied at a rate of from 1 l / ha to 2000 l / ha, especially from 10 l / ha to 1000 l / ha.

[0517] Preferred formulations may have the following composition (wt%):

[0518] Emulsifiable concentrates :

[0519] Active ingredient: 1% to 95%, preferably 60% to 90%

[0520] Surfactant: 1% to 30%, preferably 5% to 20%

[0521] Liquid carrier: 1% to 80%, preferably 1% to 35%

[0522] Dust Agent :

[0523] Active ingredient: 0.1% to 10%, preferably 0.1% to 5%

[0524] Solid carrier: 99.9% to 90%, preferably 99.9% to 99%

[0525] Suspension concentrate:

[0526] Active ingredient: 5% to 75%, preferably 10% to 50%

[0527] Water: 94% to 24%, preferably 88% to 30%

[0528] Surfactant: 1% to 40%, preferably 2% to 30%

[0529] Wettable powder :

[0530] Active ingredient: 0.5% to 90%, preferably 1% to 80%

[0531] Surfactant: 0.5% to 20%, preferably 1% to 15%

[0532] Solid carrier: 5% to 95%, preferably 15% to 90%

[0533] Granules:

[0534] Active ingredient: 0.1% to 30%, preferably 0.1% to 15%

[0535] Solid carrier: 99.5% to 70%, preferably 97% to 85%

[0536] The following examples further illustrate (but do not limit) the present invention.

[0537]

[0538]

[0539] The combination is mixed thoroughly with these adjuvants and the mixture is ground thoroughly in a suitable grinder to obtain wettable powders which can be diluted with water to give a suspension of the desired concentration.

[0540] <![CDATA[ Powders for dry seed treatment ]]> a) b) c) Active ingredients 25％ 50％ 75％ Light mineral oil 5％ 5％ 5％ Highly dispersed silicic acid 5％ 5％ - Kaolin 65％ 40％ - talc - 20％

[0541] The combination is thoroughly mixed with adjuvants and the mixture is thoroughly ground in a suitable grinder to obtain a dust that can be used directly for seed treatment.

[0542] <![CDATA[ Emulsifiable concentrates ]]> Active ingredients 10％ Octylphenol polyglycol ether (4-5 mol of ethylene oxide) 3％ Calcium dodecylbenzenesulfonate 3％ Castor oil polyglycol ether (35 mol of ethylene oxide) 4％ Cyclohexanone 30％ Xylene mixture 50％

[0543] Emulsions of any desired dilution which can be used in plant protection can be obtained from these concentrates by dilution with water.

[0544]

[0545] Ready-to-use dusts are obtained by mixing the combination with a carrier and grinding the mixture in a suitable grinder. Such dusts can also be used for dry seed dressing of seeds.

[0546] <![CDATA[ Extruder pellets ]]> Active ingredients 15％ Sodium lignin sulfonate 2％ Carboxymethyl cellulose 1％ Kaolin 82％

[0547] The combination is mixed and ground with these adjuvants, and the mixture is moistened with water.

[0548] The mixture is extruded and then dried in a stream of air.

[0549] <![CDATA[ Coated granules ]]> Active ingredients 8％ Polyethylene glycol (molecular weight 200) 3％ Kaolin 89％

[0550] This finely ground combination is applied uniformly in a mixer to the kaolin moistened with polyethylene glycol. In this way, dust-free coated granules are obtained.

[0551] Suspension concentrates

[0552] Active ingredients 40％ Propylene glycol 10％ Nonylphenol polyglycol ether (15 mol of ethylene oxide) 6％ Sodium lignin sulfonate 10％ Carboxymethyl cellulose 1％ Silicone oil (in the form of a 75% emulsion in water) 1％ water 32％

[0553] The finely ground combination is intimately mixed with adjuvants to give a suspension concentrate from which any desired dilution can be obtained by dilution with water. Using such a dilution, living plants together with plant propagation materials can be treated and protected against microbial infection by spraying, pouring or immersion.

[0554] Flowable concentrate for seed treatment

[0555] Active ingredients 40％ Propylene glycol 5％ Copolymer Butanol PO / EO 2％ Tristyrylphenol, with 10-20 moles of EO 2％ 1,2-Benzisothiazolin-3-one (in the form of a 20% solution in water) 0.5％ Monoazo-pigment calcium salt 5％ Silicone oil (in the form of a 75% emulsion in water) 0.2％ water 45.3％

[0556] The finely ground combination is intimately mixed with adjuvants to give a suspension concentrate from which any desired dilution can be obtained by dilution with water. Using such a dilution, living plants together with plant propagation materials can be treated and protected against microbial infection by spraying, pouring or immersion.

[0557] Extended-release capsule suspension

[0558] 28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of a toluene diisocyanate / polymethylene-polyphenyl isocyanate mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinyl alcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is reached. To this emulsion, 2.8 parts of a 1,6-hexanediamine mixture in 5.3 parts of water are added. The mixture is stirred until the polymerization reaction is complete. The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersant. The capsule suspension formulation contains 28% of active ingredient. The diameter of the medium capsules is 8-15 microns. The resulting formulation is applied to the seeds as an aqueous suspension in a device suitable for this purpose.

[0559] 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 emulsions (EO), oil-in-water emulsions (EW), microemulsions (ME), oil dispersions (OD), oil suspensions (OF), oil-soluble liquids (OL), soluble concentrates (SL), ultra low volume suspensions (SU), ultra low volume liquids (UL), master batches (TK), dispersible concentrates (DC), wettable powders (WP), soluble granules (SG) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

[0560] Preparation Example:

[0561] LCMS method:

[0562] Method 1:

[0563] Spectra were recorded on a mass spectrometer from Waters (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 to 900 Da) and an Acquity UPLC from Waters: binary pump, heated column compartment, diode array detector and ELSD detector. Column: UPLC HSS T3 from Waters, 1.8 μm, 30×2.1 mm, temperature: 60° C., DAD wavelength range (nm): 210 to 500, solvent gradient: A=water+5% MeOH+0.05% HCOOH, B=acetonitrile+0.05% HCOOH; gradient: 10%-100% B in 1.2 min; flow rate (ml / min) 0.85.

[0564] Method 2:

[0565] Spectra were recorded on a mass spectrometer from Waters (SQD, SQDII single quadrupole mass spectrometer) equipped with an electrospray source (polarity: positive and negative, 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 to 900 Da) and an Acquity UPLC from Waters: binary pump, heated column compartment, diode array detector and ELSD detector. Column: UPLC HSS T3 from Waters, 1.8 μm, 30×2.1 mm, temperature: 60° C., DAD wavelength range (nm): 210 to 500, solvent gradient: A=water+5% MeOH+0.05% HCOOH, B=acetonitrile+0.05% HCOOH; gradient: 10%-100% B in 2.7 min; flow rate (ml / min) 0.85

[0566] Method 3:

[0567] Spectra were recorded on a mass spectrometer (single quadrupole mass spectrometer) from Agilent equipped with multimode electrospray and APCI (polarity: positive and negative ions, capillary: 4.00 KV, corona current 4.0 μA, charging voltage, 2.00 kV, nitrogen flow: 9.0 L / min, nebulizer pressure: 40 psig, mass range: 100 to 1000 m / z, drying gas temperature 250° C., evaporator temperature 200° C.) and on a LCMS from Agilent: quaternary pump, heated column compartment, 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

[0568] Method 4:

[0569] Spectra were recorded on a mass spectrometer from Waters (SQD, SQDII single quadrupole mass spectrometer) equipped with an electrospray source (polarity: positive and negative, 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 to 800 Da) and an Acquity UPLC from Waters: binary pump, heated column compartment, diode array detector and ELSD detector. Column: UPLC HSS T3 from Waters, 1.8 μm, 30×2.1 mm, temperature: 40°C, PDA wavelength range (nm): 200 to 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH; gradient: 10%-100% B in 1.3 min; flow rate (ml / min) 0.6

[0570] Chiral SFC Method 1: In SFC (Waters Acquity UPC 2 The spectra were recorded on a 100 μm 200 μm SFC equipped with a PDA detector (Waters Acquity UPC 2 Column: Daicel SFC IC (3 μm, 0.3 cm x 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: 1 μL

[0571] Chiral SFC Method 2: In SFC (Waters Acquity UPC 2 The spectra were recorded on a 100 μm 200 μm SFC equipped with a PDA detector (Waters Acquity UPC 2 . Column: Daicel SFC IG (3 μm, 0.3 cm x 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: 1 μL

[0572] Preparation of methyl 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylate (Intermediate I1)

[0573]

[0574] 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 onto a 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.

[0575] 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).

[0576] 2-Cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid methyl ester (Intermediate I2) and 2-Cyclopropyl-6-(trifluoromethyl) Preparation of pyridine-4-carboxylic acid (intermediate I3)

[0577]

[0578] 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 II 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 under argon at 100°C for 1 hour. 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).

[0579] 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).

[0580] LC-MS (method 1): retention time 1.12 min, m / z 246 [M+H] + .

[0581] After acidification to pH 1, the aqueous layer was extracted twice more 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).

[0582] 1 H 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).

[0583] LC-MS (method 1): retention time 0.94 min, m / z 232 [M+H] + .

[0584] Preparation of 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid (Intermediate I3)

[0585]

[0586] 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 12 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 adding 1 M aqueous hydrochloric acid solution (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.

[0587] 1 H NMR (400 MHz, dimethyl sulfoxide-d6) δppm: 0.96-1.02 (m, 2H) 1.07-1.15 (m, 2H) 2.40 (tt, J 1 =8.12Hz,J 2 =4.72Hz,1H)7.88(d,J=1.10Hz,1H)8.04(s,1H)13.90-14.36(m,1H)

[0588] LC-MS (method 1): retention time 0.94 min, m / z 232 [M+H] + .

[0589] Preparation of methyl 3-cyclopropyl-5-(trifluoromethyl)benzoate (Intermediate I4)

[0590]

[0591] Under argon, a solution of bromopropyne in toluene (80 weight %, 0.89g, 0.67mL) is added to a white suspension of 9-BBN dimer (3.0g, 12mmol) in 26mL of dried tetrahydrofuran to give a light yellow solution. The mixture is refluxed for 2 hours and then cooled to room temperature. A previously degassed sodium hydroxide 4M aqueous solution (4.4mL, 18mmol) is added to give a turbid colorless solution. Under argon, at room temperature, the obtained mixture is stirred for 1 hour. The very light yellow solution of the resulting is then added to a previously degassed 3-bromo-5-(trifluoromethyl)benzoic acid methyl ester (187331-46-0, 1.5g, 5.2mmol) and tetrakis (triphenylphosphine) palladium (0) (0.30g, 0.26mmol) in a light yellow solution in 52mL of dried tetrahydrofuran to give a light yellow solution. The resulting mixture is stirred at reflux for 19 hours. The mixture was cooled at 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 in vacuo 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.

[0592] 1 H NMR (400 MHz, chloroform-d) δppm: 0.76-0.85 (m, 2H) 1.06-1.15 (m, 2H) 2.03 (tt, J 1 =8.39Hz,J 2 =5.00Hz,1H)3.96(s,3H)7.52(s,1H)7.91(s,1H)8.08(d,J=0.73Hz,1H).

[0593] 19 F NMR (377 MHz, chloroform-d) δ ppm: -62.75 (s, 3F).

[0594] Preparation of 3-cyclopropyl-5-(trifluoromethyl)benzoic acid (Intermediate I5)

[0595]

[0596] 3-cyclopropyl-5-(trifluoromethyl)benzoic acid methyl ester (7.00g, 28.7mmol) is dissolved in tetrahydrofuran (57.3mL) and water (28.7mL). Then lithium hydroxide (1.21g, 28.7mmol) is added and the obtained light yellow turbid solution is stirred at room temperature for 4 hours. The reaction mixture is diluted in ethyl acetate and water. The organic phase is washed with water twice. The combined water layer is acidified to pH 1-2 with 1N aqueous hydrochloric acid and extracted with ethyl acetate three times. The combined organic layer is washed with salt water once, dried over sodium sulfate, filtered and concentrated under reduced pressure at 60°C to obtain 3-cyclopropyl-5-(trifluoromethyl)benzoic acid, which is used without further purification.

[0597] 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).

[0598] LC-MS (method 1): retention time 0.99 min, m / z 229 [MH] - .

[0599] Preparation of 3-(trifluoromethyl)-5-vinyl-benzoic acid methyl ester (Intermediate I6)

[0600]

[0601] In a three-necked flask under argon, 3-bromo-5-(trifluoromethyl)benzoic acid methyl ester (CAS: 187331-46-0, 20g, 69.24mmol) is dissolved in toluene (312mL). Then tributyl(vinyl)tin (25.56mL, 83.09mmol) is added and the resulting solution is degassed with argon for 10min. Tetrakis(triphenylphosphine)palladium(0) (0.816543g, 0.69mmol) is added, and the resulting mixture is stirred at 110°C for 2 hours. After cooling at room temperature, the mixture is diluted with ethyl acetate (100mL), filtered through a diatomaceous earth pad, washed with ethyl acetate and the filtrate is concentrated in vacuo. The crude product is purified on silica gel by chromatography to obtain 3-(trifluoromethyl)-5-vinyl-benzoic acid methyl ester.

[0602] 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 1 =17.42Hz,J 2=10.82Hz,1H)7.82(s,1H)8.19(s,1H)8.24-8.29(m,1H).

[0603] Preparation of diphenyl (2,2,2-trifluoroethyl) sulfonium trifluoromethanesulfonate

[0604]

[0605] In an autoclave, diphenyl sulfide (36.43 mL, 211.1 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (6.207 mL, 42.22 mmol) were mixed. The mixture was stirred at room temperature for 2 min, then the autoclave was closed and heated at 150°C for 20 hours. The reactants were cooled at room temperature and a white precipitate was formed. 75 ml of ether was added, and the white solid was filtered. It was washed four times with 30 mL of ether and then dried under reduced pressure to obtain Diphenyl(2,2,2-trifluoroethyl)sulfoniumtriazine Fluoromethanesulfonate .

[0606] 1 H NMR (400 MHz, chloroform-d) δ ppm: 5.78 (d, J = 8.80 Hz, 2H) 7.89 (d, J = 8.07 Hz, 4H) 7.93-8.00 (m, 2H) 8.37 (dd, J 1 =8.62Hz,J 2 =1.28Hz,4H).

[0607] 19 F NMR (377 MHz, chloroform-d) δ ppm: -78.91 (s, 3F) -61.26 (s, 3F).

[0608] Preparation of methyl 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoate (Intermediate I7)

[0609]

[0610] In a vial under argon, 3-(trifluoromethyl)-5-vinyl-benzoate (1.9 g, 8.3 mmol) and cesium fluoride (1.5 g, 9.9 mmol) were dissolved in dimethylacetamide (33 mL) to give a colorless solution, which was degassed under argon for 20 min. 5,10,15,20-tetraphenyl-21H,23H-porphyrin iron (III) chloride (0.31 g, 0.41 mmol) was added. The reactant became a green suspension and diphenyl (2,2,2-trifluoroethyl) sulfonium trifluoromethanesulfonic acid (3.8 g, 9.1 mmol) was also added in batches. The reactant was stirred at room temperature overnight. 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 40 ° C and 160 mbar. The crude product was purified by chromatography on silica gel to give methyl 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoate.

[0611] 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).

[0612] Preparation of 3-(trifluoromethyl)-5-[2-(trifluoromethyl)cyclopropyl]benzoic acid (I8)

[0613]

[0614] 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 acidified with 2M hydrochloric acid solution. The aqueous layer was extracted twice with ethyl acetate, 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.

[0615] 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, J 1 =7.70Hz,J 2=4.77Hz,1H)7.87(s,1H)8.02(s,1H)8.05-8.08(m,1H)13.54(br s,1H).

[0616] LC-MS (method 1): retention time 1.04 min, m / z 297 [MH] - .

[0617] Preparation of methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfanyl)benzoate (Intermediate I9)

[0618]

[0619] Under argon, (2,2'-bipyridine)(trifluoromethanethiol)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). 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 flash chromatography twice on silica gel (ethyl acetate in cyclohexane) to give the desired product (1.5 g, 4.9 mmol) as a yellow gum.

[0620] 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).

[0621] LC-MS (method 1): retention time 1.21 min, m / z 279 [M–MeO+H] + .

[0622] Preparation of methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoate (Intermediate I10)

[0623]

[0624] 3-Chloroperbenzoic acid (2.3 g, 11 mmol, 2.1 eq) was added portionwise to a 0°C cooled solution of methyl 3-(trifluoromethyl)-5-(trifluoromethylsulfanyl)benzoate (intermediate I13 prepared as described above) (1.8 g, 5.3 mmol) in dichloromethane (16 mL). After stirring at room temperature for 1 hour, more 3-chloroperbenzoic acid (2.3 g, 11 mmol, 2.1 eq) was added and the reaction mixture was stirred overnight. The formed precipitate was filtered. The filtrate was washed with a 10% aqueous solution of sodium thiosulfate and treated with NaHCO 3The 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.

[0625] 1 H 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).

[0626] 19 F NMR (377MHz, chloroform-d) δppm: -77.49 (s, 3F) -62.96 (s, 3F)

[0627] Preparation of 3-(trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoic acid (I11)

[0628]

[0629] 3-(Trifluoromethyl)-5-(trifluoromethylsulfonyl)benzoic acid methyl ester (1.8 g, 5.4 mmol) was loaded into a flask and dissolved in tetrahydrofuran (16 mL) and water (11 mL). To this mixture was added lithium hydroxide monohydrate (0.26 g, 11 mmol) and the reactants were 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.

[0630] 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).

[0631] Preparation of methyl 3-(cyclopropanecarbonyl)-5-(trifluoromethyl)benzoate (Intermediate I12)

[0632]

[0633] Under argon, 3-iodo-5-(trifluoromethyl)benzoic acid methyl ester (10g, 28.78mmol) is dissolved in tetrahydrofuran (115mL). The obtained light brown solution is cooled to -78°C with a dry ice / acetone bath. The 1.3M Turbo Grignard reagent in tetrahydrofuran solution (31mL, 40.29mmol) is added dropwise over 20 minutes with a syringe, directly giving a dark solution while keeping the temperature below -65°C. The obtained mixture is stirred at -78°C for 15 minutes. Cuprous cyanide (3.125g, 34.5mmol) and anhydrous lithium chloride (1.479g, 34.5mmol) are added at once simultaneously to give a dark suspension. The obtained mixture is stirred at -78°C for 15 minutes again. Cyclopropanecarbonyl chloride (5.340mL, 57.5mmol) is finally added dropwise over 5 minutes (temperature reaches -68°C maximum). The obtained 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 20ml methanol. The obtained mixture was made to reach room temperature and the suspension obtained was filtered through diatomite. Saturated aqueous ammonium chloride and ethyl acetate were added to the filtrate. The water layer was extracted twice with ethyl acetate. The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure at 40 ° C. The crude material was purified on silica gel by chromatography to obtain 3-(cyclopropanecarbonyl)-5-(trifluoromethyl) methyl benzoate.

[0634] 1 H NMR (400 MHz, chloroform-d) δ ppm: 1.16-1.22 (m, 2H) 1.35 (quin, J = 3.76 Hz, 2H) 2.74 (tt, J 1 =7.84Hz,J 2 =4.45Hz, 1H) 4.02 (s, 3H) 8.45 (d, J = 0.73Hz, 1H) 8.51 (d, J = 0.73Hz, 1H) 8.86 (s, 1H).

[0635] Preparation of methyl 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoate (Intermediate I13)

[0636]

[0637] Under argon, 3-(cyclopropanecarbonyl)-5-(trifluoromethyl) methyl benzoate (5.5g, 20mmol) is dissolved in 2,2-difluoro-1,3-dimethyl-imidazolidine (36mL, 280mmol) to give a light yellow solution. The resulting mixture is stirred at 110°C for 5 hours to give a light brown solution. The reaction mixture is cooled to room temperature and added dropwise to 1.0L of saturated sodium bicarbonate aqueous solution stirred vigorously at 0°C (keeping the temperature below 10°C). The resulting mixture (pH 8-9) is then extracted 3 times with ethyl acetate. The combined organic layer is dried over sodium sulfate, filtered and concentrated under reduced pressure at 50°C. The crude material is purified on silica gel by chromatography to obtain 3-[cyclopropyl (difluoro) methyl]-5-(trifluoromethyl) methyl benzoate.

[0638] 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).

[0639] 19 F NMR (377 MHz, chloroform-d) δ ppm: -98.40 (s, 3F) -62.81 (s, 2F).

[0640] Preparation of 3-[Cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (I14)

[0641]

[0642] 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid methyl ester (4.45g, 15.1mmol) was dissolved in tetrahydrofuran (30.3mL) and water (15.1mL). Lithium hydroxide monohydrate (0.833g, 19.7mmol) was added and the resulting colorless turbid solution was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate and water. The organic phase was washed with water twice. The combined water layer was acidified to pH 1-2 with 1N aqueous hydrochloric acid and extracted with ethyl acetate three times. The combined organic layer was washed once with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure at 60°C to obtain 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid, which was used without further purification.

[0643] 1H 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).

[0644] LC-MS (method 1): retention time 1.03 min, m / z 279 [MH] - .

[0645] 2-(1-cyano-2-ethoxy-2-oxo-ethyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid methyl ester (intermediate Preparation of I15)

[0646]

[0647] 2-Chloro-6-(trifluoromethyl)pyridine-4-methyl-formiate (1.05g, 4.40mmol) is dissolved in dimethyl sulfoxide (13.2mL).Then ethyl 2-cyanoacetate (0.702mL, 6.60mmol), potassium carbonate (1.535g, 11.00mmol) and tetrabutylammonium bromide (0.145g, 0.440mmol) are added continuously at room temperature. The gained suspension is stirred at 90 ℃ for 1 hour and then stirred at room temperature overnight. The reaction mass is diluted with 50mL water and 100mL ethyl acetate, cooled to 0 ℃-10 ℃ and slowly quenched with 1N hydrochloric acid via a dropping funnel, until pH 3. The aqueous phase is extracted with ethyl acetate. The combined organic layer is dried over sodium sulfate and concentrated under reduced pressure at 50 ℃. The crude material was purified by chromatography on silica gel using ethyl acetate in cyclohexane to give methyl 2-(1-cyano-2-ethoxy-2-oxo-ethyl)-6-(trifluoromethyl)picolinate.

[0648] 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).

[0649] LC-MS (method 1): retention time 1.01 min, m / z 317 [M+H] + .

[0650] Preparation of methyl 2-(cyanomethyl)-6-(trifluoromethyl)pyridine-4-carboxylate (I16)

[0651]

[0652] 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 extracted with 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.

[0653] 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).

[0654] LC-MS (method 1): retention time 0.89 min, m / z 243 [MH] - .

[0655] Preparation of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (I17)

[0656]

[0657] 2-(Cyanomethyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid methyl ester (0.05g, 0.20mmol) was dissolved in dimethylformamide (2mL). Sodium hydride (24mg, 0.61mmol) was added at room temperature and the colorless solution became a dark purple suspension. After 10min, 1,2-dibromoethane (0.02mL, 0.24mmol) was added and the resulting suspension was stirred at room temperature for 15min. The reaction mixture was quenched with saturated ammonium chloride solution at 0°C-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 obtain 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid.

[0658] 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).

[0659] LC-MS (method 1): retention time 0.89 min, m / z 255 [MH]- .

[0660] Preparation of methyl 3-(cyanomethyl)-5-(trifluoromethyl)benzoate (Intermediate I18)

[0661]

[0662] 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 using a syringe. The solution was degassed under Ar for 5 min. ZnF was then added 2 (0.130 g, 1.25 mmol), Xantphos (0.0481 g, 0.0831 mmol) and Pd 2 (dba) 3 (0.0384 g, 0.0415 mmol). The resulting black suspension was stirred at 100°C for 22 hours and then cooled to room temperature.

[0663] Concentrate under reduced pressure at 50° C. The crude material is purified by chromatography on silica gel using ethyl acetate in cyclohexane to give methyl 3-(cyanomethyl)-5-(trifluoromethyl)benzoate.

[0664] 1 H NMR (400 MHz, chloroform-d) δppm: 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] - .

[0665] Preparation of methyl 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoate (Intermediate I19)

[0666]

[0667] 3-(cyanomethyl)-5-(trifluoromethyl) methyl benzoate (2.15g, 7.07mmol) is dissolved in N,N-dimethylformamide (32.3mL). Cesium carbonate (7.13g, 21.2mmol) is added to the stirred solution and the mixture is stirred at room temperature for 10min. 1,2-dibromoethane (0.68mL 7.78mmol) is added and the mixture is stirred at 60°C for 3 hours, then cooled to room temperature. Water (30mL) is added, and then the water layer is extracted with ethyl acetate (60mL). The combined organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. The crude material is purified by flash chromatography (silica gel, ethyl acetate in hexane) to obtain 3-(1-cyanocyclopropyl)-5-(trifluoromethyl) methyl benzoate.

[0668] 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).

[0669] Preparation of 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoic acid (Intermediate I20)

[0670]

[0671] 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 pH = 2. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give 3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzoic acid.

[0672] 1 H 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).

[0673] LC-MS (Method 1): retention time 0.86 min, m / z 254 [MH]-.

[0674] Preparation of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanol

[0675]

[0676] Methylmagnesium bromide (1.00M in THF, 63.2mL, 63.2mmol) was added to a solution of 3-bromo-5-(trifluoromethyl)benzaldehyde (8.00g, 31.6mmol) in tetrahydrofuran (100mL) at 0°C under nitrogen. The resulting brown reaction mixture was stirred at room temperature for 30min. The reaction mixture was quenched with saturated ammonium chloride solution. The water layer was extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure to obtain 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanol as a light yellow liquid.

[0677] 1H NMR (400MHz, DMSO-d) δppm: 7.78-7.88 (m, 2H), 7.71 (s, 1H), 5.52 (d, 1H), 4.81 (m, 1H), 1.35 (d, 3H).

[0678] Preparation of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanone

[0679]

[0680] Pyridinium chlorochromate (5.05 g, 23.4 mmol) was added to a stirred solution of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanol (7.00 g, 15.6 mmol) in dichloromethane (150 mL) in batches at 0 ° C. The obtained brown reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered through a diatomaceous earth pad, and the filtrate was evaporated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (eluted with ethyl acetate in hexane) to obtain 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanone as a colorless oil.

[0681] 1H NMR (400MHz, DMSO-d) δppm: 8.38 (1H, s), 8.26 (1H, s), 8.19 (1H, s), 2.69 (s, 1H).

[0682] Preparation of 1-[3-bromo-5-(trifluoromethyl)phenyl]cyclopropanol

[0683]

[0684] A solution of 1-[3-bromo-5-(trifluoromethyl)phenyl]ethanone (5.00g, 18.3mmol) in dichloromethane (30mL) was treated with triethylamine (3.84mL, 27.5mmol) and trimethylsilyl trifluoromethanesulfonate (6.12g, 27.5mmol) at 0°C. The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate solution (100mL). The water 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 (7.37g, 27.5mmol) and diethylzinc (1.00M in hexane, 27.5mL, 27.5mmol) 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 water 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 light 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 (eluted with ethyl acetate in hexane) to give 1-[3-bromo-5-(trifluoromethyl)phenyl]cyclopropanol as an off-white solid.

[0685] 1H 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).

[0686] Preparation of 1-bromo-3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzene (I50)

[0687]

[0688] 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. Iodomethane (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 (gradient of ethyl acetate in hexane) to give 1-bromo-3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzene as a colorless liquid.

[0689] 1H NMR (400MHz, DMSO-d) δppm: 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).

[0690] Preparation of methyl 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoate (I51)

[0691]

[0692] 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) were loaded into the autoclave. 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 diatomaceous earth. Water and ethyl acetate were added to the filtrate and the water layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The crude residue was purified on silica gel by flash chromatography (gradient of ethyl acetate in hexane) to obtain 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid methyl ester as a light yellow liquid.

[0693] 1H 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).

[0694] Preparation of 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid (I52)

[0695]

[0696] 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid methyl ester (1.00g, 3.46mmol) was dissolved in tetrahydrofuran (6.0mL) and water (3.0mL). Lithium hydroxide monohydrate (291mg, 6.93mmol) was added and the mixture was stirred at room temperature for 3 hours. The mixture was concentrated and 2N 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.

[0697] 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).

[0698] Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethylene ketone (I21)

[0699]

[0700] 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. The crude material was purified twice by flash chromatography on silica gel (eluting first with ethyl acetate:ethanol in dichloromethane 3:1 and then with ethyl acetate in cyclohexane) to give 1-(3-pyrimidin-2-ylpyrazin-2-yl)eneketone.

[0701] LCMS (method 1): retention time 0.37 min, m / z 201 [M+H + ]; 1 H-NMR (400MHz, CDCl 3 ): δppm: 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).

[0702] Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethylamine (I31)

[0703]

[0704] Ammonia (7M in methanol, 14.3mL) and sodium cyanoborohydride (0.398g, 6.02mmol) are added to a solution of 1-(3-pyrimidine-2-ylpyrazine-2-yl)ethanone (0.401g, 2.01mmol) in a saturated solution of ammonium acetate in ethanol (32mL). The reaction mixture is heated to reflux and stirred for 16.5 hours. After cooling to room temperature, it is concentrated under reduced pressure. The resulting residue is diluted in 2M sodium hydroxide (10mL) and extracted with dichloromethane. The combined organic layer is dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material is purified once by reverse phase chromatography (eluted with acetonitrile in water), then purified for the second time by flash chromatography on silica gel (eluted with methanol in dichloromethane) to obtain 1-(3-pyrimidine-2-ylpyrazine-2-yl)ethanamine as a yellow solid.

[0705] LCMS (method 1): retention time 0.19 min, m / z 202 [M+H + ]; 1 H-NMR (400MHz, CDCl 3 ): δppm: 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).

[0706] Preparation of tributyl-(5-cyclopropylpyrimidin-2-yl)stannane

[0707]

[0708] Hexa-n-butylditin (15.9 mL, 31.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.82 g, 1.57 mmol) were added to a solution of 2-chloro-5-cyclopropyl-pyrimidine (90%, 2.70 g, 15.7 mmol) in toluene (40 mL). 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. The crude material was purified by flash chromatography on silica gel (eluted with ethyl acetate in hexane) to obtain tributyl-(5-cyclopropylpyrimidine-2-yl)stannane as a yellow oil.

[0709] 1 H-NMR (400MHz, CDCl 3): δppm: 7.3 (m, 2H), 1.65 (m, 6H), 1.35 (m, 16H), 0.9 (m, 12H).

[0710] Preparation of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethanone (I23)

[0711]

[0712] Tributyl-(5-cyclopropylpyrimidine-2-yl)stannane (6.80 g, 14.9 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.33 g, 1.15 mmol) were added to a solution of 1-(3-chloropyrazine-2-yl)ethanone (90%, 2.00 g, 11.5 mmol) in toluene (20 mL). 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. The crude material was purified by flash chromatography on silica gel (eluted with ethyl acetate in hexane) to obtain 1-[3-(5-cyclopropylpyrimidine-2-yl)pyrazine-2-yl]ethanone as a brown solid.

[0713] 1 H-NMR (400MHz, CDCl 3 ): δppm: 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).

[0714] Preparation of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethylamine (I32)

[0715]

[0716] Ammonia (30%, 30 mL in water) was added to a solution of 1-[3-(5-cyclopropylpyrimidine-2-yl)pyrazine-2-yl]ethanone (90%, 1.00 g, 3.75 mmol) in a saturated solution of ammonium acetate in ethanol (75 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. The crude material was purified by reverse phase chromatography (eluted with acetonitrile in water) to obtain 1-[3-(5-cyclopropylpyrimidine-2-yl)pyrazine-2-yl]ethanamine as a brown oil.

[0717] 1H-NMR (400MHz, DMSO): δppm 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).

[0718] Preparation of tert-butyl N-(6-tributylstannyl-3-pyridyl)carbamate

[0719]

[0720] The solution of N-(6-bromo-3-pyridyl) tert-butyl carbamate (2.50g, 8.24mmol) in dry tetrahydrofuran (50mL) is cooled to -75 ℃ and n-butyl lithium (2.50M, 5.77mL, 14.4mmol) is added dropwise in 5 minutes. The reaction mixture is stirred for 1 hour at the same temperature. Then tributyltin chloride (4.69g, 14.4mmol) is added to the reaction mixture, which is then stirred at room temperature for 3 hours. The reaction mixture is quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer merged is washed with salt water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material is purified by chromatography on neutral alumina to obtain the desired product.

[0721] 1 H-NMR (400MHz, CDCl3): δppm: 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).

[0722] Preparation of tert-butyl N-[6-(3-acetylpyrazin-2-yl)-3-pyridinyl]carbamate (I28)

[0723]

[0724] 1-(3-chloropyrazine-2-yl) ethyl ketone (12.3g, 70.8mmol) and copper (I) iodide (2.70g, 14.2mmol) were added to a solution of tert-butyl N-(6-tributylstannyl-3-pyridyl)carbamate (36.0g, 70.8mmol) in toluene (720mL). The reaction mixture was purged with argon for 20min and tetrakis (triphenylphosphine) palladium (0) (4.09g, 3.54mmol) was added. The reaction was stirred for 5h at 100°C. After cooling at room temperature, the reaction mixture was filtered through a diatomaceous earth pad and the filtrate was evaporated under reduced pressure. The residue was diluted with ethyl acetate, washed with water, saline and saturated potassium fluoride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluted with ethyl acetate in n-hexane) to obtain tert-butyl N-[6-(3-acetylpyrazine-2-yl)-3-pyridyl]carbamate.

[0725] 1 H-NMR (400MHz, DMSO): δppm: 9.9 (s, 1H), 8.6–8.9 (m, 3H), 8.1–8.25 (m, 2H), 2.55 (s, 1H), 1.5 (s, 9H).

[0726] Preparation of 1-[3-(5-amino-2-pyridyl)pyrazin-2-yl]ethanone (I29)

[0727]

[0728] HCl (4.00M, 73.0mL, 0.292mol) in 1,4-dioxane is added dropwise to a solution of tert-butyl N-[6-(3-acetylpyrazine-2-yl)-3-pyridyl]carbamate (17.0g, 0.0487mol) in dichloromethane (510mL) cooled to 0°C. The mixture is stirred for 10min and then stirred at room temperature for 16 hours. The reaction mixture is concentrated in vacuo and poured into a mixture of ice-cold water and dichloromethane. The pH is adjusted to 12 with 2N sodium hydroxide solution. The water layer is extracted three times with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulfate and concentrated in vacuo. The crude material is purified by flash chromatography on silica gel (eluted with methanol in dichloromethane) to obtain 1-[3-(5-amino-2-pyridyl)pyrazine-2-yl] ketene as a yellow solid.

[0729] LC-MS (method 3): retention time 1.41 min, m / z 215.1 [M+H] +

[0730] Preparation of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethanone (I25)

[0731]

[0732] A solution of 1-[3-(5-amino-2-pyridyl)pyrazine-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, and tert-butyl nitrite (2.17 mL, 25.2 mmol) was then added dropwise. 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. The crude material was purified by reverse phase chromatography (C18; eluted with acetonitrile in water) to obtain 1-[3-(5-chloro-2-pyridyl)pyrazine-2-yl]ethanone.

[0733] 1 H-NMR (400MHz, DMSO): δppm: 8.9 (s, 1H), 8.8 (d, 1H), 8.7 (s, 1H), 8.2 (m, 2H), 2.6 (s, 3H).

[0734] Preparation of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethylamine (I35)

[0735]

[0736] To a solution of 1-[3-(5-chloro-2-pyridyl)pyrazine-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. The crude material was purified by reverse phase chromatography (eluting with acetonitrile in water) to give 1-[3-(5-chloro-2-pyridyl)pyrazine-2-yl]ethanamine.

[0737] LCMS (method 3): retention time 2.7 min, m / z = 235 [M+H + ]

[0738] Preparation of tert-butyl N-[2-(3-acetylpyrazin-2-yl)pyrimidin-5-yl]carbamate (I53)

[0739]

[0740] 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-chloropyrazine-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 min 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 at room temperature, the reaction mixture was filtered through a diatomaceous earth pad and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluted with ethyl acetate in n-hexane) to give a brown jelly. tert-Butyl N-[2-(3-acetylpyrazin-2-yl)pyrimidin-5-yl]carbamate .

[0741] LCMS (method 3): retention time 1.04 min, m / z = 216.1 [M+H + ]

[0742] Preparation of 1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethanone (I54)

[0743]

[0744] A solution of 1-[3-(5-aminopyrimidine-2-yl)pyrazine-2-yl]ethanone (2.80g, 11.7mmol) in acetonitrile (50mL) was cooled to 0 ° C. Isoamyl nitrite (2.74g, 23.4mmol) was added, followed by copper bromide (5.23g, 23.4mmol). 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. The crude material was purified by flash chromatography on silica gel (eluted with ethyl acetate in n-hexane) to obtain 1-[3-(5-bromopyrimidine-2-yl)pyrazine-2-yl]vinyl ketone as a brown solid.

[0745] 1 H-NMR (400MHz, DMSO): δppm: 9.15 (s, 2H), 8.95 (m, 1H), 8.88 (m, 1H), 2.63 (s, 3H).

[0746] LCMS (method 3): retention time 3.54 min, m / z = 279 / 281 [M+H] + (bromine mode)

[0747] Preparation of 1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethylamine (I55)

[0748]

[0749] 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.

[0750] 1 H-NMR (400MHz, DMSO): δppm: 9.22 (s, 2H), 8.70-9.00 (m, 2H), 4.50-4.80 (m, 1H), 1.42 (d, 3H).

[0751] Preparation of 3,5-dichloro-2-pyrimidin-2-yl-pyrazine

[0752]

[0753] To a solution of 3,5-dichloro-2-iodo-pyrazine (0.500 g, 1.81 mmol) in dioxane (5 mL) 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) at room temperature. 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 material, 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.

[0754] 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).

[0755] Preparation of 3-chloro-5-methoxy-2-pyrimidin-2-yl-pyrazine

[0756]

[0757] 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 mass was stirred for 2 hours at room temperature. The reaction mixture was quenched in 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.

[0758] LC-MS (method 4): retention time 0.37 min, m / z 223 [M+H + ]; 1 H NMR (400 MHz, CDCl 3 )δppm:8.95(d,2H)8.29(s,1H)7.37(t,1H)4.07(s,3H)

[0759] Preparation of 3-(1-ethoxyvinyl)-5-methoxy-2-pyrimidin-2-yl-pyrazine

[0760]

[0761] At room temperature, tributyl (1-ethoxyvinyl) stannane (0.140 mL, 0.404 mmol) and tetrakis (triphenylphosphine) palladium (0.013 g, 0.026 mmol) were added to a solution of 3-chloro-5-methoxy-2-pyrimidin-2-yl-pyrazine (0.060 g, 0.269 mmol) in dioxane (1 mL). The reaction mixture was heated to 150 ° C in a microwave and stirred 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 obtain 3- (1-ethoxyvinyl) -5-methoxy-2-pyrimidin-2-yl-pyrazine as a brown solid.

[0762] LC-MS (Method 4): retention time 1.11 min, m / z 259 [M+H+].

[0763] Preparation of 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethylene ketone (I47)

[0764]

[0765] To a solution of 3-(1-ethoxyvinyl)-5-methoxy-2-pyrimidin-2-yl-pyrazine (0.10 g, 0.387 mmol) in acetonitrile (1 mL) was 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)vinyl ketone as a white solid.

[0766] LC-MS (method 4): retention time 1.07 min, m / z 231 [M+H + ].

[0767] Preparation of 1-(6-methoxy-3-pyrimidin-2-yl-pyrazin-2-yl)ethylamine (I48)

[0768]

[0769] 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 in 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.

[0770] LC-MS (method 4): retention time 0.35 min, m / z 232 [M+H + ].

[0771] Preparation of 1-(3-chloropyrazin-2-yl)ethylamine

[0772]

[0773] To a solution of 1-(3-chloropyrazine-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 in vacuo. The crude material was purified by reverse phase chromatography (C18 column, gradient of acetonitrile in water) to give 1-(3-chloropyrazine-2-yl)ethanamine.

[0774] 1 H NMR (400 MHz, CDCl 3 )δppm:8.49(d,1H),8.26(d,1H),4.56(q,1H),1.95(br s,2H),1.44(d,3H)

[0775] Preparation of (1S)-1-(3-chloropyrazin-2-yl)ethylamine (I45)

[0776]

[0777] To a solution of 1-(3-chloropyrazin-2-yl)ethylamine (202.2 mg, 1.20 mmol) in tert-butyl methyl ether (11 mL) was added 435 (240 mg), followed by the addition of ethyl methoxyacetate (1.44 mL, 12.0 mmol). The mixture was stirred at 40 ° C for 5.5 hours. The reaction mixture was diluted with dichloromethane and filtered. The filtrate was concentrated in vacuo. The crude material was purified by flash chromatography on silica gel (gradient elution with methanol in dichloromethane) to give (1S)-1-(3-chloropyrazine-2-yl)ethylamine.

[0778] 1 H NMR (400 MHz, CDCl 3 )δppm: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,CHCl 3 )

[0779] Preparation of (1R)-1-(3-chloropyrazin-2-yl)ethanol (I44)

[0780]

[0781] 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. RuBF was then added 4 [(R,R)-TsDPEN](p-cymene) (0.0362 g, 0.0526 mmol). A cooling 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 in vacuo. The crude material was purified by flash chromatography on silica gel (gradient elution with ethyl acetate in cyclohexane) to give (1R)-1-(3-chloropyrazine-2-yl)ethanol.

[0782] 1 H-NMR (400MHz, CDCl 3 )δppm 8.49(d,1H),8.34(d,1H),5.18(m,1H),3.81(d,1H),1.52(d,3H)

[0783] Chiral SFC (Method 2): 1.98 min (minor enantiomer), 2.55 min (major enantiomer); ee = 85%

[0784] Preparation of (1S)-1-(3-chloropyrazin-2-yl)ethylamine (I45)

[0785]

[0786] (1R)-1-(3-chloropyrazin-2-yl)ethanol (87.8 mg, 0.554 mmol) was dissolved in tetrahydrofuran (1.9 mL). Then, 1,8-diazabicyclo[5.4.0]undec-7-ene (0.10 mL, 0.66 mmol) was 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.

[0787] 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.

[0788] The reaction mixture is concentrated to a volume of 1 mL and then diluted with dichloromethane. 1 M hydrochloric acid is added and the water layer is washed with dichloromethane. The water layer is alkalized to pH=14 with 4 M sodium hydroxide solution and extracted with dichloromethane. The combined organic layers are dried over magnesium sulfate and concentrated in vacuo. The crude material is purified by flash chromatography on silica gel (gradient elution with methanol in dichloromethane) to obtain (1S)-1-(3-chloropyrazine-2-yl)ethylamine.

[0789] 1 H NMR (400 MHz, CDCl 3 )δppm:8.49(d,1H),8.27(d,1H),4.56(q,1H),1.84(s,2H),1.44(d,3H)

[0790] [α] D 20 :-26.0°(c:0.960,CHCl 3 )

[0791] Preparation of (2R)-N-[(1S)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide

[0792]

[0793] To a solution of 1-(3-chloropyrazin-2-yl)ethylamine; 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 solution and extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel (eluting with methanol in dichloromethane) to give (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 (crystallization from acetonitrile / water).

[0794] Analytical data for (2R)-N-[(1R)-1-(3-chloropyrazin-2-yl)ethyl]-2-hydroxy-2-phenyl-acetamide:

[0795] LCMS (method 1): retention time 0.74 min, m / z = 291 [M+H + ]

[0796] Preparation of (1S)-1-(3-chloropyrazin-2-yl)ethylamine; hydrochloride

[0797]

[0798] A solution of (2R)-N-[(1S)-1-(3-chloropyrazine-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 alkalized with 3N sodium hydroxide and diluted and extracted with ethyl acetate. The water layer was freeze-dried 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 was produced, which was filtered and dried under reduced pressure to obtain the desired product.

[0799] LCMS (method 1): retention time 0.19 min, m / z=158 [M+H+].

[0800] Preparation of (1S)-1-(3-chloropyrazin-2-yl)-N-(cyclopropylmethyl)ethylamine (I46)

[0801]

[0802] Sodium triacetoxyborohydride (59.4 mg, 0.267 mmol) was added to a stirred solution of (1S)-1-(3-chloropyrazine-2-yl)ethylamine (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 solution was added and the aqueous layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel (eluted with ethyl acetate in cyclohexane) to give (1S)-1-(3-chloropyrazine-2-yl)-N-(cyclopropylmethyl)ethylamine.

[0803] 1 H NMR(400MHz, CDCl3)δppm-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);

[0804] [α] D 20 =-54°(c 0.327, CHCl 3 )

[0805] N-[(1S)-3-(5-bromo-2-pyridyl)-2-hydroxy-1-methyl-3-oxo-propyl]carbamic acid tert-butyl ester preparation

[0806]

[0807] 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 refilled with argon three times. Then, 2-(3-benzyl-4-methyl-thiazole-3-ium-5-yl)ethanol was added continuously; bromide (0.388 g, 1.24 mmol), 5-bromopyridine-2-carboxaldehyde (CAS 31181-90-5, 1.81 g, 9.27 mmol) and dichloromethane (6 mL), 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 layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluting with ethyl acetate in cyclohexane) to afford tert-butyl N-[(1S)-3-(5-bromo-2-pyridinyl)-2-hydroxy-1-methyl-3-oxo-propyl]carbamate as an orange gum.

[0808] LCMS (method 1): retention time 0.98 min, m / z = 359-361 [M+H+] (bromine mode); 1H-NMR (400 MHz, 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 = 2.20 Hz, 1H).

[0809] Preparation of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxo-propyl]carbamate

[0810]

[0811] To a solution of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-2-hydroxy-1-methyl-3-oxo-propyl]carbamate (15.2 g, 42.3 mmol) in dichloromethane (100 mL) and dimethyl sulfoxide (20 mL) 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 batches at 0°C. 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. The crude material was purified by flash chromatography on silica gel (eluting with ethyl acetate in cyclohexane) to afford tert-butyl N-[(1S)-3-(5-bromo-2-pyridinyl)-1-methyl-2,3-dioxo-propyl]carbamate as an orange oil.

[0812] 1H-NMR(400MHz, CDCl3)δppm: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).

[0813] Preparation of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate (I42)

[0814]

[0815] To a solution of tert-butyl N-[(1S)-3-(5-bromo-2-pyridyl)-1-methyl-2,3-dioxo-propyl]carbamate (2.00 g, 5.60 mmol) in ethanol (22 mL) was added ethylenediamine (1.91 mL, 28.0 mmol). The reaction mixture was stirred at room temperature for 60 hours in the presence of air. It was concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluted with ethyl acetate in cyclohexane) to obtain tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazine-2-yl]ethyl]carbamate as a colorless jelly.

[0816] LCMS (method 1): retention time 1.09 min, m / z = 379-381 [M+H+] (bromine mode);

[0817] 1H-NMR (400MHz, CDCl3) δppm: 1.33-1.45 (m, 9H) 1.52-1.56 (m, 3H) 5.65-5.8 3(m,2H)7.96-8.02(m,2H)8.53-8.60(m,2H)8.79(dd,J=2.20,1.10Hz,1H);

[0818] Chiral SFC (Method 1): 1.80 min (major enantiomer), 1.11 min (minor enantiomer); ee = 92%

[0819] Tert-butyl N-[(1S)-1-[6-amino-3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]carbamate (I49) Preparation

[0820]

[0821] 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-dioxo-propyl]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, 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)pyrazine-2-yl]ethyl]carbamate.

[0822] LCMS (method 1): retention time 1.04 min, m / z = 394-396 [M+H + ](bromine mode); 1 H NMR (600MHz, CDCl3) δppm: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).

[0823] N-[(1S)-1-[3-(5-bromo-2-pyridinyl)-6-methyl-pyrazin-2-yl]ethyl]carbamic acid tert-butyl ester and N- Preparation of tert-butyl [(1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazin-2-yl]ethyl]carbamate

[0824]

[0825] 1,2-Diaminopropane (16.4 mL, 190 mmol) was added to a mixture of tert-butyl N-[(1S)-3-(5-bromo-2-pyridinyl)-1-methyl-2,3-dioxo-propyl]carbamate (1.130 g, 3.16 mmol) in ethanol (12.7 mL) in 4 portions over 36 hours. Water was added, the aqueous layer was extracted with ethyl acetate, 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-pyridinyl)-6-methyl-pyrazin-2-yl]ethyl]carbamate and tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridinyl)-5-methyl-pyrazin-2-yl]ethyl]carbamate.

[0826] LCMS (method 1): retention time 1.14 and 1.15 min, m / z = 393-395 [M+H + ](bromine mode); 1 H NMR (600MHz, CDCl3) δppm (mixture): 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).

[0827] (1S)-1-[3-(5-bromo-2-pyridinyl)-6-methyl-pyrazin-2-yl]ethylamine and (1S)-1-[3-(5-bromo-2-pyridinyl)-6-methyl-pyrazin-2-yl]ethylamine Preparation of [(2-(4-(2-pyridyl)-5-methyl-pyrazin-2-yl)ethylamine

[0828]

[0829] 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-pyrazine-2-yl]ethyl]carbamate and tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)-5-methyl-pyrazine-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 a 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-pyridinyl)-6-methyl-pyrazin-2-yl]ethanamine and (1S)-1-[3-(5-bromo-2-pyridinyl)-5-methyl-pyrazin-2-yl]ethanamine as a brown oil.

[0830] LCMS (method 1): retention time 0.54 min, m / z = 293-295 [M+H + ](bromine mode); 1 H NMR(400MHz, CDCl3)δppm: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)

[0831] Preparation of (1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethylamine (I43)

[0832]

[0833] To a solution of tert-butyl N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazine-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 sodium carbonate solution. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to give (1S)-1-[3-(5-bromo-2-pyridyl)pyrazine-2-yl]ethylamine as a yellow oil.

[0834] LCMS (method 1): retention time 0.54, m / z = 279-281 [M+H+] (bromine mode); 1H-NMR (400 MHz, CDCl3) δppm: 1.47 (d, J = 6.60 Hz, 3H) 2.09 (s, 2H) 4.67-4.76 (m, 1H) 7.90-7.94 (m, 1H) 7.96-8.03 (m, 1H) 8.51 (d, J = 2.20 Hz, 1H) 8.60 (d, J = 2.57 Hz, 1H) 8.77 (dd, J = 2.20, 0.73 Hz, 1H).

[0835] 2-(1-Cyanocyclopropyl)-N-[1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethyl]-6-(trifluoromethyl)- Preparation of 4-pyridine-4-carboxamide (P32)

[0836]

[0837] 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) were added to a solution of 1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazine-2-yl]ethylamine (20.7 mg, 85.9 μmol) in N,N-dimethylformamide (1 mL) at 0°C. The reaction mixture was stirred at room temperature for 6 hours. It was then poured onto ice water and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluting with ethyl acetate in hexanes) to afford 2-(1-cyanocyclopropyl)-N-[1-[3-(5-cyclopropylpyrimidin-2-yl)pyrazin-2-yl]ethyl]-6-(trifluoromethyl)pyridine-4-carboxamide as a light brown solid.

[0838] 1 H-NMR (400MHz, DMSO): δppm: 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).

[0839] N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-3-(1-cyanocyclopropyl)-5-(trifluoromethyl) Preparation of benzamide (P17)

[0840]

[0841] Thionyl chloride (0.141 mL, 1.94 mmol) was added dropwise to a solution of 3-[cyano(cyclopropyl)methyl]-5-(trifluoromethyl)benzoic acid (130 mg, 0.484 mmol) in toluene (20 mL) 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)pyrazine-2-yl]ethylamine (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. The crude material was purified by reverse phase chromatography (eluting with acetonitrile in water) to give N-[1-[3-(5-chloro-2-pyridinyl)pyrazin-2-yl]ethyl]-3-(1-cyanocyclopropyl)-5-(trifluoromethyl)benzamide.

[0842] 1H-NMR (400MHz, DMSO): δppm: 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).

[0843] N-[1-[3-(5-chloro-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl) Preparation of pyridine-4-carboxamide (P16)

[0844]

[0845] Thionyl chloride (0.141 mL, 1.94 mmol) was added dropwise to a solution of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (130 mg, 0.482 mmol) in toluene (20 mL) 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)pyrazine-2-yl]ethylamine (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. The crude material was purified by reverse phase chromatography (eluting with acetonitrile in water) to afford N-[1-[3-(5-chloro-2-pyridinyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide as an off-white solid.

[0846] 1 H-NMR (400MHz, DMSO): δppm: 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).

[0847] N-[1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl) Preparation of pyridine-4-carboxamide (P28)

[0848]

[0849] Thionyl chloride (0.108 mL, 1.48 mmol) was added dropwise to a solution of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (100 mg, 0.371 mmol) in toluene (15 mL) 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)pyrazine-2-yl]ethylamine (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. The crude material was purified by reverse phase chromatography (eluting with acetonitrile in water) to afford N-[1-[3-(5-bromo-2-pyridinyl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide as an off-white solid.

[0850] 1 H-NMR (400MHz, DMSO): δppm: 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): δppm: -66.69.

[0851] 3-Cyclopropyl-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)-benzamide (P41) Preparation

[0852]

[0853] A mixture of 2-cyclopropyl-6-(trifluoromethyl)pyridine-4-carboxylic acid (0.10 g, 0.43 mmol, 1.0 equiv), 1-(3-pyrimidin-2-ylpyrazine-2-yl)ethylamine 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.

[0854] 1H NMR (400MHz, chloroform-d) δppm: 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),7.42(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)

[0855] 19 F NMR (376MHz, chloroform-d) δ / ppm-62.58 (s, 3F)

[0856] LC-MS (method 1): retention time 0.97 min, m / z 414 [M+H] +

[0857] 3-[Cyclopropyl(difluoro)methyl]-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzene Preparation of formamide (P30)

[0858]

[0859] At 0 ° C, 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) were added to a solution of 1-(3-pyrimidin-2-ylpyrazine-2-yl)ethylamine (50 mg, 0.22 mmol) in N, N-dimethylformamide (2 mL). 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. The crude material was purified by reverse phase chromatography (eluted with acetonitrile in water) to give 3-[cyclopropyl (difluoro) methyl]-N-[1-(3-pyrimidin-2-ylpyrazine-2-yl) ethyl]-5-(trifluoromethyl) benzamide as an off-white solid.

[0860] 1 H-NMR (400MHz, DMSO-d6): δppm: 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).

[0861] 3-(1-methoxycyclopropyl)-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzyl Preparation of amide (P47)

[0862]

[0863] At 0 ° C, thionyl chloride (0.107 mL, 1.47 mmol) was added dropwise to a solution of 3-(1-methoxycyclopropyl)-5-(trifluoromethyl)benzoic acid (130 mg, 0.490 mmol) in toluene (3 mL). 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-pyrimidine-2-ylpyrazine-2-yl)ethylamine (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. The crude material was purified by reverse phase chromatography (eluting with acetonitrile in water) to afford 3-(1-methoxycyclopropyl)-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]-5-(trifluoromethyl)benzamide as an off-white solid.

[0864] 1 H-NMR (400MHz, DMSO-d6): δppm:9.1(m,1H)8.95(m,2H)8.77(m,1H)8.66(m,1H),7.92(m,1H),7.78(m,1H),7.6 4(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)

[0865] N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-cyclopropyl-5-(trifluoromethyl)benzamide Preparation of (P58)

[0866]

[0867] At 0 ° C, thionyl chloride (0.723 mL, 9.91 mmol) was added dropwise to a solution of 3-cyclopropyl-5-(trifluoromethyl)benzoic acid (60 mg, 0.248 mmol) in toluene (8 mL). 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-bromopyrimidine-2-yl)pyrazine-2-yl]ethylamine (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. The crude material was purified by reverse phase chromatography (eluting with acetonitrile in water) to afford N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-cyclopropyl-5-(trifluoromethyl)benzamide as an off-white solid.

[0868] 1 H-NMR (400MHz, DMSO-d6): δppm:9.12(m,2H)9.00(m,1H)8.76(m,1H)8.68(m,1H),7.77(m,1H),7.5 8(m,2H),5.52-5.61(m,1H),2.05-2.12(m,1H),1.60(d,3H),0.98-1.08(m,2H),0.75-0.82(m,2H)

[0869] N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl) Preparation of pyridine-4-carboxamide (P55)

[0870]

[0871] Thionyl chloride (0.162 mL, 2.22 mmol) was added dropwise to a solution of 2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxylic acid (60 mg, 0.222 mmol) in toluene (10 mL) 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-bromopyrimidine-2-yl)pyrazine-2-yl]ethylamine (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. The crude material was purified by reverse phase chromatography (eluting with acetonitrile in water) to afford N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-2-(1-cyanocyclopropyl)-6-(trifluoromethyl)pyridine-4-carboxamide as an off-white solid.

[0872] 1 H-NMR (400MHz, DMSO-d6): δppm: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)

[0873] N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl) Preparation of 2-(4-(4-(4-yl)benzamide) (P53)

[0874]

[0875] Thionyl chloride (0.089 mL, 1.22 mmol) was added dropwise to a solution of 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (90 mg, 0.305 mmol) in toluene (10 mL) 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)pyrazine-2-yl]ethylamine (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. The crude material was purified by reverse phase chromatography (eluting with acetonitrile in water) to afford N-[1-[3-(5-bromopyrimidin-2-yl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide as a brown solid.

[0876] 1 H-NMR (400MHz, DMSO-d6): δppm:9.29(d,1H)9.14(s,2H)8.81(m,1H)8.70(m,1H),8.15-8.2 5(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)

[0877] N-[(1S)-1-[3-(5-bromo-2-pyridyl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5- Preparation of (trifluoromethyl)benzamide (P42)

[0878]

[0879] Oxalyl chloride (0.0281mL, 0.321mmol) is added to a solution of 3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzoic acid (0.0600g, 0.214mmol) in dichloromethane (0.65mL) containing a drop of N,N-dimethylformamide. After 30 minutes, the reaction mixture is concentrated in vacuo. The crude acyl chloride is dissolved in ethyl acetate (0.86mL) and (1S)-1-[3-(5-bromo-2-pyridyl)pyrazine-2-yl]ethylamine (0.0598g, 0.214mmol) and sodium bicarbonate aqueous solution (1N, 0.86mL) are added. The mixture is stirred at room temperature for 45 minutes. The layers are separated and the water layer is extracted with ethyl acetate. The combined organic layer is dried over magnesium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel (eluting with ethyl acetate in cyclohexane) to give N-[(1S)-1-[3-(5-bromo-2-pyridinyl)pyrazin-2-yl]ethyl]-3-[cyclopropyl(difluoro)methyl]-5-(trifluoromethyl)benzamide.

[0880] 1 H-NMR (400MHz, chloroform-d): δppm: 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);

[0881] [α]D20:+115°(c:0.580,CHCl3)

[0882] The compounds described in Table P were prepared by methods analogous to those described for the above Examples:

[0883]

[0884]

[0885]

[0886]

[0887]

[0888]

[0889]

[0890]

[0891]

[0892]

[0893]

[0894]

[0895]

[0896]

[0897]

[0898]

[0899]

[0900]

[0901]

[0902]

[0903] Table I: Table of intermediates

[0904]

[0905]

[0906]

[0907]

[0908]

[0909]

[0910]

[0911]

[0912]

[0913]

[0914]

[0915]

[0916]

[0917] 1) 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).

[0918] 2) 1 H NMR (400 MHz, chloroform-d) δppm: 0.76-0.85 (m, 2H) 1.06-1.15 (m, 2H) 2.03 (tt, J 1 =8.39Hz,J 2 =5.00Hz,1H3.96(s,3H)7.52(s,1H)7.91(s,1H)8.08(d,J=0.73Hz,1H); 19 FNMR (377 MHz, chloroform-d) δ ppm: -62.75 (s, 3F).

[0919] 3) 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 1 =17.42Hz,J 2 =10.82Hz,1H)7.82(s,1H)8.19(s,1H)8.24-8.29(m,1H).

[0920] 4) 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).

[0921] 5) 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).

[0922] 6) 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 (377MHz, chloroform-d) δppm: -77.49 (s, 3F) -62.96 (s, 3F)

[0923] 7) 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).

[0924] 8) 1 H NMR (400 MHz, chloroform-d) δ ppm: 1.16-1.22 (m, 2H) 1.35 (quin, J = 3.76 Hz, 2H) 2.74 (tt, J 1 =7.84Hz,J 2 =4.45Hz, 1H) 4.02 (s, 3H) 8.45 (d, J = 0.73Hz, 1H) 8.51 (d, J = 0.73Hz, 1H) 8.86 (s, 1H).

[0925] 9) 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).

[0926] 10) 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).

[0927] 11) 1 H NMR (400 MHz, CHLOROFORM-d) δ ppm: 8.30 (1H, s), 8.23 ​​(1H, s), 7.81 (1H, s), 3.99 (3H, s), 3.90 (2H, s).

[0928] 12)1 1H 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).

[0929] 13) 1 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)

[0930] 14) 1 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.93 (d, 1H), 8.84 (d, 1H), 8.78 (m, 2H), 2.64 (s, 3H), 2.36 (s, 3H)

[0931] 15) 1 1H-NMR (400 MHz, 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).

[0932] 16) 1H-NMR (400 MHz, DMSO): δ ppm 8.9 (s, 1H), 8.8 (d, 1H), 8.7 (s, 1H), 8.2 (m, 2H), 2.6 (s, 3H)

[0933] 17) 1H-NMR (400 MHz, 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)

[0934] 18) 1 H-NMR (400 MHz, 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)

[0935] 19) 1H-NMR (400MHz, DMSO): δppm 9.9(s,1H),8.6–8.9(m,3H),8.1–8.25(m,2H),2.55(s,1H),1.5(s,9H)

[0936] 20) 1 H-NMR (400MHz, chloroform-d) δppm 8.49 (d, 1H), 8.34 (d, 1H), 5.18 (m, 1H), 3.81 (d, 1H), 1.52 (d, 3H)

[0937] 21) 1H NMR (400MHz, DMSO-d) δppm: 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).

[0938] 22) 1H 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).

[0939] 23) 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).

[0940] 24) 1H-NMR (400MHz, DMSO): δppm: 9.22 (s, 2H), 8.70-9.00 (m, 2H), 4.50-4.80 (m, 1H), 1.42 (d, 3H).

[0941] By adding other insecticidal, acaricidal and / or fungicidal active ingredients, the activity of the composition according to the present invention can be significantly widened and adapted to prevailing conditions. Mixtures with compounds of formula I and other insecticidal, acaricidal and / or fungicidal active ingredients can also have other unexpected advantages, which can also be described as synergistic activities in a wider sense. For example, better tolerance of plants, reduced phytotoxicity, insects can be controlled at their different developmental stages, or better behavior during their production (e.g., during grinding or mixing, during their storage or during their use).

[0942] Here, suitable active ingredients to be added are, for example, representatives of the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations.

[0943] The following mixtures of a compound of formula I and an active ingredient are preferred (wherein the abbreviation "TX" means "a compound selected from the group consisting of 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 and E-1 to E-21, and Table P"):

[0944] Auxiliary agent, the auxiliary agent is selected from the group consisting of: petroleum (alias) (628) + TX,

[0945] Insect control active substances, the insect control active substances are selected from Avermectin + TX, Acetoquinone + TX, Acetamiprid + TX, Acetamiprid + TX, Acynonapyr + TX, Biprofen + TX, Afolan + TX, Cotton Boll + TX, Allethrin + TX, α-Cypermethrin + TX, Alpha-Cypermethrin + TX, Sulfonamide + TX, Methiocarb + TX, Triazotin + TX, Sulfamethrin + TX, Benzophene + TX, Benzpyrimoxan + TX, β-Cypermethrin + TX, β-Cypermethrin + TX, Bifenazate + TX, Bifenthrin + TX, Bifenthrin + TX, Bio-allethrin + TX, Bio-allethrin (S)-cyclopentyl isomer +TX, bio-resmethrin +TX, bistrifluan +TX, bromofenthrin +TX, bromothiophene-ethyl +TX, buprofezin +TX, butanone +TX, cadusifos +TX, carbaryl +TX, butansulfuron +TX, batan +TX, CAS No.: 1472050-04-6 +TX, CAS No.: 1632218-00-8 +TX, CAS No.: 1808115-49-2 +TX, CAS No.: 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, chloranil+TX, chlorpyrifos+TX, chloranil+TX, chloranil+TX, clenpyr+TX, cloethocarb+TX, clothianidin+TX, 2-chlorophenyl N-methylcarbamate (CPMC)+TX, benzonitrile+TX, cyantraniliprole+TX, cyclobrominamide+TX, Cyclobutrifluram+TX, pyrethroids+TX, cyclohexidine+TX, cytoxanil+TX, cytoxanil+TX, cyhalodiamide+TX, trifluoroacetic acid Cypermethrin + TX, Cypermethrin + TX, Cypermethrin + TX, Cyromazine + TX, Deltamethrin + TX, Fenpyrazone + TX, Chlormethrin + TX, Dibrom + TX, Dicloromezotiaz + TX, Fluometofen + TX, Diflubenzuron + TX, Dipropyridaz + TX, Diclofenac + TX, Dimethoate + TX, Dinotefuran + TX, Vegetable + TX, Emamectin + TX, Dextran + TX, ε-momfluorothrin + TX, ε-Methiofluthrin + TX, Cypermethrin + TX, Ethion + TX, Ethiopromide + TX, Ethofenprox + TX, Ethozolin + TX, Fenpyrazone + TX,Fluphenazine + TX, Cypermethrin + TX, Fenthiocarb + TX, Fenoxycarb + TX, Cypermethrin + TX, Fenpyroxymate + TX, Fensulfuron + TX, Fenthion + TX, Yesalin + TX, Cypermethrin + TX, Fipronil + TX, Flometoquin + TX, Flyoxaline + TX, Felocellar + TX, Fluazifop + TX, Fluazaindolizine + TX, Fentilamide + TX, Felocellar + TX, Flucitrinate + TX, Flufluazifop + TX, Fenuren + TX, flucythrin + TX, fluthiamethoxam + TX, thiamethoxam + TX, trifluthrin + TX, butene fipronil + TX, Fluhexafon + TX, fluchlorfenapyr + TX, flupyram + TX, Flupentiofenox + TX, flupyramide + TX, Flupyrimin + TX, fluralaner + TX, fluvalinate + TX, Fluxametamide + TX, thiathion + TX, γ-cyhalothrin + TX, Gossyplure, TM+TX, pyramidoxime +TX, chlorfenapyr +TX, halofenprox +TX, Heptafluthrin +TX, hexythiazox +TX, hydrazone +TX, imidophos +TX, imidacloprid +TX, imiprodinil +TX, indoxacarb +TX, iodomethane +TX, isoprodinil +TX, Isocycloseram +TX, isothiocarb +TX, ivermectin +TX, kappa-bifenthrin +TX, kappa-tefluthrin +TX, lambda-cyhalothrin +TX, lepidomectin +TX, chlorfenapyr +TX, metaflumizone +TX, metaldehyde +TX, metamex +TX, methomyl +TX, methoxyfenozide +TX, trimethomorph Ester + TX, Methiocarb + TX, Zikewei + TX, Mite + TX, Momfluorothrin + TX, Methiocarb + TX, Nitenpyram + TX, Nithiothiazide + TX, Oxydemeton + TX, Oxazosufyl + TX, Parathion-ethyl + TX, Permethrin + TX, Phenothrin + TX, Phosphamidon + TX, Piperonyl Butoxide + TX, Pirimicarb + TX, Pirimiphos-ethyl + TX, Polyhedrosis virus + TX, Promethrin + TX, Probromophos + TX, Probromophos + TX, Profluthrin + TX, Promethrin + TX, Profenofos + TX, Protrifenbute + TX, Pyrifos + TX Pyflubumide + TX, pymetrozine + TX, pyraclofos + TX, pyrafluprole + TX, pyridaben + TX, pyridalyl + TX, pyrifluquinazon + TX, pyrimidine + TX, pyrimostrobin + TX, pyraflufen + TX, pyrimostrobin + TX, pyraflufen + TX, resmethrin + TX, Sarolaner + TX, Selamectin + TX, silafluthrin + TX, spinosad + TX, spinosad + TX, spirodiclofen + TX, spiromesifen + TX, Spiropidion + TX, spirotetramat + TX, sulfonecarb + TX, tebufenozide +TX, tebufenpyrad +TX, butyl pyrimidinphos (Tebupirimiphos) +TX, tefluthrin +TX, bispyribac +TX, Tetrachloraniliprole +TX, tetrachlorfon +TX, tetramethrin +TX, tetrafluthrin +TX, acaricide +TX, flucyram +TX, θ-cypermethrin +TX, thiacloprid +TX, thiamethoxam +TX, thiocarb +TX, thiodicarb +TX, long-acting carb +TX, methyl thiophos +TX, thiophanate +TX, tioxazafen +TX, tolfenpyrad +TX, toxaphene +TX, tralomethrin +TX, transfluthrin +TX, triazophos +TX,Trichlorfon + TX, chlorpyrifos + TX, trichlorfon + TX, triflumezopyrim + TX, Tyclopyrazoflor + TX, ζ-cypermethrin + TX, seaweed extract and fermentation products derived from sugar acyl + TX, seaweed extract and fermentation products derived from sugar acyl (including urea + TX, amino acids + TX, potassium and molybdenum, and EDTA chelated manganese) + TX, seaweed extract and fermented plant products + TX, seaweed extract and fermented plant products (including plant hormones + TX, vitamins + TX, EDTA chelated copper + TX, zinc + TX, and iron + TX), azadirachtin + TX, Bacillus aizawai + TX, Bacillus chitinosporus AQ746 (NRRL registration number B-21 618)+TX, Bacillus firmus+TX, Bacillus spp. Kurstaki+TX, Bacillus mycoides AQ726 (NRRL Accession No. B-21664)+TX, Bacillus pumilus (NRRL Accession No. B-30087)+TX, Bacillus pumilus AQ717 (NRRL Accession No. B-21662)+TX, Bacillus species AQ178 (ATCC Accession No. 53522)+TX, Bacillus species AQ175 (ATCC Accession No. 55608)+TX, Bacillus species AQ177 (ATCC Accession No. 55609)+TX, unspecified Bacillus subtilis+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 subsp. Kurstaki BMP 123+TX, Beauveria bassiana+TX, D-limonene+TX, Granulovirus+TX, Harpin+TX, Helicoverpa armigera nuclear polyhedrosis virus+TX, Spodoptera exigua nuclear polyhedrosis virus+TX, Tobacco budworm nuclear polyhedrosis virus+TX, Australian Helicoverpa armigera nuclear polyhedrosis virus+TX, Metarhizium species+TX, Muscodor albus 620 (NRRL registration number 30547)+TX, Muscodor roseus A3-5 (NRRL registration number 30548)+TX,Neem-based products + TX, Paecilomyces fumosorum + TX, Paecilomyces lilacinus + TX, Pasteuria szabalensis + TX, Pasteuria penetrantis + TX, Pasteuria mycoides + TX, Pasteuria thornei + TX, Pasteurella + TX, p-cymene + TX, Plutella xylostella granulosis virus + TX, Plutella xylostella nuclear polyhedrosis virus + TX, polyhedrosis virus + TX, pyrethrum + TX, QRD 420 (terpenoid blend) + TX, QRD 452 (terpenoid blend) + TX, QRD 460 (terpenoid blend) + TX, Quillaja saponaria + TX, Rhodococcus sphaeroides AQ719 (NRRL Accession No. B-21663) + TX, Spodoptera frugiperda nuclear polyhedrosis virus + TX, Streptomyces flavus (NRRL Accession No. 30232) + TX, Streptomyces species (NRRL Accession No. B-30145) + TX, terpenoid blend + TX, and Verticillium species,

[0946] an algaecide selected from the group consisting of bethoxazin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endoxan (295) + TX, fentin (347) + TX, slaked lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX,

[0947] An anthelmintic selected from the group consisting of avermectin (1) + TX, clofosinate (1011) + TX, cyclobutrifluram + TX, doramectin (alias) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alias) [CCN] + TX, ivermectin (alias) [CCN] + TX, milbemycin oxime (alias) [CCN] + TX, moxidectin (alias) [CCN] + TX, piperazine [CCN] + TX, selamectin (alias) [CCN] + TX, spinosad (737) and thiophanate (1435) + TX,

[0948] Avicide, the avicide being selected from the group consisting of chloralose (127) + TX, endrin (1122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) and strychnine (745) + TX,

[0949] A bactericide selected from the group consisting of 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, dodesine (1112) + TX, fenaminosulf (1144) + TX, formaldehyde (404) + TX, mercury + Fen (alias) [CCN] + 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, chlorphenamine (766) + TX, and thimerosal (alias) [CCN] + TX,

[0950] A biological agent, wherein the biological agent is selected from the following group of substances: GV of cotton brown banded moth (alias) (12) + TX, Agrobacterium radiobacterium (alias) (13) + TX, Amblyseius spp. (alias) (19) + TX, Spodoptera exigua NPV (alias) (28) + TX, Anagrus atomus (alias) (29) + TX, Aphelinus abdominalis (alias) (33) + TX, Aphidius colemani (alias) (34) + TX, Aphidoletes aphidimyza (alias) (35) + TX, Spodoptera exigua NPV (alias) (38) + TX, Bacillus firmus (alias) (48) + TX, Bacillus sphaericus (alias) Neide)(scientific name)(49)+TX、Bacillus thuringiensisBerliner)(scientific name)(51)+TX、Bacillus thuringiensissubsp.aizawai)(scientific name)(51)+TX、Bacillus thuringiensissubsp.israelensis)(scientific name)(51)+TX、Bacillus thuringiensissubsp.japonensis)(scientific name)(51)+TX、Bacillus thuringiensissubsp.kurstaki)(scientific name)(51)+TX、Bacillus thuringiensissubsp.tenebrionis (scientific name) (51) + TX, Beauveria bassiana (scientific name) (53) + TX, Beauveria brongniartii (scientific name) (54) + TX, Chrysoperla carnea (scientific name) (151) + TX, Cryptolaemus montrouzieri (scientific name) (178) + TX, Codling moth GV (scientific name) (191) + TX, Dacnusa sibirica (scientific name) (212) + TX, Diglyphus isaea (scientific name) (254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus) (alias) (300) + TX, Spodoptera exigua NPV (alias) (431) + TX, Heterorhabditis bacteriophora and H. megidis (alias) (433) + TX, Hippodamia convergens (alias) (442) + TX, Leptomastix dactylopii (alias) (488) + TX, Macrolophus caliginosus (alias) (491) + TX, Spodoptera exigua NPV (alias) (494) + TX, Metaphycus helvolus (alias) (522) + TX, Metarhizium anisopliae var.acridum)(scientific name)(523)+TX, Metarhizium anisopliae var.anisopliae)(scientific name)(523)+TX, Neodiprion sertifer NPV and Neodiprion sertifer (N.lecontei)NPV(alias)(575)+TX、Phaeophyton spp.(alias)(596)+TX、Paecilomyces fumosoroseus(alias)(613)+TX、Phytoseiulus persimilis(alias)(644)+TX、Spodoptera exigua multicapsid nuclear polyhedrosisvirus(scientific name)(741)+TX、Steinernema bibionis(alias)(742)+TX、Steinernema carpocapsae(alias)(742)+TX、Steinernema glaseri(alias)(742)+TX、Steinernema riobrave)(alias)(742)+TX, Steinernema riobravis(alias)(742)+TX, Steinernema capterisci(alias)(742)+TX, Steinernema spp.(alias)(742)+TX, Trichogramma spp.(alias)(826)+TX, Typhlodromus occidentalis(alias)(844) and Verticillium lecanii(alias)(848)+TX,.

[0951] A soil disinfectant selected from the group consisting of methyl iodide (IUPAC name) (542) and methyl bromide (537) + TX,

[0952] A chemical sterilant selected from the group consisting of apholanate [CCN] + TX, bis(aziridine) methylaminophosphine sulfide (bisazir) (alias) [CCN] + TX, busulfan (alias) [CCN] + TX, diflubenzuron (250) + TX, dimatif (alias) [CCN] + TX, hemel [CCN] + TX, hempa [CCN] + TX, metepa [CCN] + TX, methiotepa [CCN] + TX, methyl apholanate [CCN] + TX, methyl thiote ... apholate)[CCN]+TX, morzid[CCN]+TX, penfluron(alias)[CCN]+TX, tepa[CCN]+TX, thiohempa(alias)[CCN]+TX, thiohempa(alias)[CCN]+TX, trothamide(alias)[CCN] and urethaneimide(alias)[CCN]+TX,

[0953] Insect pheromone, the insect pheromone is selected from the following substance group: (E)-dec-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-4,10-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. )+TX, (Z)-hexadec-13-en-11-yn-1-yl acetate (IUPAC name) (438)+TX, (Z)-eicos-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)-tetradec-9-en-1-yl acetate (IUPAC name) (784)+TX, (7E,9Z)-dodec-7,9-dien-1-yl acetate (IUPAC name) (283)+TX, (9Z,11E)-tetradec-9,11-dien-1-yl acetate (IUPAC name) (780)+TX, (9Z,12E)-tetradec-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, alpha-multistriatin (alias) [CCN] + TX, western pine beetle gathering pheromone (brevicomin) (alias) [CCN] + TX, codlelure (alias) [CCN] + TX, codle mone)(alias)(167)+TX、cuelure(alias)(179)+TX、disparlure(277)+TX、1-dodecyl acetate(IUPAC name)(286)+TX、1-dodecyl acetate(IUPAC name)(287)+TX、10-1-dodecyl acetate(IUPAC name)(284)+TX、dominicalure(alias)[CCN]+TX、ethyl 4-methyloctanoate(IUPAC name) C name) (317) + TX, eugenol (alias) [CCN] + TX, southern pine beetle aggregation pheromone (frontalin) (alias) [CCN] + TX, gossyplure (alias) (420) + TX, grandlure (421) + TX, grandlure I (alias) (421) + TX, grandlure II (alias) (421) + TX, grandlure III (alias) (421) + TX, grandlure IV (alias) (421) + TX, hexalure )[CCN]+TX、ipsdienol (alias)[CCN]+TX、ipsenol (alias)[CCN]+TX、japonilure (alias)(481)+TX、lineatin (alias)[CCN]+TX、litlure (alias)[CCN]+TX、looplure (alias)[CCN]+TX、medlure[CCN]+TX、megatomoic acid (alias)[CCN]+TX、methyl eugenol (alias)(540)+TX、muscalure (563)+TX、octadecene-2,13-diene-1-yl acetate (IUPAC name)(588)+TX、octadecene-3,13-Dien-1-yl acetate (IUPAC name) (589) + TX, orfralure (alias) [CCN] + TX, oryctalure (alias) (317) + TX, ostramone (alias) [CCN] + TX, siglure [CCN] + TX, sordidin (alias) (736) + TX, sulcatol (alias) [CCN] + TX, tetradecene-11-en-1-yl acetate (IUPAC name) (785) + TX, Mediterranean fruit fly attractant (839) + TX, Mediterranean fruit fly attractant A (alias) (839) + TX, Mediterranean fruit fly attractant B, 1 (Alias) (839) + TX, Mediterranean fruit fly attractant B 2 (alias) (839) + TX, Mediterranean fruit fly attractant C (alias) (839) and trunc-call (alias) [CCN] + TX,

[0954] An insect repellent, wherein the insect repellent is selected from the group 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, DEET [CCN] + TX, dimethyl carbate) [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1137) + TX, hexylurea [CCN] + TX, methoquin-butyl (1276) + TX, methyl neodecylamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX,

[0955] A molluscicide selected from the group consisting of di(tributyltin) oxide (IUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, chloranil (999) + TX, copper acetyl arsenite [CCN] + TX, copper sulfate (172) + TX, triphenyltin (347) + TX, iron phosphate (IUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-ethanolamine (576) + TX, Pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tazimcarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, trifenmorph (1454) + TX, trimethacarb (840) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, pyriprole [394730-71-3] + TX,

[0956] Nematicide, the nematicide is selected from the following material group: 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) ( 1065)+TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980)+TX, 5-methyl-6-thioxo-1,3,5-thiadiazin-3-yl acetic acid (IUPAC name) (1286)+TX, 6-isopentenylaminopurine (alias) (210)+TX, avermectin (1)+TX, acetofenamide [CCN]+TX, cotton bell carb (15)+TX, aldicarb (16)+TX, aldoxycarb (863)+TX, AZ60541 (compound code) + TX, benclothiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (alias) + TX, cadusafos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, carbofuran (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, cyclobutrifluram (999) + TX, cytokinin (cyto kinins)(alias)(210)+TX, dazomethane(216)+TX, DBCP(1045)+TX, DCIP(218)+TX, diamidafos(1044)+TX, dichlofenthion(1051)+TX, dicliphos(alias)+TX, dimethoate(262)+TX, doramectin(alias)[CCN]+TX, emamectin(291)+TX, emamectin benzoate(291)+TX, eprinomectin(alias)[CCN]+TX, ethoprophos(312)+TX , dibromoethane (316) + TX, fenamiphos (326) + TX, fenpyrad (alias) + TX, fenthiophos (1158) + TX, fosthiazate (408) + TX, fosthietane (1196) + TX, furfural (alias) [CCN] + TX, GY-81 (research code) (423) + TX, heterophos [CCN] + TX, iodomethane (IUPAC name) (542) + TX, isamidophos ( 1230)+TX, isazofos (1231)+TX, ivermectin (alias) [CCN]+TX, kinetin (alias) (210)+TX, mecarphon (1258)+TX, metamex (519)+TX, metamex potassium salt (alias) (519)+TX, metamex sodium salt (519)+TX, methyl bromide (537)+TX, methyl isothiocyanate (543)+TX, milbemycin oxime (alias) [CCN]+TX, moxidectin (alias) [CCN]+TX, Myrotheciumverrucaria) combination (alias) (565) + TX, NC-184 (compound code) + TX, oxamyl (602) + TX, phorate (636) + TX, phosphamidon (639) + TX, phosphocarb [CCN] + TX, sebufos (alias) + TX, selamectin (alias) [CCN] + TX, spinosad (737) + TX, terbam (alias) + TX, terbufos (773) + TX, tetrachlorothiophene (IUPAC / Chemical Abstracts name) (1422) + TX, thiafenox (alias) + TX, thionazin (1434) + TX, triazophos (820) + TX, triazuron (alias) + TX, xylenol [CCN] + TX, YI-5302 (compound code) and zeatin (alias) (210) + TX, fluensulfone [318290-98-1] + TX, fluopyram + TX,

[0957] A nitrification inhibitor selected from the group consisting of potassium ethylxanthate [CCN] and nitrapyrin (580) + TX,

[0958] A plant activator, wherein the plant activator is selected from the group consisting of acibenzolar (6) + TX, acibenzolar-S-methyl (6) + TX, probenazole (658) and Reynoutria sachalinensis extract (alias) (720) + TX,

[0959] A rodenticide, wherein the rodenticide is selected from the following substance group: 2-isovaleryl indane-1,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, α-chlorohydrin [CCN] + TX, aluminum phosphide (640) + TX, antoquinone (880) + TX, arsenic trioxide (882) + TX, barium carbonate (891) + TX, bifenthrin (912) + TX, brodifacoum (89) + TX, Bromadiolone (91) + TX, bromodiolone (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chloranone (140) + TX, cholecalciferol (alias) (850) + TX, chlorfenapyr (1004) + TX, chlorfenapyr (1005) + TX, chlorfenapyr (175) + TX, chlorfenapyr (1009) + TX, chlorfenapyr (246) + TX, chlorfenapyr (249) + TX, chlorfenapyr (273) + TX, calciferol (301) + TX, Fludioxaline (357) + TX, fluoroacetamide (379) + TX, fludioxaline (1183) + TX, fludioxaline 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, fosfomycin (1318) + TX, fosfomycin (1 336) + TX, phosphine (IUPAC name) (640) + TX, phosphorus [CCN] + TX, warfarin (1341) + TX, potassium arsenite [CCN] + TX, cypermethrin (1371) + TX, scilla glycoside (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,

[0960] A synergist, wherein the synergist is selected from the group consisting of: 2-(2-butoxyethoxy)ethyl piperate (IUPAC name) (934) + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903) + TX, farnesol with nerolidol (alias) (324) + TX, MB-599 (research code) (498) + TX, MGK264 (research code) (296) + TX, piperonyl butoxide (649) + TX, pipertal (1343) + TX, propyl isomer (1358) + TX, S421 (research code) (724) + TX, sesamex (1393) + TX, sesasmolin (1394) and sulfoxide (1406) + TX,

[0961] An animal repellent, the animal repellent being selected from the group consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper cyclohexane [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, salamine (804) + TX, trimethacarb (840) + TX, zinc cyclohexane [CCN] and ziram (856) + TX,

[0962] A virucide selected from the group consisting of: imipenem (alias) [CCN] and ribavirin (alias) [CCN] + TX,

[0963] A wound protective agent, wherein the wound protective agent is selected from the group consisting of mercuric oxide (512) + TX, octhilinone (590) and methyl thiophanate (802) + TX,

[0964] Biologically active substances, wherein the biologically active substances are selected from 1,1-bis(4-chlorophenyl)-2-ethoxyethanol+TX, 2,4-dichlorophenylbenzenesulfonate+TX, 2-fluoro-N-methyl-N-1-naphthylacetamide+TX, 4-chlorophenylphenyl sulfone+TX, acetofenamide+TX, aldicarb+TX, sago+TX, fruit manphos+TX, amine dephosphite+TX, ammonium oxalate dephosphite+TX, amitraz+TX, cypermethrin+TX, arsenic trioxide+TX, azobenzene+TX, azophos+TX, benomyl+TX, benoxafos+TX, benzyl benzoate+TX, bixafen+TX, bromothiocarb ... Phosphorus + TX, bromocriptine + TX, buprofezin + TX, butanone + TX, butanone sulfone + TX, butyl pyridaben + TX, calcium polysulfide + TX, octachlorocamphene + TX, chlormethoxam + TX, trithion + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin hydrochloride + TX, cypermethrin + TX, cypermethrin + TX, dimethoate + TX, ethyl cypermethrin + TX, cypermethrin (chloromebuform) + TX, cypermethrin + TX, propyl cypermethrin + TX, cypermethrin + TX, cypermethrin I + TX, cypermethrin II + TX, cypermethrin + TX, closantel + TX, coumaphos + TX, crotamiton + TX, Batophos + TX, thiocarb + TX, fruit insect phosphorus + TX, DCPM + TX, DDT + TX, dinafop + TX, dinafop-O + TX, dinafop-S + TX, demion-methyl + TX, demion-O + TX, demion-O-methyl + TX, demion-S + TX, demion-S-methyl + TX, demeton-S-methyl + TX, demeton-S-methylsulfon + TX, bacteriostatic + TX, dichlorvos + TX, dicliphos + TX, mitoxantrone + TX, methylfluophos + TX, dinex + TX, dinex-diclexine + TX, dimeton-4 + TX, dimeton -6+TX, anthelmintic+TX, nitropentyl+TX, nitrobenzene acaricide+TX, nitrobutyl+TX, dimethoate+TX, sulfodiphenyl+TX, dithiosulfuron+TX, DNOC+TX, dofenapyn+TX, doramectin+TX, indolephos+TX, eprinomectin+TX, phosphothion+TX, ethiprole+TX, anti-mite+TX, fenbutatin+TX, fenthiocarb+TX, fenpyrad+TX, fenpyraclostrobin+TX, fenamipyraclostrobin+TX, fentrifanil+TX, fluazifop+TX, flufenoxuron+TX, diflunisal+TX, flufenoxam+TX, FMC 1137+TX, flufenamic acid+TX, flufenamic acid hydrochloride+TX, formparanate+TX, γ-HCH+TX,Fruit green + TX, benzyl acarboxylate + TX, hexadecyl cyclopropane carboxylate + TX, isocarbophos + TX, jasmonate I + TX, jasmonate II + TX, iodine + TX, lindane + TX, propanil + TX, aphid + TX, dithiophos + TX, methylthiophene + TX, cypermethrin + TX, methyl bromide + TX, cypermethrin + TX, chlorpyrifos + TX, milbemycin + TX, propylamine + TX, monocrotophos + TX, maoguo + TX, moxidectin + TX, naled + TX, 4-chloro-2-(2-chloro-2-methyl-propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazine-3-one + TX, fluazifop + TX, nikkomycin + TX, pentamethylenediamine + TX, pentamethylenediamine 1: 1 Zinc chloride complex + TX, omethoate + TX, isothiophos + TX, sulfone + TX, pp'-DDT + TX, parathion + TX, permethrin + TX, fenthion + TX, phosalone + TX, thiophanate + TX, phosphamidon + TX, polychloroterpenes + TX, polynactins + TX, chloranil + TX, cypermethrin + TX, propoxur + TX, ethidium + TX, pyrethrin + TX, pyrethrin II + TX, pyrethrin + TX, pyrimethoxam + TX, pyrimithiophos + TX, quinalphos + TX, quintiofos + TX 、R-1492+TX、glycyrrhizin+TX、rotenone+TX、octamphos+TX、kexiandan+TX、selamectin+TX、thion+TX、SSI-121+TX、sulfilam+TX、sulfluramid+TX、sulfur+TX、sulfur+TX、flumethrin+TX、tau-fluvalinate+TX、TEPP+TX、tert-butylcarb+TX、tetrachlorothiazide+TX、thiafone+TX、thiafone+TX、thiafenox+TX、antimicrobial+TX、long-lasting thiafenphos+TX、methyl thiocarb+TX、thiafone+TX、thiafone+TX、thiazolidine+TX、thiazolidine+TX、thiazolidine+TX、thiazolidine+TX、triazuron+TX、triazuron+TX、triacin+TX、 +TX, vaniliprole +TX, bethoxazin +TX, copper dioctanoate +TX, copper sulfate +TX, cybutryne +TX, dichloronaphthoquinone +TX, dichlorophen +TX, endoxan +TX, triphenyltin +TX, slaked lime +TX, mancozeb +TX, algae quinone +TX, quinone +TX, simazine +TX, triphenyltin acetate +TX, triphenyltin hydroxide +TX, yuxu phosphorus +TX, piperazine +TX, thiophanate +TX, chloralose +TX, fenthion +TX, pyridine-4-amine +TX, strychnine +TX, 1-hydroxy-1H-pyridine-2-thione +TX, 4-(quinoxaline-2-ylamino)benzenesulfonamide +TX,8-Hydroxyquinoline sulfate + TX, bronopol + TX, copper hydroxide + TX, cresol + TX, dipyrithione + TX, dodesine + TX, sodium sulfone + TX, formaldehyde + TX, mercury plus phenacetin + TX, kasugamycin + TX, kasugamycin hydrochloride hydrate + TX, nickel di(dimethyldithiocarbamate) + TX, trichloromethylpyridine + TX, octhilthione + TX, oxolinic acid + TX, oxytetracycline + TX, potassium hydroxyquinoline sulfate + TX, thiabendazole + TX, streptomycin + TX, streptomycin sesquisulfate + TX, chlorothiazide + TX, thimerosal + TX, cotton brown-banded moth GV + TX, Agrobacterium radiobacterium + TX, Amblyseius spp. + TX, celery armyworm NPV + TX, Anagrus atomus + TX, Aphelinus abdominalis + TX, cotton aphid parasitic wasp (Aphidius colemani+TX, Aphidoletes aphidimyza+TX, Spodoptera alfalfa NPV+TX, Bacillus sphaericus Neide+TX, Beauveria brongniartii+TX, Chrysoperla carnea+TX, Cryptolaemus montrouzieri+TX, Codling moth GV+TX, Dacnusasibirica+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, Cabbage armyworm NPV+TX, Metaphycus helvolus+TX, Metarhizium anisopliae var. acridum+TX, Metarhizium anisopliae var. anisopliae+TX, Neodiprion sertifer NPV and N. lecontei NPV+TX,+TX, Paecilomyces fumosoroseus +TX, Phytoseiulus persimilis +TX, Steinernema bibionis +TX, Steinernema carpocapsae +TX, Steinernema glaseri +TX, Steinernema riobrave +TX, Steinernema riobravis +TX, Steinernema scapterisci +TX, Steinernema spp. +TX, Trichogramma +TX, Typhlodromus occidentalis +TX, Verticillium lecanii +TX, Steinernema spp. +TX, lecanii)+TX, apholanate+TX, bis(aziridine) methylaminophosphine sulfide (bisazir)+TX, busulfan+TX, dimatif+TX, hemel+TX, hempa+TX, metepa+TX, methiotepa+TX, methylapholate+TX, morzid+TX, penfluron+TX, tepa+TX, thiohempa+TX, thiotepa+TX, trothamide+TX, urethaneimide+TX, (E)-dec-5-en-1-yl acetate and (E)-dec-5-en-1-ol+TX, (E)-tridec-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)-eicos-13-ene-10- Ketone + TX, (Z)-tetradec-7-ene-1-al + TX, (Z)-tetradec-9-ene-1-ol + TX, (Z)-tetradec-9-ene-1-yl acetate + TX, (7E,9Z)-dodec-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-methylnon-5-ol and 4-methylnon-5-one+TX, α-polystyrene+TX, western pine beetle aggregation pheromone+TX, codlelure+TX, codlemone+TX, cuelure+TX, epoxide nonadecane+TX, dodec-8-en-1-yl acetate+TX, dodec-9-en-1-yl acetate+TX, dodec-8+TX, 10-10-dien-1-yl acetate+TX, dominicalure+TX, 4-methyloctanoic acid ethyl ester+TX, eugenol+TX, southern pine beetle aggregation pheromone (f rontalin)+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, litlure+TX, looplure+TX, medlure+TX, megatomoic acid+TX, methyl eugenol+TX, muscalure+TX, 18-decane-2,13-diene-1-yl acetate+TX, 18-decane-3,13-diene-1-yl acetate+TX, orfralure+TX, oryctalure+TX, ostramone+TX, siglure+TX, sordidin+TX, sulcatol+TX, 14-decane-11-ene-1-yl acetate+TX, trimedlure+TX, Mediterranean fruit fly attractant A+TX, Mediterranean fruit fly attractant B, 1 +TX, Mediterranean fruit fly attractant B 2+TX, Mediterranean fruit fly attractant C+TX, trunc-call+TX, 2-(octylthio)ethanol+TX, butopyronoxyl+TX, butoxy(polypropylene glycol)+TX, dibutyl adipate+TX, dibutyl phthalate+TX, dibutyl succinate+TX, DEET+TX, dimethyl carbate)+TX, dimethyl phthalate+TX, ethyl hexanediol+TX, hexamide+TX, methoquin-butyl+TX, methylneodecanamide+TX, oxamate+TX, picaridin+TX, 1-dichloro-1-nitroethane+TX, 1,1-dichloro-2,2-di(4-ethylphenyl)ethane+TX, 1,2-dichloropropane and 1,3-dichloropropylene+TX, 1-bromo-2-chloroethane+ TX, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate + TX, 2,2-dichlorovinyl 2-ethylsulfinylethyl methyl phosphate + TX, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate + TX, 2-(2-butoxyethoxy)ethyl thiocyanate + TX, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate + TX, 2-(4-chloro-3,5-xylyloxy)ethanol + TX, 2-chlorovinyl diethyl phosphate + TX, 2-imidazolidinone + TX, 2-isovaleryl indan-1,3-di 1-Hydroxy-1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, 1-nitropropene, +TX, neonicotinoids +TX, ethyl thiophanate (athidathion) +TX, methyl pyrifos +TX, Bacillus thuringiensis δ-endotoxin +TX, barium hexafluorosilicate +TX, barium polysulfide +TX, fumonisin +TX, Bayer 22 / 190 +TX, Bayer 22408 +TX, β-cyfluthrin +TX, β-cypermethrin +TX, bioethanomethrin +TX, biopermethrin +TX, bis (2-chloroethyl) ether +TX, borax +TX, bromophenazone +TX, bromo-DDT +TX, hexachlorvinphos +TX, cypermethrin +TX,Butathiofos + TX, butyl phosphine + TX, calcium arsenate + TX, calcium cyanide + TX, carbon disulfide + TX, carbon tetrachloride + TX, badan hydrochloride + TX, cevadine + TX, bornyl + TX, chlordane + TX, chlordecone + TX, chloroform + TX, chloropicrin + TX, chlornitrile oxime + TX, chlorprazophos + TX, cis-resmethrin + TX, cismethrin + TX, clocythrin (alias) + TX, copper acetoarsenite + TX, copper arsenate + TX, copper oleate + TX, coumithoate + TX, cryolite + TX, CS 708+TX, benzonitrile+TX, cypermethrin+TX, cypermethrin+TX, cypermethrin+TX, d-carbofuran+TX, DAEP+TX, dazomethane+TX, decarbofuran+TX, diamidafos+TX, isochlorphos+TX, dimethophos+TX, dicresyl+TX, cypermethrin+TX, dieldrin+TX, diethyl 5-methylpyrazol-3-yl phosphate+TX, dior+TX, tetrafluthrin+TX, demicarb+TX, pyrethrin+TX, methylchlorfenapyr+TX, difenocarb+TX, propanol+TX, pentotropol+TX, dinoseb+TX, fenpyroxene+TX, vegetable phosphorus+TX, thiopyrafos+TX, DSP+TX, ecdysterone+TX, EI 1642+TX, EMPC+TX, EPBP+TX, etaphos+TX, ethiobencarb+TX, ethyl formate+TX, ethylene dibromide+TX, ethylene dichloride+TX, ethylene oxide+TX, EXD+TX, ethiobencarb+TX, ethiobencarb+TX, fenitrothion+TX, fenoxacrim+TX, cypermethrin+TX, fenthion+TX, ethylfenthion+TX, flucofuron+TX, butylfenthion+TX, phosphonium phosphate+TX, butylcyclothion+TX, furamicarb+TX, pyrethroid+TX, biguanide salt+TX, biguanide acetate+TX, tetramethoate Sodium thiocarbonate + TX, halfenprox + TX, HCH + TX, HEOD + TX, heptachlor + TX, cypermethrin + TX, HHDN + TX, hydrogen cyanide + TX, quinoline + TX, IPSP + TX, chlorfenapyr + TX, carbochlorin + TX, isodrin + TX, isoflavone + TX, transplanting spirit + TX, rice blast spirit + TX, oxathiophos + TX, juvenile hormone I + TX, juvenile hormone II + TX, juvenile hormone III + TX, chlorpentyl + TX, methoprene + TX, lead arsenate + TX, bromophenylphos + TX, acetamiprid + TX, thiathion + TX, m-isopropyl methyl carbamate + TX,Magnesium phosphide + TX, phosphorus azide + TX, methyl aphidite + TX, aphidite + TX, mercurous chloride + TX, methyl sulfoxide + TX, metamethylenetetramine + TX, metamethylenetetramine potassium salt + TX, metamethylenetetramine sodium salt + TX, methylsulfonyl fluoride + TX, butylene phosphonate + TX, methoprolol + TX, methyl ether thiocyanate + TX, methoxychlor + TX, methyl isothiocyanate + TX, methyl chloroform + TX, dichloromethane + TX, oxadiazine + TX, anticide + TX, naphthion + TX, naphthalene + TX, NC-170 + TX, nicotine + TX, nicotine sulfate + TX, nithiazine + TX, pronicotine + TX, O-5-dichloro-4-iodophenyl O-ethylethyl phosphonothioate + TX, O,O-diethyl O-4-methyl-2-oxo-2H-benzopyran-7-yl phosphonothioate + TX, O,O-diethyl O-6-methyl-2-propylpyrimidin-4-yl phosphonothioate + TX, O,O,O',O'-tetrapropyl dithiodipyrophosphate + TX, oleic acid + TX, p-dichlorobenzene + TX, methyl parathion + TX, pentachlorophenol + TX, pentachlorophenyl laurate + TX, PH 60-38+TX, fenthion+TX, parathion+TX, phosphine+TX, methyl phoxim+TX, methamidophos+TX, polychlorinated dicyclopentadiene isomers+TX, potassium arsenite+TX, potassium thiocyanate+TX, precocious element I+TX, precocious element II+TX, precocious element III+TX, amimidophos+TX, profluthrin+TX, fenthion+TX, pyraclostrobin+TX, anti-pyrethroids+TX, quassia extract (quassia) + TX, quinalphos-methyl + TX, oxathion + TX, iodophos + TX, resmethrin + TX, rotenone + TX, thiamethoxam + TX, ryanodine + TX, sabadilla + TX, octamethrin + TX, clostridium + TX, SI-0009 + TX, thiamethoxam + TX, sodium arsenite + TX, sodium cyanide + TX, sodium fluoride + TX, sodium hexafluorosilicate + TX , sodium pentachlorophenol + TX, sodium selenate + TX, sodium thiocyanate + TX, sulcofuron + TX, sulcofuron-sodium + TX, sulfuryl fluoride + TX, thiopromide + TX, tar + TX, thiamethoxam + TX, TDE + TX, butylpyrimidinphos + TX, dimethoate + TX, cyclopentyl thiocarb + TX, tetrachloroethane + TX, thiochlorvos + TX, thiophanate-sodium + TX, Cyclohexanil + TX, cypermethrin + TX, cypermethrin + TX, cypermethrin sodium + TX, tetrabromothrin + TX, permethrin + TX, trichlormetaphos-3 + TX, cypermethrin + TX, chlorpyrifos + TX, tolprocarb + TX, chlorpyrifos + TX, chlorpyrifos + TX, chlorpyrifos + TX, chlorpyrifos + TX, chlorpyrifos + TX, veratridine + TX, XMC + TX,Zetamethrin + TX, zinc phosphide + TX, tolfenphos + TX, chlorfluanidine + TX, tetrafluanidine + TX, bis(tributyltin) oxide + TX, bromoacetamide + TX, iron phosphate + TX, niclosamide-ethanolamine + TX, tributyltin oxide + TX, pyrifos + TX, snail killer + TX, 1,2-dibromo-3-chloropropane + TX, 1,3-dichloropropylene + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide + TX, 3-(4-chlorophenyl)-5-methylrhodanine + TX, 5-methyl-6-thioxo-1,3,5-thiadiazine -3-acetic acid + TX, 6-isopentenylaminopurine + TX, 2-fluoro-N-(3-methoxyphenyl)-9H-purine-6-amine + TX, benclothiaz + TX, cytokinin + TX, DCIP + TX, furfural + TX, isamidophos + TX, kinetin + TX, verrucosporium mycorrhizal composition + TX, tetrachlorothiophene + TX, xylenol + TX, zeatin + TX, potassium ethylxanthate + TX, acibenzolar + TX, acibenzolar-S-methyl + TX, Reynoutria sachalinensis) extract + TX, α-chlorohydrin + TX, Antu + TX, barium carbonate + TX, bismuth urea + TX, brodifacoum + TX, brodifacoum + TX, brodifacoum + TX, chlordifacoum + TX, cholecalciferol + TX, chlorfenapyr + TX, clofodine + TX, clofodine + TX, clofodine + TX, clofodine + TX, clofodine + TX, clofodine + TX, clofodine + TX, calciferol + TX, fludioxaline + TX, fluoroacetamide + TX, fludioxaline Pyridine + TX, flurbiprofen hydrochloride + TX, warfarin + TX, chloranil + TX, chloranil + TX, chloranil + TX, chloranil + TX, chloranil + TX, sodium fluoroacetate + TX, thallium sulfate + TX, warfarin + TX, 2-(2-butoxyethoxy)ethyl piperate + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone + TX, farnesol with nerolidol + TX, synergistic acetylene ether + TX, MGK 264+TX, piperonyl ether+TX, piperonyl aldehyde+TX, piperonyl ester (propyl isomer)+TX, S421+TX, piperonyl powder+TX, sesasmolin+TX, sulfoxide+TX, anthraquinone+TX, copper cyclohexaneate+TX, copper oxychloride+TX, dicyclopentadiene+TX, salen+TX, zinc cyclohexaneate+TX, zinc thiram+TX, imanin+TX, ribavirin+TX, mercuric oxide+TX, thiophanate-methyl+TX, azaconazole+TX, bifenthrin+TX, oxadiazole+TX, cyproconazole+TX, fenpropimorph+TX, diniconazole+TX, epoxiconazole+TX, fenbuconazole+TX, fluquinconazole+TX, flusilazole+TX, flutriafol+TX, furopyram+TX, hexaconazole+TX, imazalil+TX,Imidazole + TX, ioconazole + TX, metconazole + TX, myclobutrazol + TX, paclobutrazol + TX, pyrifenox + TX, prochloraz + TX, propiconazole + TX, pyraconazole + TX, simeconazole + TX, tebuconazole + TX, fluconazole + TX, triadimefon + TX, triadimenol + TX, triflumizole + TX, trichlorfon + TX, pyrimidine + TX, chlorfenapyr + TX, flufenapyr + TX, bupirimate + TX, dimethirimol + TX, ethirimol + TX, dodecanol + TX, Cyclomorph + TX, fenpropidine + TX, fenpropimorph + TX, spiroxamorph + TX, tridemorph + TX, cyprodinil + TX, pyraclostrobin + TX, pyrimethanil + TX; fenpiclonil + TX, fludioxonil + TX, benalaxyl + TX, furalaxyl + TX, metalaxyl + TX, R-metalaxyl + TX; furamide + TX; oxadixyl + TX, carbendazim + TX, debacarb + TX, oxadixyl + TX, thiabendazole + TX, chlozolinate + TX, dichlo zoline + TX, myclozoline + TX, procymidone + TX, vinclozoline + TX, boscalid + TX, carboxin + TX, furamide + TX, flutolanil + TX, oxacarb + TX, penthiopyrad + TX, thiofuran + TX, docodine + TX, biguanide + TX, azoxystrobin + TX, enestroburin + TX, enestroburin + TX, flutolanil + TX, fluoxastrobin + TX, Kresoxim-methyl + TX, fenoxystrobin + TX, trifloxystrobin + TX, trifloxystrobin + TX, picoxystrobin + TX, pyraclostrobin + TX, pyraclostrobin + TX, ferbam + TX, mancozeb + TX, maneb + ​​TX, methanamide + TX, methyl propineb + ​​TX, maneb + ​​TX, captamipan + TX, captan + TX, pyraclostrobin + TX, foltan + TX, tolylfluanid + TX, Bordeaux mixture + TX, copper oxide + TX, mancozeb + TX, quinoline copper + TX, phthalostrobin + TX, kefansan + TX, isoblastin + TX, chlorpyrifos + TX, tolclofos-methyl + TX, captamipan + TX, benzathine + TX, blasticidin + TX,Chloroneb + ​​TX, chlorothalonil + TX, cyfluanid + TX, cymoxanil + TX, cyclobutrifluram + TX, diclocymet + TX, diclomezine + TX, dicloran + TX, diethofencarb + TX, oxadiazine + TX, flumorph + TX, dithianon + TX, ethaboxam + TX, etridiazole + TX, famoxadone + TX, fenamidone + TX, rice blast Fenoxanil + TX, ferimzone + TX, fluazinam + TX, fluopicolide + TX, flusulfamide + TX, flupyraclostrobin + TX, fenoxam + TX, fosetyl-aluminium + TX, hymexazol + TX, propineb + ​​TX, cyazofamid + TX, methasulfocarb + TX, mefenamic acid + TX, pencycuron + TX, phthalide + TX, polyoxy Polyoxins + TX, propamocarb + TX, pyrimidine + TX, proquinazid + TX, pyroquilon + TX, pyriofenone + TX, quinoxyfen + TX, pentachloronitrobenzene + TX, thiazide + TX, triazoxide + TX, tricyclazole + TX, trimethoprim + TX, validamycin + TX, valeramide + TX, zoxamide + TX, mandipropamid + TX, flubeneteram + TX 、isopyrazam + TX、sedaxane + TX、benzovinflumizone + TX、flutriazole + TX、3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3',4',5'-trifluoro-biphenyl-2-yl)-amide + TX、isoflucypram + TX、isothianid + TX、dipymetitrone + TX、6-ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithia[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, Jiaxiangjunzhi + TX, lvbenmixianan + TX, dichlobentiaz ox+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-quinolinyl)oxy]phenyl]propan-2-ol+TX, oxathiapiprolin+TX, tert-butyl N-[6-[[[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridinyl]carbamate+TX, pyraziflumid+TX, inpyrfluxam+TX, trolprocarb+TX, chlorfluanidazole+TX, ipfentr ifluconazole + TX, 2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, N'-(2,5-dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine + TX, 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-piperidinyl]thiazol-4-yl]-4,5-dihydroisoxazol-5-yl]-3-chloro-phenyl] methanesulfonate + TX, N-[6-[[(Z)-[ (1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamic acid but-3-ynyl ester + TX, N-[[5-[4-(2,4-dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamic acid methyl ester + TX, 3-chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine + TX, pyridachlometyl + 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, pyraclostrobin+TX, indazolesulfazoline+TX, fluopicolide+TX, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamine+TX, florylpicoxamid+TX, fenpicoxamid+TX, isobutylethoxyquinoline+TX, ipflufenoquin+TX, quinofumelin+TX, isopropylthiocyanate Amine + 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, benzathiostrobin + TX, cyanothiostrobin + TX, 5-amino-1,3,4-thiadiazole-2-thiol zinc salt (2:1) + TX, fluopyram + TX, fluthiazolin + TX, fluopyram + TX, pyrapropoyne + 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, metyltetraprole + TX, 2-(difluoromethyl)-N-((3R)-1,1,3-trimethylindan-4-yl)pyridine-3-carboxamide + TX, α-(1,1-dimethylethyl)-α-[4'-(trifluoromethoxy)[1,1'-diphenyl]-4-yl]-5-pyrimidinemethanol + TX, fluoxapip rolin+TX, enoxastrobin+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, 4-[[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-ethyl + TX, syringoxystrobin + TX, zhongshengmycin + TX, thiophanate-methyl + TX, zinc thiazole + TX, amectotractin + TX, iprodione + TX; N'-[5-bromo-2-methyl-6-[(1S)-1-methyl-2-propoxy-ethoxy]-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridinyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds can be prepared by WO 2015 / 155075); N'-[5-bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridinyl]-N-ethyl-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 can be prepared by the method described in WO2018 / 228896); 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 method described in WO2018 / 228896); 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 method 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 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 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-3,3-dimethyl-1-isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole + TX (these compounds can be prepared by WO 2...

Claims

1. A compound having formula I in R 1 It is H; The A 1 and the substituent R 2a and R 2b The cyclic group is selected from K-1 to K-15 R 3 It is methyl; R 4 is 2-pyridine, 2-pyrimidine, 2-pyridine substituted by a substituent selected from cyclopropyl or halogen, or 2-pyrimidine substituted by a substituent selected from cyclopropyl or halogen; R 5a and R 5b It is hydrogen; or an agrochemically acceptable salt, stereoisomer or tautomer of the compound of formula I.

2. The compound according to claim 1, wherein the compound is an enantiomer of the compound of formula I.

3. A compound according to claim 1 or claim 2, in, R 4 Selected from O-1 to O-8 4. A composition comprising a compound according to any one of claims 1 to 3, one or more adjuvants and diluents, and optionally one or more other active ingredients.

5. A method for combating and controlling insects, mites, nematodes or molluscs, the method comprising applying an insecticidal, acaricidal, nematicidal or molluscicidal effective amount of a compound according to any one of claims 1 to 3 or a composition according to claim 4 to a pest, a location of a pest, or a plant susceptible to attack by a pest, wherein methods for treating the human or animal body by surgery or therapy and diagnostic methods performed on the human or animal body are excluded.

6. A method for protecting plant propagation materials from attacks by insects, mites, nematodes or molluscs, the method comprising treating the propagation materials or the site in which the propagation materials are planted with an effective amount of a compound according to any one of claims 1 to 3 or a composition according to claim 4.

7. Use of the compound according to any one of claims 1 to 3 or the composition according to claim 4 in the preparation of a medicament for controlling parasites in or on an animal in need thereof.

8. A compound having formula IIab to IIae Where R 1 is as defined in claim 1 and R 4 As defined in claim 3.

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