Organically active condensed bicyclic aromatic heterocyclic compounds

Abstract

The compounds of formula (I) wherein the substituents are as defined in claim 1 and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of these compounds may be used as insecticides. [Formula 1] TIFF2023501208000226.tif47158

Description

[Technical Field]

[0001] The present invention relates to quinazoline compounds that are effective in killing pests, particularly insecticidal compounds, processes for preparing the same, compositions containing these compounds, and their use for controlling animal pests, including arthropods, particularly insects or representative members of the order Acarina. [Background technology]

[0002] International Publication No. 2017192385 describes certain heteroaryl-1,2,4-triazole and heteroaryl-tetrazole compounds used to control ectoparasites in animals (including mammals and non-mammalians).

[0003] Novel quinazoline and quinoline compounds with pest-cidicating activity have been discovered here. [Overview of the Initiative] [Means for solving the problem]

[0004] The present invention, therefore, in a first embodiment, relates to the compound of formula I. [ka] (In the formula: A1, A2, and A3 are independent of each other, N or CR Y and; A4 and A5 are independent of each other, N or CR Y and; Q is [ka] and; R1 is hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonyl C1-C6 alkyl, hydroxycarbonyl C1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilane C1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, C3-C4 cycloalkyl C1-C2 alkyl- (where the C3-C4 cycloalkyl group is substituted with one or two halogen atoms), oxetan-3-yl-CH2-, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, benzyl, or benzyl substituted with 1 to 3 substituents independently selected from halogen, C1-C6 alkoxy and C1-C6 haloalkyl; R 2a and R 2b are each hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, NO2, SF5, CN, C(O)NH2, C(O)OH, C(S)NH2, C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted with 1 to 3 substituents independently selected from R x C3-C6 cycloalkylcarbonyl, phenyl, phenyl substituted with 1 to 3 substituents independently selected from R x heteroaryl, heteroaryl substituted with 1 to 3 substituents independently selected from R x OR6, piperidin-2-one-1-yl, piperidin-2-one-1-yl substituted with 1 to 2 substituents independently selected from R x pyridin-2-one-1-yl, pyridin-2-one-1-yl substituted with 1 to 2 substituents independently selected from R x azetidin-1-yl, azetidin-1-yl substituted with 1 to 2 substituents independently selected from R x pyrrolidin-1-yl, pyrrolidin-1-yl substituted with 1 to 2 substituents independently selected from R xPyrrolidine-1-yl, C3-C6 cycloalkyl, C1-C4 alkyl, R are substituted with 1-2 substituents independently selected from the above. z C3-C6 cycloalkylC1-C4 alkyl; C3-C6 cycloalkylC1-C3 alkoxy, R substituted with 1-2 substituents independently selected from x C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C5 cyanoalkyl, C1-C5 cyanoalkoxy, C1-C4 alkylsulfanyl, R substituted with 1-2 substituents independently selected from x C1-C4 alkylsulfanyls, C1-C4 alkylsulfonyls, R are substituted with 1-3 substituents independently selected from the above. x C1-C4 alkylsulfonyls, C1-C4 alkylsulfinyls, and R are substituted with 1-3 substituents independently selected from the above. x Independently selected from C1-C4 alkylsulfinyl molecules substituted with 1-3 substituents independently selected from; R3 is a C1-C3 alkyl or C1-C3 haloalkyl; R4 is pyridine, pyrimidine, pyrazine, or pyridazine; or R4 is pyridine, pyrimidine, pyrazine, or pyridazine, each of which is independently substituted with one or two substituents independently selected from a five-membered heteroaryl ring which may be optionally substituted with one or three substituents independently selected from halogens, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, and halogens, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy; R 4a These are pyridine, pyrimidine, pyrazine, pyridazine; or R 4ais pyridine, pyrimidine, pyrazine, or pyridazine, each of which is independently substituted with 1 to 3 substituents independently selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, hydroxyl, cyano, and C1-C3 haloalkoxy; or R 4a Y1, Y2, Y3 and Y4 [ka] And here, R' 4a , R' 4b and R' 4c These are selected independently of each other and independently of Y1-Y4 from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy; R5 is hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, C3-C4 alkoxy C(O)-, (C1-C3 alkoxy)2CH-, halogen, CN, NH2C(O), amino (i.e., NH2), (C1-C3 alkyl)amino, di(C1-C3 alkyl)amino, hydroxy, C3-C4 halocycloalkyl, C3-C4 cyanocycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfonyl, C1-C4 alkylsulfonyl The following are fluhonyl, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl) sulfonylamino, (C1-C3 alkyl) sulfonyl(C1-C3 alkyl)amino, (C1-C3 alkyl) NHC(O), (C1-C3 alkyl) 2NC(O), (C1-C3 cycloalkyl) NHC(O), (C1-C3 cycloalkyl)(C1-C3 alkyl) NC(O), (C1-C3 alkyl) C(O)(C1-C3 alkyl) N, (C1-C3 alkyl) C(O) NH, (C1-C3 alkyl) C(O), (C1-C3 alkoxy) C(O), HC(O), diphenylmethaneimine, C1-C3 haloalkoxy, phenyl, or a 5-membered aromatic heterocycle; or R5 is a phenyl compound substituted with 1 to 3 substituents selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, CN, and hydroxyl; or R5 is a five-membered aromatic heterocycle substituted with one to three substituents selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, CN, and hydroxyl; R 5a and R 5bThese are independently selected from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy; R6 is phenyl, benzyl, heteroaryl, or C3-C6 cycloalkyl; or R6 is phenyl, benzyl, heteroaryl, or C3-C6 cycloalkyl, and each of these is independently R x It is substituted with 1 to 3 substituents independently selected from; R x These are independently selected from halogens, C1-C3 alkyls, C1-C3 haloalkyls, C1-C3 alkoxys, C1-C3 haloalkoxys, NO2, SF5, CN, C(O)NH2, C(S)NH2, C1-C4 haloalkylsulfanyls, C1-C4 haloalkylsulfinyls, C1-C4 haloalkylsulfonyls, C1-C4 alkylsulfanyls, C1-C4 alkylsulfinyls, and C1-C4 alkylsulfonyls; R Y This is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN and cyclopropyl; and R Z (Selected from oxo, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, and CN) Alternatively, the present invention relates to agriculturally chemistry-acceptable salts, stereoisomers, enantiomers, tautomers, and N-oxides of the compound of formula I. [Modes for carrying out the invention]

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

[0006] In each case, the compound of formula I according to the present invention is in free form, oxidized form as an N-oxide, or salt form, for example, a salt form that can be used agriculturally.

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

[0008] The compound of formula I according to the present invention also includes hydrates that may be formed during salt formation.

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

[0010] When used herein, "C1~C nThe term "haloalkyl" refers to a linear or branched saturated alkyl radical having 1 to n carbon atoms bonded via any of the carbon atoms (as described above), where some or all of the hydrogen atoms in these radicals may be substituted with fluorine, chlorine, bromine and / or iodine, i.e., 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, It is one of the following: 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. The term "C1-C2 fluoroalkyl" refers to a C1-C2 alkyl radical having 1, 2, 3, 4, or 5 fluorine atoms, such as difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl, or pentafluoroethyl.

[0011] When used herein, "C1~C nThe term "alkoxy" refers to a linear or branched saturated alkyl radical having 1 to n carbon atoms (as described above) bonded via an oxygen atom, i.e., one of the following radicals: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy, or 1,1-dimethylethoxy radicals. As used herein, "alkoxy" refers to a linear or branched saturated alkyl radical having 1 to n carbon atoms (as described above), i.e., one of the following radicals: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy, or 1,1-dimethylethoxy radicals. n The term "alkoxy" refers to a C1-C alkyl radical in which one or more hydrogen atoms on the alkyl radical are substituted by the same or different halo atoms. n This refers to alkoxy radicals (examples include trifluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy, 3,3,3-trifluoropropoxy, and 4-chlorobutoxy).

[0012] When used herein, "C1~C n The term "cyanoalkyl" refers to a linear or branched saturated chain having 1 to n carbon atoms. n This refers to alkyl radicals (as described above), in which one of the hydrogen atoms in these radicals is substituted by a cyano group, such as cyanomethyl, 2-cyanoethyl, 2-cyanopropyl, 3-cyanopropyl, 1-(cyanomethyl)-2-ethyl, 1-(methyl)-2-cyanoethyl, 4-cyanobutyl, etc.

[0013] When used in this specification, "C3~C n The term "cycloalkyl" refers to 3- to n-membered cycloalkyl groups such as cyclopropane, cyclobutane, cyclopentane, and cyclohexane.

[0014] "C3~C n The term "cycloalkylcarbonyl," as used herein, refers to a 3- to n-membered cycloalkyl group bonded to a carbonyl (C=O) group to which the carbonyl group is bonded in the remainder of the molecule. Similarly, as used herein, "C1-C n "Alkylcarbonyl", "C1~C nThe terms "alkoxycarbonyl," "phenyloxycarbonyl," and "benzyloxycarbonyl" refer to alkyl, alkoxy, phenyloxy, and benzyloxy groups bonded to the carbonyl (C=O) group that is bonded to the remainder of the molecule.

[0015] As used herein, the term "C3-C4 cycloalkyl-C1-C2 alkyl" refers to a three- or four-membered cycloalkyl group having either a methylene or ethylene group, the methylene or ethylene group being bonded to the remainder of the molecule. In this case, the C3-C4 cycloalkyl-C1-C2 alkyl- group is substituted, and the substituent may be on the cycloalkyl and / or alkyl group.

[0016] The term "C3-C6 cycloalkyl C1-C4 haloalkoxy," as used herein, refers to a 3-6 member cycloalkyl group bonded to a 1-4 member haloalkoxy group that is bonded to the remainder of the molecule.

[0017] When used herein, "aminocarbonyl C1-C" n The term "alkyl" refers to an alkyl radical, where one of the hydrogen atoms in the radical is substituted by a CONH2 group.

[0018] When used herein, "hydroxycarbonyl C1-C" n The term "alkyl" refers to an alkyl radical in which one of the hydrogen atoms in the radical is replaced by a COOH group.

[0019] When used herein, "C1~C n The term "alkylsulfanyl" refers to C1-C1 atoms bonded via a sulfur atom. n This refers to the alkyl portion. Similarly, as used herein, "C1~C n "Haloalkylthio" or "C1~C n The term "haloalkylsulfanyl" refers to a C1-C1 atom bonded via a sulfur atom.n This refers to the haloalkyl portion. Similarly, "C3~C n The term "cycloalkylsulfanyl" refers to a 3- to n-membered cycloalkyl moiety bonded via a sulfur atom.

[0020] When used herein, "C1~C n The term "alkylsulfinyl" refers to a C1-C group bonded via a sulfur atom in the S(=O) group. n This refers to the alkyl portion. Similarly, as used herein, "C1~C n "Haloalkylsulfinyl" or "C1~C n The term "haloalkylsulfinyl" refers to a C1-C group bonded via a sulfur atom in the S(=O) group. n This refers to the haloalkyl portion. Similarly, "C3~C n The term "cycloalkylsulfinyl" refers to a 3- to n-membered cycloalkyl moiety bonded via a sulfur atom of the S(=O) group.

[0021] When used herein, "C1~C n The term "alkylsulfonyl" refers to a C1-C molecule bonded via two sulfur atoms (S=O). n This refers to the alkyl portion. Similarly, as used herein, "C1~C n "Haloalkylsulfonyl" or "C1~C n The term "haloalkylsulfonyl" refers to a C1-C group bonded via two sulfur atoms (S=O). n This refers to the haloalkyl portion. Similarly, "C3~C n The term "cycloalkylsulfonyl" refers to a 3- to n-membered cycloalkyl moiety bonded via two sulfur atoms (S=O).

[0022] When used in this specification, "trimethylsilane C1-C n The term "alkyl" refers to an alkyl radical, in which one of the hydrogen atoms in the radical is substituted by a -Si(CH3)3 group.

[0023] When used in this specification, "C2~C n The term "alkenyl" refers to a linear or branched alkenyl chain having 2 to n carbon atoms and one or two double bonds, such as ethenyl, prop-1-enyl, and buta-2-enyl.

[0024] When used in this specification, "C2~C n The term "haloalkenyl" refers to a C2-C2 atom substituted with one or more halo atoms, which may be identical or different. n This refers to the alkenyl portion.

[0025] When used in this specification, "C2~C n The term "alkynyl" refers to a linear or branched alkynyl chain having 2 to n carbon atoms and one triple bond, such as ethynyl, prop-2-inyl, and buta-3-inyl.

[0026] When used in this specification, "C2~C n The term "haloalkynyl" refers to a C2-C atom substituted with one or more halo atoms, which may be identical or different. n This refers to the alkynyl portion.

[0027] A halogen, or "halo," generally refers to fluorine, chlorine, bromine, or iodine. This also applies to halogens combined with other meanings, such as haloalkyl.

[0028] As used herein, the term "heteroaryl" refers to a five-membered or six-membered aromatic monocyclic ring having one to three heteroatoms independently selected from N, O, and S. Examples are heteroaryls J-1 to J-35 shown in Scheme A below. Preferably, preferred heteroaryls are pyridyl, pyrimidyl, and pyrazolyl.

[0029] Scheme A: Heteroaryl J-1~J-35: [ka] R4 and R 4a The pyridine, pyrimidine, pyrazine, and pyridazine groups (unsubstituted or substituted) are each bonded to the remainder of the compound via carbon atoms in their respective rings.

[0030] As used herein, the term “control” means reducing the number of pests, eliminating pests, and / or preventing further damage from pests, thereby reducing damage to plants or plant-derived products.

[0031] When used herein, for example, Q a The wavy lines in Y-1 represent bonding / connection points to the remainder of the compound.

[0032] As used herein, the term “pest” refers to insects and mollusks found in agriculture, horticulture, forestry, and the storage of plant-derived products (such as fruits, grains, and lumber); as well as pests associated with damage to man-made structures. The term “pest” encompasses all stages of the pest’s life cycle.

[0033] As used herein, the term "effective amount" refers to the amount of a compound or salt thereof that produces the desired effect with a single or multiple application.

[0034] The effective amount can be readily determined by those skilled in the art by using known techniques and by observing the results obtained under similar circumstances. In determining the effective amount, numerous factors are considered, in particular, but not limited to, the type of plant or plant-derived product to be applied; the pests to be controlled and their life cycles; the specific compound to be applied; the type of application; and other relevant circumstances.

[0035] As those skilled in the art will understand, the compound of formula I contains a stereodiene center indicated by an asterisk in the following structure, [ka] In the formula, R1, R 2a , R 2b R3, Q, A1, A2, A3, A4, and A5 are as defined in the first embodiment.

[0036] This invention aims to provide both racemic compounds and individual enantiomers. Compounds with preferred stereochemistry are listed below. [ka]

[0037] Particularly preferred compounds of the present invention are those of formula I'a: (In the formula, R1, R 2a , R 2b (R3, Q, A1, A2, A3, A4 and A5 are as defined in the first embodiment.) The compounds of formula (I'a), as well as stereoisomers, enantiomers, tautomers, and N-oxides of the compound of formula (I'a), and agriculturally acceptable salts.

[0038] Where used herein, the term "optionally substituted" means that the group being referred to is either unsubstituted or substituted with a specified substituent. For example, "C3-C4 cycloalkyl groups may be optionally substituted with one or two halo atoms" means C3-C4 cycloalkyl groups, C3-C4 cycloalkyl groups substituted with one halo atom, and C3-C4 cycloalkyl groups substituted with two halo atoms.

[0039] Embodiments of the present invention are provided as follows.

[0040] In one embodiment of each aspect of the present invention, A. A1, A2, and A3 are independent of each other, N or CR Y And, provided that two or fewer of these three are N; or B.A1 and A3 are N, and A2 is CR Y is; or C.A1, A2, and A3 are N or CH, independently of each other; or D.A1, A2, and A3 are N or CH independently of each other, provided that two or fewer of these three are N; or E.A1 is N, and A2 and A3 are CH; or F.A1 and A2 are CH, and A3 is N; or G.A1 and A3 are N, and A2 is CH; or H.A1 and A3 are N, and A2 is CH That is the case.

[0041] In one embodiment of each aspect of the present invention, A.A4 is CR Y And A5 is N; or B.A4 is CR Y And A5 is CH; or C.A4 is CH, and A5 is N; or D.A4 is N, and A5 is CH; or E.A4 and A5 are both CH That is the case.

[0042] In one embodiment of each aspect of the present invention, A.A1 is N, A2 and A3 are CH, and A4 and A5 are both CH; or B.A1 and A2 are CH, A3 is N, and A4 and A5 are both CH; C.A1 and A3 are N, A2 is CH, and A4 is CR Y And A5 is CH; or D.A1 and A3 are N, A2 is CH, A4 is CH, and A5 is N; or E.A1 and A3 are N, A2 is CH, and A4 is N, and A5 is CH; or F.A1 and A3 are N, A2 is CH, A4 is N or CH, and A5 is CH; or G.A1 and A3 are N, A2 is CH, A4 is CH, and A5 is N or CH; or H.A1 and A3 are N, A2 is CH, and A4 and A5 are both N; or I. A1 and A3 are N, A2 is CH, and A4 and A5 are both CH That is the case.

[0043] In one embodiment of each aspect of the present invention, R1 is A. Hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonyl C1-C6 alkyl, hydroxycarbonyl C1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilane C1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, C3-C4 cycloalkyl C1-C2 alkyl- (where the C3-C4 cycloalkyl is substituted with one or two halogen atoms), oxetane-3-yl-CH2-, C1-C3 alkylcarbonyl, C1-C3 alkoxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl or benzyl; or B. Hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonyl C1-C6 alkyl, hydroxycarbonyl C1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilane C1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, benzyloxycarbonyl or benzyl; or C. Hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonyl C1-C6 alkyl, hydroxycarbonyl C1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, benzyloxycarbonyl or benzyl; or D. Hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, benzyloxycarbonyl or benzyl; or E. Hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C2-C4 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, benzyloxycarbonyl or benzyl; or F. Hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C2-C4 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, benzyloxycarbonyl or benzyl; or G. Hydrogen, methyl, ethyl, cyanomethyl, methoxymethyl, cyclopropyl-methyl, allyl, propargyl, benzyloxycarbonyl or benzyl; or H. Hydrogen, methyl, ethyl, allyl, propargyl or cyclopropyl-methyl; or I. Hydrogen, methyl, propargyl or cyclopropyl-methyl is.

[0044] In one embodiment of each aspect according to the present invention, R 2a is A. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, C3-C6 cycloalkylcarbonyl, phenyl, heteroaryl selected from J-1 to J-35, wherein each of C3-C4 cycloalkyl, phenyl or heteroaryl is independently substituted with 1 to 3 substituents R x and; OR6, piperidin-2-one-1-yl, pyridin-2-one-1-yl, azetidin-1-yl optionally substituted with R x , pyrrolidin-1-yl, C3-C6 cycloalkyl C1-C4 alkyl substituted with one or two substituents R Z , C3-C6 cycloalkyl C1-C3 alkoxy optionally substituted with R x , C1-C5 cyanoalkyl, C1-C5 cyanoalkoxy, C1-C4 alkylsulfanyl optionally substituted with 1 to 3 substituents R x , C1-C4 alkylsulfonyl optionally substituted with 1 to 3 substituents R x , or C1-C4 alkylsulfinyl optionally substituted with 1 to 3 substituents R x ; or B. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, C3-C6 cycloalkylcarbonyl, phenyl, pyrazolyl, wherein each of C3-C4 cycloalkyl, phenyl, pyrazolyl is independently substituted with 1 to 3 substituents R x and; OR6, piperidin-2-one-1-yl, pyridin-2-one-1-yl, azetidin-1-yl optionally substituted with R x , pyrrolidin-1-yl, C3-C6 cycloalkyl C1-C4 alkyl optionally substituted with one or two substituents R Z [[ID=XX]]and; C3-C6 cycloalkyl C1-C3 alkoxy optionally substituted with R x , C1-C5 cyanoalkyl, C1-C5 cyanoalkoxy, C1-C4 alkylsulfanyl optionally substituted with 1 to 3 substituents R xC1-C4 alkylsulfanyl which may be optionally substituted, or 1-3 substituents R x C1-C4 alkylsulfonyl which may be optionally substituted, or 1-3 substituents R x C1-C4 alkylsulfinyl which may be optionally substituted; or C. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, C3-C6 cycloalkylcarbonyl, phenyl or pyrazolyl, wherein each of C3-C4 cycloalkyl, phenyl and pyrazolyl is independently substituted with 1-2 substituents R x substituted with, OR6, R x azetidin-1-yl which may be optionally substituted, 1 or 2 substituents R Z C3-C6 cycloalkyl C1-C4 alkyl which may be optionally substituted, R x C3-C6 cycloalkyl C1-C3 alkoxy which may be optionally substituted, 1-3 substituents R x C1-C4 alkylsulfanyl which may be optionally substituted, 1-3 substituents R x C1-C4 alkylsulfonyl which may be optionally substituted, or 1-3 substituents R x C1-C4 alkylsulfinyl which may be optionally substituted; or D. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, C3-C4 cycloalkyl substituted with 1-2 substituents R x C3-C6 cycloalkylcarbonyl, OR6, C3-C6 cycloalkyl C1-C4 alkyl substituted with 1 or 2 substituents R Z C3-C6 cycloalkyl C1-C4 alkyl substituted with 1 or 2 substituents R, C1-C4 alkylsulfanyl, 1-3 substituents R x C1-C4 alkylsulfanyl substituted with 1-3 substituents R, C1-C4 alkylsulfonyl, 1-3 substituents R xC1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, or 1-3 substituents R, which are replaced by x C1-C4 alkylsulfinyl substituted by; or E. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, halogen, C1-C3 alkyl, and C1-C3 haloalkyl, independently selected from 1-2 substituents Substituted C3-C4 cycloalkyl, C3-C4 cycloalkylcarbonyl, C3-C4 cycloalkylmethyl, oxo, halogen, C1-C3 alkyl, and C1-C3 haloalkyl, independently selected from 1-2 substituents Substituted C3-C4 cycloalkylmethyl, C1-C2 alkylsulfanyl substituted by 1-3 halogens, or C1-C2 alkylsulfonyl substituted by 1-3 halogens; or F. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, halogen, methyl, and trifluoromethyl, independently selected from 1-2 substituents Substituted cyclopropyl, cyclopropylcarbonyl, oxo, halogen, and trifluoromethyl, independently selected from 1-2 substituents Substituted cyclopropylmethyl, or C 1- C2 alkylsulfanyl substituted by 1-3 halogens, or C 1- C2 alkylsulfonyl; or G. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkyl sulfanyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C6 cycloalkyl; C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl substituted with 1-3 substituents independently selected from cyano and halogen, cyclopropylcarbonyl, C3-C6 cycloalkyl, C1-C4 alkyl; oxo, C1-C3 alkyl , C3-C6 cycloalkyl, C1-C4 alkyl, C1-C5 cyanoalkyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfinyl, C3-C6 cycloalkylsulfanyl, C3-C6 cycloalkylsulfinyl or C3-C6 cycloalkylsulfonyl substituted with 1-5 substituents independently selected from C1-C3 haloalkyl, cyano, and halogen; or H. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkyl sulfanyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C6 cycloalkyl, C3-C4 cycloalkylcarbonyl, C3-C6 cycloalkyl C1-C4 alkyl substituted with one or two substituents independently selected from C1-C3 haloalkyl, cyano and halogen; oxo, C3-C6 cycloalkyl C1-C4 alkyl, C1-C5 cyanoalkyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C3-C6 cycloalkylsulfanyl, C3-C6 cycloalkylsulfinyl or C3-C6 cycloalkylsulfonyl substituted with one to three substituents independently selected from C1-C3 haloalkyl, cyano and halogen; or I. C3-C6 cycloalkyl, C3-C4 cycloalkylcarbonyl, C3-C6 cycloalkylC1-C4 alkyl, C3-C6 cycloalkylC1-C4 alkyl, C3-C6 cycloalkylC1-C4 alkyl, C3-C6 cycloalkylC1-C4 alkyl, C1-C5 cyanoalkyl, C1-C4 alkylsulfonyl, C1-C4 haloalkyl, C1-C4 haloalkyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C3-C6 cycloalkylsulfanyl, C3-C6 cycloalkylsulfinyl or C3-C6 cycloalkylsulfonyl, substituted with one or two substituents independently selected from hydrogen, halogen, C1-C3 haloalkyl, C1-C3 haloalkyl, and halogen; or J. Hydrogen, halogen, C3-C4 cycloalkyl, C3-C4 cycloalkylcarbonyl; C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkyl sulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN, which may be optionally substituted with one or two substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl; or K. Halogen, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl or C1-C3 haloalkoxy; or L. Halogen, C1-C2 haloalkyl, C1-C2 haloalkylsulfanyl, C1-C2 haloalkylsulfonyl or C1-C2 haloalkoxy; or M. Chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl or trifluoromethylsulfonyl; or N. Fluorine, chlorine, bromine, iodine, trifluoromethylsulfanyl, trifluoromethylsulfonyl or trifluoromethyl; or O. Trifluoromethyl, fluorine, bromine, or chlorine That is the case.

[0045] In one embodiment of each aspect of the present invention, R 2b teeth A. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, cyclopropylcarbonyl, one or two substituents R Z C3-C6 cycloalkyl, C1-C4 alkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, or CN, which may be optionally substituted with R x A C1-C4 alkylsulfanyl which may be optionally substituted, 1-3 substituents R x A C1-C4 alkylsulfonyl which may be optionally substituted, or 1-3 substituents R x C1-C4 alkylsulfinyl which may be optionally substituted; or B. Hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl; C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkyl sulfanyl, C1-C3 haloalkyl sulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN, which may be optionally substituted with one or two substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl; or C. Halogen, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl or C1-C3 haloalkoxy; or D. Halogens, C1-C2 haloalkyls, C1-C2 haloalkylsulfanyls, C1-C2 haloalkylsulfonyls, or C1-C2 haloalkoxys; or E. Chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethylsulfonyl; or F. Fluorine, chlorine, bromine, iodine, trifluoromethylsulfanyl, trifluoromethylsulfonyl or trifluoromethyl; or G. Trifluoromethyl, fluorine, bromine, or chlorine That is the case.

[0046] In one embodiment of each aspect of the present invention, R3 is A. C1-C3 alkyl or C1-C3 haloalkyl; or B. Methyl or trifluoromethyl; or C. Methyl is.

[0047] In one embodiment of each aspect of the present invention, Q is A. Q a ; or B. Q b is.

[0048] In one embodiment of each aspect of the present invention, Q a is A. Q a -1 to Q a -16 is selected; or B. Q a -1, Q a -6, Q a -7, Q a -10 and Q a -15 is selected; or C. Q a -1 or Q a -15 is.

Chemical formula

Chemical formula

[0049] In one embodiment of each aspect of the present invention, Q b is A. Q b -1 to Q b -13 is selected; or B. Q b -1 is.

Chemical formula

[0050] In one embodiment of each aspect of the present invention, R4 is A. Pyridine or pyrimidine; where pyridine or pyrimidine is independently C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; halo J-13 may be optionally substituted with 1 to 3 substituents independently selected from halogens, C1-C3 alkyls, C1-C3 haloalkyls, C1-C3 alkoxys and C1-C3 haloalkoxys; J-20 may be optionally substituted with 1 to 3 substituents independently selected from halogens, C1-C3 alkyls, C1-C3 haloalkyls, C1-C3 alkoxys and C1-C3 haloalkoxys, and may also be optionally substituted with one substituent selected from 1H-tetrazole-5-yl; or B. Pyridine or pyrimidine, where the pyridine or pyrimidine is independently substituted with one substituent selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; optionally substituted with C1-C3 haloalkyl (J-13); optionally substituted with C1-C3 haloalkyl (J-20); and optionally substituted with one substituent selected from 1H-tetrazole-5-yl; or C. Pyridine, where pyridine is optionally substituted with one substituent selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; J-13 which may be optionally substituted with C1-C3 haloalkyl; J-20 which may be optionally substituted with C1-C3 haloalkyl; and 1H-tetrazole-5-yl; or D. Pyrimidine, where the pyrimidine is optionally substituted with one substituent selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; optionally substituted with trifluoromethyl (J-13); optionally substituted with trifluoromethyl and 1H-tetrazole-5-yl (J-20); or E. Pyridine, pyrimidine, pyrazine, or pyridazine, where pyridine, pyrimidine, pyrazine, or pyridazine may be optionally substituted with one substituent selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, F, Cl, Br, CN, and C1-C6 haloalkoxy; or F. Pyridine, pyrimidine, pyrazine, or pyridazine, where pyridine, pyrimidine, pyrazine, or pyridazine may be optionally substituted with one substituent selected from C1-C3 alkyl, C3-C4 cycloalkyl, F, Cl, Br, CN, and C1-C6 haloalkoxy; or G. Pyridine, pyrimidine, pyrazine, or pyridazine, wherein the pyridine, pyrimidine, pyrazine, or pyridazine may be optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy, and 2,2,2-trifluoroethoxy; H. Pyridine or pyrimidine, wherein the pyridine or pyrimidine may be optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy; or I. 5-Cyclopropylpyridine, 5-Fluoropyridine, 5-Chloropyridine, 5-Bromopyridine, 5-Difluoromethoxypyridine, 5-Trifluoromethoxypyridine, 5-Cyanopyridine, 5-(2,2-Difluoroethoxy)-Pyridine, 5-(2,2,2-Trifluoroethoxy)-Pyridine, Pyridine, 5-Cyclopropylpyrimidine, 5-Fluoropyrimidine, 5-Chloropyrimidine, 5-Bromopyrimidine, 5-Difluoromethoxypyrimidine, 5-Trifluoromethoxypyrimidine, 5-Cyanopyrimidine, 5-(2,2-Difluoroethoxy)-Pyrimidine, 5-(2,2,2-Trifluoroethoxy)-Pyrimidine, or Pyrimidine; or J. 5-Cyclopropylpyridine-2-yl, 5-Fluoropyridine-2-yl, 5-Chloropyridine-2-yl, 5-Bromopyridine-2-yl, 5-Difluoromethoxypyridine-2-yl, 5-Trifluoromethoxypyridine-2-yl, 5-Cyanopyridine-2-yl, 5-(2,2-Difluoroethoxypyridine-2-yl, 5-(2,2,2-Trifluoroethoxy)pyridine-2-yl, Pyridine-2-yl, 5-Cyclopropyl Ropyrimidin-2-yl, 5-fluoropyrimidin-2-yl, 5-chloropyrimidin-2-yl, 5-bromopyrimidin-2-yl, 5-difluoromethoxypyrimidin-2-yl, 5-trifluoromethoxypyrimidin-2-yl, 5-cyanopyrimidin-2-yl, 5-(2,2-difluoroethoxy)pyrimidin-2-yl, 5-(2,2,2-trifluoroethoxy)pyrimidin-2-yl, or pyrimidin-2-yl; or K. pyrimidine-2-yl, pyridine-2-yl, 5-bromopyrimidine-2-yl, 5-bromopyridine-2-yl, 5-cyanopyrimidine-2-yl or 5-cyanopyridine-2-yl; or L. pyrimidine-2-yl, 5-bromopyrimidine-2-yl, 5-bromopyridine-2-yl, or 5-cyanopyridine-2-yl That is the case.

[0051] In one embodiment of each aspect of the present invention, R 4a teeth A. Pyridine, pyrimidine, pyrazine, or pyridazine, where pyridine, pyrimidine, pyrazine, or pyridazine may be independently substituted with one substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy, and selected from Y-1-Y-4; or B. Pyridine, pyrimidine, pyrazine, or pyridazine, where pyridine, pyrimidine, pyrazine, or pyridazine may be independently substituted with one substituent selected from F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy, and 2,2,2-trifluoroethoxy, and selected from Y-1 to Y-4; or C. Pyridine or pyrimidine, where the pyridine or pyrimidine may be optionally substituted with one substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy, and selected from Y-1-Y-4; or D. Pyridine or pyrimidine, where the pyridine or pyrimidine may be optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy, and selected from Y-1 to Y-4; or E. 5-Cyclopropylpyridine, 5-Fluoropyridine, 5-Chloropyridine, 5-Bromopyridine, 5-Difluoromethoxypyridine, 5-Trifluoromethoxypyridine, 5-Cyanopyridine, 5-(2,2-Difluoroethoxy)-Pyridine, 5-(2,2,2-Trifluoroethoxy)-Pyridine, Pyridine, 5-Cyclopropylpyrimidine, 5-Fluoropyrimidine, 5-Chloropyrimidine, 5-Bromopyrimidine, 5-Difluoromethoxypyrimidine, 5-Trifluoromethoxypyrimidine, 5-Cyanopyrimidine, 5-(2,2-Difluoroethoxy)-Pyrimidine, 5-(2,2,2-Trifluoroethoxy)-Pyrimidine, Pyrimidine or 1,2,3-Triazole; or F. 5-Cyclopropylpyridine-2-yl, 5-Fluoropyridine-2-yl, 5-Chloropyridine-2-yl, 5-Bromopyridine-2-yl, 5-Difluoromethoxypyridine-2-yl, 5-Trifluoromethoxypyridine-2-yl, 5-Cyanopyridine-2-yl, 5-(2,2-Difluoroethoxy)-pyridine-2-yl, 5-(2,2,2-Trifluoroethoxy)-pyridine-2-yl, Pyridine-2-yl, 5-Cyclopropylpyrimidine-2-yl 5-fluoropyrimidine-2-yl, 5-chloropyrimidine-2-yl, 5-bromopyrimidine-2-yl, 5-difluoromethoxypyrimidine-2-yl, 5-trifluoromethoxypyrimidine-2-yl, 5-cyanopyrimidine-2-yl, 5-(2,2-difluoroethoxy)-pyrimidine-2-yl, 5-(2,2,2-trifluoroethoxy)-pyrimidine-2-yl, pyrimidine-2-yl, or 1,2,3-triazole-2-yl (or Y2); or G. 1,2,3-Triazole-2-yl (or Y2), pyrimidine-2-yl, or 5-cyanopyridine-2-yl That is the case.

[0052] In one embodiment of each aspect of the present invention, Y-1 is R 4a If selected as R' 4a and R' 4c They are mutually independent, A. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy; or B. From hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or C. Both are hydrogen That is the case.

[0053] In one embodiment of each aspect of the present invention, Y-2 is R 4a If selected as, A.R' 4b and R' 4cThese are independently selected from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy; or B.R' 4b and R' 4c These are independently selected from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or A.R' 4b and R' 4c They are both hydrogen; or B.R' 4b R' is hydrogen, and 4c is cyclopropyl That is the case.

[0054] In one embodiment of each aspect of the present invention, Y-3 is R 4a If selected as R' 4a and R' 4b They are mutually independent, A. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy; or B. Hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or C. Both are hydrogen That is the case.

[0055] In one embodiment of each aspect of the present invention, Y-4 is R' 4a If selected as, A.R' 4a , R' 4b and R' 4c These are independently selected from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy; or B.R' 4a , R' 4b and R' 4cThese are independently selected from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy and difluoromethoxy; or C.R. 4a , R' 4b and R' 4c Are they all hydrogen? or D.R. 4a and R' 4c R' is hydrogen, and 4b is CN.

[0056] In one embodiment of each aspect of the present invention, R5 is A. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, halogen, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl)C(O), (C1-C3 alkoxy)C(O), HC(O), C1-C3 haloalkoxy, or a 5-membered aromatic heterocycle, where the 5-membered aromatic heterocycle may be optionally substituted with 1 to 3 substituents selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, CN, or hydroxyl; or B. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, halogen, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl)C(O), (C1-C3 alkoxy)C(O), HC(O) or C1-C3 haloalkoxy; or C. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, halogen, Cl, Br, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl)C(O), (C1-C3 alkoxy)C(O) or C1-C2 haloalkoxy; or D. Hydrogen, C1-C3 alkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, C1-C3 haloalkoxy, halogen, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl)C(O), HC(O) or (C1-C3 alkoxy)C(O); or E. Hydrogen, C1-C2 alkyl, C1-C2 alkoxy, C3-C4 cycloalkyl, C1-C2 haloalkoxy, halogen, C1-C2 alkoxy-C1-C2 alkyl, C1-C2 alkoxy-C1-C2 alkoxy-C1-C2 alkyl, (C1-C2 alkyl)C(O), HC(O) or (C1-C2 alkoxy)C(O); or F. Hydrogen, methyl, trifluoromethoxy, methoxy, cyclopropyl, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, difluoromethoxy, 2,2,2-trifluoroethyl, chloro, bromo, methoxyethoxy, methylcarbonyl or methoxycarbonyl; or G. Hydrogen That is the case.

[0057] In one embodiment of each aspect of the present invention, R 5a teeth A. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy; or B. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl or C1-C3 alkoxy; or C. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl or C1-C3 alkoxy; or D. Hydrogen, halogen, CN, C1-C3 alkyl or C1-C3 alkoxy; or E. Hydrogen or halogen; or F. Hydrogen That is the case.

[0058] In one embodiment of each aspect of the present invention, R 5b teeth A. Hydrogen, halogen, CN, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy; or B. Hydrogen, halogen, or C1-C3 alkoxy; or C. Hydrogen That is the case.

[0059] In one embodiment of each aspect of the present invention, R6 is A. Phenyl, benzyl, heteroaryl, or C3-C6 cycloalkyl, each of which is independently R x It may be optionally substituted with one substituent selected from; or B. Phenyl, benzyl, cyclopropyl, or cyclopropyl is R x It is substituted with one substituent selected from the following.

[0060] In one embodiment of each aspect of the present invention, R x The following can be selected independently: A. Halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; or BF, Cl, Br, OCF2H, OCH3, or CN.

[0061] In one embodiment of each aspect of the present invention, R Z The following can be selected independently: A. Oxo, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; or B. Oxo, F, Cl, Br, OCF2H, OCH3, or CN.

[0062] In one embodiment of each aspect of the present invention, R Y The following can be selected independently: A. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN and cyclopropyl; or B. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, and cyclopropyl; or C. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; or D. Hydrogen, methyl, trifluoromethyl, and methoxy; or E. Hydrogen.

[0063] Accordingly, the present invention relates to substituents R1, R as defined above. 2a , R 2b This makes available compounds of formula I having R3, Q, A1, A2, A3, A4, and A5 in all combinations / permutations. Thus, for example, A1, A2, and A3 are in the first embodiment (i.e., A1, A2, and A3 are independent of each other, N or CR). Y And, here, R Y This is Embodiment D (i.e., R Y (is independently selected from hydrogen, methyl, trifluoromethyl, and methoxy); A4 and A5 are Embodiment B (i.e., A4 is CR Y And A5 is CH, where R Y This is Embodiment B (i.e., R Y (i.e., hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen or cyclopropyl); R1 is of Embodiment B (i.e., hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonyl C1-C6 alkyl, hydroxycarbonyl C1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilane C1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, benzyloxycarbonyl or benzyl); R 2aEmbodiment L (i.e., halogen, C1-C2 haloalkyl, C1-C2 haloalkylsulfanyl, C1-C2 haloalkylsulfonyl or C1-C2 haloalkoxy); R 2b R3 is of Embodiment B (i.e., halogen, C1-C3 haloalkyl or C1-C3 haloalkoxy); R3 is of Embodiment B (i.e., hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl; C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkyl sulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy, or CN, which may be optionally substituted with one or two substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl); Q is of Embodiment A (i.e., Q is Q a And here, Q a This is Embodiment B (i.e., Q a Q a -1, Q a -6, Q a -7, Q a -10 and Q a It is possible that it is selected from -15; and R 4 Compounds of formula I are available in embodiment G (i.e., pyridine or pyrimidine, where pyridine or pyrimidine may be optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy).

[0064] In one embodiment, the compound of formula I is of formula Iaa, Iab, or Iac (where the asterisk indicates a stereocenter), and in the formula R1, R 2a , R 2b R3 is as defined in the first embodiment, and Q1 corresponds to Q as defined in the first embodiment, with each being the corresponding embodiment as described above. [ka]

[0065] In one embodiment, compounds having the preferred stereochemistry described in formula I'a may also be preferred for compounds of formulas Iaa, Iab, and Iac. In a preferred embodiment, a compound of formula Iab having the following stereochemistry: [ka] (In the formula, R1, R 2a , R 2b (where R3 and Q1 are as defined in the first embodiment), as well as stereoisomers, enantiomers, tautomers and N-oxides of the compound of formula (I'ab), and phytochemically acceptable salts thereof are preferred.

[0066] In one embodiment, Q1 is AQ aa ~Q ag and Q ba ~Q bf Selected from; or BQ aa ~Q ag Selected from; or CQ ba ~Q bf Selected from; or DQ aa Q ab Q ac Q af Q ag Q ba Q bb Q bc Q bd Q be and Q bf Selected from; or EQ aa Q ab Q ac Q af Q af Q ba Q bb and Q bf Selected from; or FQ aa Q ab Q ac Qaf Q ba Q bb and Q bf Selected from. [ka]

[0067] In one embodiment of each aspect of the present invention, the compound of formula I is A1, A2, and A3, independently of each other, N or CR. Y (Here, R Y (is hydrogen, methyl, trifluoromethyl, and methoxy); A4 has N or CH, and A5 has CH; R1 has hydrogen, methyl, propargyl, or cyclopropylmethyl; R 2a As such, cyclopropyl substituted with 1-2 substituents independently selected from hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, halogen, methyl and trifluoromethyl, cyclopropylcarbonyl, oxo, cyclopropylmethyl substituted with 1-2 substituents independently selected from halogen and trifluoromethyl, or C substituted with 1-3 halogens 1- C2 alkylsulfanyl, or C substituted with 1 to 3 halogens 1- Having C2 alkylsulfonyl; R 2b As, it has hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl; C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 haloalkyl sulfanyl, C1-C3 haloalkyl sulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN, which may be optionally substituted with 1-2 substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl; as R3, it has methyl; and as Q, Q a -1~Q a -16 and Q b -1~Q b -13 is selected, and here R4(Q a -1~Q aJ-13 may be optionally substituted with C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; J-13 may be optionally substituted with C1-C3 haloalkyl; J-20 may be optionally substituted with C1-C3 haloalkyl; and R 4a (Q b -1~Q b (Regarding -13) is pyridine or pyrimidine, where pyridine or pyrimidine may be optionally substituted with one substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy, and Y-1-Y-4 (where R' 4a , R' 4b and R' 4c These are selected independently of each other and independently of Y-1 to Y-4 from hydrogen, halogen, CN, C1 to C3 alkyl, C1 to C3 haloalkyl, C3 to C4 cycloalkyl, C1 to C3 alkoxy, and C1 to C3 haloalkoxy.

[0068] In one embodiment of each aspect of the present invention, the compound of formula I is represented by formula Iaa, Iab or Iac, and has hydrogen, methyl, propargyl or cyclopropyl-methyl as R1; R 2aAs such, cyclopropyl substituted with 1-2 substituents independently selected from hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, halogen, methyl and trifluoromethyl, cyclopropylcarbonyl, oxo, cyclopropylmethyl substituted with 1-2 substituents independently selected from halogen and trifluoromethyl, or C substituted with 1-3 halogens 1- C2 alkylsulfanyl, or C substituted with 1 to 3 halogens 1- Having C2 alkylsulfonyl; R 2b As, it has hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl; C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 haloalkyl sulfanyl, C1-C3 haloalkyl sulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN, which may be optionally substituted with 1-2 substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl; as R3, it has methyl; and as Q, Q a -1~Q a -16 and Q b -1~Q b -13 is selected, and here R4(Q a -1~Q a J-13 may be optionally substituted with C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; J-13 may be optionally substituted with C1-C3 haloalkyl; J-20 may be optionally substituted with C1-C3 haloalkyl, and J-20 may be optionally substituted with 1H-tetrazole-5-yl; and R 4a (Q b-1~Q b (Regarding -13) is pyridine or pyrimidine, where pyridine or pyrimidine may be optionally substituted with one substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy, and Y-1-Y-4 (where R' 4a , R' 4b and R' 4c These are selected independently of each other and independently of Y-1 to Y-4 from hydrogen, halogen, CN, C1 to C3 alkyl, C1 to C3 haloalkyl, C3 to C4 cycloalkyl, C1 to C3 alkoxy, and C1 to C3 haloalkoxy.

[0069] In one embodiment of each aspect of the present invention, the compound of formula I is represented by formula Iaa, Iab, or Iac, and R1 has hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It has a halogen, a C1-C3 haloalkyl, a C1-C3 haloalkylsulfanyl, a C1-C3 haloalkylsulfonyl, or a C1-C3 haloalkoxy; R 2b It has a halogen, a C1-C3 haloalkyl, a C1-C3 haloalkylsulfanyl, a C1-C3 haloalkylsulfonyl, or a C1-C3 haloalkoxy as R3; and as Q, Q a -1~Q a -16 and Q b -1~Q b -13 is selected, and here R4(Q a -1~Q aJ-13 may be optionally substituted with C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; J-13 may be optionally substituted with C1-C3 haloalkyl; J-20 may be optionally substituted with C1-C3 haloalkyl, and J-20 may be optionally substituted with 1H-tetrazole-5-yl; and R 4a (Q b -1~Q b (Regarding -13) is pyridine or pyrimidine, where pyridine or pyrimidine may be optionally substituted with one substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy, and Y-1-Y-4 (where R' 4a , R' 4b and R' 4c These are selected independently of each other and independently of Y-1 to Y-4 from hydrogen, halogen, CN, C1 to C3 alkyl, C1 to C3 haloalkyl, C3 to C4 cycloalkyl, C1 to C3 alkoxy, and C1 to C3 haloalkoxy.

[0070] In one embodiment of each aspect of the present invention, the compound of formula I is represented by formula Iaa, Iab, or Iac, and R1 has hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It has a halogen, a C1-C3 haloalkyl, a C1-C3 haloalkylsulfanyl, a C1-C3 haloalkylsulfonyl, or a C1-C3 haloalkoxy; R 2b It has a halogen, a C1-C3 haloalkyl, a C1-C3 haloalkylsulfanyl, a C1-C3 haloalkylsulfonyl, or a C1-C3 haloalkoxy as R3; and as Q, Q a-1~Q a -16 and Q b -1~Q b -13 is selected, and here R4(Q a -1~Q a J-13 may be optionally substituted with C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; J-13 may be optionally substituted with C1-C3 haloalkyl; J-20 may be optionally substituted with C1-C3 haloalkyl, and J-20 may be optionally substituted with 1H-tetrazole-5-yl; and R 4a (Q b -1~Q b (Regarding -13) is pyridine or pyrimidine, where pyridine or pyrimidine may be optionally substituted with one substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy, and Y-1-Y-4 (where R' 4a , R' 4b and R' 4c (Each of these is hydrogen) and is selected from.

[0071] In one embodiment of each aspect of the present invention, the compound of formula I is represented by formula Iaa, Iab, or Iac, and R1 has hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a As such, it has halogens, C1-C2 haloalkyls, C1-C2 haloalkylsulfanyls, C1-C2 haloalkylsulfonyls, or C1-C2 haloalkoxys; R 2b It has a halogen, a C1-C2 haloalkyl, a C1-C2 haloalkylsulfanyl, a C1-C2 haloalkylsulfonyl, or a C1-C2 haloalkoxy as R3; and as Q, Qa -1~Q a -16 and Q b -1~Q b -13 is selected, and here R4(Q a -1~Q a J-13 may be optionally substituted with C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; J-13 may be optionally substituted with C1-C3 haloalkyl; J-20 may be optionally substituted with C1-C3 haloalkyl, and J-20 may be optionally substituted with 1H-tetrazole-5-yl; and R 4a (Q b -1~Q b (Regarding -13) is pyridine or pyrimidine, where pyridine or pyrimidine may be optionally substituted with one substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy, and Y-1-Y-4 (where R' 4a , R' 4b and R' 4c (Each of these is hydrogen) and is selected from.

[0072] In one embodiment of each aspect of the present invention, the compound of formula I is represented by formula Iaa, Iab, or Iac, and R1 has hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a As such, it has halogens, C1-C2 haloalkyls, C1-C2 haloalkylsulfanyls, C1-C2 haloalkylsulfonyls, or C1-C2 haloalkoxys; R 2bIt has a halogen, a C1-C2 haloalkyl, a C1-C2 haloalkylsulfanyl, a C1-C2 haloalkylsulfonyl, or a C1-C2 haloalkoxy as R3; and as Q, Q a -1 or Q b Selected from -1, where R4(Q a J-13 may be optionally substituted with C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; J-13 may be optionally substituted with C1-C3 haloalkyl; J-20 may be optionally substituted with C1-C3 haloalkyl, and J-20 may be optionally substituted with 1H-tetrazole-5-yl; and R 4a (Q b (Regarding -1) is pyridine or pyrimidine, where the pyridine or pyrimidine may be optionally substituted with one substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy, and Y-1-Y-4 (where R' 4a , R' 4b and R' 4c (Each of these is hydrogen) and is selected from.

[0073] In one embodiment of each aspect of the present invention, the compound of formula I is represented by formula Iaa, Iab, or Iac, and R1 has hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It contains chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, or trifluoromethylsulfonyl; R 2bIt has chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, and trifluoromethylsulfonyl as R3; and as Q, Q a -1 or Q b Selected from -1, where R4(Q a J-13 may be optionally substituted with C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halo, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkyl, C1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-; J-13 may be optionally substituted with C1-C3 haloalkyl; J-20 may be optionally substituted with C1-C3 haloalkyl, and J-20 may be optionally substituted with 1H-tetrazole-5-yl; and R 4a (Q b (Regarding -1) is pyridine or pyrimidine, where the pyridine or pyrimidine may be optionally substituted with one substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy, and Y-1-Y-4 (where R' 4a , R' 4b and R' 4c (Each of these is hydrogen) and is selected from.

[0074] In one embodiment of each aspect of the present invention, the compound of formula I is represented by formula Iaa, Iab, or Iac, and R1 has hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It contains chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, or trifluoromethylsulfonyl; R 2bIt has chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, and trifluoromethylsulfonyl as R3; and as Q, Q a -1 or Q b Selected from -1, where R4(Q a (Regarding -1) is pyridine or pyrimidine, where pyridine or pyrimidine may be optionally substituted with one substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy; and R 4a (Q b Y-1 to Y-4 (where R' 4a , R' 4b and R' 4c (Each of these is hydrogen) and is selected from.

[0075] In one embodiment of each aspect of the present invention, the compound of formula I is represented by formula Iaa, Iab, or Iac, and R1 has hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It contains chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, or trifluoromethylsulfonyl; R 2b It has chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, and trifluoromethylsulfonyl as R3; and as Q, Q a -1 or Q b Selected from -1, where R4(Q a-1) is 5-cyclopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5-difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cyclopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2-trifluoroethoxy)-pyrimidine or pyrimidine; and, R 4a (Q b Regarding -1), these are 5-cyclopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5-difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cyclopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2-trifluoroethoxy)-pyrimidine, pyrimidine, or 1,2,3-triazole.

[0076] In one embodiment of each aspect of the present invention, the compound of formula I is represented by formula Iab or I'ab, which has as R1 embodiment H (preferably hydrogen, methyl, propargyl, or cyclopropyl-methyl); R 2a Embodiment N (preferably trifluoromethyl, fluorine, chlorine, or bromine); R 2b Embodiment F has (preferably fluorine, chlorine, or trifluoromethyl); R3 has methyl; and Q1 has Q aa ~Q ag and Q ba ~Q bf (Preferably, Q aaQ ab Q ac Q af Q ba Q bb and Q bf (Selected from) Selected from.

[0077] 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 auxiliary agents and diluents, and optionally one or more other active ingredients.

[0078] In a third aspect, the present invention makes available a method for controlling and eliminating insects, mites, nematodes, or mollusks, which comprises the step of applying an insecticidal, acaricidal, nematodetic, or molluscicidal amount of the compound defined in the first aspect or the composition defined in the second aspect to a pest, a pest habitat, or a plant susceptible to attack by the pest.

[0079] In a fourth aspect, the present invention makes available a method for protecting plant propagation material from attacks by insects, mites, nematodes, or mollusks, which includes the step of treating the propagation material or the location 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.

[0080] In a fifth aspect, the present invention makes available plant propagation material such as seeds that contains, is treated with, or is attached to a compound of formula I as defined in the first aspect or a composition as defined in the second aspect.

[0081] In a further embodiment, the present invention provides a method for controlling parasites in or on an animal in need thereof, comprising the step of administering an effective amount of a compound of formula I as defined in the first embodiment. The present invention further provides a method for controlling ectoparasites on an animal in need thereof, comprising the step of administering an effective amount of a compound of formula I as defined in the first embodiment. The present invention further provides a method for preventing and / or treating diseases transmitted by ectoparasites, comprising the step of administering an effective amount of a compound of formula I as defined in the first embodiment to an animal in need thereof.

[0082] Compounds of formula I can be prepared by those skilled in the art by following known methods. More specifically, compounds and intermediates of formulas I and I'a can therefore be prepared as described below in the scheme and examples. Specific stereodiene centers are left unspecified for the sake of brevity and are not intended in any way to limit the teachings provided by the scheme.

[0083] The process for preparing the compound of formula I according to the present invention is carried out by methods known to those skilled in the art.

[0084] Compounds of formula I can be formed, for example, as shown in scheme 1.

[0085] Scheme 1: [ka] The reaction of a compound of formula II (wherein X1 is a leaving group such as a halogen or sulfonate, such as a chloride) with a compound of formula III yields a compound of formula I (wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3 and Q have the same meanings as those given above for the compound of formula I). ​​This reaction can be carried out without a solvent or in a solvent, preferably in an organic solvent such as acetonitrile, within a temperature range of -100 to +300°C, preferably around ambient temperature of ~200°C, in the absence or presence of a catalyst such as a metal catalyst such as a palladium complex, and with or without the addition of a base such as an inorganic base such as potassium carbonate or an organic base such as triethylamine. The compounds of formula II are known or can be prepared by methods known to those skilled in the art.

[0086] Scheme 2: [ka] Compounds of formula III can be formed, for example, as shown in scheme 2. Compounds of formula III are obtained by treating a compound of formula V with an amine of formula XIX (wherein X2 is a leaving group such as a halogen or sulfonate, such as bromide). This reaction can be carried out without a solvent or in a solvent, preferably in an organic solvent such as acetonitrile, at a temperature range of -100 to +300°C, preferably around ambient temperature of ~200°C, with or without the addition of an inorganic base such as potassium carbonate or an organic base such as triethylamine. Alternatively, treatment of a compound of formula VII with an amine of formula XIX yields a compound of formula III. This reaction can be carried out in the presence or absence of an acid such as a Lewis acid such as acetic acid or zinc bromide, in a solvent such as methanol, or without a solvent, with or without a catalyst such as a hydrogenation catalyst such as palladium carbon, in or without an acid such as methanol, or in the presence or absence of an acid such as methanol. This reaction can be carried out in a temperature range of -100 to +300°C, preferably at ambient temperature ~200°C. Methods for the alkylation and reductive alkylation of amines, and the conditions for carrying them out, are well known to those skilled in the art. The amines of formula XIX are known or can be prepared by methods known to those skilled in the art.

[0087] Scheme 3: [ka] Alternatively, the compound of formula I can be formed, for example, as shown in Scheme 3. The reaction of the amine of formula IV with the compound of formula V (wherein X2 is a leaving group such as a halogen or sulfonate, such as bromide) yields the compound of formula I (wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3 and Q have the same meanings as those above for the compound of formula I). ​​This reaction can be carried out without a solvent or in a solvent, preferably in a solvent such as an organic solvent such as acetonitrile, within a temperature range of -100 to +300°C, preferably around ambient temperature of ~200°C, with or without the addition of a base such as an inorganic base such as potassium carbonate or an organic base such as triethylamine. Such methods for alkylating amines and the conditions for carrying them out are well known to those skilled in the art. Alternatively, the reaction of an amine of formula IVa with a compound of formula VII yields a compound of formula I (wherein R1 is H, and A1, A2, A3, A4, A5, R2a, R2b, R3, and Q have the same meanings as those given above for the compound of formula I). ​​This reaction is carried out in the presence or absence of a reducing agent, such as hydrogen or a hydride such as sodium borohydride, with or without a catalyst, such as a hydrogenation catalyst such as palladium carbon, with or without an acid, such as a Lewis acid such as acetic acid or zinc bromide, in or without a solvent, such as methanol. This reaction can be carried out in a temperature range of -100 to +300°C, preferably at ambient temperature ~200°C. Such methods for the reductive alkylation of amines and the set of conditions for carrying them out are well known to those skilled in the art.

[0088] Scheme 4: [ka] Compounds of formula V can be formed, for example, as shown in Scheme 4. Treatment of a compound of formula VIII with a halogenating agent such as chlorine, bromine, or N-bromosuccinimide yields a compound of formula V (wherein the leaving group Q is a halogen such as chloride or bromide). This reaction is carried out with or without a solvent, preferably with or without additives such as a radical initiator such as benzoyl peroxide or azoisobutyronitrile in the solvent. This reaction can be carried out with or without exposure to visible or UV light, and can be carried out in a temperature range of -100 to +300°C, preferably at ambient temperature ~200°C. Alternatively, a compound of formula VII can be treated with a reducing agent, followed by a reaction with a sulfonyl chloride such as methanesulfonyl chloride to yield a compound of formula V (wherein the leaving group Q is a sulfonate such as mesylate). This reaction can be carried out in or without a solvent, in the presence or absence of a base, such as an inorganic base like potassium carbonate or an organic base like an amine base like trimethylamine, and can be carried out within a temperature range of -100 to +300°C, preferably at ambient temperature of ~200°C. Suitable reducing agents can be hydrogen or hydrides such as sodium borohydride, in or without a catalyst, such as a hydrogenation catalyst like palladium-carbon, in or without an acid, such as a Lewis acid like acetic acid or zinc bromide, in a solvent like methanol, or without a solvent. This reaction can be carried out within a temperature range of -100 to +300°C, preferably at ambient temperature of ~200°C. Such methods for halogenation, reduction of carbonyl compounds, and sulfonylation of alcohols, as well as the conditions for carrying them out, are well known to those skilled in the art. The amines of formula VII and the compounds of formula VIII are known or can be prepared by methods known to those skilled in the art.

[0089] Scheme 5: [ka] Alternatively, compounds of formula I in which R1 is different from H can be formed, for example, as shown in Scheme 5. Compounds of formula Ia can be treated with compounds of formula VI (wherein X3 is a leaving group such as a halogen or sulfonate, such as a chloride, bromide, iodide, or mesylate) to yield compounds of formula I (wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3, and Q have the same meanings as those above for compounds of formula I). ​​This reaction can be carried out without a solvent or in a solvent, preferably in a solvent such as an organic solvent such as acetonitrile, within a temperature range of -100 to +300°C, preferably around ambient temperature of ~200°C, with or without the addition of a base such as an inorganic base such as potassium carbonate or an organic base such as triethylamine. Such methods for alkylating amines and the conditions for carrying them out are well known to those skilled in the art.

[0090] Scheme 6: [ka] The compound of formula Ib can be formed, for example, as shown in scheme 6. The reaction of the compound of formula II (wherein X1 is a leaving group such as a halogen or sulfonate, such as a chloride) with the compound of formula IX yields the compound of formula X. This reaction can be carried out without a solvent or in a solvent, preferably in an organic solvent such as acetonitrile or N,N-dimethylformamide, in a temperature range of -100 to +300°C, preferably around ambient temperature of ~200°C, in the absence or presence of a catalyst such as a metal catalyst such as a palladium complex, and with or without the addition of a base such as an inorganic base such as potassium carbonate or an organic base such as triethylamine. Subsequent treatment of compound X with a known compound XIII yields the compound of formula XI. This reaction can be carried out without a solvent or in a solvent, preferably in a solvent such as an organic solvent such as dichloromethane, within a temperature range of -100 to +300°C, preferably at an ambient temperature of ~100°C or ~50°C, without a base, or in the presence of a base such as an inorganic base such as potassium carbonate or an organic base such as triethylamine. Further reaction of compound XI with hydrazine XII yields the compound of formula Ib (wherein A1, A2, A3, A4, A5, R2a, R2b, R3 and R4 have the same meanings as those described above for the compound of formula I). ​​This reaction can be carried out without a solvent or in a solvent, preferably in a solvent such as an organic solvent such as 1,4-dioxane, acetic acid, or a mixture of 1,4-dioxane and acetic acid, within a temperature range of -100 to +300°C, preferably at an ambient temperature of ~200°C or ~80°C. In this conversion sequence, the intermediate compounds of formulas X and XI can be used as crude products for subsequent steps, or they can be purified, for example by chromatography, and used in the purified form for the next conversion.

[0091] Scheme 7: [ka] Compounds of formula Ic can be formed, for example, as shown in Scheme 7. The reaction of a compound of formula XVII with an amine of formula XIX yields a compound of formula XVI. This reaction is carried out in the presence or absence of a reducing agent, such as hydrogen or a hydride such as sodium borohydride, with or without a catalyst, such as a hydrogenation catalyst such as palladium carbon, with or without an acid, such as a Lewis acid such as acetic acid or zinc bromide, in or without a solvent, such as methanol. This reaction can be carried out in a temperature range of -100 to +300°C, preferably at ambient temperature ~200°C. Such methods for the reductive alkylation of amines and the set of conditions for carrying them out are well known to those skilled in the art. The subsequent reaction of the intermediate of formula XVI with a compound of formula II yields a compound of formula XIV. This reaction can be carried out without a solvent or in a solvent, preferably in an organic solvent such as acetonitrile, within a temperature range of -100 to +300°C, preferably around ambient temperature of ~200°C, in the absence or presence of a catalyst such as a metal catalyst such as a palladium complex, and with or without the addition of a base such as an inorganic base such as potassium carbonate or an organic base such as triethylamine. Subsequently, the intermediate of formula XIV is reacted with the compound of formula XV to yield the compound of formula Ic (wherein A1, A2, A3, A4, A5, R2a, R2b, R1, R3 and R4 have the same meanings as those described above for the compound of formula I, and M1 in R4-M1 is, for example, a metal such as lithium, or -MgCl, -ZnBr, or -B(OH)2; or R4-M1 represents a boronic acid ester such as pinacol ester of boronic acid, or a stanan such as R4-Sn(n-Bu)3). Such transformations are known to those skilled in the art as Suzuki-, Kumada-, Negishi-, or Still-coupling reactions, respectively. These reactions are carried out in a temperature range of -100 to +300°C, preferably at ambient temperature of ~200°C, in the presence of a catalyst, such as a metal catalyst like a palladium catalyst, and a ligand, such as a phosphine ligand, an N-heterocyclic carbene (NHC) ligand, or a phosphate ligand. The reaction can be carried out in or without the presence of an additional metal catalyst, such as a copper salt like CuI.This reaction can be carried out with or without an inorganic base such as potassium carbonate, sodium hydroxide, or cesium carbonate, or an organic base such as an amine base such as triethylamine. The reaction is preferably carried out in a solvent, with or without. If the reaction mixture is heated, the reaction can be carried out by conventional heating, such as under microwave irradiation or by heating the reaction vessel in an oil bath. By an alternative route, compound XVII can be reacted with the compound of formula XV to yield intermediate XVIII. This reaction is carried out under essentially the same set of conditions as described for the conversion of intermediate XIV to the compound of formula Ic. Intermediate XVIII is then reacted with amine IV to yield the compound of formula Ic (wherein R1 is hydrogen, and A1, A2, A3, A4, A5, R2a, R2b, R3, and R4 have the same meanings as described above for the compound of formula I). This reaction is essentially carried out under the same conditions as described above for the conversion of compound XVII to intermediate XVI, in the presence of a reducing agent. Furthermore, another route allows the intermediate compound of formula XVIII to be reacted with the amine of formula XIX to yield the intermediate of formula IIIa. This reaction is essentially carried out under the same conditions as described above for the conversion of compound XVII to intermediate XVI, in the presence of a reducing agent. Subsequently, the intermediate of formula IIIa reacts with the compound of formula II to yield the compound of formula Ic (wherein A1, A2, A3, A4, A5, R2a, R2b, R1, R3, and R4 have the same meanings as described above for the compound of formula I). ​​This reaction is essentially carried out under the same conditions as described above for the conversion of intermediate XVI to intermediate XIV. In these different sequences, the intermediate compounds of formulas XIV, XVI, XVIII, and IIIa can be used as crude products in each of the subsequent steps, or they can be purified, for example by chromatography, and used in the purified form for the next conversion. The compounds of formula XVII are known, or they can be prepared by methods known to those skilled in the art.

[0092] Compounds of formula Id [ka] This is the amine of formula IIIb. [ka] (wherein R1, R3, R4a, R5a, and R5b are as described in Formula I) and the compound of Formula II [ka] It can be prepared by reaction with (wherein A1, A2, A3, A4, A5, R2a and R2b are as described in Formula I, and X1 is a leaving group such as a halogen such as a chloride or a sulfonate).

[0093] Chemistry will be described in more detail in Scheme 8.

[0094] Scheme 8: [ka] The reaction of a compound of formula II (wherein X1 is a leaving group such as a halogen or sulfonate, such as a chloride) with a compound of formula IIIb yields a compound of formula Id (wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3, R4a, R5a, and R5b have the same meanings as those described above for the compound of formula I). ​​This reaction can be carried out without a solvent or in a solvent, preferably in an organic solvent such as acetonitrile, within a temperature range of -100 to +300°C, preferably around ambient temperature of ~200°C, in the absence or presence of a catalyst such as a metal catalyst such as a palladium complex, and with or without the addition of a base such as an inorganic base such as potassium carbonate or an organic base such as triethylamine.

[0095] The formation of the compound of formula IIIb is shown in Scheme 9. The compound of formula IIIb is formed at room temperature in a suitable solvent, preferably in acetic acid, as in International Publication No. 2002 / 088073, page 35, by the compound of formula XX (wherein R1 is as defined in formula I) and the compound of formula IIIc (wherein R3, R 4a , R 5a and R 5b It can be prepared by the treatment described in Formula I. Alternatively, other reagent systems for reductive amination use a combination of Ti(i-OiPr)4 and NaBH4 (see Synthesis 2003(14), 2206).

[0096] The amine of formula IIIc is obtained by biocatalytic deracemization of the amine of formula IIId. This can be carried out, for example, using a lipase, such as Candida Antarctica lipase B or Pseudomonas fluorescens lipase in its final immobilized form (e.g., Novozym® 435), in the presence of an acyl donor, such as ethyl methoxy or vinyl acetate, in a suitable solvent such as acetonitrile or methyl tert-butyl ether, at a temperature of 20°C to 100°C. Such processes are described, for example, in J. Org. Chem. 2007, 72, 6918-6923 or Adv. Synth. Catal. 2007, 349, 1481-1488. The predicted stereochemical results of such enzymatic deracemization are known to those skilled in the art and have been demonstrated, for example, in literature such as J.Org.Chem.1991,56,2656-2665 or J.Am.Chem.Soc.2015,137,3996-4009.

[0097] Scheme 9: [ka] In an alternative process, the compound of formula IIIc is the compound of formula XXII (wherein R3, R 4a , R 5aand R 5b (As shown in Equation I), it can be obtained according to the synthesis described in Scheme 10.

[0098] Scheme 10: [ka] The amine in formula IIIc is the intermediate in formula XXII (wherein R3, R 4a , R 5a and R 5b The intermediate can be obtained from the alcohol of formula XXI (wherein Z3 is NPhth or NBoc2, and Z3 is NPhth or NBoc2). Such intermediates can be obtained from the alcohol of formula XXI by the Mitsunobu reaction, which involves treating the alcohol of formula XXI with diisopropyl azodicarboxylate in the presence of a phosphine such as triphenylphosphine or tributylphosphine, and an amine such as phthalimide or bis(tert-butoxycarbonyl)amine. The Mitsunobu reaction is known to those skilled in the art to promote stereocenter inversion, as described, for example, in Chem. Rev. 2009, 109, 2551-2651. The amine of formula XXII can then be converted to the amine of formula IIIc by treatment with hydrazine if Z3=NPhth, or by treatment with an acid such as trifluoroacetic acid if Z3=NBoc2.

[0099] Alternatively, the amine of formula IIIc can be converted to the azide of formula XXIII (where R3, R3, R3) by treatment with triphenylphosphine and water (Staudinger reaction), or by hydrogenation using a palladium catalyst in the presence of hydrogen, for example. 4a , and R 4b The azide of formula XXIII is obtained by reduction of the alcohol of formula XXI (where R3, R3, R3) in a solvent such as toluene or THF, in the presence of a base such as DBU, using an azidating reagent such as diphenylphosphoryl azide. 4a , and R 4bThis is obtained by the process described in Equation I. Such a process is known to those skilled in the art to involve the inversion of the stereocenter and is described in literature such as, for example, Adv.Synth.Catal.2018,360,2157-2165.

[0100] The alcohol in formula XXI is the ketone in formula XXIV (wherein R3, 4a , R 5a and R 5b It can be obtained by the enantioselective reduction of (as shown in Formula I). ​​Such reduction can be carried out with a chiral ligand such as RuCl[(R,R)-TsDPEN](mesitylene) or RuBF4[(R,R)-TsDPEN](p-cymene), in the presence of a hydrogen donating system such as HCOOH / Et3N or HCO2NH4, and using a catalyst such as ruthenium or rhodium. Such processes are described in literature such as J.Org.Chem.2017,82,5607.

[0101] Alternatively, the compound of formula IIIc may also be prepared as described in scheme 11.

[0102] Scheme 11: [ka] The amine of formula IIIc is, for example, the amine of formula XXV (wherein R3, R) obtained by using an acid such as trifluoroacetic acid or hydrochloric acid. 4a , R 5a and R 5b The amine of formula XXV can be prepared by deprotection of the diamine of formula XXVII (wherein R is as shown in formula I). 5a and R 5b The diketone of formula XXVI (wherein R3 and R are as shown in formula I) 4aThe diketone of formula XXVI can be obtained by condensation to the hydroxyketone of formula XXVII (wherein R3 and R3 are as shown in formula I). ​​This condensation can be carried out in the presence of a suitable solvent such as ethanol or isopropanol, and an oxidizing agent such as air or DDQ. The diketone of formula XXVI can be obtained by condensation to the hydroxyketone of formula XXVII (wherein R3 and R3 are as shown in formula I). 4a It can be formed by oxidation of the aldehyde (as shown in formula I). ​​This oxidation can be carried out, for example, by SO3-pyridine in the presence of DMSO and a base such as triethylamine, or alternatively, by sodium hypochlorite in the presence of a catalyst such as TEMPO / Bu4NHSO4. Examples of such oxidation can be found in literature such as Synlett, 2014, 25, 596, or J.Am.Chem.Soc. 1990, 112, 5290-5313. The hydroxyketone of formula XXVII is formed by oxidation of the aldehyde of formula XXIX (wherein R is shown in the formula). 4a The cross-benzoin condensation can be performed between the aldehyde of formula XXVIII (wherein R3 is as described in formula I) and the aldehyde of formula XXVIII (wherein R3 is as described in formula I). ​​The aldehyde of formula XXVIII is commercially available in chiral form, such as Boc-L-alaninal (CAS 79069-50-4) or t-butyl N-[(1S)-1-(cyclopropylmethyl)-2-oxo-ethyl]carbamate (CAS 881902-36-9). The cross-benzoin condensation is carried out by conventional methods using an organocatalyst such as a triazolium salt or thiazolium salt in a suitable solvent such as DCM or THF, at a temperature of -20°C to the boiling point of the solvent, in the presence of a base such as potassium t-butoxide or isopropyldiethylamine. Examples of catalysts involved in such transformations are described in literature such as J.Am.Chem.Soc.2014,136,7539-7542, or Org.Lett.2016,18,4518-4521.

[0103] Scheme 12: [ka] As shown in Scheme 12, the compound of formula Id is alternatively the compound of formula XXX (wherein A1, A2, A3, A4, A5, R1, R) in the presence of the palladium catalyst detailed in Scheme 7. 2a , R 2b , R3, R 5a and R 5b This is as defined in Equation I, and also, X 07 It can be prepared by the reaction of a leaving group (such as chlorine, bromine, or iodine) with a compound of formula XXXI (Still reaction) or a compound of formula XXXII (Suzuki-Miyaura reaction).

[0104] The compound of formula XXX is the amine of formula XXXIII and the compound of formula II (wherein A1, A2, A3, A4, A5, R) under the conditions detailed in Scheme 1. 2a , R 2b The compounds can be prepared by coupling (X1 is described in Scheme 1). Under the same conditions, if R1=H, the compound of formula XXX can be obtained directly from the compound of formula XXXIV.

[0105] The compound of formula XXXIII can be prepared by treating the compound of formula XXXIV with the compound of formula XXXV (wherein R1 is as defined in formula I) at room temperature in a suitable solvent, preferably in acetic acid, as described in International Publication No. 2002 / 088073, page 35, in the presence of, for example, NaBH(OAc)3 or NaBH3CN. Alternatively, other reagent systems for reductive amination use a combination of Ti(i-OiPr)4 and NaBH4 (see Synthesis 2003(14), 2206).

[0106] The amine of formula XXXIV can be prepared by deracemization methods, for example, involving the selective acylation of one enantiomer. Such examples are described in more detail in Scheme 13.

[0107] Scheme 13: [ka] The amine of formula XXXIV is the amine of formula XXXIVa (wherein R3, R 5a and R 5b The result is as shown in Equation 1, and also, X 07 It can be obtained by biocatalyzed deracemization of a leaving group (such as bromine, chlorine, or iodine). This can be carried out, for example, using a lipase in its final immobilized form (e.g., Novozym® 435), such as Candida Antarctica lipase B or Pseudomonas fluorescens lipase, in the presence of an acyl donor, such as ethyl methoxy or vinyl acetate, in a suitable solvent such as acetonitrile or methyl tert-butyl ether, at a temperature of 20°C to 100°C. Such processes are described, for example, in J. Org. Chem. 2007, 72, 6918-6923, or Adv. Synth. Catal. 2007, 349, 1481-1488. The predicted stereochemical results of such enzymatic deracemization are known to those skilled in the art and have been demonstrated, for example, in literature such as J.Org.Chem.1991,56,2656-2665 or J.Am.Chem.Soc.2015,137,3996-4009.

[0108] Alternatively, the resolution of the amine of formula XXXIVa, which yields the amine of formula XXXIV, can be achieved using an asymmetric auxiliary, as described in Scheme 14.

[0109] Scheme 14: [ka] The amine of formula XXXIV is an intermediate of formula XXXVII (wherein R3, R 5a and R 5b The compound is as shown in formula 1, and X 07 X is a leaving group such as bromine, chlorine or iodine, and X 12 *Since ( is an asymmetric auxiliary group), it can be prepared by treatment with an acid such as HCl or a base such as NaOH. The asymmetric auxiliary group of formula LII is, for example, mandelic acid or chloroformic acid (1R)-menthyl. The intermediate of formula XXXVII can be formed by coupling the asymmetric auxiliary group of formula XXXVI (wherein X0 is a leaving group such as chlorine) with the amine of formula XXXIVa, according to the conditions detailed in Scheme 1. Examples of such deracemization processes have been reported in literature such as J.Org.Chem.2007,72,485-493.

[0110] Alternatively, the amine of formula XXXIV can be formed as described in scheme 15.

[0111] Scheme 15: [ka] Alternatively, the amine of formula XXXIV is an intermediate of formula XXIIa (wherein R3, R 5a and R 5b As shown in Equation I, X 07 R is a leaving group such as a halogen or sulfonate, such as bromide, and Z3 is NPhth or NBoc2). Such intermediates can be obtained from alcohols of formula XXIa (wherein R3, R 5a and R 5b This is as described in formula I, and also, X 07 Since ( is a leaving group), it can be obtained by the Mitsunobu reaction, in which the alcohol of formula XXIa is treated with diisopropyl azodicarboxylate in the presence of a phosphine such as triphenylphosphine or tributylphosphine, and an amine such as phthalimide or bis(tert-butoxycarbonyl)amine. The Mitsunobu reaction is known to those skilled in the art to promote stereocenter inversion, as described, for example, in Chem. Rev. 2009, 109, 2551-2651. The amine of formula LIII can then be converted to the amine of formula IId by treatment with hydrazine if Z3=NPhth, or by treatment with TFA if Z3=NBoc2.

[0112] Alternatively, the amine of formula XXXIV may be treated with triphenylphosphine and water (Staudinger reaction), or hydrogenated, for example, using a palladium catalyst in the presence of hydrogen, to produce the azide of formula XXIIIa (wherein R3, 5a and R 5b This is as described in formula I, and also, X 07 These can be obtained by reduction of a leaving group (such as a halogen or sulfonate), for example, bromide. The azide of formula XXIIIa can be obtained by treatment of the alcohol of formula XXIa with an azidating agent such as diphenyl phosphoryl azide in a solvent such as toluene or THF in the presence of a base such as DBU. Such processes are known to those skilled in the art to promote stereocenter inversion and are described in literature such as, for example, Adv.Synth.Catal.2018,360,2157-2165.

[0113] The alcohol of formula XXIa is the ketone of formula XXIVa (wherein R3, R 5a and R 5b This is as described in formula I, and also, X 07 These can be obtained by enantioselective reduction of a leaving group (such as a halogen or sulfonate), for example, bromide. Such reduction can be carried out with a chiral ligand such as RuCl[(R,R)-TsDPEN](mesitylene) or RuBF4[(R,R)-TsDPEN](p-cymene), in the presence of a hydrogen donating system such as HCOOH / Et3N or HCO2NH4, and using a catalyst such as ruthenium or rhodium. Such processes are described in literature such as J.Org.Chem.2017,82,5607.

[0114] Compound of formula II [ka] (wherein X1 is a leaving group such as a halogen or sulfonate, such as a chloride) can be formed as shown in schemes 16-18, for example.

[0115] Scheme 16: [ka] Compounds of formula IIa (wherein R2a, R2b, A4, and A5 are as described in formula I) can be prepared according to reaction scheme 16. Compounds of formula XLII are known or can be prepared by methods known to those skilled in the art. For example, as described in J.Org.Chem.2018,83,930, compounds of formula XLI can be obtained by reacting a compound of formula XL, for example, with an electrophilic iodinating reagent such as N-iodosuccinimide in a solvent such as hexafluoroisopropanol. Compounds of formula XLII can be obtained by cyanation of the compound of formula XLI with copper(I) cyanide at a temperature such as 100°C in a solvent such as DMF (similar method to that described in International Publication No. 2005 / 100298, page 44). Treatment of the compound of formula XLII with formic acid and sulfuric acid at a temperature of 80-100°C yields the compound of formula XLIII (similar to the method described in International Publication No. 2018 / 206539, page 80). The subsequent conversion to the compound of formula IIa is achieved by reflux, for example, with thionyl chloride, in the presence of a catalytic amount of N,N-dimethylformamide, according to methods known to those skilled in the art (similar to the method described in International Publication No. 2015 / 54572, page 263).

[0116] Scheme 17: [ka] The compound of formula IIb (wherein R2a, R2b, A4, and A5 are as described in formula I) can be prepared according to reaction scheme 17. The compound of formula XLII, prepared according to scheme 16, is reacted with chlorosulfonyl isocyanate, as described, for example, in Synth.Commun.1988,18,525, and then further reacted with water under reflux to obtain the intermediate of formula XLIV. The subsequent conversion of the intermediate of formula XLIV to the compound of formula IIa can optionally be achieved using a chlorinating agent such as POCl3 in the presence of a base such as N,N-diisopropylethylamine. These chlorination methods are well known to those skilled in the art.

[0117] Scheme 18: [ka] The compound of formula IIc (wherein R2a, R2b, A4, and A5 are as described in formula I) can be prepared according to reaction scheme 18 (similar to the method found in ChemCatChem 2017, 10, 965). Meldrumic acid is converted to compound XLV by reflux in trimethylorthoformate, and further converted to compound XLVI by adding aniline of formula XL in the same pot. Reflux of compound XLVI in diphenyl ether yields 4-hydroxyquinoline of formula XLVII. The compound of formula IIc is then obtained by chlorination of compound XLVII using a chlorinating reagent such as POCl3, which is well known to those skilled in the art.

[0118] Compounds of formula IVc [ka] This can be formed, for example, as shown in Scheme 19.

[0119] Scheme 19: [ka] The compound of formula IVc (wherein Z is H, C1-C3 alkyl, cyclopropyl, or CF3, and R2a, R2b, A4, and A5 are as described in formula I) can be prepared according to reaction scheme 20. The compound of formula XLII, prepared according to scheme 16, is reacted at a high temperature such as 180°C in the presence of the compound of formula XLVIII, as described, for example, in Eur.J.Med.Chem.2017, 141,446, to yield the amine of formula IVc.

[0120] Alternatively, compounds of formula Iab can be formed, for example, as shown in scheme 20.

[0121] Scheme 20: [ka] The compound of formula Iab (wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I) can be prepared according to scheme 21, similar to the method described in International Publication No. 2010 / 093419, page 225. The compound of formula XLII, prepared according to scheme 16, is treated with N,N-dimethylformamide dimethylacetal at a high temperature, preferably 90°C, to yield the formamidine product of formula XLVIII. The compound of formula Iab can be obtained by reaction with the amine of formula III at a high temperature, preferably 120°C, preferably in a suitable solvent such as acetic acid.

[0122] Compounds of formula If [ka] This can be formed, for example, as shown in Scheme 21.

[0123] Scheme 21: [ka] The compound of formula If (wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I) can be prepared according to scheme 21. The compound of formula Ie is obtained by the reaction of the compound of formula IIb, prepared as shown in scheme 17 using the method described in scheme 1, with the amine of formula III. As described in Heterocycles 1996, 43, 2607, the intermediate of formula LI is obtained by treating the compound of formula Ie under acidic conditions, preferably with acetic acid, and preferably at a high temperature of 70-80°C. Methylation of the compound of formula LI to obtain the compound of formula If can be achieved, as is well known to those skilled in the art, using an electrophilic methyl source such as dimethyl sulfate or methyl iodide in the presence of a base such as potassium carbonate or sodium hydride.

[0124] Compounds of formula Ig [ka] This can be formed, for example, as shown in Scheme 22.

[0125] Scheme 22: [ka] The compound of formula Ig (wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I) can be prepared according to scheme 22. The compound of formula XLII prepared in scheme 16 is treated with a diazotizing agent, preferably isoamylnitrile, in a diiodomethane solvent at a high temperature, preferably 80°C, as described in J.Org.Chem.1990,55,2543, to yield the intermediate of formula LX. Reduction of the compound of formula LX is achieved in a solvent such as toluene, preferably at a low temperature, preferably -78°C, in the presence of a selective reducing agent such as diisobutylammonium hydride (DIBALH), to yield the compound of formula LXI. Subsequent Sonogashira coupling in a solvent such as triethylamine, accompanied by trimethylsilylacetylene, in the presence of a suitable palladium catalyst and a copper catalyst, preferably bis(triphenylphosphine)palladium chloride and copper(I) iodide, yields the compound of formula LXII. The compound of formula LXIII is obtained by cyclization with ammonia in methanol. The method is similar to that described, for example, in Eur.J.Med.Chem.2016, 118, 170. Preferably, the N-oxide of formula LXIV is obtained by treatment of the compound of formula LXIII with an oxidizing agent such as 3-chloro-perbenzoic acid or hydrogen peroxide in a solvent such as dichloromethane. Such oxidation is well known to those skilled in the art. The compound of formula Ig is obtained by coupling the compound of formula LXIV with the amine of formula III in the presence of a suitable activator such as bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®), and optionally in the presence of a base such as N,N-diisopropylethylamine (similar to the method described in International Publication No. 2016 / 123627, page 87).

[0126] Compounds of formula IId [ka] (wherein X1 is a leaving group such as a halogen or sulfonate, such as a chloride) can be formed, for example, as shown in Scheme 23.

[0127] Scheme 23: [ka] The compound of formula IId (wherein R2a, R2b, A4, and A5 are as described in formula I) can be prepared according to scheme 23. The compound of formula XLI prepared in scheme 16 is treated with tributyl(1-ethoxyvinyl)tin, preferably with a palladium catalyst such as Pd(PPh3)4, at a high temperature, preferably 105°C, as described in European Patent No. 1782811, page 57, to yield the intermediate of formula LXV. Treatment of the compound of formula LXV with aqueous sodium nitrite in the presence of an acid such as hydrochloric acid or a sulfuric acid / acetic acid mixture, preferably at a low temperature of 0-5°C (similar to Bioorg. Med. Chem. Lett., 25, 919), yields the compound of formula LXVI. The compound of formula IId is then obtained by chlorination of the compound of formula LXVI, as is well known to those skilled in the art, using a chlorinating reagent such as POCl3, optionally in the presence of a base such as amine N,N-diisopropylethylamine.

[0128] Compounds of formula IIe [ka] (wherein X1 is a leaving group such as a halogen or sulfonate, such as a chloride) can be formed, for example, as shown in Scheme 24.

[0129] Scheme 24: [ka] The compound of formula IIe (wherein R2a, R2b, A4, and A5 are as described in formula I) can be prepared according to scheme 24. The compound of formula XL is heated with ethyl 2-cyano-3-ethoxyacrylate at a high temperature, preferably 140°C, as described in Tetrahedron Letters, 2015, 56, 5112, to yield the intermediate of formula LXVII. The compound of formula LXVIII is obtained by heating the compound of formula LXVII at a high temperature, preferably 260°C, in a solvent, preferably diphenyl ether or a diphenyl ether-biphenyl eutectic mixture (Dowtherm A®). The subsequent conversion to the compound of formula IIe is achieved by reflux, for example with thionyl chloride, in the presence of a catalytic amount of N,N-dimethylformamide, according to methods known to those skilled in the art (as in U.S. Patent Application Publication No. 2003 / 212276, page 15).

[0130] Compounds of formula Ih [ka] This can be formed, for example, as shown in Scheme 25.

[0131] Scheme 25: [ka] Compounds of formula Ih (wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I) can be prepared according to scheme 25. Compounds of formula XLII prepared in scheme 16 are treated with hydrogen peroxide as an aqueous solution or urea adduct in methanol-water solvent, preferably in the presence of a base such as potassium carbonate (as in International Publication 2011 / 4276, page 132) to yield intermediates of formula LXX. Compounds of formula LXX are obtained by treatment of compounds of formula LXX with aqueous sodium nitrite in the presence of an acid such as hydrochloric acid or a sulfuric acid / acetic acid mixture, preferably at a low temperature of 0-5°C (as in U.S. Patent Application Publication 2014 / 0275072, paragraph 133). Compound Ih can be obtained by coupling the compound of formula LXXI with the amine of formula III in the presence of a suitable activator such as (benzotriazole-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBoP®) and a base such as N,N-diisopropylethylamine (similar to the method described on page 55 of International Publication No. 2014 / 085528).

[0132] Compounds of formula Ii [ka] This can be formed, for example, as shown in Scheme 26.

[0133] Scheme 26: [ka] Compounds of formula Ii (wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I) can be prepared according to scheme 26. Compounds of formula Iaa prepared in schemes 1, 5, or 6 are treated with a fluorinating reagent, preferably 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanbis(tetrafluoroborate) (Selectfluor), preferably in a solvent such as acetonitrile (as in International Publication No. 2018 / 34917, page 91), to yield compounds of formula Ii.

[0134] Compounds of formula Ij [ka] This can be formed, for example, as shown in Scheme 27.

[0135] Scheme 27: [ka] Compounds of formula Ij (wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I) can be prepared according to scheme 27. Compounds of formula Iaa prepared in schemes 1, 5, or 6 are treated with a chlorinating reagent, preferably N-chlorosuccinimide, in the presence of catalytic dimethyl sulfoxide (DMSO), preferably in a solvent such as dichloromethane (as in Nature Catalysis, 2020, 3, 107), to yield compounds of formula Ij.

[0136] Compounds of formula Im [ka] This can be formed, for example, as shown in Scheme 28.

[0137] Scheme 28: [ka] Compounds of formula Im (wherein R1, R2a, R2b, R3, A1, A2, A3, A4, A5 are as described in formula I) can be prepared according to scheme 28. Compounds of formula Ik prepared in schemes 1, 3, 5, 6, 20, 21, 22, 25, 26, or 27 are treated with ammonium sulfide in a solvent, preferably pyridine, and optionally in the presence of a base, preferably triethylamine (as in International Publication No. 2017 / 192385, page 60), to yield compounds of formula Im.

[0138] Compounds of formula In [ka] This can be formed, for example, as shown in Scheme 29.

[0139] Scheme 29: [ka] Compounds of formula In (wherein R1, R2a, R2b, R3, A1, A2, A3, A4, A5 are as described in formula I) can be prepared according to scheme 29. Compounds of formula Im prepared in scheme 28 are reacted with 3-bromo-1,1,1-trifluoroacetone in a solvent such as N,N-dimethylformamide or acetonitrile (as in International Publication No. 2010 / 136817, page 110) to yield compounds of formula LXXII. Compounds of formula In can be obtained by treating compounds of formula LXXII with trifluoroacetic anhydride in the presence of a base such as triethylamine, preferably in a solvent such as tetrahydrofuran or acetonitrile (as in J.Med.Chem., 2013, 56, 8712).

[0140] Depending on the method or reaction conditions, the reactants can be reacted in the presence of a base. Suitable bases include alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamides, alkylenediamides, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides, and carbocyclic amines. Examples include 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]undeca-7-ene (DBU).

[0141] The reactants can react with each other as they are, i.e., without adding a solvent or diluent. However, in most cases, it is advantageous to add an inert solvent or diluent, or a mixture thereof. When the reaction is carried out in the presence of a base, the base used in excess, such as triethylamine, pyridine, N-methylmorpholine, or N,N-diethylaniline, can also act as a solvent or diluent.

[0142] The reaction is most advantageous when carried out at a temperature range of approximately -80°C to approximately +140°C, preferably approximately -30°C to approximately +100°C, and often within the range of approximately +80°C from the ambient temperature.

[0143] Depending on the selection of suitable reaction conditions and starting materials, for example, in one reaction step, one substituent may be simply substituted with another substituent according to the present invention, or multiple substituents may be substituted with other substituents according to the present invention in the same reaction step.

[0144] Salts of the compounds of formula I can be prepared by known methods. For example, acid addition salts of the compounds of formula I can be obtained by treatment with a suitable acid or a suitable ion exchange reagent, and salts with a base can be obtained by treatment with a suitable base or a suitable ion exchange reagent.

[0145] Salts of the compound of formula I can be conventionally converted, for example, to acid addition salts of free compound I by treatment with a suitable basic compound or a suitable ion exchange reagent, and to base salts by treatment with a suitable acid or a suitable ion exchange reagent.

[0146] Salts of the compound of formula I can be converted to other salts of the compound of formula I, acid addition salts, such as other acid addition salts, by treating an inorganic salt, such as a hydrochloride salt, with a suitable metal salt, such as a sodium salt, barium salt, or silver salt of an acid, such as silver acetate, in a suitable solvent in which the inorganic salt forming silver chloride is insoluble and therefore precipitates from the reaction mixture, in a manner known to the body.

[0147] Depending on the procedure or reaction conditions, a compound of formula I having salt-forming properties can be obtained in free form or as a salt.

[0148] The compounds of formula I and, if necessary, their tautomers, may exist in free or salt form, in one form of a possible isomer or as a mixture thereof, depending on the number, absolute and relative configuration of chiral carbon atoms present in the molecule and / or the configuration of non-aromatic double bonds present in the molecule, in the form of pure isomers such as anticarpone and / or diastereomers, or as a mixture of enantiomers such as racemates, diastereomer mixtures or racemic mixtures; the present invention relates to pure isomers and also to all possible mixtures of isomers, and should be understood in this sense above and below, respectively, even if stereochemical details are not specifically described for each.

[0149] A mixture of diastereomers or racemic compounds of formula I can be separated into pure diastereomers or racemic forms based on physicochemical differences of the components, for example by fractional crystallization, distillation and / or chromatography, in the free or salt forms obtained depending on the selected starting materials and procedure.

[0150] Enantiomer mixtures such as racemates obtained by similar methods can be broken down into optical enantiomers by known methods, for example, by recrystallization from an optically active solvent, by chromatography in a chiral adsorbent, for example by high-performance liquid chromatography (HPLC) in acetylcellulose using a suitable microorganism, by cleavage by a specific immobilized enzyme via the formation of an inclusion compound, for example using a chiral crown ether into which only one enantiomer is combined, or by conversion to a diastereomer salt, for example by reacting the basic final product racemate with an optically active acid such as a carboxylic acid, for example camphoric acid, tartaric acid, or malic acid, or a sulfonic acid, for example camphor sulfonic acid, and separating the diastereomer mixture thus obtained, for example by fractional crystallization based on different solubility, to obtain a diastereomer from which the desired enantiomer can be released by the action of a suitable substance, for example a basic substance.

[0151] Pure diastereomers or enantiomers can be obtained not only by separating a suitable mixture of isomers according to the present invention, but also by generally known diastereoselective or enantioselective synthesis methods, such as using starting materials with stereochemical properties, and performing the method according to the present invention.

[0152] N-oxides can be prepared by reacting the compound of formula I with a suitable oxidizing agent, such as an H2O2 / urea adduct, in the presence of an acid anhydride, such as trifluoroacetic anhydride. Such oxidation is known from literature such as J.Med.Chem.,32(12),2561-73,1989 or International Publication No. 2000 / 15615.

[0153] When individual components have different biological activities, it is advantageous to isolate or synthesize biologically more effective isomers, such as enantiomers or diastereomers, or mixtures of isomers, such as mixtures of enantiomers or diastereomers.

[0154] The compounds of formula I and, optionally, their tautomers may be obtained in free form or salt form, and optionally in hydrate form, and / or in other solvents, such as solvents that have been used to crystallize compounds existing in solid form.

[0155] The compounds of formula I shown in Tables D-1 to D-66 below can be prepared according to the method described above. The following examples illustrate the present invention and are intended to show preferred compounds of formula I in the form of compounds of formula ID. [ka]

[0156] Table D-1 provides 12 compounds D-1.001 to D-1.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a is Cl, and R 2bis Cl, and Q is as defined in Table Z. For example, D-1.002 is [ka] That is the case.

[0157] Table D-2 provides 12 compounds D-2.001 to D-2.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a is Cl, and R 2b is Cl, and Q is as defined in Table Z.

[0158] Table D-3 provides 12 compounds D-3.001 to D-3.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a is Cl, and R 2b is Cl, and Q is as defined in Table Z.

[0159] Table D-4 provides 12 compounds D-4.001 to D-4.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a is Cl, and R 2b is Cl, and Q is as defined in Table Z.

[0160] Table D-5 provides 12 compounds D-5.001 to D-5.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a is Cl, and R 2b is Cl, and Q is as defined in Table Z.

[0161] Table D-6 provides 12 compounds D-6.001 to D-6.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a is Cl, and R 2b is Cl, and Q is as defined in Table Z.

[0162] Table D-7 provides 12 compounds D-7.001 to D-7.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a CF3 and R 2b is CF3, and Q is as defined in Table Z.

[0163] Table D-8 provides 12 compounds D-8.001 to D-8.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a CF3 and R 2b is CF3, and Q is as defined in Table Z.

[0164] Table D-9 provides 12 compounds D-9.001 to D-9.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a CF3 and R 2b is CF3, and Q is as defined in Table Z.

[0165] Table D-10 provides 12 compounds D-10.001 to D-10.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a CF3 and R 2bis CF3, and Q is as defined in Table Z.

[0166] Table D-11 provides 12 compounds D-11.001 to D-11.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a CF3 and R 2b is CF3, and Q is as defined in Table Z.

[0167] Table D-12 provides 12 compounds D-12.001 to D-12.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a CF3 and R 2b is CF3, and Q is as defined in Table Z.

[0168] Table D-13 provides 12 compounds D-13.001 to D-13.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a CF3 and R 2b is Cl, and Q is as defined in Table Z.

[0169] Table D-14 provides 12 compounds D-14.001 to D-14.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a CF3 and R 2b is Cl, and Q is as defined in Table Z.

[0170] Table D-15 provides 12 compounds D-15.001 to D-15.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a CF3 and R 2b is Cl, and Q is as defined in Table Z.

[0171] Table D-16 provides 12 compounds D-16.001 to D-16.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a CF3 and R 2b is Cl, and Q is as defined in Table Z.

[0172] Table D-17 provides 12 compounds D-17.001 to D-17.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a CF3 and R 2b is Cl, and Q is as defined in Table Z.

[0173] Table D-18 provides 12 compounds D-18.001 to D-18.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a CF3 and R 2b is Cl, and Q is as defined in Table Z.

[0174] Table D-19 provides 12 compounds D-19.001 to D-19.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a is Cl, and R 2bis CF3, and Q is as defined in Table Z.

[0175] Table D-20 provides 12 compounds D-20.001 to D-20.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a is Cl, and R 2b is CF3, and Q is as defined in Table Z.

[0176] Table D-21 provides 12 compounds D-21.001 to D-21.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a is Cl, and R 2b is CF3, and Q is as defined in Table Z.

[0177] Table D-22 provides 12 compounds D-22.001 to D-22.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a is Cl, and R 2b is CF3, and Q is as defined in Table Z.

[0178] Table D-23 provides 12 compounds D-23.001 to D-23.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a is Cl, and R 2b is CF3, and Q is as defined in Table Z.

[0179] Table D-24 provides 12 compounds D-24.001 to D-24.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a is Cl, and R 2b is CF3, and Q is as defined in Table Z.

[0180] Table D-25 provides 12 compounds D-25.001 to D-25.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a is Cl, and R 2b is Br, and Q is as defined in Table Z.

[0181] Table D-26 provides 12 compounds D-26.001 to D-26.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a is Cl, and R 2b is Br, and Q is as defined in Table Z.

[0182] Table D-27 provides 12 compounds D-27.001 to D-27.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a is Cl, and R 2b is Br, and Q is as defined in Table Z.

[0183] Table D-28 provides 12 compounds D-28.001 to D-28.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a is Cl, and R 2bis Br, and Q is as defined in Table Z.

[0184] Table D-29 provides 12 compounds D-29.001 to D-29.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a is Cl, and R 2b is Br, and Q is as defined in Table Z.

[0185] Table D-30 provides 12 compounds D-30.001 to D-30.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a is Cl, and R 2b is Br, and Q is as defined in Table Z.

[0186] Table D-31 provides 12 compounds D-31.001 to D-31.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a is Br, R 2b is Cl, and Q is as defined in Table Z.

[0187] Table D-32 provides 12 compounds D-32.001 to D-32.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a is Br, R 2b is Cl, and Q is as defined in Table Z.

[0188] Table D-33 provides 12 compounds D-33.001 to D-33.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a is Br, R 2b is Cl, and Q is as defined in Table Z.

[0189] Table D-34 provides 12 compounds D-34.001 to D-34.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a is Br, R 2b is Cl, and Q is as defined in Table Z.

[0190] Table D-35 provides 12 compounds D-35.001 to D-35.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a is Br, R 2b is Cl, and Q is as defined in Table Z.

[0191] Table D-36 provides 12 compounds D-36.001 to D-36.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, R 2a is Br, R 2b is Cl, and Q is as defined in Table Z.

[0192] Table D-37 provides 12 compounds D-37.001 to D-37.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a CF3 and R 2bis Br, and Q is as defined in Table Z.

[0193] Table D-38 provides 12 compounds D-38.001 to D-38.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a CF3 and R 2b is Br, and Q is as defined in Table Z.

[0194] Table D-39 provides 12 compounds D-39.001 to D-39.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, R 2a CF3 and R 2b is Br, and Q is as defined in Table Z.

[0195] Table D-40 provides 12 compounds D-40.001 to D-40.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a CF3 and R 2b is Br, and Q is as defined in Table Z.

[0196] Table D-41 provides 12 compounds D-41.001 to D-41.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a CF3 and R 2b is Br, and Q is as defined in Table Z.

[0197] Table D-42 provides 12 compounds D-42.001 to D-42.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a CF3 and R 2b is Br, and Q is as defined in Table Z.

[0198] Table D-43 provides 12 compounds D-43.001 to D-43.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a is Br, R 2b is CF3, and Q is as defined in Table Z.

[0199] Table D-44 provides 12 compounds D-44.001 to D-44.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a is Br, R 2b is CF3, and Q is as defined in Table Z.

[0200] Table D-45 provides 12 compounds D-45.001 to D-45.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, R 2a is Br, R 2b is CF3, and Q is as defined in Table Z.

[0201] Table D-46 provides 12 compounds D-46.001 to D-46.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a is Br, R 2bis CF3, and Q is as defined in Table Z.

[0202] Table D-47 provides 12 compounds D-47.001 to D-47.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a is Br, R 2b is CF3, and Q is as defined in Table Z.

[0203] Table D-48 provides 12 compounds D-48.001 to D-48.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, R 2a is Br, R 2b is CF3, and Q is as defined in Table Z.

[0204] Table D-49 provides 12 compounds D-49.001 to D-49.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a is Br, R 2b is Br, and Q is as defined in Table Z.

[0205] Table D-50 provides 12 compounds D-50.001 to D-50.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a is Br, R 2b is Br, and Q is as defined in Table Z.

[0206] Table D-51 provides 12 compounds D-51.001 to D-51.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a is Br, R 2b is Br, and Q is as defined in Table Z.

[0207] Table D-52 provides 12 compounds D-52.001 to D-52.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a is Br, R 2b is Br, and Q is as defined in Table Z.

[0208] Table D-53 provides 12 compounds D-53.001 to D-53.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a is Br, R 2b is Br, and Q is as defined in Table Z.

[0209] Table D-54 provides 12 compounds D-54.001 to D-54.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, R 2a is Br, R 2b is Br, and Q is as defined in Table Z.

[0210] Table D-55 provides 12 compounds D-55.001 to D-55.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a CF3 and R 2bI is and Q is as defined in Table Z.

[0211] Table D-56 provides 12 compounds D-56.001 to D-56.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a CF3 and R 2b I is and Q is as defined in Table Z.

[0212] Table D-57 provides 12 compounds D-57.001 to D-57.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a CF3 and R 2b I is and Q is as defined in Table Z.

[0213] Table D-58 provides 12 compounds D-58.001 to D-58.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a CF3 and R 2b I is and Q is as defined in Table Z.

[0214] Table D-59 provides 12 compounds D-59.001 to D-59.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a CF3 and R 2b I is and Q is as defined in Table Z.

[0215] Table D-60 provides 12 compounds D-60.001 to D-60.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R 2a CF3 and R 2b I is and Q is as defined in Table Z.

[0216] Table D-61 provides 12 compounds D-61.001 to D-61.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, R 2a is I, R 2b is CF3, and Q is as defined in Table Z.

[0217] Table D-62 provides 12 compounds D-62.001 to D-62.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R 2a is I, R 2b is CF3, and Q is as defined in Table Z.

[0218] Table D-63 provides 12 compounds D-63.001 to D-63.012 with formula IDs, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, R 2a is I, R 2b is CF3, and Q is as defined in Table Z.

[0219] Table D-64 provides 12 compounds D-64.001 to D-64.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, R 2a is I, R 2bis CF3, and Q is as defined in Table Z.

[0220] Table D-65 provides 12 compounds D-65.001 to D-65.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R 2a is I, R 2b is CF3, and Q is as defined in Table Z.

[0221] Table D-66 provides 12 compounds D-66.001 to D-66.012 with formula IDs, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, R 2a is I, R 2b is CF3, and Q is as defined in Table Z.

[0222] [Table 1-1] [Table 1-2]

[0223] Certain intermediate compounds of formulas II(i), III(i), IV(i), V(i), VII(i), XI(i), and XIV(i), some of which are novel, are also available. For example: Compound of formula II(i) (wherein (i)X1 is Cl, and A1, A2, A3, A4, A5, R 2a and R 2b (ii) is defined in any one of Tables D-1 to D-66; where (i) X1 is Br, and A1, A2, A3, A4, A5, R 2a and R 2b (This is defined in any one of Tables D-1 to D-66). [ka]

[0224] Compounds of formula III(i) (wherein (i)R1 is H and Q is as defined in Table Z; (ii) where (i)R1 is CH3 and Q is as defined in Table Z; and (iii) where (i)R1 is CH2-cyclopropyl and Q is as defined in Table Z). [ka]

[0225] Compound of formula IV(i) (wherein A1, A2, A3, A4, A5, R 2a and R 2b (This is defined in any one of Tables D-1 to D-66). [ka]

[0226] Compound of formula V(i) (wherein (i)X2 is Cl and Q is as defined in Table Z; (ii) where (i)X2 is Br and Q is as defined in Table Z; and (iii) where (i)X2 is I and Q is as defined in Table Z). [ka]

[0227] Compounds of formula VII(i) (wherein Q is as defined in Table Z). [ka]

[0228] Compound of formula XI(i) (wherein A1, A2, A3, A4, A5, R1, R 2a and R 2b(This is defined in any one of Tables D-1 to D-66). [ka]

[0229] Compounds of formula XIV(i), where A1, A2, A3, A4, A5, R1, R 2a and R 2b (This is defined in any one of Tables D-1 to D-66). [ka]

[0230] In a further embodiment, the present invention thus makes available compounds of formulas II(i), III(i), IV(i), V(i), VII(i), XI(i), and XIV(i), wherein each example, A1, A2, A3, A4, A5, R1, R 2a and R 2b Q and Q are as defined in Formula I in the first embodiment; and with respect to Formula II(i), X1 is a halogen, preferably chloro or bromo. Furthermore, the corresponding embodiments illustrated for Formula I are also applicable to compounds of Formulas II(i), III(i), IV(i), V(i), VII(i), XI(i) and XIV(i).

[0231] The compound of Formula I according to the present invention is an active ingredient that is beneficial preventively and / or therapeutically in the field of pest control even at low application rates, and it has a very favorable biocidal spectrum and exhibits good tolerance by warm-blooded animal species, fish, and plants. The active ingredient according to the present invention acts not only on commonly susceptible animal pests such as insects or representative examples of mites (Acarina), but also on all or individual developmental stages of resistant animal pests. The insecticidal or acaricidal activity of the active ingredient according to the present invention may manifest directly, i.e., immediately or only after some time has elapsed, as the destruction of pests, for example, during molting, or indirectly, for example, as reduced oviposition and / or hatching rates.

[0232] Examples of the above animal pests are as follows: From the order Acarina, for example, Acaritus spp., Aculus spp., Acaricalus spp., Aceria spp., Acarus siro, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp., Calipitrimerus spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides spp., Eotetranychus spp.) 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.), genera Rhizoglyphus, Sarcoptes, Steneotarsonemus, Tarsonemus, and Tetranychus; From the order Anoplura, for example, The genera Haematopinus, Linognathus, Pediculus, Pemphigus, and Phylloxera; From the order Coleoptera, for example, Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp., Astylus atromaculatus, Atenius spp., Atomaria linearis, Chaetocnema tibialis, Cerotoma spp., Connoderus spp., Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp., Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus spp., Heteronychus arator, Hypothenemus hampei, Lagria vilosa, Leptinotarsa ​​decemLineata, Lissorhoptrus spp., Liogenys spp., Maecolaspis spp., Maledra castanea, Megascelis spp.) Melighetes aeneus, Melolontha spp., Myochrous armatus, Orycaephilus spp., Otiorhynchus spp., Phyllophaga spp., Phlyctinus spp., Popillia spp.), Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp., Scarabaeidae family, Sitophilus spp., Sitotroga spp., Somaticus spp., Sphenophorus spp., Sternechus subsignatus, Tenebrio spp., Tribolium spp., and Trogoderma spp.; From the order Diptera, for example, Genus Aedes, Anopheles, Antherigona soccata, Bactrocea oleae, Bibio hortulanus, Bradysia, Calliphora erythrocephala, Ceratitis, Chrysomyia, Culex, Cuterebra, Dacus, Delia, Drosophila melanogaster, 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., Riveria quadrifasciata, Scatella spp., Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp., and Tipula spp.; From the order Hemiptera, for example, Acanthocoris scabrator, Acrosternum spp., Adelphocoris lineolatus, Aleurodes spp., Amblypelta nitida, Bathycoelia thalassina, Blissus spp., Cimex spp., Clavigralla tomentosicollis, Creontiades spp., Distantiella theobroma, Dichelops furcatus, Dysdercus spp., Edessa spp.) Euchistus spp., Eurydema pulchrum, Eurygaster spp., Halyomorpha halys, Horcias nobilellus, Leptocorisa spp., Lygus spp., Margarodes spp., Murgantia histrionic, Neomegalotomus spp., Nesidiocoris tenuis, Nezara spp., Nysius simulans, Oebalus insularis Piesma spp., Piezodorus spp., Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophara spp.), *Thyanta* spp., *Triatoma* spp., *Vatiga illudens*; Acyrthosium pisum, Adalges spp., Agalliana ensigera, Aganoscena targionii, Aleurodicus spp., Aleurocanthus spp., Aleurolobus barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiella (spp.), Aphididae family, Aphis spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli, Bemisia spp, Brachycaudus spp, Brevicoryne brassicae, Cacopsylla spp, Cavariella aegopodii Scop., Ceroplaster spp.), Chrysomphalus aonidium, Greenhouse scale insect (Chrysomphalus dictyospermi), Cicadella spp., White leafhopper (Cofana spectra), Cryptomyzus spp., Cicadulina spp., Flat scale insect (Coccus hesperidum), Dalbulus maidis, Dialeurodes spp., Citrus psyllid (Diaphorina citri), Diuraphis noxia, Dysaphis spp., Empoasca spp., Apple woolly aphid (Eriosoma larigerum), Erythroneura spp., Gascardia spp., Glycaspis brimblecombei, Hyadaphis pseudobrassicae, Hyalopterus spp., Hyperomyzus pallidus, Idioscopus clypealis, Jacobiasca lybica, Laodelphax spp., Lecanium corni, Lepidosaphes spp., Lopaphis erysimi), Lyogenys maidis, Macrosiphum spp., Mahanarva spp., Metcalfa pruinosa, Metopolophium dirhodum, Myndus crudus, Myzus spp.), Neotoxoptera sp., Nephotettix spp., Nilaparvata spp., Nippolachnus piri Mats, Odonaspis ruthae, Oregma lanigera Zehnter, Parabemisia myricae, Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., Peregrinus maidis, Perkinsiella spp., Phorodon humuli), Phylloxera spp., Planococcus spp., Pseudaulacaspis spp., Pseudococcus spp., Cotton flea beetle (Pseudatomoscelis seriatus), Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Quesada gigas, Lightning leafhopper (Recilia dorsalis), Rhopalosiphum spp., Saissetia spp., Scaphoideus (spp.), Schizaphis spp., Sitobion spp.), Sogatella furcifera, Spissistilus festinus, Tarophagus Proserpina, Toxoptera spp., Trialeurodes spp., Tridiscus sporoboli, Trionymus spp., Trioza erytreae, Unaspis citri, Zygina flammigera, Zyginidia scutellaris; From the order Hymenoptera, for example, The genera Acromyrmex, Arge, Atta, Cephus, Diprion, Diprionidae, Gilpinia polytoma, Hoplocampa, Lasius, Monomorium pharaonis, Neodiprion, Pogonomyrmex, Slenopsis invicta, Solenopsis, and Vespa; From the order Isoptera, for example, Coptotermes spp., Corniternes cumulans, Incisitermes spp., Macrotermes spp., Mastotermes spp., Microtermes spp., Reticulitermes spp.; Solenopsis geminate From the order Lepidoptera, for example, Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyresthia spp., Argyrotaenia spp., Autographa spp., Bucculatrix thurberiella, Busseola fusca, Cadra cautella, Carposina nipponensis), Chilo spp., Choristoneura spp., Chrysoteuchia topiaria, Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleophora spp., Colias lesbia, Cosmophila flava, Crambus spp., Crocidolomia binotalis, Cryptophlebia leucotreta, Cydalima perspectalis Cydia spp., Diaphania perspectalis, Diatraea spp., Diparopsis castanea, Earias spp.), Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp., Epinotia spp., Estigmene acrea, Etiella zinckinella, Eucosma spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia jaculiferia, Grapholita spp., Hedya nubiferana, Heliothis spp.), Hellula undalis, Herpetogramma spp., Hyphantria cunea, Keiferia lycopersicella, Lasmopalpus lignosellus, Leucoptera scitella, Lithocollethis spp., Lobesia botrana, Loxostege bifidalis, Lymantria spp., Lyonetia spp., Malacosoma spp., Mamestra brassicae, Manduca sexta), Mythimna spp., Noctua spp., Operophtera spp., Orniodes indica, Ostrinia nubilalis, Pammene spp., Pandemis spp.), pine moth (Panolis flammea), Papaipema nebris, cotton beetle (Pectinophora gossypiela), coffee leafminer (Perileucoptera coffeella), Pseudaletia unipuncta, potato moth (Phthorimaea operculella), cabbage white butterfly (Pieris rapae), Pieris spp., diamondback moth (Plutella xylostella), Prays spp., Pseudoplusia spp., Rachiplusia nu, Richia albicosta, Scirpophaga spp., Sesamia (spp.), genera Sparganothis, Spodoptera, Sylepta derogate, Synanthedon, Thaumetopoea, Tortrix, Trichoplusia ni, Tuta absoluta, and Yponomeuta spp.); From the order Mallophaga, for example, The genera Damalinea and Trichodectes; From the order Orthoptera, for example, The genera Blatta, Blattella, Grillosa, Leucophaea maderae, Locusta, Neocurtilla hexadactyla, Periplaneta, Scapteriscus, and Schistocerca; From the order Psocoptera, for example, Liposcelis genus (Liposcelis spp.) From the order Siphonaptera, for example, The genera Ceratophyllus, Ctenocephalides, and Xenopsylla cheopis; From the order Thysanoptera, for example, Calliothrips phaseoli, Frankliniella spp., Heliothrips spp., Hercinotothrips spp., Parthenothrips spp., Scirtothrips aurantii, Sericothrips variabilis, Taeniothrips spp., Thrips spp. From the silvery-eyed species (Thysanura), for example, the European silverfish (Lepisma saccharina).

[0233] In a further embodiment, the present invention also relates to plant parasitic nematodes (endoparasitic, semi-endoparasitic, and ectoparasitic nematodes), particularly root-knot nematodes, northern root-knot nematodes (Meloidogyne hapla), sweet potato root-knot nematodes (Meloidogyne incognita), Javan root-knot nematodes (Meloidogyne javanica), arenaria root-knot nematodes (Meloidogyne arenaria), and other species of the genus Meloidogyne; cyst-forming nematodes, potato cyst nematodes (Globodera rostochiensis), and other species of the genus Globodera; wheat cyst nematodes (Heterodera avenae), soybean cyst nematodes (Heterodera glycines), sugar beet cyst nematodes (Heterodera schachtii), clover cyst nematodes (Heterodera (trifolii), and other species of the cyst nematode genus Heterodera; Seed gall nematodes, species of the genus Anguina; Stem nematodes and leaf nematodes, species of the genus Aphelenchoides; Sting nematodes, Belonolaimus longicaudatus, and other species of the genus Belonolaimus; Pine wood nematode, Bursaphelenchus xylophilus) and other species of the genus Bursaphelenchus; petroleum nematodes, species of Criconema, Criconemella, Criconemoides, and Mesocriconema; stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci, and other species of the genus Ditylenchus; cycad nematodes and species of Dolichodorus;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; Spear nematodes, species of the genus Hoploaimus; False root-knot nematodes, species of the genus Nacobbus; Pufferfish nematodes, Longidorus elongatus Longidorus species (elongatus) and other species of the genus Longidorus; pin nematodes, species of the genus Pratylenchus; root nematodes, wheat root nematodes (Pratylenchus neglectus), northern root nematodes (Pratylenchus penetrans), Platylenchus curvitatus, Platylenchus goodeyi and other species of the genus Pratylenchus; banana root nematodes (Radopholus similis) and other species of the genus Radopholus; false sedge nematodes, Rotylenchus robustus, Rotylenchus reniformis Rotylenchus species (reniformis) and other Rotylenchus species; species of the genus Scutellonema; Trichodorus primitivus and other Trichodorus species; species of the genus Paratrichodorus;Plant parasitic nematodes such as Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other species of the genus Tylenchorhynchus; Tylenchulus species and other species of the genus Tylenchulus; Xiphenema species and other species of the genus Xiphenema; and species of the genera Subanguina, Hypsoperine, Macroposthonia, Melinius, Punctodera and Quinisulcius This may relate to methods for preventing damage to plants and parts thereof caused by other plant-parasitic nematode species (such as spp.).

[0234] The compounds of the present invention may also be active against mollusks. Examples include, for example, the family Ampullariidae; the genus Arion (Arion ater, Arion circumscriptus, Arion hortensis, Arion rufus); the family Bradybaenidae (Bradybaena fruticum); the genus Cepaea (Cepaea hortensis, Cepaea hortensis) Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Heliceria (H. itala, H. obvia); Helicidae (Helicigona albumum) arbustorum); Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Monoa Examples include the genera Lymnaea, Milax (M. gagates, M. marginatus, M. sowerbyi), Opeas, Pomacea (Pomacea canaticulata), Vallonia, and Zanitoides.

[0235] The active ingredients according to the present invention can be used to control, i.e., suppress or destroy, the above-mentioned types of pests that occur particularly in plants, especially useful plants and ornamental plants in agriculture, horticulture and forestry, or in organs such as fruits, flowers, leaves, stems, tubers or roots of such plants, and in some cases even plant organs that are formed at a later time remain protected from these pests.

[0236] Suitable target crops include, in particular, grains such as wheat, barley, rye, oats, rice, maize, or sorghum; beets such as sugar beets or fodder beets; fruits such as apples, pears, plums, peaches, almonds, cherries, or berries; pome fruits such as strawberries, raspberries, or blackberries; drupes or soft fruits; legumes such as kidney beans, lentils, peas, or soybeans; rapeseed, mustard, poppies, olives, sunflowers, palms, castor beans, cocoa, or ground potatoes. Oil crops such as nuts; cucurbitaceous plants such as pumpkins, cucumbers, or melons; fiber plants such as cotton, flax, hemp, or jute; citrus fruits such as oranges, lemons, grapefruit, or tangerines; vegetables such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, or bell peppers; plants of the Lauraceae family such as avocados, cinnamon, or camphor; and further, tobacco, nuts, coffee, eggplant, sugarcane, tea, pepper, grapes, hops, plants of the Plantaginaceae family, and latex plants.

[0237] The compositions and / or methods of the present invention may also be used with any ornamental and / or vegetable crops, including flowers, shrubs, broad-leaved trees and evergreen trees.

[0238] For example, the present invention applies to the following ornamental species: species of the genera Ageratum, Alonsoa, Anemone, Anisodontea capsenisis, Anthemis, Antirrhinum, Aster, Begonia (e.g., B. elatior, B. semperflorens, B. tubereux), Bougainvillea, and Brachycome. spp.), Brassica spp. (ornamental), Calceolaria spp., Capsicum annuum, Catharanthus roseus, Canna spp., Centaurea spp., Chrysanthemum spp., Cineraria spp. (C. maritime), Coreopsis spp., Crassula coccinea, Cuphea ignea, Dahlia spp., Delphinium spp., Dicentra Spectabilis), species of the genus Dorotheantus, Eustoma grandiflorum, species of the genus Forsythia, species of the genus Fuchsia, Geranium gnaphalium, species of the genus Gerbera, Gomphrena globosa, species of the genus Heliotropium, species of the genus Helianthus, species of the genus Hibiscus.), species of the genus Hortensia, species of Hydrangea, species of Hypoestes phyllostachya, species of Impatiens (African balsam (I. Walleriana)), species of Iresines, species of Kalanchoe, Lantana (Lantana camara), Malva (Lavatera trimestris), Leonotis leonurus, species of Lilium, species of Mesembryanthemum, species of Mimulus, species of Monarda spp.), species of the genus Nemesia, species of Tagetes, species of Dianthus (carnation), species of Canna, species of Oxalis, species of Bellis, species of Pelargonium (ivy geranium (P. peltatum), honeysuckle (P. Zonale)), species of Viola (pansy), species of Petunia, species of Phlox, species of Plectranthus, species of Poinsettia spp.), species of the genus Parthenocissus (Parthenocissus spp.) (American ivy (P. quinquefolia), ivy (P. tricuspidata)), species of the genus Primula (Primula spp.), species of Ranunculus (Ranunculus spp.), species of Rhododendron (Rhododendron spp.), species of Rosa (Rosa spp.) (rose), species of Rudbeckia (Rudbeckia spp.), species of Saintpaulia (African violet spp.), species of Salvia (Salvia spp.)It can be used in any of the following species of bedding plants: Scaevola aemola, Schizanthus wisetonensis, species of Sedum, species of Solanum, species of Surfinia, species of Tagetes, species of Nicotinia, species of Verbena, species of Zinnia, and other bedding plants.

[0239] For example, the present invention includes the following vegetable species: Allium spp. (garlic (A. sativum), onion (A. cepa), shallot (A. oschaninii), leek (A. Porrum), scallion (A. ascalonicum), green onion (A. fistulosum)), chervil (Anthriscus cerefolium), celery (Apium graveolus), asparagus (Asparagus officinalis), beet (Beta vulgarus), Brassica spp. (wild cabbage (B. Oleracea), Chinese cabbage (B. Pekinensis), turnip (B. rapa)), chili pepper (Capsicum annuum), chickpea (Cicer arietinum), endive (Cichorium endivia), and Cichorum species. (Chicory (C. intybus), Endive (C. endivia)), Watermelon (Citrillus lanatus), Cucumis spp. (Saffron (C. sativus), Melon (C. melo)), Cucurbita spp. (Pumpkin (C. pepo), Pumpkin (C. maxima)), Cyanara spp. (Artichoke (C. scolymus), Cardoon (C. cardunculus)), Carrot (Daucus carota), Fennel (Foeniculum vulgare), Hypericum spp., Lettuce (Lactuca sativa), Tomato (Lycopersicon) (spp.) (Tomato (L. esculentum), Tomato (L. lycopersicum)), Mentha species (Mentha spp.), Basil (Ocimum basilicum), Parsley (Petroselinum crispum), Phaseolus species (Phaseolus spp.) (Pinguicula (P. vulgaris), Red bean (P.It can be used in any of the following: coccineus), pea (Pisum sativum), radish (Raphanus sativus), round-leaved rhubarb (Rheum rhaponticum), species of the genus Rosemarinus (Rosemarinus spp.), species of the genus Salvia (Salvia spp.), yellow rose lily (Scorzonera hispanica), eggplant (Solanum melongena), spinach (Spinacea oleracea), species of the genus Valerianella (Valerianella spp.) (wild lettuce (V. locusta), V. eriocarpa (V. eriocarpa)), and broad bean (Vicia faba).

[0240] Preferred ornamental species include African violets, begonias, dahlias, gerberas, hydrangeas, verbena, roses, kalanchoe, poinsettias, asters, cornflowers, coreopsis, delphiniums, monardas, phlox, rudbeckia, sedums, petunias, violas, balsam, geraniums, chrysanthemums, ranunculus, fuchsias, salvias, hydrangeas, rosemary, sage, St. John's wort, mint, shishito peppers, tomatoes, and cucumbers.

[0241] The active ingredient according to the present invention is particularly suitable for controlling bean aphids (Aphis craccivora), corn, rice, and soybean crops, as well as bean aphids (Diabrotica balteata), false tobacco budworms (Heliothis virescens), green peach aphids (Myzus persicae), diamondback moths (Plutella xylostella), and Egyptian armyworms (Spodoptera littoralis). The active ingredient according to the present invention is particularly suitable for controlling armyworms (Mamestra) (preferably in vegetables), codling moths (Cydia pomonella) (preferably in apples), species of the genus Empoasca (preferably in vegetables and vineyards), species of the genus Leptinotarsa ​​(preferably in potatoes), and rice stem borer (Chilo supressalis) (preferably in rice).

[0242] Compounds of formula I are particularly suitable for the control of the following pests. One or more hemipteran pests, such as the tobacco whitefly (Bemisia tabaci), bean aphid (Aphis craccivora), peach aphid (Myzus persicae), rhopalosiphum padi, brown planthopper (Nilaparvata lugens), and Euschistus heros (preferably those found on vegetables, soybeans, and sugarcane). One or more lepidopteran pests, such as the Egyptian armyworm (Spodoptera littoralis), Spodoptera frugiperda, diamondback moth (Plutella xylostella), rice leaf borer (Cnaphalocrocis medinalis), codling moth (Cydia pomonella), Chrysodeixis includes, soybean leaf borer (Chilo suppressalis), sorghum leaf borer (Elasmopalpus lignosellus), Pseudoplusia includens, and tomato leaf borer (Tuta absoluta) (preferably those found in vegetables and corn). • One or more thrips belonging to the order Thripidae, such as onion thrips (Thrips tabaci) and citrus thrips (Frankliniella occidentalis) (preferably those found on vegetables), and • Soil pests (such as those of the order Coleoptera), for example, the species Diabrotica balteata, species of the genus Agriotes, and the Colorado potato beetle (Leptinotarsa ​​decemLineata) (preferably those found in vegetables and corn)

[0243] The term “crop” should be understood to also include crops transformed by the use of recombinant DNA technology, for example, to synthesize one or more selectively acting toxins, such as those known to be derived from toxin-producing bacteria, particularly bacteria of the genus Bacillus.

[0244] Toxins that may be expressed by such transgenic plants include, for example, insecticidal proteins derived from Bacillus cereus or Bacillus popilliae; or δ-endotoxins, such as Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, insecticidal proteins derived from Bacillus thuringiensis or plant insecticidal proteins (Vip), such as Vip1, Vip2, Vip3 or Vip3A; or bacterial colony-forming nematodes, such as Photorhabdus luminescens, Xenorhabdus nematophilus, and other species of the genus Photorhabdus (Photorhabdus spp. or Xenorhabdus). Insecticidal proteins (spp.); toxins produced by animals, such as scorpion venom, arachnid venom, wasp venom, and neurotoxins specific to other insects; toxins produced by fungi, such as Streptomycetes toxins; plant lectins, such as pea lectin, barley lectin, or saxifrage lectin; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patain, cystatin, and papain inhibitors; lysine, maize-RIP, abrin, rufin, saporine Examples include ribosome-inactivating proteins (RIPs) such as ribosomal protein (RIP) or briodin; steroid metabolic enzymes such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitors, and HMG-COA-reductase; ion channel blockers such as sodium channel or calcium channel blockers; juvenile hormone esterase, diuretic hormone receptor, stilbenzyl synthase, bibenzyl synthase, chitinase, and glucanase.

[0245] In relation to the present invention, δ-endotoxins are understood, for example, Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C or plant insecticidal proteins (Vip), such as Vip1, Vip2, Vip3 or Vip3A, and more specifically, as hybrid toxins, cleavage toxins and modified toxins. Hybrid toxins are produced by recombination through novel combinations of different domains of those proteins (see, for example, International Publication No. 02 / 15701). Cleavage toxins, such as cleavage Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the natural toxin are substituted. In such amino acid substitutions, preferably, a protease recognition sequence that does not exist in nature is inserted into the toxin; for example, in the case of Cry3A055, a cathepsin-G recognition sequence is inserted into the Cry3A toxin (see International Publication No. 03 / 018810).

[0246] Examples of such toxins or transgenic plants capable of synthesizing such toxins are disclosed, for example, in European Patent Publication No. 0374753, International Publication No. 93 / 07278, International Publication No. 95 / 34656, European Patent Publication No. 0427529, European Patent Publication No. 451878, and International Publication No. 03 / 052073.

[0247] Methods for preparing such transgenic plants are generally known to those skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparations are known, for example, from International Publication No. 95 / 34656, European Patent Application Publication No. 0367474, European Patent Application Publication No. 0401979, and International Publication No. 90 / 13651.

[0248] The toxins contained in transgenic plants confer resistance to pests. Such insects are found in various insect taxonomic groups, but are particularly common in beetles (Coleoptera), diptera (Diptera), and moths (Lepidoptera).

[0249] Transgenic plants containing one or more genes encoding insecticidal resistance and expressing one or more toxins are known, and some of them are commercially available. Examples of such plants include: YieldGard® (maize variety expressing Cry1Ab toxin); YieldGard Rootworm® (maize variety expressing Cry3Bb1 toxin); YieldGard Plus® (maize variety expressing Cry1Ab and Cry3Bb1 toxins); Starlink® (maize variety expressing Cry9C toxin); Herculex I® (maize variety expressing Cry1Fa2 toxin and the enzyme phosphinothrysin N-acetyltransferase (PAT) for resistance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety expressing Cry1Ac toxin); Bollgard I® (cotton variety expressing Cry1Ac toxin); Bollgard These include II (registered trademark) (a cotton variety expressing Cry1Ac and Cry2Ab toxins); VipCot (registered trademark) (a cotton variety expressing Vip3A and Cry1Ab toxins); NewLeaf (registered trademark) (a potato variety expressing Cry3A toxin); NatureGard (registered trademark), Agrisure (registered trademark) GT Advantage (GA21 glyphosate resistance trait), Agrisure (registered trademark) CB Advantage (Bt11 corn borer (CB) trait), and Protecta (registered trademark).

[0250] Further examples of such transgenic crops are as follows: 1. Bt11 maize, manufactured by Syngenta Seeds SAS (Chemin de l'Hobit 27, F-31 790 St. Sauveur, France), registration number C / FR / 96 / 05 / 10. Genetically modified maize that has been given resistance to attacks by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) through transgenic expression of the cleavage Cry1Ab toxin. Bt11 maize also expresses the enzyme PAT through genetic modification to obtain resistance to the herbicide glufosinate ammonium.

[0251] 2. Bt176 maize, manufactured by Syngenta Seeds SAS (Chemin de l'Hobit 27, F-31 790 St. Sauveur, France), registration number C / FR / 96 / 05 / 10. Genetically modified maize that has been given resistance to attacks by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) through transgenic expression of the Cry1Ab toxin. Bt176 maize also expresses the enzyme PAT through genetic modification to obtain resistance to the herbicide glufosinate ammonium.

[0252] 3. MIR604 maize, manufactured by Syngenta Seeds SAS (Chemin de l'Hobit 27, F-31 790 St. Sauveur, France), registration number C / FR / 96 / 05 / 10. This maize was made insect-resistant through transgenic expression of a modified Cry3A toxin. The toxin is Cry3A055, modified by the insertion of a cathepsin-G protease recognition sequence. The preparation of such transgenic maize plants is described in international publication 03 / 018810.

[0253] 4. MON 863 maize, registration number C / DE / 02 / 9, manufactured by Monsanto Europe SA (270-272 Avenue de Tervuren, B-1150 Brussels, Belgium). MON 863 expresses the Cry3Bb1 toxin and is resistant to certain Coleoptera insects.

[0254] 5. IPC 531 cotton manufactured by Monsanto Europe SA (270-272 Avenue de Tervuren, B-1150 Brussels, Belgium), registration number C / ES / 96 / 02.

[0255] 6. 1507 maize, registration number C / NL / 00 / 10, manufactured by Pioneer Overseas Corporation (Avenue Tedesco, 7 B-1160 Brussels, Belgium). Genetically modified maize for the expression of protein Cry1F to obtain resistance to certain Lepidoptera insects and PAT protein to obtain resistance to the herbicide glufosinate ammonium.

[0256] 7. NK603×MON 810 maize, registration number C / GB / 02 / M3 / 03, manufactured by Monsanto Europe SA (270-272 Avenue de Tervuren, B-1150 Brussels, Belgium). This hybrid maize variety is bred using conventional methods by crossing the genetically modified varieties NK603 and MON 810. NK603×MON 810 maize also expresses, through genetic modification, the protein CP4 EPSPS obtained from the Agrobacterium sp. strain CP4, which provides resistance to the herbicide Roundup® (containing glyphosate), and the Cry1Ab toxin obtained from Bacillus thuringiensis subsp. kurstaki, which provides resistance to certain Lepidoptera, including the European corn borer.

[0257] Transgenic crops of insect-tolerant plants are also described in the BATS (Zentrum fuer Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003 (http: / / bats.ch).

[0258] The term “crops” should be understood to include crops transformed by the use of recombinant DNA technology so that selectively active antipathogenic substances can be synthesized, such as so-called “pathogenicity-associated proteins” (PRP, see, for example, European Patent Application Publication No. 0392225). Examples of such antipathogenic substances and transgenic plants capable of synthesizing such antipathogenic substances are known, for example, from European Patent Application Publication No. 0392225, International Publication No. 95 / 33818 and European Patent Application Publication No. 0353191. 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.

[0259] Crops can also be improved to increase their resistance to fungal pathogens (e.g., Fusarium, anthracnose, or Phytophthora), bacteria (e.g., Pseudomonas), or viruses (e.g., potato leaf curl virus, tomato yellow necrosis virus, cucumber mosaic virus).

[0260] The crops include varieties that have high resistance to nematodes, such as soybean cyst nematodes.

[0261] Crops that are abiotically tolerant include, for example, those that exhibit high tolerance to drought, high salinity, high temperature, low temperature, frost, or light due to the expression of NF-YB or other proteins known in the art.

[0262] Examples of antipathogenic substances that may be expressed by such transgenic plants include ion channel blockers such as sodium channel or calcium channel blockers, such as viral KP1, KP4, or KP6 toxins; stilbene synthase; vibenzyl synthase; chitinase; glucanase; so-called "pathogenicity-associated proteins" (PRPs; see, for example, European Patent Application Publication No. 0392225); antipathogenic substances produced by microorganisms, such as peptide antibiotics or heterocyclic antibiotics (see, for example, International Publication No. 95 / 33818); or proteins or polypeptide factors involved in plant pathogen defense (so-called "plant disease resistance genes" as described in International Publication No. 03 / 000906).

[0263] Further applications of the compositions according to the present invention include the protection of stored goods and storage rooms, and the protection of raw materials (such as wood and textiles), flooring materials and buildings, and hygiene, particularly the protection of humans, livestock and productive livestock from the above-mentioned types of pests.

[0264] The present invention provides a compound of a first embodiment used in therapeutic applications. The present invention provides a compound of a first embodiment used in the control of parasites within or on animals. The present invention further provides a compound of a first embodiment used in the control of ectoparasites on animals. The present invention further provides a compound of a first embodiment used in the prevention and / or treatment of diseases caused by ectoparasites.

[0265] The present invention provides the use of a compound in a first embodiment for producing a pharmaceutical product for controlling parasites within or on animals. The present invention further provides the use of a compound in a first embodiment for producing a pharmaceutical product for controlling ectoparasites on animals. The present invention further provides the use of a compound in a first embodiment for producing a pharmaceutical product for preventing and / or treating diseases caused by ectoparasites.

[0266] The present invention provides the use of a compound according to a first embodiment in the control of parasites within or on animals. The present invention further provides the use of a compound according to a first embodiment in the control of ectoparasites on animals.

[0267] When used in relation to parasites in or on animals, the term “control” means reducing the number of pests or parasites, eradicating pests or parasites, and / or preventing further pest or parasitic infestations.

[0268] When used in relation to parasites within or on animals, the term “to treat” means to suppress, delay, halt, or regress the progression or severity of an existing symptom or disease.

[0269] When used in relation to parasites within or on animals, the term “prevent” refers to the avoidance of symptoms or diseases that progress within the animal.

[0270] When used in relation to parasites within or on animals, the term “animal” can refer to mammals and non-mammals such as birds or fish. In the case of mammals, this can be humans or non-human mammals. Non-human mammals include, but are not limited to, domesticated animals and companion animals. Domesticated animals include, but are not limited to, cattle, camelids, pigs, sheep, goats, and horses. Companion animals include, but are not limited to, dogs, cats, and rabbits.

[0271] A "parasite" is a harmful organism that lives inside or on a host animal and benefits from the nutrients provided at the expense of the host animal. An "endoparasite" is a parasite that lives inside the body of a host animal. An "ectoparasite" is a parasite that lives on the surface of a host animal. Examples of ectoparasites, though not limited to these, include mites, insects, and crustaceans (e.g., sea slaters). The subclass Acari (or Acarina) includes ticks and mites. Ticks, though not limited to these, include members of the following genera: Rhipicaphalus, for example, Rhipicaphalus (Boophilus) microplus and Rhipicaphalus sanguineus; Amblyomma; Dermacentor; Haemaphysalis; Hyalomma; Ixodes; Rhipicentor; Margaropus; Argas; Otobius; and Ornithodoros. Mites include, but are not limited to, members of the following genera: Chorioptes, e.g., bovine sarcoptes; Psoroptes, e.g., sheep sarcoptes; Cheyletiella; Dermanyssus, e.g., moth mite (Dermanyssus gallinae); Ortnithonyssus; Demodex, e.g., canine demodex mite (Dermanyssus canis); Sarcoptes, e.g., scabies mite (Sarcoptes scabiei); and Psorergates.Insects include, but are not limited to, members of the following orders: fleas (Siphonaptera), diptera, gnaths, lepidoptera, coleoptera, and homoptera. Members of the flea order (Siphonaptera) include, but are not limited to, the cat flea (Ctenocephalides felis) and the dog flea (Ctenocephatides canis). Members of the order Diptera include, but are not limited to, species of the genus Musca; botflies, e.g., Gasterophilus intestinalis and Oestrus ovis; stable flies; horseflies, e.g., species of the genera Haematopota and Tabunus; haematobia, e.g., Haematobia irritans; stable flies (Stomoxys); blowflies (Lucilia); midges; and mosquitoes. Members of the order Mycnae include, but are not limited to, blood-sucking lice and biting lice, e.g., sheep lice (Bovicola Ovis) and cow lice (Bovicola Bovis).

[0272] When used in relation to parasites in or on animals, the term “effective dose” refers to the amount or dosage of the compound or salt thereof of the present invention or its salts that produces the desired effect in or on an animal in one or more doses. The effective dose can be readily determined by a diagnostician skilled in the art by using known techniques and by observing the results obtained under similar circumstances. In determining the effective dose, the diagnostician will consider a number of factors, including, but not limited to, the species of mammal; its size, age, and general health; the parasite being controlled and the degree of invasiveness; the specific disease or disorder associated; the degree of complications or severity in the disease or disorder; the individual’s response; the specific compound administered; the mode of administration; the bioavailability characteristics of the administered preparation; the selected dosage administration plan; the use of concomitant drugs; and other relevant circumstances.

[0273] The compounds of the present invention may be administered to animals by any route having the desired effect, including, but not limited to, topical, oral, parenteral, and subcutaneous administration. Topical administration is preferred. Suitable formulations for topical administration include, for example, solutions, emulsions, and suspensions, which may be in the form of pour-on, spot-on, spray-on, spray-lace, or dip. Alternatively, the compounds of the present invention may be administered by ear tag or collar.

[0274] The salt forms of the compounds of the present invention include both pharmaceutically acceptable salts and veterinarily acceptable salts, which may differ from agriculturally acceptable salts. Pharmaceutical and veterinarily acceptable salts, as well as general methodologies for preparing them, are well known in the art. See, for example, Gould, PL, “Salt selection for basic drugs”, International Journal of Pharmaceutics, 33:201-217 (1986); Bastin, RJ, et al., “Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities”, Organic Process Research and Development, 4:427-435 (2000); and Berge, SM, et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Sciences, 66:1-19, (1977). Those skilled in the art will understand that the compounds of the present invention can be readily converted to salts such as hydrochlorides and isolated as such salts using techniques and conditions well known to those skilled in the art. In addition, those skilled in the art of synthesis will understand that the compounds of the present invention can be readily converted from the corresponding salts to the corresponding free bases and can be isolated as such salts.

[0275] The present invention also provides a method for controlling pests (such as mosquitoes and other pathogenic animals; see also http: / / www.who.int / malaria / vector_control / irs / en / ). In one embodiment, the method for controlling pests includes the step of applying the composition of the present invention to a target pest, its habitat, or surface or substrate by brush application, roller application, spraying, coating, or immersion. For example, the application of IRS (Indoor Residual Spray) to surfaces such as walls, ceilings, or floors is envisioned by the method of the present invention. In another embodiment, such a composition is envisioned to be applied to a substrate such as a nonwoven or fabric material in the form of a net, clothing, bedding, curtains, and tents (or in a form that can be used to manufacture these).

[0276] In one embodiment, a method for controlling such pests includes the step of applying an organismally effective amount of the composition of the present invention to a target pest, its habitat, or a surface or substrate so as to impart effective, persistent pest control activity to the surface or substrate. Such application may be carried out by brush application, roller application, spraying, coating, or immersion of the organismally effective composition of the present invention. For example, IRS application on surfaces such as walls, ceilings, or floors is envisioned by the method of the present invention to impart effective, persistent pest control activity to the surface. In another embodiment, such a composition is envisioned for the persistent control of pests on substrates such as fabric materials in the form of nets, clothing, bedding, curtains, and tents (or forms that may be used in the manufacture thereof).

[0277] The substrate, including the nonwoven fabric, cloth, or net to be treated, may be made from natural fibers such as cotton, raffia, jute, flax, sisal, hemp cloth, or wool, or from synthetic fibers such as polyamide, polyester, polypropylene, or polyacrylonitrile. Polyester is particularly preferred. Methods for treating textiles are known, for example, from International Publication No. 2008 / 151984, International Publication No. 2003 / 034823, U.S. Patent No. 5631072, International Publication No. 2005 / 64072, International Publication No. 2006 / 128870, European Patent No. 1724392, International Publication No. 2005113886, or International Publication No. 2007 / 090739.

[0278] A further field of application of the composition according to the present invention is the field of trunk injection / trunk treatment of all ornamental trees and all kinds of fruit trees and nut-bearing trees.

[0279] In the field of tree trunk injection / trunk treatment, the compounds according to the present invention are particularly suitable for the wood-boring insects of the Lepidoptera and Coleoptera mentioned above, and especially for the wood-boring insects listed in Tables A and B below.

[0280] [Table 2]

[0281] [Table 3-1] [Table 3-2]

[0282] The present invention can be used to control any insect pests that may be present in turfgrass, including, for example, beetles, caterpillars, fire ants, ground pearls, millipedes, pill bugs, mites, mole crickets, scale insects, mealybugs, ticks, spittlebugs, southern chinch bugs, and ground bugs. The present invention can also be used to control insect pests at various stages of their life cycle, including eggs, larvae, nymphs, and adults.

[0283] In particular, the present invention relates to ground beetles (genera: Cyclocephala spp. (e.g., masked chafer, C. lurida), Rhizotrogus spp. (e.g., European chafer, R. majalis), Cotinus spp. (e.g., blue-spotted chafer, C. nitida), Popillia spp. (e.g., Japanese beetle, P. japonica), Phyllophaga spp. (e.g., May / June beetle), and Ataenius). (e.g., Black turfgrass ataenius, A. spretulus), Maladera spp. (e.g., red velvet beetle, M. castanea, and Tomarus spp.), cottony cushion scales (Margarodes spp.), mole crickets (tawny, southern, and brachyptera; Scapteriscus spp., mole cricket (Gryllotalpa africana)), and leather jackets (European crane fly, Tipula genus). It can be used to control insect pests that feed on turfgrass roots, including spp.)).

[0284] The present invention can also be used to control insect pests of turfgrass that live in straw, including armyworms (such as Spodoptera frugiperda and common armyworms (Pseudaletia unipuncta), etc.), cutworms, weevils (such as Sphenophorus spp., S. venatus verstitus and S. parvulus), and sod webworms (such as Crambus spp., tropical sod webworm, and Herpetogramma phaeopteralis).

[0285] The present invention can also be used to control insect pests that live on the ground and feed on grass leaves, including the Southern kink bug (Blissus insularis, etc.), Bermudagrass mites (Eriophyes cynodoniensis), African rhodesgrass mealybugs (Antonina graminis), two-lined spittlebugs (Propsapia bicincta), leafhoppers, cutworms (Noctuidae), and wheat aphids.

[0286] This invention can also be used to control other pests of turfgrass, such as the red imported fire ant (Solenopsis invicta), which builds ant mounds in lawns.

[0287] In the field of hygiene, the compositions according to the present invention are effective against external parasites such as hard ticks, soft ticks, scabies mites, chiggers, flies (stable flies and licking flies), parasitic fly larvae, lice, pubic lice, biting lice, and fleas.

[0288] Examples of such parasites are as follows: Among the orders Anoplurida, these include the genera Haematopinus, Linognathus, Pediculus, Phtirus, and Solenopotes.

[0289] Among the orders Mallophagida, the genera Trimenopon, Menopon, Trinoton, Bovicola, Werneckiella, Lepikentron, Damalina, Trichodectes, and Felicola are included.

[0290] Among the order Diptera and its suborders Nematocerina and Brachycerina, for example, the genera Aedes, Anopheles, Culex, Simulium, Eusimulium, Phlebotomus, Lutzomyia, Culicoides, Chrysops, Hybomitra, Atylotus, Tabanus, and Haematopota spp.) , Philippomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp. (spp.), Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp., and Melophagus spp..

[0291] Within the order Siphonapterida, for example, there are genera such as Pulex spp., Ctenocephalides spp., Xenopsylla spp., and Ceratophyllus spp..

[0292] Among the order Heteropterida, for example, there are genera such as bed bugs (Cimex spp.), assassin bugs (Triatoma spp.), Rhodnius spp., and Panstrongylus spp.

[0293] Among the order Blattardia, for example, the oriental cockroach (Blatta orientalis), the American cockroach (Periplaneta americana), the German cockroach (Blattelagermanica), and the genus Supella.

[0294] Among the subclass Acaria (Acarida), suborder Metastigmata, and suborder Mesostigmata, for example, the genera Argas, Ornithodorus, Otobius, Ixodes, Amblyomma, Boophilus, Dermacentor, Haemophysalis, Hyalomma, Rhipicephalus, Dermanyssus, and Railietia. (spp.), Pneumonyssus spp., Sternostoma spp., and Varroa spp..

[0295] Among the orders Acari (Actinedida) (Prostigmata) and Acaridida (Astigmata), for example, the genera Acarapis, Cheyletiella, Ornithocheyletia, Myobia, Psorergates, Demodex, Trombicula, Listrophorus, Acarus, Tyrophagus, Caloglyphus, and Hypodectes. spp.), Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp., and Laminosioptes spp..

[0296] The compositions according to the present invention are also suitable for protecting materials such as wood, textiles, plastics, adhesives, glues, paints, paper and cardboard, leather, flooring materials and buildings from insect infestation.

[0297] The composition according to the present invention can be used, for example, against the following pests: European house beetle (Hylotrupes bajulus), Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, pine wood beetle (Ernobius mollis), large wood beetle (Priobium carpini), flat bark beetle (Lyctus brunneus), African flat bark beetle (Lyctus africanus), American flat bark beetle (Lyctus planicollis), oak flat bark beetle (Lyctus *) and beetles such as Dinoderus minutus, as well as hymenopteran insects such as Sirex juvencus, Urocerus gigas, Urocerus gigas taignus and Urocerus augur, and Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucifugus Termites such as *Lucifugus*, *Mastotermes darwiniensis*, *Zootermopsis nevadensis*, and *Coptotermes formosanus*, as well as silverfish such as *Lepisma saccharina*.

[0298] Compounds of formulas I and I'a, or salts thereof, are particularly suitable for controlling one or more pests selected from the families: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae, and Heteroderidae. In preferred embodiments of each model, compound TX (where the abbreviation "TX" means "one compound selected from the compounds defined in Tables D-1 to D-66 and Table P") controls one or more pests selected from the families: Noctuidae, Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Tortricidae, Delphacidae, Aphididae, Noctuidae, Crambidae, Meloidogynidae and Heteroderidae.

[0299] The compounds of formulas I and I'a, or their salts, are found in the genera: species of Spodoptera, Plutella, Frankliniella, Thrips, Euschistus, Cydia, Nilaparvata, Myzus, Aphis, Diabrotica, Rhopalosiphum, Pseudoplusia, and Chilo It is particularly suitable for controlling one or more pests selected from (spp). In preferred embodiments of each model, compound TX (where the abbreviation "TX" means "one compound selected from the compounds defined in Tables D-1 to D-66 and Table P") is a genera: species of Spodoptera, Plutella, Frankliniella, Thrips, Euschistus, Cydia, Nilaparvata, Myzus, Aphis, Diabrotica, Rhopalosiphum, and Pseudoplusia. Control one or more pests selected from the genus Chilo (spp.) and Chilo species (Chilo spp.).

[0300] Compounds of formulas I and I'a, or salts thereof, are particularly suitable for controlling one or more species of the following: Egyptian armyworm (Spodoptera littoralis), diamondback moth (Plutella xylostella), citrus thrips (Frankliniella occidentalis), onion thrips (Thrips tabaci), Euschistus heros, codling moth (Cydia pomonella), brown planthopper (Nilaparvata lugens), peach aphid (Myzus persicae), chrysodeixis includens, bean aphid (Aphis craccivora), Diabrotica balteata, Rhopalosiphum padi, and soybean leaf borer (Chilo suppressalis).

[0301] In preferred embodiments of each aspect, compound TX (where the abbreviation "TX" means "one compound selected from the compounds defined in Tables D-1 to D-66 and Table P") is the Egyptian armyworm (Spodoptera littoralis), diamondback moth (Plutella xylostella), citrus thrips (Frankliniella occidentalis), onion thrips (Thrips tabaci), Euschistus heros, codling moth (Cydia pomonella), brown planthopper (Nilaparvata lugens), peach aphid (Myzus persicae), chrysodeixis includens, bean aphid (Aphis craccivora), Diabrotica balteata, and Rhopalosiphum Padia, as well as the Egyptian armyworm (Spodoptera littoralis) +TX, diamondback moth (Plutella xylostella) +TX, and other rice stem borers (Chilo Suppressalis); citrus thrips (Frankliniella occidentalis) +TX, onion thrips (Thrips tabaci) +TX, Euschistus heros +TX, codling moth (Cydia pomonella) +TX, brown planthopper (Nilaparvata lugens) +TX, peach aphid (Myzus persicae) +TX, Chrysodeixis includens +TX, bean aphid (Aphis craccivora) +TX, Diabrotica balteata +TX, Rhopalosiphum padi Control one or more species of Padi)+TX and Chilo suppressalis+TX.

[0302] In one embodiment of each aspect, one compound from the compounds in Tables D-1 to D-66 and Table P is used in cotton, vegetables, maize, cereals, rice, and soybean crops against the following insects: Egyptian armyworm (Spodoptera littoralis), diamondback moth (Plutella xylostella), citrus thrips (Frankliniella occidentalis), onion thrips (Thrips tabaci), Euschistus heros, codling moth (Cydia pomonella), brown planthopper (Nilaparvata lugens), peach aphid (Myzus persicae), chrysodeixis includens, bean aphid (Aphis craccivora), diabrotica balteata, and rhopalosiphum. It is suitable for controlling Padia and the rice stem borer (Chilo Suppressalis).

[0303] In one embodiment, one compound from Tables D-1 to D-66 and Table P is suitable for controlling armyworms (Mamestra) (preferably in vegetables), codling moths (Cydia pomonella) (preferably in apples), species of the genus Empoasca (preferably in vegetables and vineyards), species of the genus Leptinotarsa ​​(preferably in potatoes), and rice stem borer (Chilo supressalis) (preferably in rice).

[0304] The compounds according to the present invention may have any number of advantages, including, in particular, advantageous levels of biological activity for protecting plants from insects or excellent properties for use as agricultural chemical active ingredients (e.g., high biological activity, advantageous activity range, and a high safety profile (improved physicochemical properties or high biodegradability to above-ground and subterranean non-target organisms such as fish, birds, and bees)). In particular, it has been unexpectedly found that certain compounds of formula (I) may exhibit an advantageous safety profile, especially to non-target arthropods such as honeybees, solitary honeybees, and bumblebees, most specifically the European honeybee (Apis mellifera).

[0305] The compounds according to the present invention can be used as pesticides in their unmodified form, but they are generally incorporated into compositions using various methods with additives such as carriers, solvents, and surfactants. The formulations may be in various physical forms, such as powder, gel, wettable powder, water-dispersible granules, water-dispersible tablets, effervescent pellets, emulsifying concentrates, microemulsifying concentrates, oil-in-water emulsions, oily flowables, aqueous dispersions, oily dispersions, suspend emulsions, capsule suspensions, emulsifying granules, soluble liquids, water-soluble concentrates (containing water or a hydrated organic solvent as a carrier), impregnated polymer films, or other forms known from, for example, the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations may be used directly or diluted before use. Dilution can be performed, for example, with water, liquid fertilizers, trace elements, biological substances, oils, or solvents.

[0306] The formulation can be prepared, for example, by mixing the active ingredient with compounding aids to obtain a composition in the form of fine solids, granules, solution, dispersion, or emulsion. The active ingredient can also be compounded with other aids such as fine solids, mineral oil, vegetable oil or animal oil, modified vegetable oil or modified animal oil, organic solvents, water, surfactants, or combinations thereof.

[0307] The active ingredient may also be contained in extremely fine microcapsules. Microcapsules contain the active ingredient in a porous carrier. This allows for the release of the active ingredient into the environment in a controlled amount (e.g., slow-release). Microcapsules typically have a diameter of 0.1 to 500 microns. They contain the active ingredient in an amount of about 25 to 95% by weight of the capsule. The active ingredient may be in the form of a solid mass, fine particles in a solid or liquid dispersion, or a suitable solution. The encapsulation membrane may contain, for example, natural or synthetic rubber, cellulose, styrene / butadiene copolymer, polyacrylonitrile, polyacrylate, polyester, polyamide, polyurea, polyurethane or chemically modified polymers and xanthogenic starch or other polymers known to those skilled in the art. Alternatively, extremely fine microcapsules may be formed by containing the active ingredient in the form of fine particles in a solid matrix of a base, but the microcapsule itself is not encapsulated.

[0308] Suitable compounding agents for preparing the compositions according to the present invention are known in themselves. Suitable liquid carriers include water, toluene, xylene, petroleum ether, vegetable oil, acetone, methyl ethyl ketone, cyclohexanone, acid anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl ester of acetate, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-Trichloroethane, 2-Heptanone, α-Pinene, d-Limonene, Ethyl Lactate, Ethylene Glycol, Ethylene Glycol Butyl Ether, Ethylene Glycol Methyl Ether, γ-Butyrolactone, Glycerol, Glycerol Acetate, Glycerol Diacetate, Glycerol Triacetate, Hexadecane, Hexylene Glycol, Isoamyl Acetate, Isobornyl Acetate, Isooctane, Isophorone, Isopropylbenzene, Isopropyl Myristate, Lactic Acid, Laurylamine, Mesityl Oxide, Methoxypropanol, Methyl Isoamyl Ketone, Methyl Isobutyl Ketone, Methyl Laurate, Methyl Octanoate, Methyl Oleate, Methylene Chloride, m-Xylene, n-Hexane, n-Octylamine, Octadecanoic Acid, Octylamine Acetate High molecular weight alcohols such as 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 amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, and N-methyl-2-pyrrolidone can be used.

[0309] Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, keelberger, limestone, calcium carbonate, bentonite, calcium montmorillonite, cotton husk, wheat flour, soy flour, pumice, wood flour, crushed walnut shells, lignin, and similar substances.

[0310] Numerous surfactants can be advantageously used in both solid and liquid formulations, particularly in formulations that can be diluted with a carrier before use. Surfactants can be anionic, cationic, nonionic, or polymeric, and these can be used as emulsifiers, wetting agents, or suspending agents, or for other purposes. Typical surfactants include, for example, alkyl sulfate salts such as diethanolammonium lauryl sulfate; alkylaryl sulfonate salts such as calcium dodecylbenzenesulfonate; alkylphenol / alkylene oxide addition products such as nonylphenol ethoxylate; alcohol / alkylene oxide addition products such as tridecyl alcohol ethoxylate; soaps such as sodium stearate; alkylnaphthalene sulfonate salts such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinates such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters such as sorbitol oleate; quaternary amines such as lauryltrimethylammonium chloride; polyethylene glycol esters of fatty acids such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkyl phosphate esters; as well as further substances described, for example, in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood, New Jersey (1981).

[0311] Further auxiliary agents that may be used in pest control formulations include crystallization inhibitors, viscosity modifiers, suspension agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, defoaming agents, complexing agents, neutralizing agents or pH adjusters and buffering agents, corrosion inhibitors, fragrances, wetting agents, uptake enhancers, trace elements, plasticizers, lubricants, dispersants, thickeners, antifreezes, fungicides, and liquid and solid fertilizers.

[0312] The composition according to the present invention may contain additives comprising vegetable oil or animal oil, mineral oil, alkyl esters of such oils, or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the present invention is generally 0.01 to 10% based on the mixture applied. For example, the oil additive can be added to the spray tank at a desired concentration after the spray mixture has been prepared. Preferred oil additives include mineral oil or vegetable oil such as rapeseed oil, olive oil, or sunflower oil, emulsified vegetable oil, alkyl esters of vegetable oils such as methyl derivatives, or animal oils such as fish oil or beef tallow. Preferred oil additives include C8 to C 22 Alkyl esters of fatty acids, especially C 12 ~C 18 These are methyl derivatives of fatty acids, including, for example, methyl esters of lauric acid, palmitic acid, and oleic acid (methyl laurate, methyl palmitate, and methyl oleate, respectively). Many oil derivatives are found in the Compendium of Herbicide Adjuvants, 10 th This information is publicly available from Edition, Southern Illinois University, 2010.

[0313] The compositions of the present invention generally comprise 0.1 to 99% by weight, particularly 0.1 to 95% by weight, of the compound of the present invention and 1 to 99.9% by weight of compounding aids (preferably including 0 to 25% by weight of a surfactant). Commercial products may preferably be formulated as concentrates, but end users will typically utilize diluted formulations.

[0314] The application rate varies widely and depends on soil properties, application method, crop plants, pests being controlled, major weather conditions, and other factors that depend on the application method, timing, and target crop. As general guidelines suggest, the compound may be applied in amounts of 1 to 2000 l / ha, and especially 10 to 1000 l / ha.

[0315] A preferred formulation may have the following composition (by weight): Emulsifiable concentrate: Active ingredient: 1-95%, preferably 60-90% Surfactants: 1-30%, preferably 5-20% Liquid carrier: 1-80%, preferably 1-35%

[0316] Powder: Active ingredient: 0.1-10%, preferably 0.1-5% Solid carriers: 99.9-90%, preferably 99.9-99%

[0317] Suspension concentrate: Active ingredient: 5-75%, preferably 10-50% Water: 94-24%, preferably 88-30% Surfactants: 1-40%, preferably 2-30%

[0318] Wettable powder: Active ingredient: 0.5-90%, preferably 1-80% Surfactants: 0.5-20%, preferably 1-15% Solid carrier: 5-95%, preferably 15-90%

[0319] Granules: Active ingredient: 0.1-30%, preferably 0.1-15% Solid carrier: 99.5-70%, preferably 97-85%

[0320] The following examples further illustrate, but are not limited to, the present invention.

[0321] [Table 4]

[0322] A hydrated agent can be obtained by thoroughly mixing the composite with an auxiliary agent, thoroughly grinding the mixture in a suitable mill, and diluting it with water to obtain a suspension of the desired concentration.

[0323] [Table 5]

[0324] The compound is thoroughly mixed with an auxiliary agent, and the mixture is thoroughly ground in a suitable mill to obtain a powder that can be used directly for seed treatment.

[0325] [Table 6]

[0326] Any emulsion of the required dilution, suitable for plant protection, can be obtained from this concentrate by diluting it with water.

[0327] [Table 7]

[0328] A ready-to-use powder is obtained by mixing the compound with a carrier and grinding the mixture in a suitable mill. Such powders can also be used for drying and coating seeds.

[0329] [Table 8]

[0330] The composite material is mixed with an auxiliary agent and ground, and the mixture is moistened with water. The mixture is extruded and then dried in an airflow.

[0331] [Table 9]

[0332] In a mixer, the finely ground composite is uniformly applied to kaolin moistened with polyethylene glycol. This yields coated granules that do not generate dust.

[0333] [Table 10]

[0334] By thoroughly mixing the finely ground composite with an auxiliary agent, a suspension concentrate can be obtained, from which a suspension of any desired dilution can be obtained by diluting with water. Using such dilutions, living plants and plant propagation materials can be treated and protected from microbial parasitism by spraying, pouring, or immersion.

[0335] [Table 11]

[0336] By thoroughly mixing the finely ground composite with an auxiliary agent, a suspension concentrate can be obtained, from which a suspension of any desired dilution can be obtained by diluting with water. Using such dilutions, living plants and plant propagation materials can be treated and protected from microbial parasitism by spraying, pouring, or immersion.

[0337] Slow-release capsule suspension Mix 28 parts of the compound with 2 parts of an aromatic solvent and 7 parts of a toluene diisocyanate / polymethylene-polyphenyl isocyanate mixture (8:1). Emulsify this mixture 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 achieved. Add a mixture of 2.8 parts of 1,6-diaminohexane in 5.3 parts of water to this emulsion. Stir the mixture until the polymerization reaction is complete. Stabilize the resulting capsule suspension by adding 0.25 parts of a thickener and 3 parts of a dispersant. The capsule suspension formulation contains 28% of the active ingredient. The diameter of the medium-sized capsules is 8-15 microns. Apply the resulting formulation to seeds as an aqueous suspension in an apparatus suitable for this purpose.

[0338] Examples of formulation types include emulsion concentrates (EC), suspension concentrates (SC), suspension emulsions (SE), capsule suspensions (CS), water-dispersible granules (WG), emulsifying granules (EG), emulsions, water-in-oil (EO), emulsions, oil-in-water (EW), microemulsions (ME), oil dispersions (OD), oil-miscible flowables (OF), oil-miscible liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), industrial concentrates (TK), dispersible concentrates (DC), wettable powders (WP), soluble granules (SG), or any technically preferred formulations combined with agriculturally acceptable auxiliaries. [Examples]

[0339] Preparation example: LCMS method: Method 1: The spectra were recorded using a Waters mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) equipped with an electrospray source (polarity: cations and anions, capillary: 3.00kV, cone range: 30V, extractor: 2.00V, source temperature: 150℃, desolvation temperature: 350℃, cone gas flow: 50l / h, desolvation gas flow: 650l / h, mass range: 100~900Da) and a Waters Acquity UPLC: binary pump, heated column compartment, diode-array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm, Temperature: 60°C, DAD wavelength range (nm): 210~500, Solvent gradient: A = Water + 5% MeOH + 0.05% HCOOH, B = Acetonitrile + 0.05% HCOOH, Gradient: 10~100% B over 1.2 minutes; Flow (ml / min) 0.85.

[0340] Method 2: The spectra were recorded using a Waters mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) equipped with an electrospray source (polarity: cations and anions, capillary: 3.00kV, cone range: 41V, extractor: 2.00V, source temperature: 150℃, desolventing temperature: 5000℃, cone gas flow: 50l / h, desolventing gas flow: 1000l / h, mass range: 110~800Da) and a Waters Acquity UPLC: binary pump, heated column compartment, diode-array detector and ELSD detector. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm, Temperature: 40°C, PDA wavelength range (nm): 200~400, Solvent gradient: A = Water + 5% Acetonitrile + 0.1% HCOOH, B = Acetonitrile + 0.05% HCOOH, Gradient: 10~100% B in 1.3 minutes; Flow (ml / min): 0.6

[0341] Method 3: The spectra were recorded using a Waters Corporation mass spectrometer (SQD, SQDII, or QDA single quadrupole mass spectrometer) equipped with an electrospray source (polarity: cations and anions, capillary: 0.8~3.00kV, cone: 5~30V, source temperature: 120~150℃, desolvation temperature: 350~600℃, cone gas flow: 50~150l / h, desolvation gas flow: 650~1000l / h, mass range: 50~900Da) and a Waters Corporation Acquity UPLC: binary pump, heated column compartment diode-array detector, and ELSD. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm, Temperature: 60°C, DAD wavelength range (nm): 210~400, Runtime: 1.5 minutes; Solvent: A = Water + 5% MeOH + 0.05% HCOOH, B = Acetonitrile + 0.05% HCOOH; Flow rate (ml / min) 0.85, Gradient: 10% B composition over 0.2 minutes, then 10~100% B over 1.0 minute, 100% B composition over 0.2 minutes, 100~10% B over 0.05 minutes, 10% B composition over 0.05 minutes.

[0342] Method 4: The spectra were recorded using a Waters Corporation mass spectrometer (SQD, SQDII, or QDA single quadrupole mass spectrometer) with an electrospray source (polarity: cations and anions, capillary: 3.00kV, cone: 41V, source temperature: 150°C, desolvation temperature: 500°C, cone gas flow: 50l / h, desolvation gas flow: 1000l / h, mass range: 110-800Da) and a Waters Corporation Acquity UPLC: binary pump, heated column compartment diode-array detector, and ELSD. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm, Temperature: 40°C, DAD wavelength range (nm): 200~400, Runtime: 1.6 minutes; Solvent: A = Water + 5% Acetonitrile + 0.1% HCOOH, B = Acetonitrile + 0.05% HCOOH; Flow rate (ml / min) 0.6, Gradient: 10~50% B in 0.2 minutes, then 50~100% B in 0.5 minutes, 100% B final composition in 0.6 minutes, 100~10% B in 0.05 minutes, 100%~10% B in 0.1 minutes, then 10% B final composition in 0.2 minutes.

[0343] Method 5: The spectra were recorded using the following equipment: an Agilent Technologies mass spectrometer (SQD, SQDII, or QDA single quadrupole mass spectrometer) with an electrospray source (polarity: cations and anions, capillary: 4.00kV, fragmenter: 100V, gas temperature (C): 350, gas flow: 11 l / min, mass range: 110-1000 Da) and an Agilent HPLC from Agilent Technologies: column: KINETEX EVO C18, 2.6 μm, 50 × 4.6 mm, Temperature: 40°C, DAD wavelength range (nm): 210~400, Runtime: 2.5 minutes; Solvent: A = Water + 5% Acetonitrile + 0.1% HCOOH, B = Acetonitrile + 0.1% HCOOH; Flow rate (ml / min) 1.8, Gradient: 10~100% B in 0.9 minutes, 100% B fixed composition in 0.9 minutes, 100~10% B in 0.4 minutes, 10% B fixed composition in 0.3 minutes.

[0344] Example 1: Preparation of N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (compound P.5) [ka] Step A: Preparation of 5-[[2,4-bis(trifluoromethyl)anilino]methylene]-2,2-dimethyl-1,3-dioxane-4,6-dione (intermediate I-1) [ka] 2,2-dimethyl-1,3-dioxane-4,6-dione (3.46 g, 24 mmol, 1.2 equivalents) and trimethoxymethane (11 mL, 96 mmol, 4.8 equivalents) were heated under reflux for 90 minutes. Next, 2,4-bis(trifluoromethyl)aniline (4.72 g, 20 mmol, 1 equivalent) was added at the same temperature, and the solution was stirred for 50 minutes. When stirring and heating were stopped, a solid began to precipitate. The solid was collected at room temperature, washed with cyclohexane, and air-dried. A second collection of the solid could be recovered from the filtrate and washed with cyclohexane. Product I-1 was obtained as an off-white solid (6.27 g, 82%). 1 H NMR(400MHz,CDCl3)δ ppm:1.80(s,6H),7.64(d,J=8.80Hz,1H),7.96(d,J=8.44Hz,1H),7.98-8.03(m,1H),8.67(d,J=13.20Hz,1H),11.87(br d,J=12.84Hz,1H).

[0345] Step B: Preparation of 6,8-bis(trifluoromethyl)-1H-quinoline-4-one (intermediate I-2) [ka] 5-[[2,4-bis(trifluoromethyl)anilino]methylene]-2,2-dimethyl-1,3-dioxane-4,6-dione (I-1, 3.12 g, 8.14 mmol) was added to diphenyl ether (15 mL) under reflux. The mixture was stirred under reflux for 30 minutes and then cooled to room temperature. The reaction was diluted with cyclohexane (20 mL), and the precipitate was filtered and washed with a large amount of cyclohexane. The desired product was obtained as a light-brown powder (1.63 g, 71%). 1 H NMR(400MHz,DMSO-d6)δ ppm:6.33(br s,1H),7.97(br s,1H),8.33(s,1H),8.66(br s,1H),11.57(br s,1H). LC-MS (Method 3): Retention time 0.86 min, m / z282[M+H + ].

[0346] Step C: Preparation of 4-chloro-6,8-bis(trifluoromethyl)quinoline (intermediate I-3) [ka] To a flask containing 6,8-bis(trifluoromethyl)-1H-quinoline-4-one (I-3, 2.76 g, 9.81 mmol), phosphorus trichloride (3 mL, 31.5 mmol, 3.21 equivalents) was added, and the mixture was stirred at 100°C for 15 minutes, then cooled to room temperature, and then placed in an ice bath. The reaction was inactivated with water, and aqueous ammonia was added until the pH reached 8-9. The mixture was then extracted three times with dichloromethane (3 × 100 mL), and concentrated under reduced pressure to obtain the desired product as a light brown powder (2.5 g, 8.3 mmol, 85%). 1 H NMR(400MHz,CDCl3)δ ppm:7.75(d,J=4.77Hz,1H),8.34(s,1H),8.82(s,1H),9.08(d,J=4.77Hz,1H). LC-MS (Method 3): Retention time 1.18 min, m / z 300[M+H + ].

[0347] Step D: Preparation of (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]propanamide (intermediate I-4) [ka] To a solution of 4-chloro-6,8-bis(trifluoromethyl)quinoline (I-3, 1.51 g, 5.04 mmol) in N,N-dimethylformamide (50 mL), (2S)-2-aminopropanamide hydrochloride (3.24 g, 25.2 mmol, 5.00 equivalents) and potassium carbonate (4.88 g, 35.3 mmol, 7 equivalents) were added. This reaction mixture was heated overnight at 100 °C. The reaction was cooled, diluted with water, and extracted three times with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by flash chromatography in silica gel (ethyl acetate in cyclohexane) yielded the desired product as a brown solid (541 mg, 31% yield). 1 H NMR(400MHz,DMSO-d6)δ ppm:1.49-1.58(m,3H),4.09-4.19(m,1H),6.49-6.55(m,1H),7.13-7.22(m,1H),7.63-7 .71(m,1H),7.83-7.90(m,1H),8.17-8.24(m,1H),8.60-8.66(m,1H),9.23-9.29(m,1H). LC-MS (method 3): retention time 0.75 min, m / z352[M+H + ].

[0348] Step E: Preparation of (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]-N-(dimethylaminomethylene)propanamide (compound I-5) [ka] To a solution of (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]propanamide (I-4, 0.74 g, 2.1 mmol) in 2-methyltetrahydrofuran (21 mL), 1,1-dimethoxy-N,N-dimethylmethaneamine (0.56 mL, 4.2 mmol, 2 equivalents) was added, and the reaction mixture was stirred at 50°C for 30 minutes. The reaction was cooled and concentrated under reduced pressure to obtain (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]-N-(dimethylaminomethylene)propanamide (I-5) as a brown solid (755 mg, 80%). 1 H NMR(400MHz,DMSO-d6)δ ppm:1.57(d,J=6.97Hz,3H),2.98-3.09(m,3H),3.10-3.19(m,3H),4.22-4.37(m,1H),6.45-6.55(m, 1H),7.83-7.94(m,1H),8.17-8.25(m,1H),8.43-8.52(m,1H),8.52-8.60(m,1H),9.20-9.31(m,1H).

[0349] Step F: Preparation of N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (compound P.5) [ka] (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolyl]amino]-N-(dimethylaminomethylene)propanamide (I-5 prepared above, 755 mg, 1.86 mmol, 1 equivalent) was dissolved in 2-methyltetrahydrofuran (7.4 mL). Next, pyrimidine-2-ylhydrazine hydrochloride (0.49 g, 3.35 mmol) and acetic acid (4.65 mL) were added, and the reaction was stirred at 80°C for 1 hour. The reaction was cooled, diluted with ethyl acetate, and extracted with water. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by flash chromatography in silica gel (ethyl acetate in cyclohexane) yielded the desired product (P.5) as a light brown solid (631.5 mg, 75% yield). 1 H NMR(400MHz,DMSO-d6)δ ppm:1.76(d,J=6.97Hz,3H),5.96(quin,J=7.06Hz,1H),6.60(d,J=5.87Hz,1H),7.51-7.62(m,1H),8. 15-8.22(m,2H),8.26(d,J=7.34Hz,1H),8.55(d,J=5.50Hz,1H),8.92(d,J=5.14Hz,2H),9.14(s,1H). LC-MS (Method 3): Retention time 0.88 min, m / z455[M+H + ].

[0350] Example 2: Preparation of N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazoline-4-amine (compound P.16) [ka] Step A: Preparation of 2-iodo-4,6-bis(trifluoromethyl)aniline (intermediate I-6) [ka] 2,4-Bis(trifluoromethyl)aniline (CAS No. 367-71-5, 1.50 g, 6.2 mmol) was dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol, and the solution was cooled to 0°C. N-iodosuccinimide (1.47 g, 6.2 mmol, 1 equivalent) was added, and the reaction was carried out at 0°C for 1 hour, then stirred overnight at room temperature. The reaction was concentrated under reduced pressure, and the crude material was purified by flash chromatography with silica gel (ethyl acetate in cyclohexane) to obtain product (I-6) as a bright pink crystalline solid (2.09 g, 95%). 1 H NMR(400MHz,CDCl3)δ ppm:5.08(br s,2H),7.70-7.74(m,1H),8.06(d,J=1.47Hz,1H).

[0351] Step B: Preparation of 2-amino-3,5-bis(trifluoromethyl)benzonitrile (intermediate I-7) [ka] In a sealed test tube, 2-iodo-4,6-bis(trifluoromethyl)aniline (I-6, 1.00 g, 2.82 mmol), N,N-dimethylformamide (5.63 mL), and copper(I) cyanide (0.31 g, 3.38 mmol, 1.2 equivalents) were charged. The mixture was stirred overnight at 100°C. The mixture was cooled, filtered through Celite, and extracted twice with MTBE (2 × 20 mL). The combined organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Purification by flash chromatography using silica gel (ethyl acetate in cyclohexane) yielded the desired product (I-7) as a brown solid (567 mg, 79%). 1 H NMR(400MHz,CDCl3)δ ppm:5.33(br s,2H),7.83-7.90(m,2H). 19 F NMR(377MHz,CDCl3)δ ppm:-63.94(s,1 F),-62.19(s,1 F). LC-MS (Method 3): Retention time 1.01 min, m / z 253[MH - ].

[0352] Step C: Preparation of 6,8-bis(trifluoromethyl)quinazolin-4-ol (intermediate I-8) [ka] In a flask, 2-amino-3,5-bis(trifluoromethyl)benzonitrile (I-7, 8.8 g, 35 mmol), formic acid (83 mL), and sulfuric acid (2.8 mL, 52 mmol, 1.5 equivalents) were charged, and the mixture was stirred at 50°C for 3 hours. The reaction was then cooled to room temperature and slowly poured into 300 mL of ice water, and stirred for 15 minutes. The resulting solid was filtered and dried to obtain the desired product (I-8) as an off-white solid (8.9 g, 91%). 1 1H NMR (400MHz, DMSO-d6) δ ppm: 1 H NMR (400MHz, solvent) δ ppm 8.31-8.47(m,2H),8.61(s,1H),12.97(br s,1H). LC-MS (method 3): retention time 0.90 min, m / z283[M+H + ].

[0353] Step D: Preparation of 4-chloro-6,8-bis(trifluoromethyl)quinazoline (intermediate I-9) [ka] Five drops of N,N-dimethylformamide were added to a solution of 6,8-bis(trifluoromethyl)quinazolin-4-ol (I-8, 0.5 g, 5.04 mmol) in thionyl chloride (8.87 mL). The reaction mixture was heated at 100°C for 1 hour, at which point the reaction became homogeneous. The reaction was cooled and concentrated under reduced pressure to obtain the desired product (I-9), which was used directly in the next step. 1H NMR(400MHz,CDCl3)δ ppm:8.50(s,1H),8.84(s,1H),9.33(s,1H). 19 F NMR(377MHz,CDCl3)δ ppm:-62.86(s,1 F),-60.78(s,1 F). LC-MS (method 3): retention time 0.75 min, m / z352[M+H + ].

[0354] Step E: Preparation of N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazoline-4-amine (compound P.16) [ka] In a flask, 4-chloro-6,8-bis(trifluoromethyl)quinazoline (I-9, 200 mg, 0.67 mmol), 1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethylammonium chloride (prepared according to International Publication No. 2019 / 197468) (201 mg, 0.80 mmol, 1.2 equivalents), potassium carbonate (276 mg, 2.0 mmol, 3 equivalents), and acetonitrile (3 mL) were charged and heated at 80°C for 4 hours. The reaction was cooled, the salt was removed by filtration, and the resulting crude product was concentrated under reduced pressure. Purification by flash chromatography with silica gel (ethyl acetate in cyclohexane) yielded the desired product (P.16) as a beige solid (120 mg, 40%). 1 H NMR(400MHz,CDCl3)δ ppm:1.85(d,J=6.97Hz,3H),6.71(quin,J=6.97Hz,1H),7.49(t,J=4.77Hz,1H),8.14(s,1H),8.16(s,1H),8.27(br d,J=4.03Hz,1H),8.38(s,1H),8.68(s,1H),9.01(d,J=4.77Hz,2H). LC-MS (Method 3): Retention time 0.97 min, m / z455[M+H + ].

[0355] Example 3: Preparation of 2-chloro-N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazoline-4-amine (compound P.25) [ka] Step A: Preparation of 6,8-bis(trifluoromethyl)quinazoline-2,4-diol (intermediate I-10) [ka] 2-amino-3,5-bis(trifluoromethyl)benzonitrile (I-7 prepared in Example 2, 2 g, 7.87 mmol) and dichloromethane (20 mL) were charged into a flask. Chlorosulfonyl isocyanate (0.85 mL, 9.44 mmol, 1.2 equivalents) was added to this mixture, and the resulting mixture was stirred for 3 hours. This reaction was concentrated under reduced pressure, and the residue was heated in water (50 mL) at 100°C for 18 hours. The resulting white solid was isolated by filtration to obtain the desired product (I-10) (800 mg, 34%). 1 H NMR(400MHz,CD3CN)δ ppm:8.20-8.23(m,1H),8.50(s,1H),8.73(br s,1H),9.51(br s,1H).

[0356] Step B: Preparation of 2,4-dichloro-6,8-bis(trifluoromethyl)quinazoline (intermediate I-11) [ka] 6,8-bis(trifluoromethyl)quinazoline-2,4-diol (I-10, 100 mg, 0.34 mmol) and phosphorus oxychloride (0.32 mL, 3.4 mmol, 10 equivalents) were charged into a flask. Next, N,N-diisopropylethylamine (0.118 mL, 0.67 mmol, 2 equivalents) was added to this mixture, and the resulting mixture was heated at 100°C for 2 hours. This reaction was concentrated under reduced pressure, and the crude material was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain the desired product (I-11) as an off-white solid (84 mg, 75%). 1 H NMR(400MHz,CD3CN)δ ppm:8.66(s,1H),8.90(s,1H).

[0357] Step C: Preparation of 2-chloro-N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazoline-4-amine (compound P.25) [ka] In a flask, 2,4-dichloro-6,8-bis(trifluoromethyl)quinazoline (I-11, 100 mg, 0.30 mmol), 1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethylammonium chloride (prepared according to International Publication No. 2019 / 197468) (68 mg, 0.27 mmol, 0.9 equivalents), potassium carbonate (123 mg, 0.90 mmol, 3 equivalents), and acetonitrile (1.5 mL) were charged and heated at 80°C for 16 hours. The reaction was cooled, diluted with water, and extracted twice with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by flash chromatography in silica gel (ethyl acetate in cyclohexane) yielded the desired product (P.25) as a pale yellow solid (60 mg, 41% yield). 1H NMR(400MHz,DMSO-d6)δ ppm:1.79(d,J=6.72Hz,3H)6.38(t,J=6.72Hz,1H)7.65(t,J=4.65Hz,1H)8.18(s,1H)8.37(br s,1H)8.99(d,J=4.65Hz,2H)9.24(br s,1H)9.90(br d,J=6.36Hz,1H). LC-MS (Method 4): Retention time 1.09 min, m / z 489[M+H + ].

[0358] Example 4: Preparation of N-methyl-N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazoline-4-amine (compound P.27) [ka] In a flask, N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazoline-4-amine (P.16 prepared in Example 2, 148 mg, 0.33 mmol), cesium carbonate (319 mg, 0.98 mmol, 3 equivalents), acetonitrile (1.3 mL), and iodomethane (0.041 mL, 0.65 mmol, 2 equivalents) were charged. The mixture was heated overnight at 50°C. The reaction was cooled and diluted with water (10 mL). The mixture was extracted three times with ethyl acetate (3 × 10 mL), the combined organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Purification by flash chromatography using silica gel (ethyl acetate in cyclohexane) yielded the desired product (P.27) (92 mg, 60%). 1 H NMR(400MHz,CDCl3)δ ppm:1.98(d,J=6.97Hz,3H),3.37(s,3H),6.89(q,J=6.97Hz,1H),7.23(t,J=4.95 Hz,1H),8.11(s,1H),8.24(d,J=6.60Hz,2H),8.57(d,J=4.77Hz,2H),8.60(s,1H). LC-MS (Method 3): Retention time 0.97 min, m / z455[M+H + ]. 19 F NMR(376MHz,CDCl3)δ ppm:-62.40(s,1 F),-61.33(s,1 F). LC-MS (Method 3): Retention time 1.01 min, m / z469[M+H + ].

[0359] Example 5: 8-Chloro-N-(cyclopropylmethyl)-2-methoxy-N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6-(trifluoromethyl)quinazoline-4-amine (compound P.36) [ka] Step A: Preparation of 8-chloro-4-[cyclopropylmethyl-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]amino]-6-(trifluoromethyl)-1H-quinazolin-2-one (intermediate I-12) [ka] 2,8-Dichloro-N-(cyclopropylmethyl)-N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6-(trifluoromethyl)quinazoline-4-amine (P.49, 180 mg, 0.35 mmol, prepared in the same manner as P.25 in Example 3) and acetic acid (1.8 mL) were charged into a flask. The mixture was stirred at 80°C for 2 hours. The reaction was concentrated under reduced pressure, and the residue was purified by reverse-phase chromatography (acetonitrile in water) to obtain the desired product (I-12) (90 mg, 52%). 1H NMR(400MHz,DMSO-d6)δ ppm:0.02-0.07(m,1H),0.09-0.16(m,1H),0.25-0.32(m,1H),0.35-0.41(m,1H),0.77-0.85(m,1H),1.87(d,3H),3.06(dd,1 H),3.36(dd,1H),6.40-6.46(m,1H),7.38(t,1H),7.69(s,1H),8.19(s,1H),8.25(s,1H),8.54(d,2H),10.84-10.92(m,1H).

[0360] Step B: Preparation of 8-chloro-N-(cyclopropylmethyl)-2-methoxy-N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6-(trifluoromethyl)quinazoline-4-amine (compound P.36) [ka] 8-Chloro-4-[cyclopropylmethyl-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]amino]-6-(trifluoromethyl)-1H-quinazolin-2-one (I-12, 35 mg, 0.07 mmol) was dissolved in acetonitrile (0.53 mL) and potassium carbonate (30 mg, 0.21 mmol, 3 equivalents), followed by the addition of dimethyl sulfate (7.5 μL, 0.08 mmol, 1.1 equivalents). The resulting mixture was heated at 80°C for 5 hours. The reaction was cooled and filtered through Celite with acetonitrile washings. The filtrate was concentrated under reduced pressure, and the crude material was purified by reverse-phase chromatography (acetonitrile in water) to obtain the desired product (P.36) (90 mg, 52%). 1 H NMR(400MHz, methanol-d4)δ ppm:0.23(qd,1H),0.31-0.06 (m,1H),0.55-0.39(m,2H),0.94-0.83(m,1H),2.02(d,3H),3.36(dd,1H),3.56(dd,1H),3 .97(s,3H),6.78(q,1H),7.29(t,1H),8.08(d,1H),8.18(s,1H),8.21(d,1H),8.42(d,2H). LC-MS (Method 4): Retention time 1.17 min, m / z 505[M+H + ].

[0361] Example 6: Preparation of 6,8-dibromo-N-[1-(3-pyrimidine-2-ylpyrazine-2-yl)ethyl]quinazoline-4-amine (compound P.38) [ka] Step A: Preparation of N'-(2,4-dibromo-6-cyanophenyl)-N,N-dimethylformamidine (intermediate I-13) [ka] To a solution of 2-amino-3,5-dibromobenzonitrile (CAS No. 68385-95-5, 150 mg, 0.54 mmol) in methanol (5 mL), 1,1-dimethoxy-N,N-dimethylmethaneamine (0.228 mL, 1.63 mmol, 3 equivalents) was added, and the reaction was stirred at 80°C for 1 hour. The mixture was concentrated under reduced pressure to obtain product (I-13) as a solid (179 mg, 99.5%), which was used directly in the next step. LC-MS (Method 3): Retention time 1.17 min, m / z 505[M+H + ].

[0362] Step B: Preparation of 1-(3-pyrimidine-2-ylpyrazine-2-yl)ethanone (intermediate I-14) [ka] Tributyl(pyrimidine-2-yl)stananane (CAS No. 153435-63-3, 25 g, 67.7 mmol, 1 equivalent), 1-(3-chloropyrazine-2-yl)ethanone (CAS No. 2142-68-9, 12.37 g, 71.12 mmol, 1.05 equivalent), and toluene (500 mL) were charged into a flask. The reaction mixture was purged with nitrogen for 10 minutes, and then copper(I) iodide (2.58 g, 13.55 mmol, 0.2 equivalent) and tetrakis(triphenylphosphine)palladium(O) (3.91 g, 3.39 mmol, 0.05 equivalent) were added. The reaction was then heated at 95°C for 5 hours. The mixture was cooled, filtered through a Celite pad with ethyl acetate washings, and the filtrate was concentrated under reduced pressure. The product (I-14) was obtained as a brown solid by purification using flash chromatography with silica gel (ethyl acetate in cyclohexane) (10 g, 51.6%). LC-MS (Method 4): Retention time 0.37 min, m / z 201[M+H + ].

[0363] Step C: Preparation of 1-(3-pyrimidine-2-ylpyrazine-2-yl)ethaneamine (intermediate I-15) [ka] 1-(3-pyrimidine-2-ylpyrazine-2-yl)ethanone (I-14, 500 mg, 2.5 mmol, 1 equivalent), ammonium acetate (3.85 g, 50.0 mmol, 20 equivalents), and ethanol (25 mL) were charged into a flask. Then, aqueous NH3 (28%) (7.5 mL) and sodium borohydride (0.50 g, 7.5 mmol, 3 equivalents) were added, and the mixture was heated at 80°C for 2 hours. The mixture was cooled and concentrated under reduced pressure. The crude material was purified by reverse-phase column chromatography (C18 40-60 μm, acetonitrile in water) to obtain the product (I-15) as a brown gum (210 mg, 42%). 1H NMR(400MHz,DMSO-d6)δ ppm:1.50(d,J=6.6Hz,3H),4.93(d,J=6.6Hz,1H),7.70(t,J=5.0Hz,1H),8.86(d,J=2.3Hz,1H),8.90(d,J=2.4Hz,1H),9.07(d,J=4.9Hz,2H).

[0364] Step D: Preparation of 6,8-dibromo-N-[1-(3-pyrimidine-2-ylpyrazine-2-yl)ethyl]quinazoline-4-amine (compound P.38) [ka] 1-(3-pyrimidine-2-ylpyrazine-2-yl)ethanone (I-15, 120 mg, 0.59 mmol, 1.1 equivalents), N'-(2,4-dibromo-6-cyanophenyl)-N,N-dimethylformamidine (I-13, 179 mg, 0.54 mmol, 1 equivalent), and acetic acid (2.7 mL) were charged into a vial. The mixture was stirred at 120°C for 1 hour. 1-(3-pyrimidine-2-ylpyrazine-2-yl)ethanone (I-15, 135 mg) from another batch was added, and stirring was continued until the reaction was complete. The mixture was cooled, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, and concentrated under reduced pressure. The desired product (I-7) was obtained as a brown solid (83 mg, 32%) by flash chromatography using silica gel (ethyl acetate in cyclohexane), followed by reverse-phase purification (acetonitrile in water). 1 H NMR(400MHz,DMSO-d6)δ ppm:1.71(d,J=6.97Hz,3H),5.92(quin,J=6.79Hz,1H),7.53(t,J=4.77Hz,1H),8.15(s,1H),8.28(d,J=1.83Hz,1H),8 .65(d,J=1.83Hz,1H),8.66(d,J=2.57Hz,1H),8.74(d,J=2.20Hz,1H),8.77(d,J=6.97Hz,1H),8.92(d,J=5.14Hz,2H). LC-MS (Method 3): Retention time 0.87 min, m / z 488[M+H + ].

[0365] Example 7: Preparation of 6-[5-[1-[[2-methyl-6,8-bis(trifluoromethyl)quinazoline-4-yl]amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (compound P.60) [ka] Step A: Preparation of 2-methyl-6,8-bis(trifluoromethyl)quinazoline-4-amine (intermediate I-16) [ka] 2-amino-3,5-bis(trifluoromethyl)benzonitrile (I-7 prepared in Example 2, 300 mg, 1.18 mmol) and acetamide (0.7 g, 11.8 mmol, 10 equivalents) were charged into a sealed test tube. The mixture was stirred at 180°C for 4 days. The reaction was then cooled to room temperature and diluted with water (25 mL). The mixture was extracted three times with ethyl acetate (3 × 20 mL), the combined organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain the desired product (I-16) as a pale yellow solid (102 mg, 29%). 19 F NMR(377MHz,DMSO-d6)δ ppm:-60.36(s,1 F),-59.63(s,1 F). LC-MS (Method 3): Retention time 0.95 min, m / z296[M+H + ].

[0366] Step B: Preparation of 6-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile (intermediate I-18) [ka] To a solution of 2-bromopropanamide (CAS No. 5875-25-2, 4.00 g, 26.3 mmol, 1 equivalent) in dichloromethane, N,N-dimethylformamide dimethylacetal (CAS No. 4637-24-5, 5.58 mL, 39.5 mmol, 1.5 equivalents) was added. The mixture was heated under reflux for 30 minutes. The reaction was then cooled to room temperature and concentrated under reduced pressure to obtain the desired crude product 2-bromo-N-(dimethylaminomethylene)propanamide (I-17) as a yellow oil (5.6 g, 98%), which was used directly in the next step. 1 H NMR(400MHz,CDCl3)δ ppm:1.85(d,J=6.97Hz,3H),3.14(d,J=0.73Hz,3H),3.17(s,3H),4.55(q,J=6.85Hz,1H),8.49(s,1H).

[0367] 5-cyano-2-hydrazinopyridine (CAS No. 104408-24-4, 4.68 g, 25.2 mmol, 1.05 equivalent) was added to a solution of 2-bromo-N-(dimethylaminomethylene)propanamide (I-17, 5.40 g, 24 mmol, 1 equivalent) in 1,4-dioxane (54 mL). Next, acetic acid (54 mL) was slowly added. The resulting red solution was heated at 80°C for 1 hour. The reaction was cooled and concentrated under reduced pressure. The mixture was then placed in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution and water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The desired product (I-18) was obtained as a white solid by flash chromatography using silica gel (ethyl acetate in cyclohexane) (3.1 g, 46%). 1 H NMR(400MHz,CDCl3)δ ppm:2.26(d,J=6.97Hz,3H),6.43(q,J=6.97Hz,1H),8.05(s,1H),8.14-8.20(m,2H),8.85(dd,J=1.83,1.10Hz,1H). LC-MS (Method 3): Retention time 0.88 minutes, m / z 278-280 (Br pattern) [M+H + ].

[0368] Step C: Preparation of 6-[5-[1-[[2-methyl-6,8-bis(trifluoromethyl)quinazoline-4-yl]amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (compound P.60) [ka] In a sealed test tube, 2-methyl-6,8-bis(trifluoromethyl)quinazoline-4-amine (I-16, 106 mg, 0.36 mmol), acetonitrile (1.43 mL), cesium carbonate (351 mg, 1.08 mmol, 3 equivalents), and 6-[5-(1-bromoethyl)-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-18, 110 mg, 0.40 mmol, 1.1 equivalents) were charged, and the reaction mixture was heated at 50°C for 3 hours. The reaction was cooled, diluted with water (60 mL), and extracted three times with ethyl acetate (3 × 60 mL). The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography in silica gel (ethyl acetate in cyclohexane) to obtain the desired product as a yellow solid (134 mg, 76% yield). 1 H NMR(400MHz,DMSO-d6)δ ppm:1.49-1.58(m,3H),4.09-4.19(m,1H),6.49-6.55(m,1H),7.13-7.22(m,1H),7.63-7 .71(m,1H),7.83-7.90(m,1H),8.17-8.24(m,1H),8.60-8.66(m,1H),9.23-9.29(m,1H). LC-MS (Method 3): Retention time 1.16 min, m / z494[M+H + ].

[0369] Example 8: Preparation of 6,8-dichloro-N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]quinoline-4-amine (compound P.67) [ka] To a solution of 6,8-dichloroquinoline-4-amine (100 mg, 0.469 mmol) in N,N-dimethylformamide (0.94 mL), sodium hydride (20.7 mg, 0.516 mmol, 1.10 equivalents) was added dropwise at room temperature. The reaction mixture was stirred at this temperature for 10 minutes. Next, a solution of 2-[5-(1-bromoethyl)-1,2,4-triazole-1-yl]pyrimidine (intermediate I-20 prepared as described above, 125 mg, 0.493 mmol, 1.05 equivalents) in N,N-dimethylformamide (0.94 mL) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. This was poured into 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 using silica gel (ethyl acetate in cyclohexane, followed by methanol in dichloromethane) to obtain the desired product as a pale orange solid (39 mg, 0.10 mmol). 1 ¹H NMR (400 MHz, chloroform-d) δ ppm: 1.75-1.84 (m,3H), 6.08-6.20 (m,1H), 6.28-6.37 (m,1H), 6.51-6.58 (m,1H), 7.45-7.51 (m,1H), 7.75-7.86 (m,2H), 8.17-8.12 (m,1H), 8.60-8.66 (m,1H), 8.94-9.02 (m,2H). LC-MS (Method 1): Retention time 0.63 min, m / z 386-390 [M+H + (Dichloro pattern).

[0370] Example 9: Preparation of 6,8-dichloro-N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]quinazoline-4-amine (compound P.68) [ka] Step A: Preparation of 2-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyrimidine (intermediate I-20) [ka] To a solution of 2-bromopropanamide (CAS 5875-25-2, 1.50 g, 9.38 mmol) in dichloromethane (37.5 mL), 1,1-dimethoxy-N,N-dimethylmethaneamine (CAS 4637-24-5, 2.49 mL, 18.8 mmol, 2.00 equivalents) was added at room temperature. The reaction mixture was heated to below 40°C and stirred for 2.5 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to quantitatively obtain crude intermediate (I-19). LC-MS (Method 1): Retention time 0.26 min, m / z 207-209[M+H + ](Br pattern).

[0371] A mixture of intermediate I-1 (1.94 g, 9.38 mmol), acetic acid (28.1 mL), and pyrimidine-2-ylhydrazine (1.24 g, 11.3 mmol, 1.20 equivalents) was heated to below 65°C and stirred for 2 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The crude material was purified by flash chromatography in silica gel (ethyl acetate in cyclohexane) to obtain the desired product (I-20) as a pale yellow solid (1.70 g, 6.69 mmol). 1 ¹H NMR (400 MHz, chloroform-d) δ ppm: 2.20-2.31 (m,3H), 6.34-6.48 (m,1H), 7.37-7.45 (m,1H), 8.05-8.15 (m,1H), 8.88-8.95 (m,2H). LC-MS (Method 1): Retention time 0.66 min, m / z254-256[M+H + ](Br pattern).

[0372] Step B: Preparation of 6,8-dichloro-N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]quinazoline-4-amine (compound P.68) [ka] To a solution of 6,8-dichloroquinazoline-4-amine (400 mg, 1.87 mmol) in acetonitrile (7.47 mL), cesium carbonate (1.83 g, 5.61 mmol, 3.00 equivalents) and 2-[5-(1-bromoethyl)-1,2,4-triazole-1-yl]pyrimidine (intermediate I-20 prepared as described above, 522 mg, 2.06 mmol, 1.10 equivalents) were added at room temperature. The reaction mixture was heated to below 50°C and stirred overnight. After cooling to room temperature, the reaction mixture was diluted with water and extracted three times with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography in silica gel (ethyl acetate in cyclohexane) to obtain the desired product as a yellow solid (351 mg, 0.907 mmol). LC-MS (Method 1): Retention time 0.81 min, m / z 387-391[M+H + (Dichloro pattern).

[0373] Example 10: Preparation of N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-5,7-bis(trifluoromethyl)isoquinoline-1-amine (compound P.83) [ka] Step A: Preparation of 2-iodo-3,5-bis(trifluoromethyl)benzonitrile (intermediate I-21) [ka] 2-amino-3,5-bis(trifluoromethyl)benzonitrile (I-7, prepared as in Example 2, 2.19 g, 8.62 mmol, 1 equivalent) was dissolved in diiodomethane (6.9 mL) and acetonitrile (13.8 mL). Isoamylnitrile (2.3 mL, 16.4 mmol, 1.9 equivalents) was then added under an argon atmosphere. The reaction was stirred at 50°C for 60 minutes, and then stirred at 80°C for another 60 minutes. The reaction was concentrated under reduced pressure and diluted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a crude mixture of oil and solid. The oil was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane), and the resulting solid was combined with the crude solid material to obtain the desired product (I-21) (2.2 g, 70%). 1 H NMR(400MHz,CDCl3)δ ppm:7.99-8.02(m,1H),8.03-8.07(m,1H).

[0374] Step B: Preparation of 3,5-bis(trifluoromethyl)-2-(2-trimethylsilylethynyl)benzaldehyde (intermediate I-23) [ka] 2-iodo-3,5-bis(trifluoromethyl)benzonitrile (I-21 prepared above, 3.52 g, 9.64 mmol, 1 equivalent) was dissolved in toluene (72 mL), the solution was cooled to -78°C and stirred for 90 minutes. The reaction was inactivated by warming it to room temperature and slowly adding aqueous hydrogen chloride solution (1 M, 50 mL). The mixture was extracted with ethyl acetate (50 mL), the combined organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to obtain crude 2-iodo-3,5-bis(trifluoromethyl)benzaldehyde (I-22), which was used directly in the next step.

[0375] 2-iodo-3,5-bis(trifluoromethyl)benzaldehyde (I-22 prepared above, 3.5 g, 9.51 mmol, 1 equivalent) was dissolved in triethylamine (47.5 mL) under an Ar atmosphere. Next, copper(I) iodide (0.073 g, 0.38 mmol, 0.04 equivalents), bis(triphenylphosphine)palladium(II) dichloride (0.135 g, 0.19 mmol, 0.02 equivalents), and trimethylsilylacetylene (3.39 mL, 23.8 mmol, 2.5 mmol) were added sequentially, and the mixture was stirred at 80°C. After 17 hours, the reaction was cooled, concentrated under reduced pressure, and the materials were dissolved in ethyl acetate. The organic layer was washed twice with diluted aqueous hydrogen chloride (2 × 20 mL), washed with brine, filtered, and concentrated under reduced pressure. The desired product (I-23) was obtained by purification using flash chromatography with silica gel (ethyl acetate in cyclohexane) (1.076 g, 33%). 1 H NMR(400MHz,CDCl3)δ ppm:6.33(br s,1H),7.97(br s,1H),8.33(s,1H),8.66(br s,1H),11.57(br s,1H). LC-MS (Method 3): Retention time 1.34 min, m / z 339[M+H + ].

[0376] Step C: Preparation of 5,7-bis(trifluoromethyl)isoquinoline (intermediate I-24) [ka] 3,5-Bis(trifluoromethyl)-2-(2-trimethylsilylethynyl)benzaldehyde (I-23 prepared above, 1.075 g, 3.18 mmol, 1 equivalent) was weighed in a microwave test tube, and ammonia solution (10 mL, 7 M in methanol) was added. The test tube was capped and irradiated in a microwave reactor at 130°C for 15 minutes. The solvent was then removed under reduced pressure to obtain the desired product (I-24) (820 mg, 97%). 1H NMR(400MHz,CDCl3)δ ppm:7.99-8.10(m,1H),8.26(s,1H),8.53(s,1H),8.85(d,J=6.24Hz,1H),9.50(s,1H). LC-MS (method 3): retention time 1.05 min, m / z266[M+H + ].

[0377] Step D: Preparation of 2-oxide-5,7-bis(trifluoromethyl)isoquinoline-2-ium (intermediate I-25) [ka] 5,7-Bis(trifluoromethyl)isoquinoline (I-24 prepared above, 875 mg, 3.3 mmol, 1 equivalent) was placed in acetic acid (5.5 mL), and H2O2 (35 wt%) (0.85 mL, 9.9 mmol, 3 equivalents) was added. The mixture was then heated to 70°C. After 17 hours, the reaction was cooled, diluted with ethyl acetate and water, and NaOH (4 M) was added until the pH reached 12. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the desired product (I-25) (1.040 g, quantitative). 1 ¹H NMR (400 MHz, CDCl3) δ ppm: 1 H NMR (400MHz, solvent) δ ppm 8.05(br d,J=7.34Hz,1H),8.08(s,1H),8.20(s,1H),8.36(dd,J=7.52,1.65Hz,1H),8.90(s,1H). LC-MS (method 3): retention time 0.85 min, m / z282[M+H + ].

[0378] Step E: Preparation of N-[1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-5,7-bis(trifluoromethyl)isoquinoline-1-amine (compound P.83) [ka] To a flask containing 2-oxide-5,7-bis(trifluoromethyl)isoquinoline-2-ium (I-25 prepared above, 50 mg, 0.18 mmol, 1 equivalent) and 1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethanamine hydrochloride (prepared in the same manner as in International Publication No. 2019 / 197468, page 128, 80.6 mg, 0.356 mmol, 2 equivalents), N,N-diisopropylethylamine (0.155 mL, 0.89 mmol, 5 equivalents) and bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®, 211 mg, 0.44 mmol, 2.5 equivalents) dissolved in dichloromethane (0.89 mL), the reaction was stirred at room temperature. After 4 hours, N,N-diisopropylethylamine (0.155 mL, 0.89 mmol, 5 equivalents) and bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®, 211 mg, 0.44 mmol, 2.5 equivalents) were added. After 17 hours, the reaction was filtered, and the crude material was purified by flash chromatography with silica gel (ethyl acetate in cyclohexane) to obtain the desired product P.38 (30 mg, 37%). 1 H NMR(400MHz,CDCl3)δ ppm:1.84(d,J=6.60Hz,3H),6.15-6.97(m,1H),6.56(quin,J=7.06Hz,1H),7.04(dd,J=5.69,2.02Hz,1H),7.44(t,J=4.77Hz,1H),7.63(br d,J=7.34Hz,1H),7.92(d,J=6.24Hz,1H),7.94(br s,1H),8.10(s,1H),8.41(s,1H),8.98(d,J=4.77Hz,2H). 19 F NMR(377MHz,CDCl3)δ ppm:-62.15(s,1 F),-61.08(s,1 F). LC-MS (Method 3): Retention time 1.08 min, m / z454[M+H + ].

[0379] Example 11: Preparation of 6-[5-[(1R)-1-[[6,8-bis(trifluoromethyl)sinnolin-4-yl]amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (compound P.135) Step A: Preparation of 6,8-bis(trifluoromethyl)cinolin-4-ol (I-26) [ka] 1-[2-amino-3,5-bis(trifluoromethyl)phenyl]ethanone (CAS-No.: 1805121-99-6, 1.25 g, 4.61 mmol, 1 equivalent) was dissolved in glacial acetic acid (18.4 ml) and 70% sulfuric acid (0.92 ml, 12.1 mmol, 2.63 equivalents). The solution was cooled to 22°C, and an ice-cold solution of sodium nitrite (389 mg, 5.53 mmol, 1.2 equivalents) in water (3.55 ml) was added dropwise while cooling. After 45 minutes, triethylamine (1.81 ml, 12.91 mmol, 2.8 equivalents) was added, and the reaction was stirred at room temperature for 17 hours. This was poured into 100 ml of ice water and extracted with ethyl acetate (2 × 60 ml). The combined organic layers were washed with saturated Na2CO3 solution and brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. Purification by flash chromatography using silica gel (ethyl acetate in cyclohexane) yielded the desired product (I-26) (907 mg, 63%). 1 H NMR(400MHz,CDCl3)δ ppm:10.32(br s,1H)8.79(s,1H)8.21(s,1H)7.99(s,1H). 19 F NMR(377MHz,CDCl3)δ ppm:-60.61(s,3F)-62.65(s,3F). LC-MS (Method 3) Retention time 0.88 min m / z283[M+H + ].

[0380] Step B: Preparation of 4-chloro-6,8-bis(trifluoromethyl)cinolin (I-27) [ka] 6,8-Bis(trifluoromethyl)cinnolin-4-ol (I-26, 840 mg, 2.98 mmol, 1 equivalent) was suspended in toluene (5.95 ml), and phosphorus trichloride (0.31 ml, 3.28 mmol, 1.1 equivalents) was added. The mixture was heated at 50°C for 17 hours. This reaction was deactivated with a saturated ammonium chloride solution and diluted with ethyl acetate. The pH was adjusted to 10-12 with aqueous ammonia. The organic layer was washed five times with brine. This was dried over anhydrous MgSO4 and concentrated under reduced pressure to obtain (I-27) (1.04 g, 93% yield, 80% purity). 1 H NMR(400MHz,CDCl3)δ ppm:9.67(s,1H)8.78(s,1H)8.43(s,1H). 19 F NMR(377MHz,CDCl3)δ ppm:-59.6(s,3F)-63.4(s,3F). LC-MS (Method 3) Retention time 1.11 min m / z301[M+H + ].

[0381] Step C: Preparation of (2S)-2-[[6,8-bis(trifluoromethyl)cinolin-4-yl]amino]propanamide (I-28) [ka] 4-Chloro-6,8-bis(trifluoromethyl)cinoline (I-27, 1.04 g, 3.46 mmol, 1 equivalent), potassium carbonate (2.39 g, 17.3 mmol, 5 equivalents), and (2S)-2-aminopropanamide hydrochloride (2.22 g, 17.3 mmol, 5 equivalents) were heated in NMP (13.8 ml) at 50°C for 60 hours. The reaction mixture was diluted with water (100 ml) and ethyl acetate (100 ml). The organic layer was washed with water (30 ml) and brine (30 ml), dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain (I-28) (1.57 g, 73%). 1H NMR(400MHz,DMSO-d6)δ ppm:9.35(s,1H)8.78(s,1H)8.38-8.19(m,2H)7.76(s,1H)7.29(s,1H)4.41(quin,J=7.0Hz,1H)1.56(d,J=7.0Hz,3H) 19 F NMR(377MHz,DMSO-d6)δ ppm:-58.9(s,3F)-60.9(s,3F) LC-MS (Method 3): Retention time 0.86 min, m / z353[M+H + ].

[0382] Step D: Preparation of (NE,2S)-2-[[6,8-bis(trifluoromethyl)sinnolin-4-yl]amino]-N-(dimethylaminomethylene)propanamide (I-29) [ka] (2S)-2-[[6,8-bis(trifluoromethyl)sinnolin-4-yl]amino]propanamide (I-28, 500 mg, 1.42 mmol, 1 equivalent) was mixed with 2-methyltetrahydrofuran (14.2 ml) and DMF-DMA (377 μl, 2.84 mmol, 2 equivalents), and the mixture was heated at 50°C for 30 minutes. This reaction mixture was evaporated under reduced pressure to obtain (I-29) (642 mg, 99%). LC-MS (Method 3): Retention time 0.92 min, m / z 408[M+H + ].

[0383] Step E: Preparation of 6-[5-[(1R)-1-[[6,8-bis(trifluoromethyl)sinnolin-4-yl]amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (compound P.135) [ka] (NE,2S)-2-[[6,8-bis(trifluoromethyl)cinnolin-4-yl]amino]-N-(dimethylaminomethylene)propanamide (I29, 306 mg, 0.75 mmol, 1 equivalent) was dissolved in 2-methyltetrahydrofuran (3 ml). 6-Hydradinylnicotinonitrile (191 mg, 1.35 mmol, 1.8 equivalents) and acetic acid (1.88 ml) were added. The mixture was heated at 70°C for 1 hour. It was cooled to 25°C and diluted with ethyl acetate (30 ml). This was washed with water, saturated Na2CO3 solution and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The desired product (P.135) (87 mg, 24%) was obtained by flash chromatography using silica gel (ethyl acetate in cyclohexane) followed by reverse-phase purification (acetonitrile in water). 1 H NMR(400MHz,CDCl3)δ ppm:9.03-8.99(m,2H)8.94(br s,1H)8.30(s,1H),8.27-8.23(m,2H)8.06(s,1H)6.44(q,J=6.6Hz,1H)1.95(d,J=6.6Hz,3H). 19 F NMR(377MHz,CDCl3)δ ppm:-60.14(s,3F)-62.78(s,3F). LC-MS (Method 3): Retention time 1.01 min, m / z 480[M+H + ].

[0384] Example 12: Preparation of 4-[[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazole-3-yl]ethyl]amino]-6,8-bis(trifluoromethyl)quinoline-3-carbonitrile (compound P.139) [ka] Step A: Preparation of ethyl(Z)-3-[2,4-bis(trifluoromethyl)anilino]-2-cyanoprop-2-enoate (compound I-30) [ka] A mixture of ethyl (ethoxymethylene) cyanoacetate (1.46 g, 8.47 mmol, 2 equivalents) and 2,4-bis(trifluoromethyl)aniline (1 g, 4.23 mmol, 1 equivalent) was heated at 140°C for 1 hour. The mixture was cooled to 25°C and washed with a 30:70 mixture of TBME:cyclohexane. The solid was filtered off and dried to obtain (I-30) (490 mg, 33%). 1 H NMR(400MHz,DMSO-d6)δ ppm:11.34(br d,J=12.5Hz,1H)8.82(d,J=12.4Hz,1H)810-8.18(m,2H)8.05(s,1H)4.28(q,J=7.2Hz,2H)1.28(t,J=7.1Hz,3H). LC-MS (Method 4): Retention time 1.19 min, m / z 353[M+H + ].

[0385] Step B: Preparation of 4-oxo-6,8-bis(trifluoromethyl)-1H-quinoline-3-carbonitrile (compound I-31) [ka] Ethyl(Z)-3-[2,4-bis(trifluoromethyl)anilino]-2-cyanoprop-2-enoate (I-30, 500 mg, 1.42 mmol, 1 equivalent) was heated at 260°C for 8 hours in phenyl ether-biphenyl eutectic point (2.5 ml). After cooling to room temperature, the solution was diluted with cyclohexane to precipitate the product. This product was washed with t-butyl methyl ether and dried under reduced pressure to obtain (I-31) (180 mg, 41%). 1 H NMR(400MHz,DMSO-d6)δ ppm:8.68(s,1H)8.66(s,1H)8.45(s,1H). LC-MS (Method 4): Retention time 0.95 min, m / z 307[M+H + ].

[0386] Step C: Preparation of 4-chloro-6,8-bis(trifluoromethyl)quinoline-3-carbonitrile (compound I-32) [ka] 4-Oxo-6,8-bis(trifluoromethyl)-1H-quinoline-3-carbonitrile (I-31, 600 mg, 1.96 mmol, 1 equivalent) and thionyl chloride (6 ml, 80.6 mmol, 41 equivalents) were mixed with N,N-dimethylformamide (30 μl, 0.39 mmol, 0.2 equivalents). The mixture was heated at 80°C for 3 hours. This was concentrated under reduced pressure and purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain (I-32) (423 mg, 66%). 1 H NMR(400MHz,CDCl3)δ ppm:9.24(s,1H)8.86(s,1H)8.47(s,1H). LC-MS (Method 4): Retention time 1.16 min, m / z 325[M+H + ].

[0387] Step D: Preparation of t-butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxoethyl]carbamate (Compound I-33) [ka] t-butyl N-[(1S)-2-amino-1-methyl-2-oxo-ethyl]carbamate (70 g, 353 mmol, 1 equivalent) was mixed with 2-methyltetrahydrofuran (1.12 l) and DMF-DMA (70 ml, 530 mmol, 1.5 equivalents), and the mixture was heated at 40°C for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain (I-33) (105 g, 97% yield, 80% purity). 1 H NMR(400MHz,CDCl3)δ ppm:8.38(s,1H)5.98-6.15(m,1H)4.25-4.37(m,1H)3.16(s,3H)3.09(s,3H)1.46(s,9H)1.40(m,3H).

[0388] Step E: Preparation of N-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazole-3-yl]ethyl]carbamate (compound I-34) [ka] t-butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxoethyl]carbamate (I-33, 80% purity, 50 g, 164 mmol, 1 equivalent) was dissolved in 1,4-dioxane (510 ml). 6-hydrazinopyridine-3-carbonitride (33.1 g, 247 mmol, 1.5 equivalents) and glacial acetic acid (510 ml) were added. The mixture was heated at 90°C for 30 minutes. After cooling to 25°C, the reaction mixture was concentrated under reduced pressure. Purification by flash chromatography using silica gel (ethyl acetate in cyclohexane) yielded (I-34) (23 g, 32%). 1 H NMR(400MHz,CDCl3)δ ppm:8.80(dd,J=1.90,0.8Hz,1H)8.10-8.20(m,1H)7.98(s,1H)5.92-6.02(m,1H)5.77(br d,J=8.6Hz,1H)4.12(q,J=7.1Hz,2H)1.58(d,J=6.8Hz,3H)1.42(s,6H).

[0389] Step F: Preparation of [(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazole-3-yl]ethyl]ammonium; 2,2,2-trifluoroacetate (compound I-35) [ka] t-butyl N-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazole-3-yl]ethyl]carbamate (I-34, 1.1 g, 3.5 mmol, 1 equivalent) was dissolved in methanol (11 ml), and trifluoroacetic acid (5.6 ml, 70 mmol, 20 equivalents) was added. The mixture was stirred at 25°C for 2 hours. This reaction mixture was concentrated under reduced pressure.

[0390] MTBE was added to crude oil and stirred for 5 minutes. The MTBE was drained, and a second dose of MTBE was added. The product precipitated, was filtered off, and dried to obtain (I-35) (600 mg, 50%). LC-MS (Method 5): Retention time 0.31 min, m / z215[M+H + ].

[0391] Step G: Preparation of 4-[[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazole-3-yl]ethyl]amino]-6,8-bis(trifluoromethyl)quinoline-3-carbonitrile (compound P.139) [ka] In a round-bottom flask, [(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazole-3-yl]ethyl]ammonium; 2,2,2-trifluoroacetate (I-34, 546 mg, 1.66 mmol, 1.2 equivalents), 4-chloro-6,8-bis(trifluoromethyl)quinoline-3-carbonitride (I-32, 450 mg, 1.3863 mmol, 1 equivalent), and potassium carbonate (581 mg, 4.16 mmol, 3 equivalents) were suspended in acetonitrile (9 ml). This reaction mixture was heated at 60°C for 2 hours. The reaction mixture was deactivated with water and stirred for 20 minutes. P.139 (432 mg, 62%) precipitated as a solid, which was filtered, washed with water, and dried under reduced pressure. 1 H NMR(400MHz,DMSO-d6)δ ppm 9.30(s,1H)8.95(d,J=7.8Hz,1H)8.89-8.93(m,1H) 8.73(s,1H)8.49(dd,J=8.6,2.1Hz,1H)8.35(s,1H)8.31(s,1H)8.07(d,J=8.7Hz,1H) 6.58(t,J=7.1Hz,1H) 1.91(d,J=6.6Hz,3H). 19 F NMR(377MHz,DMSO-d6)δ ppm -59.16(s,3F),-60.26(s,3F). LCMS (Method 4): Retention time: 1.18 minutes, m / z 503 [M+H + ].

[0392] Example 13: Preparation of 6-chloro-N-methyl-8-(trifluoromethyl)-N-[(1S)-1-[2-[5-[4-(trifluoromethyl)thiazole-2-yl]-2-pyridyl]-1,2,4-triazole-3-yl]ethyl]quinazoline-4-amine (compound P.142) [ka] Step A: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-36) [ka] 4,6-dichloro-8-(trifluoromethyl)quinazoline (CAS-No.: 1565368-05-9, 100 mg, 0.37 mmol, 1 equivalent), [(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazole-3-yl]ethyl]ammonium; 2,2,2-trifluoroacetate (I-35 from Example 12, 74% purity, 199 mg, 0.45 mmol, 1.2 equivalents), cesium carbonate (366 mg, 1.12 mmol, 3 equivalents), and acetonitrile (1 ml) were charged into a flask. The reaction mixture was stirred at 25°C for 16 hours. This was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium 2SO4, and concentrated under reduced pressure. The crude material was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain the desired product (I-36) (107 mg, 64%). 1H NMR(400MHz,DMSO-d6)δ ppm:9.11(d,J=6.9Hz,1H)9.04(d,J=1.5Hz,1H)8.98-9.00(m,1H)8.93(d,J=2.2Hz,1H)8.57(dd,J=8.6 ,2.2Hz,1H)8.34(s,1H)8.18-8.23(m,2H)8.06-8.10(m,1H)6.37(t,J=6.85Hz,1H)1.74(,J=7.0Hz,3H). LCMS (Method 4): Retention time: 1.07 min, m / z445[M+H + ].

[0393] Step B: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-37) [ka] 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-36, 1.40 g, 3.15 mmol, 1 equivalent) was weighed in a sealable test tube together with acetonitrile (15.7 ml), cesium carbonate (3.08 g, 9.44 mmol, 3 equivalents) and iodomethane (396 μl, 6.29 mmol, 2 equivalents). The test tube was closed and heated at 50°C for 16 hours. After cooling to 25°C, it was extracted twice with ethyl acetate. This was washed with water and brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. This was purified by flash chromatography using silica gel (ethyl acetate in dichloromethane 1:3) to obtain (I-37). 1H NMR(600MHz,DMSO-d6)δ ppm 8.50(dd,J=8.5,2.20Hz,1H)8.45(s,2H)8.32(s,1H)8.32(s,1H)8.22(d,J=1.9Hz,1H)8.09( d,J=2.1Hz,1H)8.05(d,J=8.5Hz,1H)6.67(q,J=6.9Hz,1H)3.26(s,3H)1.83(d,J=6.9Hz,3H). LCMS (Method 3): Retention time: 1.08 min, m / z459[M+H + ].

[0394] Step C: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl].methyl-amino]ethyl]-1,2,4-triazole-1-yl]pyridine-2-carbocioamide (I-38) [ka] A solution of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-37, 600 mg, 1.31 mmol, 1 equivalent) in pyridine (4.8 ml) was mixed with ammonium sulfide solution in water (2.23 ml, 6.54 mmol, 5 equivalents). The mixture was stirred at 25°C for 16 hours. This was diluted with water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. This was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain (I-38) (468 mg, 73%). 1H NMR(400MHz,DMSO-d6)δ ppm 10.06(br s,1H)9.66(br s,1H)8.44(s,1H)8.40(s,1H)8.41(d,J=7.4Hz,2H)8.27(s,1H)8.17(d,J=2.0Hz,1H)8.05(d ,J=2.1Hz,1H)7.89(d,J=8.0Hz,1H)6.68(d,J=7.0Hz,1H)3.26(s,3H)1.83(d,J=7.0Hz,3H). 19 F NMR(377MHz,DMSO-d6)δ ppm -59.39(s,3F). LCMS (Method 4): Retention time: 1.10 min, m / z493[M+H + ].

[0395] Step D: Preparation of 2-[6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazole-1-yl]-3-pyridyl]-4-(trifluoromethyl)-5H-thiazole-4-ol (I-39) [ka] 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl].methyl-amino]ethyl]-1,2,4-triazole-1-yl]pyridine-2-carbocioamide (I-38, 100 mg, 0.20 mmol, 1 equivalent) was dissolved in N,N-dimethylformamide (2.5 ml). 3-bromo-1,1,1-trifluoroacetone (32.2 μl, 0.30 mmol, 1.5 equivalents) was added to this solution, and the mixture was heated at 60°C for 2 hours. The mixture was cooled to 25°C and diluted with ethyl acetate. The mixture was washed with water and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure.

[0396] This was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain (I-39) (103 mg, 76%, 90% purity). 1¹H NMR (400MHz, acetonitrile-d3) δ ppm: 8.52 (d, J=4.4Hz, 1H) 8.32 (ddd J=12.2, 8.6, 2.3Hz) 8.07-8.15 (m, 1H) 8.06-8.12 (m, 1H), 8.03 (s, 1H) 7.95 (dd, J=8.6, 5.1Hz, 1H) 7.8 (d, J=2.3Hz, 1H) 7.73 (d, J=2.2Hz, 1H) 6.76 (t, J=7.6Hz, 1H) 5.05 (br dd,J=16.7,2.6Hz,1H)3.78(dd,J=13.0Hz,10.8Hz,1H)3.61(s,1H)3.47-3.5 5(m,1H)3.12(d,J=7.5Hz,3H)2.09-2.21(m,5H)1.87(dd,J=6.9,1.3Hz,3H). LCMS (Method 4): Retention time: 1.17 min, m / z604[M+H + ].

[0397] Step E: Preparation of 6-chloro-N-methyl-8-(trifluoromethyl)-N-[(1S)-1-[2-[5-[4-(trifluoromethyl)thiazole-2-yl]-2-pyridyl]-1,2,4-triazole-3-yl]ethyl]quinazoline-4-amine (compound P.142) [ka] To a solution of 2-[6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazole-1-yl]-3-pyridyl]-4-(trifluoromethyl)-5H-thiazole-4-ol (I-39, 100 mg, 0.17 mmol, 1 equivalent) in tetrahydrofuran (4 ml), triethylamine (58.4 μl, 0.41 mmol, 2.5 equivalents) was added and the mixture was cooled to 0°C. Trifluoroacetic anhydride (118 μl, 0.83 mmol, 5 equivalents) was added at 0°C. The reaction mixture was warmed to room temperature and stirred for 16 hours. It was inactivated with a saturated NaHCO3 solution and extracted with ELISA (2 × 20 ml). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain a gummy mass. The crude material was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain the desired product P.142 (47 mg, 48% yield). 1 H NMR(400MHz,DMSO-d6)δ ppm 8.65(s,1H)8.55(s,1H)8.50(dd,J=8.5,2.3Hz,1H)8.31(s,1H)8.27-8.30(m,1H)8.06(s,1H)7.97(d,J=8.3Hz 1H)7.85(s,1H)6.65(br d,J=6.8Hz,1H)3.10(s,3H)1.88(d,J=6.8Hz,3H). 19 F NMR(377MHz,DMSO-d6)δ ppm -59.6(s,3 F)-62.5(s,3 F). LCMS (Method 4): Retention time: 1.26 minutes, m / z 585 [M+H + ].

[0398] Example 14: Preparation of N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)-1,2,3-benzotriazine-4-amine (compound P.145) [ka] Step A: Preparation of 2-amino-3,5-bis(trifluoromethyl)benzamide (I-40) [ka] 2-amino-3,5-bis(trifluoromethyl)benzonitrile (CAS-No. 473740-86-2, 1.00 g, 3.94 mmol, 1 equivalent) and potassium carbonate (109 mg, 0.79 mmol, 0.2 equivalents) were dissolved in methanol (15 ml) and water (2 ml). While stirring at 25°C, urea hydrogen peroxide (1.14 g, 11.81 mmol, 3 equivalents) was added and the mixture was stirred for 1 hour.

[0399] After adding the second batch of urea hydrogen peroxide (1.14 g, 11.81 mmol, 3 equivalents), the mixture was stirred for 16 hours. Sodium metabisulfite (1 g) was added and the mixture was stirred for 5 minutes. This was diluted with ethyl acetate. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The crude material was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain the desired product (I-40) (818 mg, 76%). 1 H NMR(400MHz,DMSO-d6)δ ppm 8.22-8.39(br s,1H)8.18(s,1H)7.78(s,1H)7.50-7.70(br s,3H). LCMS (Method 3): Retention time: 0.91 min, m / z273[M+H + ].

[0400] Step B: Preparation of 6,8-bis(trifluoromethyl)-3H-1,2,3-benzotriazine-4-one (I-41) [ka] A solution of 2-amino-3,5-bis(trifluoromethyl)benzamide (I-40, 816 mg, 3 mmol, 1 equivalent) in 12 ml of 1 N hydrogen chloride was stirred at 0°C for 20 minutes. A solution of sodium nitrite (414 mg, 6 mmol, 2 equivalents) in 10 ml of water was added dropwise over 40 minutes. The mixture was then stirred at 0°C for 2 hours. 4 M sodium hydroxide was added to adjust the pH to 8, and the mixture was vigorously stirred for 15 minutes. The solid was filtered off, and the filtrate was acidified to pH 2-3 with HCl. The solid product was filtered off and dried to obtain (I-41) (382 mg, 45%). 1 H NMR(400MHz,DMSO-d6)δ ppm 15.56-15.89(br s,1H)8.77(s,1H)8.71(s,1H). LCMS (Method 3): Retention time: 0.92 min, m / z284[M+H + ].

[0401] Step C: Preparation of t-butyl N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]carbamate (I-42) [ka] t-butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate (I-33 from Example 12, 4.23 g, 17.4 mmol, 1 equivalent) and pyrimidine 2-ylhydrazine (2.87 g, 26.1 mmol, 1.5 equivalents) were mixed with 1,4-dioxane (43.5 ml) and glacial acetic acid (43.5 ml). The mixture was heated at 90°C for 35 minutes. This was concentrated under reduced pressure and purified by flash column chromatography in silica gel (ethyl acetate in cyclohexane) to obtain the desired product (I-42) (4.03 g, 80%). 1H NMR(400MHz,CDCl3)δ ppm 8.89(d,J=4.8Hz,2H)8.03(s,1H)7.37(t,J=5.0Hz,1H)5.91-6.11(m,1H)5.55-5-77(m,1H)1.58(d,J=6.6Hz,3H)1.35-1.47(m,9H). LCMS (Method 3): Retention time: 0.73 min, m / z291[M+H + ].

[0402] Step D: Preparation of [(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]ammonium; 2,2,2-trifluoroacetate (I-43) [ka] t-butyl N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]carbamate (I-42, 36.0 g, 86.6 mmol, 1 equivalent) was dissolved in dichloromethane (540 ml), and trifluoroacetic acid (180 ml, 2.27 mol, 26.2 equivalents) was added. The mixture was stirred at 25°C for 2 hours. This reaction mixture was concentrated under reduced pressure.

[0403] 72 ml of t-butyl methyl ether was added to the crude oil and stirred for 5 minutes. MTBE was drained, and 72 ml of acetonitrile was added. The product precipitated, was filtered off, and dried to obtain (I-43) (22.3 g, 83%). 1 H NMR(400MHz,DMSO-d6)δ ppm 9.02(d,2H)8.55-8.75(br s,3H)8.37(s,1H)7.68(t,1H)5.34(m,1H)3.20-4.40(br s,1H)1.63(d,3H). LC-MS (Method 5): Retention time 0.27 min, m / z191[M+H + ].

[0404] Step E: Preparation of N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)-1,2,3-benzotriazine-4-amine (compound P.145) [ka] 6,8-Bis(trifluoromethyl)-3H-1,2,3-benzotriazine-4-one (I-41, 129 mg, 0.45 mmol, 1 equivalent), (1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethaneamine; 2,2,2-trifluoroacetic acid (I-43, 180 mg, 0.59 mmol, 1.3 equivalents); and N-ethyl-N-isopropyl-propan-2-amine (0.325 ml, 1.86 mmol, 4.1 equivalents) were dissolved in dimethyl sulfoxide (4.5 ml).

[0405] After stirring at room temperature for 5 minutes, benzotriazole-1-yloxy(tripyrrolidine-1-yl)phosphonium salt; hexafluorophosphate (662 mg, 1.27 mmol, 2.8 equivalents) was added. The resulting mixture was stirred at room temperature for 16 hours. This was diluted with water (50 ml) and extracted with ethyl acetate (3 × 50 ml). The combined organic layer was dried over anhydrous sodium 2SO4 and concentrated under reduced pressure. Purification by flash chromatography with silica gel (ethyl acetate in cyclohexane) yielded the desired product (P.145) (68 mg, 33% yield). 1 H NMR(400MHz,DMSO-d6)δ ppm 9.64(d,J=7.0Hz,1H)9.34(s,1H)8.98(d,J=4.8Hz,2H)8.61(s,1H)8.17(s,1H)7.64(t,J=5.0Hz,1H)6.57(m,1H)1.82(d,J=7.0Hz,3H). 19 F NMR(377MHz,DMSO-d6)δ ppm -58.5(s,3 F)-61.2(s,3 F). LC-MS (Method 3) Retention time 0.92 min, m / z456[M+H + ].

[0406] Example 15: Preparation of 3-fluoro-N-methyl-N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (compound P.176) [ka] Step A: Preparation of N-methyl-N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine(I-44) [ka] Sodium hydride (60% by mass, 13.2 mg, 0.33 mmol, 1.5 equivalents) was charged into a dry vial and cooled to 0°C. A solution of N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (P.5 Example 1, 100 mg, 0.22 mmol, 1 equivalent) in tetrahydrofuran (0.88 ml) was added. After stirring for 5 minutes, iodomethane (20.8 μl, 0.33 mmol, 1.5 equivalents) was added and the mixture was stirred at 25°C for 3.5 hours. This was deactivated with saturated NH4Cl solution (5 ml) and diluted with water (20 ml). This was extracted with ethyl acetate (3 × 20 ml). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The desired product (I-44) was obtained by purification using silica gel flash chromatography (ethyl acetate in cyclohexane) (41 mg, 40%). 1H NMR(400MHz,CDCl3)δ ppm 8.65(d,J=5.1Hz,1H)8.43(s,1H)8.20(d,J=1.1Hz,1H)8.09(s,1H)8.08(d,J=4.8Hz,2H)6.93 (t,J=4.8Hz,1H)6.68(d,J=5.1Hz,1H)6.25(q,J=7.0Hz,1H)2.88(s,3H)2.08(d,J=7.0Hz,3H). LC-MS (Method 3) Retention time 1.04 min, m / z468[M+H + ].

[0407] Step B: Preparation of 3-fluoro-N-methyl-N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (compound P.176) [ka] N-methyl-N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (30 mg, 0.064 mmol, 1 equivalent) was dissolved in acetonitrile (321 μl). Selectfluor (23.7 mg, 0.064 mmol, 1 equivalent) was added and the mixture was stirred at room temperature for 17 hours. A second batch of Selectfluor (12 mg, 0.032 mmol, 0.5 equivalents) was added and the mixture was stirred for an additional 7 hours. A third batch of Selectfluor (12 mg, 0.032 mmol, 0.5 equivalents) was added and the mixture was stirred for 17 hours. The mixture was inactivated with MeOH, filtered, and purified with RP18 silica. P.176 (18 mg, 58% yield). 1 H NMR(400MHz,CDCl3)δ ppm 8.68(d,J=3.7Hz,1H)8.51(s,1H)8.15(s,3H)8.11(s,1H)6.91(t,J=4.8Hz,1H)6.03(q,J=7.0Hz,1H)3.09(d,J=3.7Hz,3H)2.02(d,J=7.0Hz,3H). 19F NMR(377MHz,CDCl3)δ ppm -60.52(s,3 F)-62.51(s,3 F)-133.71(s,1 F). LC-MS (Method 3) Retention time 1.10 minutes, m / z487[M+H + ].

[0408] Example 16: Preparation of 3-chloro-N-methyl-N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (P.181) [ka] Step A: Preparation of 3-chloro-N-methyl-N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (compound P.181) [ka] N-methyl-N-[(1S)-1-(2-pyrimidine-2-yl-1,2,4-triazole-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (I-44 Example 15, 41 mg, 0.088 mmol, 1 equivalent) was dissolved in dichloromethane (0.88 ml) and cooled to -19°C. N-chlorosuccinimide (13 mg, 0.096 mmol, 1.1 equivalents) was added and the mixture was stirred at -19°C for 1 hour. The mixture was then stirred at room temperature for 20 hours. Additional N-chlorosuccinimide (13 mg, 0.096 mmol, 1.1 equivalents) and dimethyl sulfoxide (31.5 μl) were added. After 17 hours, complete conversion was obtained. This was concentrated under reduced pressure and purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain the desired product P.181 (14 mg, 32% yield). 1H NMR(600MHz,DMSO-d6,120℃)δ ppm 8.86(s,1H)8.41(d,J=4.7Hz,2H)8.24(s,1H)8.13(s,1H)7.24(t,J=4.8Hz,1H)5.91(q,J=7.0Hz,1H)3.15(s,3H)1.86(d,J=6.9Hz,3H). LC-MS (Method 3) Retention time 1.14 min, m / z502[M+H + ].

[0409] Example 17: Preparation of 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbocioamide (P.190) [ka] Step A: Preparation of 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-45) [ka] t-butyl N-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazole-3-yl]ethyl]carbamate (I-34, 75% purity, 13 g, 31 mmol, 1 equivalent) was dissolved in dichloromethane (195 ml), and trifluoroacetic acid (78 ml, 982 mmol, 31.7 equivalents) was added. The mixture was stirred at 25°C for 1 hour. This reaction mixture was concentrated under reduced pressure.

[0410] Dichloromethane (195 ml) was added to the crude oil and basicized with a saturated Na2CO3 solution. The aqueous layer was extracted with dichloromethane (2 × 200 ml). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain a white solid. This was washed with TBME and dried under reduced pressure to obtain (I-45) (7 g, 87%, 88% purity). 1H NMR(400MHz,DMSO-d6)δ ppm 9.06(s,1H)8.55(d,1H)8.23(s,1H)8.06(d,1H)4.67-4.87(m,1H)1.47(d,3H).

[0411] Step B: Preparation of 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazoline-4-yl]amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-46) [ka] 4-chloro-6,8-bis(trifluoromethyl)quinazoline (I-9 Example 2, 4.0 g, 13.3 mmol, 1 equivalent) was dissolved in acetonitrile (40 ml). 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-45, 85% purity, 3.35 g, 13.3 mmol, 1 equivalent) and cesium carbonate (8.67 g, 26.6 mmol, 2 equivalents) were added, and the mixture was stirred at 25°C for 16 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate (3 × 50 ml). The combined organic layer was dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and subsequently purified by flash chromatography with silica gel (ethyl acetate in cyclohexane) to obtain the desired product (I-46) (5.1 g, 80%). 1 H NMR(400MHz,DMSO-d6)δ ppm 9.47(d,1H)9.27(s,1H)9.04(s,1H)8.58(d,1H)8.44(s,1H)8.36(s,1H)8.21(s,1H)8.09(d,1H)6.42(quin.,1H)1.77(d,3H). LC-MS (Method 5) Retention time 1.59 min, m / z479[M+H + ].

[0412] Step C: Preparation of 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazoline-4-yl]-methyl-amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-47) [ka] 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazoline-4-yl]amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-46, 294 mg, 0.61 mmol, 1 equivalent), acetonitrile (4.92 ml), cesium carbonate (601 mg, 1.84 mmol, 3 equivalents), and iodomethane (77.3 μl, 1.23 mmol, 2 equivalents) were charged into a sealable test tube. The vial was sealed and heated at 50°C for 16 hours. After cooling to 25°C, the mixture was diluted with water (10 ml) and extracted with ethyl acetate (3 × 10 ml). The combined organic compounds were washed with brine, dried over anhydrous sodium 2SO4, and concentrated under reduced pressure. This was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain the desired product (I-47) (250 mg, 83%). 1 H NMR(400MHz,CDCl3)δ ppm 8.55(s,1H)8.35(d,J=5.9Hz,2H)8.24(s,1H)8.11-8.20(m,2H)8.03(s,1H)6.88(q,J=6.97Hz,1H)1.96(d,J=6.97Hz,3H). 19 F NMR(377MHz,CDCl3)δ ppm -61.33(s,3F)-62.39(s,3F). LC-MS (Method 3) Retention time 1.11 min, m / z493[M+H + ].

[0413] Step D: Preparation of 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazoline-4-yl]-methyl-amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbothioamide (P.190) [ka] 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazoline-4-yl]-methyl-amino]ethyl]-1,2,4-triazole-1-yl]pyridine-3-carbonitrile (I-47, 300 mg, 0.61 mmol, 1 equivalent) was dissolved in pyridine (2.4 ml), and ammonium sulfide solution (20% by mass, 1.04 ml, 3.05 mmol, 5 equivalents) was added. The reaction mixture was stirred at 25°C for 16 hours. This was diluted with water and extracted with ethyl acetate (4 times). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. This was purified by flash chromatography using silica gel (ethyl acetate in cyclohexane) to obtain (P.190) (78 mg, 24%). 1 H NMR(400MHz,DMSO-d6)δ ppm 10.04(br s,1H)9.65(br s,1H)8.55(s,1H)8.27-8.41(m,5H)7.91(d,J=8.44Hz,1H)6.76(br d,J=6.85Hz,1H). 19 F NMR(377MHz,DMSO-d6)δ ppm -59.74(s,3F)-60.75(s,3F). LC-MS (Method 4) Retention time 1.12 min, m / z 528[M+H + ].

[0414] [Table 12-1] [Table 12-2] [Table 12-3] [Table 12-4] [Table 12-5] Table 12-6 Table 12-7 Table 12-8 Table 12-9 Table 12-10 Table 12-11 Table 12-12 Table 12-13 Table 12-14 Table 12-15 Table 12-16 Table 12-17 Table 12-18 Table 12-19 Table 12-20 Table 12-21 Table 12-22 Table 12-23 Table 12-24 Table 12-25 Table 12-26 Table 12-27 Table 12-28 Table 12-29 Table 12-30 Table 12-31 Table 12-32 Table 12-33 Table 12-34 Table 12-35 Table 12-36 Table 12-37 Table 12-38 Table 12-39 Table 12-40 Table 12-41 Table 12-42 Table 12-43 Table 12-44 Table 12-45 Table 12-46 Table 12-47 Table 12-48 Table 12-49 Table 12-50 Table 12-51 Table 12-52 Table 12-53 Table 12-54

[0415] Table 13-1 [Table 13-2] [Table 13-3] [Table 13-4]

[0416] [Table 14-1] [Table 14-2] [Table 14-3] [Table 14-4]

[0417] [Table 15-1] [Table 15-2]

[0418] The activity of the compositions according to the present invention can be considerably broadened by adding other insecticidal, acaricidal, and / or fungicidal active components to suit general situations. Mixtures of the compound of Formula I with other insecticidal, acaricidal, and / or fungicidal active components may also have further unexpected advantages, which may be described as synergistic activity in a broader sense. For example, there may be better tolerance by plants, reduced plant toxicity, the ability to control insects at different developmental stages, or better behavior during their manufacture, e.g., during grinding or mixing, during storage, or during use.

[0419] Suitable additives to the active ingredients in this specification include, for example, the following types of active ingredients: organophosphorus compounds, nitrophenol derivatives, thiourea, juvenile hormones, formamidine, benzophenone derivatives, urea, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoids, and Bacillus thuringiensis preparations.

[0420] The following mixtures of the compound of formula I and the active substance are preferred (the abbreviation "TX" means "one compound selected from the compounds defined in Tables D-1 to D-66 and Table P"): Auxiliary agent selected from the group of substances consisting of petroleum (alternative name) (628) + TX, Abamectin + TX, Acequinosil + TX, Acetamiprid + TX, Acetoprol + TX, Acrinatrin + TX, Acinonapir + TX, Afidopiropen + TX, Afoxolanal + TX, Alanicarb + TX, Arethrin + TX, α-Cypermethrin + TX, α-Methrin + TX, Amidoflumet + TX, Aminocarb + TX, Azocyclotin + TX, Bensaltap + TX, Benzochimate + TX, Benzpyrimoxane + TX, β-Cyfluthrin + TX, β-Cypermethrin + TX, Bifenazate + TX, Bifenthrin + TX, Binapacril + TX, Biorethrin+TX, Biorethrin S)-cyclopentyl isomer+TX, Violethmethrin+TX, Bistriflurone+TX, Brofuranilide+TX, Broflutrinate+TX, Bromophos-ethyl+TX, Buprofezin+TX, Butocarboxim+TX, Kazsaphos+TX, Carbaryl+TX, Carbosulfan+TX, Cartap+TX, CAS No.: 1472050-04-6+TX, CAS No.: 1632218-00-8+TX, CAS No.: 1808115-49-2+TX, CAS No.: 2032403-97-5+T X, CAS number: 2044701-44-0+TX, CAS number: 2128706-05-6+TX, CAS number: 2249718-27-0 (or CAS2246757-58-2)+TX, CAS number: 907187-07-9+TX, Chlorantraniliprole+TX, Chlordan+TX, Chlorfenapyr+TX, Chloroprallethrin+TX, Chromafenozide+TX, Clenpyrin+TX, Chloetocarb+TX, Clothianidin+TX, 2-Chlorophenyl N-methylcarbamate (CPMC)+TX, Cyanophenphos+TX, Cyantra Niliprole + TX, Cyclaniliprole + TX, Cyclobtrifluram + TX, Cycloprothrin + TX, Cycloxapride + TX, Cycloxapride + TX, Cyenopyrafen + TX, Cietoprafen + TX, Cyflumetofen + TX, Cyfluthrin + TX, Cyhalodianide + TX, Cyhalothrin + TX, Cypermethrin + TX, Cyphenothrin + TX, Cyprofuranilide + TX, Cyromazine + TX, Deltamethrin + TX, Diafenthiuron + TX, Dialifos + TX, Dibrom + TX, Dichloromezothiaz + TX, Diflovidazine + TX,Diflubenzuron + TX, Dimepropyridaz + TX, Dinactin + TX, Dinocap + TX, Dinotefuran + TX, Dioxabenzophos + TX, Emamectin (Emamectin benzoate) + TX, Empenthrin + TX, ε-Monfluorothrin + TX, ε-Metofluthrin + TX, Esfenvalerate + TX, Ethion + TX, Ethiprole + TX, Etofenprox + TX, Ethoxazole + TX, Funfar + TX, Phenazaquin + TX, Fenfluthrin + TX, Fenitrothion + TX, Phenobucarb + TX, Phenothiocarb + T X, Phenoxycarb + TX, Fenpropathrin + TX, Fenximate + TX, Fensulfothion + TX, Fenthion + TX, Fentin acetate + TX, Fenvalerate + TX, Fipronil + TX, Flomethoxine + TX, Flonicamide + TX, Fluacrypyrim + TX, Fluazindolidine + TX, Fluazuron + TX, Flubendiamide + TX, Flubendimine + TX, Flucitrinate + TX, Flucycloxurone + TX, Flucitrinate + TX, Fluensulfone + TX, Fluphenelim + TX, Flufenprox + TX, Flufiprole + TX, Fluhexaphon + TX, Flumethrin + TX, Fluopyram + TX, Flupentiofenox + TX, Flupyridiflon + TX, Flupyrimin + TX, Flularaner + TX, Fluvalinate + TX, Fluxamethamide + TX, Fostiazate + TX, γ-Cyhalotrin + TX, Gossiplua (trademark) + TX, Guadipyr + TX, Halofenozide + TX, Halofenozide + TX, Halofenprox + TX, Heptafluthrin + TX, Hexithiazox + TX, Hydramethylnon + TX, Imiciaphos + TX, Imidaclor Prid+TX, Imiprothrin+TX, Indoxacarb+TX, Iodomethane+TX, Iprodione+TX, Isocycloceram+TX, Isothioate+TX, Ivermectin+TX, κ-Bifenthrin+TX, κ-Tefluthrin+TX, Lambda-Cyhalotrin+TX, Lepimectin+TX, Lufenuron+TX, Metaflumizone+TX, Metaldehyde+TX, Metam+TX, Methomyl+TX, Methoxyphenozide+TX, Metofluthrin+TX, Metocarb+TX, Mexacalbate+TX, Milbemectin+TX, Monfluorothrin+TX,Nicrossamide + TX, Nicofluprol + TX, Nitenpyram + TX, Nichiazine + TX, Omethoate + TX, Oxamyl + TX, Oxazosulfyl + TX, Parathion-ethyl + TX, Permethrin + TX, Phenothrin + TX, Phosphocarb + TX, Piperonyl butoxide + TX, Pyrimikab + TX, Pyrimifos-ethyl + TX, Polyhedravirus + TX, Prallethrin + TX, Profenofos + TX, Profenofos + TX, Profluthrin + TX, Propargit + TX, Propetamfos + TX, Propoxul + TX, Prothiofo S+TX, Protrifenbut+TX, Piflubmid+TX, Pymetrozine+TX, Piraclofos+TX, Pirafluprole+TX, Pyridaben+TX, Pyridaryl+TX, Pyrifluquinazon+TX, Pyrimidifen+TX, Pyriminostrobin+TX, Pyriprole+TX, Pyriproxyfen+TX, Resmethrin+TX, Saloraner+TX, Selamectin+TX, Silafluofen+TX, Spinetoram+TX, Spinosad+TX, Spirodiclofen+TX, Spiromesifen+TX, Spiropidione+TX, Spirotetramat+TX, Sulfoxaflor+TX, Tebufenozide+TX, Tebufenpyrad+TX, Tebupirimiphos+TX, Tefluthrin+TX, Temephos+TX, Tetrachlorantraniliprole+TX, Tetradiphon+TX, Tetramethrin+TX, Tetramethylfluthrin+TX, Tetranactin+TX, Tetraniliprole+TX, θ-Cypermethrin+TX, Thiacloprid+TX, Thiamethoxam+TX, Thiocyclam+TX, Thiodicarb+TX, Thiofanox+TX, Thiometon+TX, Thiosultap+TX, Thioxazafen+TX, Tolf Enpyrad+TX, Toxaphene+TX, Tralomethrin+TX, Transfluthrin+TX, Triazamate+TX, Triazophos+TX, Trichlorfon+TX, Trichloronate+TX, Trichlorofon+TX, Triflumesopyrin+TX, Cyclopyrazoflor+TX, ζ-Cypermethrin+TX, Fermentation products derived from seaweed extract and Melasse+TX, Fermentation products derived from seaweed extract and Melasse containing urea+TX, Amino acids+TX, Potassium and molybdenum and EDTA-chelated manganese+TX, Seaweed extract and fermented plant products+TX,Fermented plant products containing seaweed extract and plant hormones + TX, vitamins + TX, EDTA-chelated copper + TX, zinc + TX, and iron + TX, azadirachtin + TX, Bacillus aizawai + TX, Bacillus chitinosporus AQ746 (NRRL acceptance number B-21 618) + TX, Bacillus firmus + TX, Bacillus kurstaki + TX, Bacillus mycoides AQ726 (NRRL acceptance number B-21664) + TX, Bacillus pumilus (NRRL acceptance number B-30087) + TX, Bacillus pumilus (Bacillus pumilus)AQ717(NRRL acceptance number B-21662)+TX, Bacillus sp. species AQ178(ATCC acceptance number 53522)+TX, Bacillus sp. species AQ175(ATCC acceptance number 55608)+TX, Bacillus sp. species AQ177(ATCC acceptance number 55609)+TX, Bacillus subtilis (unspecified)+TX, Bacillus subtilis AQ153(ATCC acceptance number 55614)+TX, Bacillus subtilis AQ30002(NRRL acceptance number B-50421)+TX, Bacillus subtilis (Bacillus Bacillus subtilis)AQ30004 (NRRL acceptance number B-50455)+TX, Bacillus subtilis AQ713 (NRRL acceptance number B-21661)+TX, Bacillus subtilis AQ743 (NRRL acceptance number B-21665)+TX, Bacillus thuringiensis AQ52 (NRRL acceptance number B-21619)+TX, Bacillus thuringiensis BD#32 (NRRL acceptance number B-21530)+TX,Bacillus thuringiensis subspec. kurstaki BMP 123+TX, Beauveria bassiana+TX, D-limonene+TX, Granulovirus+TX, Harbin+TX, Helicoverpa armigera nuclear polynuclear virus+TX, Helicoverpa zea nuclear polynuclear virus+TX, Heliothis virescens nuclear polynuclear virus+TX, Heliothis punctigera nuclear polynuclear virus+TX, Metarhizium spp. species+TX, Muscodor albus 620 (NRRL acceptance number 30547)+TX, Muscodor roseus roseus)A3-5 (NRRL acceptance number 30548) + TX, Neem tree-derived products + TX, Paecilomyces fumosoroseus + TX, Paecilomyces lilacinus + TX, Pasteuria nishizawae + TX, Pasteuria penetrans + TX, Pasteuria ramosa + TX, Pasteuria thornei + TX, Pasteuria usgae + TX, P-cymene + TX, Diamondback moth (Plutella xylostella) granulosis virus + TX, Diamondback moth (Plutella Xylostella) Nucleopolynuclear virus + TX, Polyhedra virus + TX, Pyrethrum + TX, QRD 420 (terpenoid blend) + TX, QRD 452 (terpenoid blend) + TX, QRD 460 (terpenoid blend) + TX, Quillaja saponaria + TX, Rhodococcus globerulus AQ719 (NRRL acceptance number B-21663) + TX,Spodoptera frugiperda nucleomultinuclear virus + TX, Streptomyces galbus (NRRL acceptance number 30232) + TX, Streptomyces sp. (NRRL acceptance number B-30145) + TX, terpenoid blend + TX, and insect control active substances selected from species of the genus Verticillium. , Algicidal agents selected from the group consisting of vethoxazine [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, sibutrin [CCN] + TX, diclon (1052) + TX, dichlorophen (232) + TX, endotar (295) + TX, fenthin (347) + TX, slaked lime [CCN] + TX, narbaum (566) + TX, quinoclamin (714) + TX, quinonamide (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347), and triphenyltin hydroxide (IUPAC name) (347) + TX. Anthelmintics selected from the group of substances consisting of abamectin (1) + TX, crufomate (1011) + TX, cyclobutrifluram + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737), and thiophanate (1435) + TX. A birdicide selected from the group consisting of chloralose (127) + TX, endrin (1122) + TX, fenthion (346) + TX, pyridine-4-amine (IUPAC name) (23), and strychnine (745) + TX. 1-H-pyridine-2-thion (IUPAC name) (1222) + TX, 4-(quinoxaline-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, dichlorophene (232) + TX, dipyrithione (1105) + TX, dodicine (1112) + TX, phenaminosulf (1144) + TX, formaldehyde (404) + TX, hydrargafen (alternative name) [CCN] + A bactericide selected from the group of substances consisting of TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis(dimethyldithiocarbamate) (IUPAC name) (1308) + TX, nitrapyrine (580) + TX, octylinone (590) + TX, oxolinic acid (606) + TX, oxytetracycline (611) + TX, potassium hydroxyquinoline sulfate (446) + TX, probenazole (658) + TX, streptomycin (744) + TX, streptomycin sesquisulfate (744) + TX, tecrophthalam (766) + TX, and thiomersal (alternative name) [CCN] + TX. Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter (alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis (alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX, Aphidoletes aphidimiza aphidimyza) (alternative name) (35) + TX, Autographa californica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX, Bacillus thuringiensis Berliner (scientific name) (51) + TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51) + TX, Bacillus thuringiensis subsp. islaensis subsp.israelensis)(scientific name)(51)+TX, Bacillus thuringiensis subsp.japonensis(scientific name)(51)+TX, Bacillus thuringiensis subsp.kurstaki(scientific name)(51)+TX, Bacillus thuringiensis subsp.tenebryonis(scientific name)tenebrionis) (scientific name) (51) + TX, Beauveria bassiana (alternative name) (53) + TX, Beauveria brongniartii (alternative name) (54) + TX, Chrysoperla carnea (alternative name) (151) + TX, Cryptolaemus montrouzieri (alternative name) (178) + TX, Cydia pomonella GV (alternative name) (191) + TX, Dacnusa sibirica (alternative name) (212) + TX, Diglyphus isaea (alternative name) (254) + TX, Encarsia formosa) (scientific name) (293) + TX, desert parasitic wasp (Eretmocerus eremicus) (alternative name) (300) + TX, American tobacco budworm (Helicoverpa zea) NPV (alternative name) (431) + TX, Heterorhabditis bacteriophora and H. megidis (alternative name) (433) + TX, ladybug (Hippodamia convergens) (alternative name) (442) + TX, Leptomastix dactylopii (alternative name) (488) + TX, Macrolophus caliginosus (alternative name) (491) + TX, cutworm (Mamestra brassicae)NPV (alternative name)(494)+TX, Metaphycus helvolus (alternative name)(522)+TX, Metarhizium anisopliae var.acridum (scientific name)(523)+TX, Metarhizium anisopliae var.anisopliae (scientific name)(523)+TX, Neodiprion sertifer NPV and N. reconti (N.lecontei)NPV (alternative name)(575)+TX, Orius spp. (alternative name)(596)+TX, Paecilomyces fumosoroseus (alternative name)(613)+TX, Phytoseiulus persimilis (alternative name)(644)+TX, Spodoptera exigua polycapsid nucleus polyhedrosis virus (scientific name)(741)+TX, Steinernema bibionis (alternative name)(742)+TX, Steinernema carpocapsae (alternative name)(742)+TX, Steinernema felthiae (Steinernema feltiae) (alternative name) (742) + TX, Steinernema glaseri (alternative name) (742) + TX, Steinernema riobrave (alternative name) (742) + TX, Steinernema riobravis (alternative name) (742) + TX, Steinernema scapterisci (alternative name) (742) + TX, Steinernema spp. (alternative name) (742) + TX, Trichogramma spp. (alternative name) (826) + TX, Typhlodromus osidentalis A biological agent selected from the group of substances consisting of *Occidentalis* (alternative name) (844) and *Verticillium lecanii* (alternative name) (848) + TX. A soil sterilizer selected from the group consisting of iodomethane (IUPAC name) (542) and methyl bromide (537) + TX, A sterilizing agent selected from the group of substances consisting of aphorate [CCN]+TX, bisadil (alternative name) [CCN]+TX, busulfan (alternative name) [CCN]+TX, diflubenzuron (250)+TX, dimatif (alternative name) [CCN]+TX, hemel [CCN]+TX, hempa [CCN]+TX, metepa [CCN]+TX, methiotepa [CCN]+TX, methyl aphorate [CCN]+TX, molzide [CCN]+TX, penfluron (alternative name) [CCN]+TX, tepa [CCN]+TX, thiohempa (alternative name) [CCN]+TX, thiotepa (alternative name) [CCN]+TX, tretamine (alternative name) [CCN], and uredepa (alternative name) [CCN]+TX. (E)-deca-5-en-1-yl acetate and (E)-deca-5-en-1-ol (IUPAC name)(222)+TX, (E)-trideca-4-en-1-yl acetate (IUPAC name)(829)+TX, (E)-6-methylhepta-2-en-4-ol (IUPAC name)(541)+TX, (E,Z)-tetradeca-4,1 0-diene-1-ylacetate (IUPAC name)(779)+TX, (Z)-dodeca-7-ene-1-ylacetate (IUPAC name)(285)+TX, (Z)-hexadeca-11-enal (IUPAC name)(436)+TX, (Z)-hexadeca-11-ene-1-ylacetate (IUPAC name)(437)+TX, (Z)-hex Sadeca-13-en-11-in-1-ylacetate (IUPAC name) (438) + TX, (Z)-icosa-13-en-10-on (IUPAC name) (448) + TX, (Z)-tetradeca-7-en-1-ar (IUPAC name) (782) + TX, (Z)-tetradeca-9-en-1-ol (IUPAC name) (783) + TX, ( Z)-Tetradeca-9-ene-1-ylacetate (IUPAC name)(784)+TX, (7E,9Z)-Dodeca-7,9-diene-1-ylacetate (IUPAC name)(283)+TX, (9Z,11E)-Tetradeca-9,11-diene-1-ylacetate (IUPAC name)(780)+TX, (9Z,12E)-Tetradeca-9,12-Diene-1-yl acetate (IUPAC name) (781) + TX, 14-Methyloctadeca-1-ene (IUPAC name) (545) + TX, 4-Methylnonan-5-ol and 4-Methylnonan-5-one (IUPAC name) (544) + TX, α-Multistriatin (alternative name) [CCN] + TX, Brevicomin (alternative name) [CCN] + TX, Chodrelua (alternative name) [CCN] + TX, Codremon (alternative name) (167) + TX, Curea ( Alternative name)(179)+TX, Dispara(277)+TX, Dodeca-8-en-1-ylacetate(IUPAC name)(286)+TX, Dodeca-9-en-1-ylacetate(IUPAC name)(287)+TX, Dodeca-8+TX, 10-dien-1-ylacetate(IUPAC name)(284)+TX, Dominicala(alternative name)[CCN]+TX, 4-methyloctanoate ethyl(IUPAC name)(317)+TX, Eugenol(alternative name )[CCN]+TX, Frontalin (alternative name)[CCN]+TX, Gossiplua (alternative name)(420)+TX, Grandlua (421)+TX, Grandlua I (alternative name)(421)+TX, Grandlua II (alternative name)(421)+TX, Grandlua III (alternative name)(421)+TX, Grandlua IV (alternative name)(421)+TX, Hexalua[CCN]+TX, Ipsdienol (alternative name)[CCN]+TX, Ipsenol (alternative name)[ CCN]+TX, Japonila (alternative name) (481)+TX, Lineatin (alternative name) [CCN]+TX, Littlea (alternative name) [CCN]+TX, Lupula (alternative name) [CCN]+TX, Medolua [CCN]+TX, Megatomoic acid (alternative name) [CCN]+TX, Methyl eugenol (alternative name) (540)+TX, Muscarua (563)+TX, Octadeca-2,13-diene-1-ylacetate (IUPAC name) (588)+TX, Octadeca-3,13-Diene-1-Ilacetate (IUPAC name)(589)+TX, Orphlurua (alternative name)[CCN]+TX, Orictalua (alternative name)(317)+TX, Ostramon (alternative name)[CCN]+TX, Sigrua[CCN]+TX, Solzidine (alternative name)(736)+TX, Sulcatol (alternative name)[CCN]+TX, Tetradeca-11-en-1-Ilacetate (IU Insect pheromones selected from the group of substances consisting of PAC name)(785)+TX, trimedlua(839)+TX, trimedlua A(alternative name)(839)+TX, trimedlua B1(alternative name)(839)+TX, trimedlua B2(alternative name)(839)+TX, trimedlua C(alternative name)(839), and trunk-call(alternative name)[CCN]+TX, Insect repellents selected from the group consisting of 2-(octylthio)ethanol (IUPAC name) (591) + TX, butopyrronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (IUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (IUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethyl carbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethylhexanediol (1137) + TX, hexaamide [CCN] + TX, methquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] and picaridin [CCN] + TX. Bis(tributyltin) oxide (IUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, chloetocarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (IUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachloro A molluscicide selected from the group consisting of lophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tadimucarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, triphenmorph (1454) + TX, trimetacarb (840) + TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347) + TX, and pyriprole [394730-71-3] + TX. AKD-3088 (compound code) + TX, 1,2-dibromo-3-chloropropane (IUPAC / chemical abstract name) (1045) + TX, 1,2-dichloropropane (IUPAC / chemical abstract 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 abstract name) (IUPAC name)(1065)+TX, 3-(4-chlorophenyl)-5-methylrhodanine(IUPAC name)(980)+TX, 5-methyl-6-thioxo-1,3,5-thiadiadinane-3-ylacetic acid(IUPAC name)(1286)+TX, 6-isopentenylaminopurine(alternative name)(210)+TX, abamectin(1)+TX, acetoprole[CCN]+TX, aranicarb(15)+TX, aldicarb(16)+TX, aldoxycarb(863)+TX, AZ60541 (compound code) + TX, bencrotiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (alternative name) + TX, kazusafos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, carbosulfan (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, chloetocarb (999) + TX, cyclobutriflurum + TX, cytokinin (alternative name) (210) + T X, Dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, Diamidaphos (1044) + TX, Diclofenthion (1051) + TX, Diclifos (alternative name) + TX, Dimethoate (262) + TX, Doramectin (alternative name) [CCN] + TX, Emamectin (291) + TX, Emamectin benzoate (291) + TX, Eprinomectin (alternative name) [CCN] + TX, Etoprofos (312) + TX, Ethyl dibromide Len(316)+TX, Fenamifos(326)+TX, Fenpyrad(alternative name)+TX, Fensulfothione(1158)+TX, Fosthiazate(408)+TX, Fosthiethane(1196)+TX, Furfural(alternative name)[CCN]+TX, GY-81(development code)(423)+TX, Heterophos[CCN]+TX, Iodomethane(IUPAC name)(542)+TX, Isamidophos(1230)+TX, Isazofos(1231)+TX, Ibe Lumectin (alternative name) [CCN] + TX, Kinetin (alternative name) (210) + TX, Mecarphone (1258) + TX, Metam (519) + TX, Metam-potassium (alternative name) (519) + TX, Metam-sodium (519) + TX, Methyl bromide (537) + TX, Methyl isothiocyanate (543) + TX, Milbemycin oxime (alternative name) [CCN] + TX, Moxidectin (alternative name) [CCN] + TX, Mulberry dark spot disease fungus (MyrotheciumVerrucaria composition (alternative name) (565) + TX, NC-184 (compound code) + TX, oxamyl (602) + TX, phorate (636) + TX, phosphamidone (639) + TX, phosphocarb [CCN] + TX, sebuphos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) + TX, terbam (alternative name) + TX, terbuphos (773) + TX, tetrachlorothiophene (IU Nematicidals selected from the group consisting of substances comprising PAC / chemical abstract name)(1422)+TX, thiafenox(alternative name)+TX, thionazine(1434)+TX, triazophos(820)+TX, triazurone(alternative name)+TX, xylenol[CCN]+TX, YI-5302(compound code), and zeatin(alternative name)(210)+TX, fluensulfone[318290-98-1]+TX, and fluopyram+TX. A nitrification inhibitor selected from the group consisting of potassium ethylxanthogenicate [CCN] and nitrapyrine (580) + TX, A plant activator selected from the group consisting of acibenzolar(6)+TX, acibenzolar-S-methyl(6)+TX, probenazole(658), and Japanese knotweed (Reynoutria sachalinensis) extract (alternative name)(720)+TX, 2-Isovalerylindan-1,3-dione (IUPAC name) (1246) + TX, 4-(Quinoxaline-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, α-chlorohydrin [CCN] + TX, aluminum phosphide (640) + TX, antu (880) + TX, arsenic trioxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodiphacomum (89) + TX, bromadiolon (containing alpha-bromadiolon) (mu) + TX, Bromethaline (92) + TX, Calcium cyanide (444) + TX, Chloralose (127) + TX, Chlorophacinone (140) + TX, Cholecalciferol (alternative name) (850) + TX, Coumacrole (1004) + TX, Coumafuryl (1005) + TX, Coumatetralyl (175) + TX, Crimidine (1009) + TX, Diphenacome (246) + TX, Difethialone (249) + TX, Diphacinone (273) + TX, Ergocalciferol (301) + TX, Furocumafen (357) + TX, Fluoroacetamide (379) + TX, Flupropadine (1183) + TX, Flupropadine hydrochloride (1183) + TX, γ-HCH (430) + TX, HCH (430) + TX, Hydrogen cyanide (444) + TX, Iodomethane (IUPAC name) (542) + TX, Lithodan (430) + TX, Magnesium phosphide (IUPAC name) (640) + TX, Methyl bromide (537) + TX, Norbormid (1318) + TX, Fosacetim (1336) + TX, Ho A rodenticide selected from the group of substances consisting of sphing (IUPAC name) (640) + TX, phosphorus [CCN] + TX, pidocroline (1341) + TX, potassium arsenite [CCN] + TX, pyrinulone (1371) + TX, siriloside (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. Synergistic agents selected from the group consisting of 2-(2-butoxyethoxy)ethylpiperonylate (IUPAC name) (934) + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohexa-2-enone (IUPAC name) (903) + TX, farnesol and nerolidol (alternative name) (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piperotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesamolin (1394) and sulfoxide (1406) + TX, An animal repellent selected from the group consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatin (422) + TX, guazatin acetate (422) + TX, methiocarb (530) + TX, pyridine-4-amine (IUPAC name) (23) + TX, thyram (804) + TX, trimetacarb (840) + TX, zinc naphthenate [CCN], and thyram (856) + TX. A virucidal agent selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX. A wound protectant selected from the group consisting of mercuric oxide (512) + TX, octylinone (590), and thiophanate-methyl (802) + TX. 1,1-Bis(4-chlorophenyl)-2-ethoxyethanol + TX, 2,4-Dichlorophenylbenzenesulfonate + TX, 2-Fluoro-N-methyl-N-1-cinnamaldehyde + TX, 4-Chlorophenylphenylsulfone + TX, Acetoprole + TX, Aldoxycarb + TX, Amidithione + TX, Amidothioate + TX, Amitone + TX, Amitone Hydrogen Oxalate + TX, Amitraz + TX, Aramite + TX, Arsenic Trioxide + TX, Azobenzene + TX, Azothoate + TX, Benomyl + TX, Benoxaphos + TX, Benzylbenzoate Fragrance salt + TX, Bixafen + TX, Brofenvalerate + TX, Bromocyclene + TX, Bromophos + TX, Bromopropylate + TX, Buprofezin + TX, Butocarboxime + TX, Butoxycarboxime + TX, Butylpyridaben + TX, Calcium polysulfate + TX, Canfechlor + TX, Carbanolate + TX, Carbophenothion + TX, Simiazole + TX, Tinomethionate + TX, Chlorbenside + TX, Chlordimeform + TX, Chlordimeform hydrochloride + TX, Chlorphenetol + TX, Chlorfensone + TX Chlorofensilfide + TX, Chlorobenzilate + TX, Chloromebform + TX, Chloromethirone + TX, Chloropropylate + TX, Chlorthiophos + TX, Synerin I + TX, Synerin II + TX, Synerin + TX, Closantel + TX, Coumaphos + TX, Crotamiton + TX, Clothoxyphos + TX, Cuflaev + TX, Cyanthoate + TX, DCPM + TX, DDT + TX, Demefion + TX, Demefion-O + TX, Demefion-S + TX, Demeton-methyl + TX, Demeton-O + TX, Demeton-O-methyl + TX Demeton-S+TX, Demeton-S-methyl+TX, Demeton-S-methylsulfone+TX, Diclofluanide+TX, Dichlorvos+TX, Dicrifos+TX, Dienochlor+TX, Dimefox+TX, Dynex+TX, Dynexdicrexin+TX, Dinocap-4+TX, Dinocap-6+TX, Dinoctone+TX, Dinopenton+TX, Dinosulfone+TX, Dinotervon+TX, Dioxathion+TX, Diphenylsulfone+TX, Disulfiram+TX, DNOC+TX, Dofenapine+TX, Doramectin+TX, Endothion+TX,Epilinomectin + TX, Ethoate-methyl + TX, Etrimophos + TX, Phenazaflor + TX, Fenbutatin oxide + TX, Phenothiocarb + TX, Fenpyrad + TX, Fenpyroximate + TX, Fenpyrazamine + TX, Fenson + TX, Fentriphanil + TX, Flubenzimin + TX, Flucycloxurone + TX, Fluenetil + TX, Fluolbenside + TX, FMC 1137 + TX, Formethanate + TX, Formethanate hydrochloride + TX, Formparanate + TX, γ-HCH + TX, Gliodin + TX, Halfenprox + TX, Hexadecylcyclopropane carboxylate + TX, Isocarbofos + TX, Jasmolin I + TX, Jasmolin II + TX, Jodofenphos + TX, Lindan + TX, Malonoben + TX, Mecarbam + TX, Mephosphoran + TX, Mesulfen + TX, Methacryphos +TX, Methyl bromide +TX, Methylcarb +TX, Mexacalbate +TX, Milbemycin oxime +TX, Mipahox +TX, Monoclotophos +TX, Morphothion +TX, Moxidectin +TX, Nared +TX, 4-Chloro-2-(2-Chloro-2-methylpropyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one +TX, Niflulidide +TX, Nikcomycin +TX, Nitrilacarb +TX, Nitrilacarb 1:1 salt Zinc complex + TX, Omethoate + TX, Oxydeprophos + TX, Oxydisulfon + TX, pp'-DDT + TX, Parathion + TX, Permethrin + TX, Fencapton + TX, Phosalone + TX, Phosphamide + TX, Polychloroterpene + TX, Polynactin + TX, Proclonol + TX, Promacil + TX, Propoxul + TX, Protidathion + TX, Protoate + TX, Pyrethrin I + TX, Pyrethrin II +TX, Pyrethrin+TX, Pyridafenthion+TX, Pyrimitate+TX, Quinalphos+TX, Quinthiophos+TX, R-1492+TX, Phosglycine+TX, Rotenone+TX, Shuradan+TX, Sebuphos+TX, Selamectin+TX, Sofamide+TX, SSI-121+TX, Sulfiram+TX, Sulfuramide+TX, Sulfotep+TX, Sulfur+TX, Diflovidazine+TX, τ-Fulvalinate+TX, TEPP+TX, Terbam+TX,Tetradiphon + TX, Tetrasul + TX, Thiafenox + TX, Thiocarboxim + TX, Thiofanox + TX, Thiometon + TX, Thioquinox + TX, Turingiencin + TX, Triamiphos + TX, Triatene + TX, Triazophos + TX, Triazurone + TX, Triphenophos + TX, Trinactin + TX, Bamidthion + TX, Vaniliprole + TX, Bethoxazine + TX, Copper nioctanonate + TX Copper sulfate + TX, Sibutrin + TX, Diclon + TX, Dichlorophene + TX, Endotar + TX, Fetin + TX, Slaked lime + TX, Narbam + TX, Quinocramin + TX, Quinonamide + TX, Simazine + TX, Triphenyltin acetate + TX, Triphenyltin hydroxide + TX, Culfomate + TX, Piperazine + TX, Thiophanate + TX, Chloralose + TX, Fenthion + TX, Pyridine-4-amine + T X, 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, doditin + TX, phenaminosulf + TX, formaldehyde + TX, hydrargafen + TX, kasugamycin + TX, kasugamycin hydrochloride hydrate + TX, nickel bis(dimethyldithiocarbamate) + TX, nitrapyrine + TX, octylinone + TX, oxolinic acid + TX, oxytetracycline + TX, potassium hydroxyquinoline sulfate + TX, probenazole + TX, streptomycin + TX, streptomycin sesquisulfate + TX, tecrophthalam + TX, thiomersal + TX, apple tortrix (Adoxophyes) orana) GV+TX, Agrobacterium radiobacter+TX, Amblyseius spp. species+TX, Anagrapha falcifera NPV+TX, Anagrus atomus+TX, Aphelinus abdominalis+TX, Aphidius colemani+TX,Aphidoletes aphidimyza + TX, Autographa californica NPV + TX, Bacillus sphaericus Neide + TX, Beauveria brongniartii + TX, Chrysoperla carnea + TX, Cryptolaemus montrouzieri + TX, Cydia pomonella GV + TX, Dacnusa sibirica + TX, Diglyphus isaea + TX, Encarsia formosa + TX, Eretmocerus eremicus)+TX, Heterorhabditis bacteriophora and H. megidis+TX, Hippodamia convergens+TX, Leptomastix dactylopii+TX, Macrolophus caliginosus+TX, Mamestra brassicae NPV+TX, Metaphycus helvolus+TX, Metarhizium anisopliae var. acridum+TX, Metarhizium anisopliae var. anisopliae+TX, Neodiprion sertifer)NPV and N. lecontei NPV+TX, species of the genus Orius (Orius spp.)+TX, Paecilomyces fumosoroseus+TX, Phytoseiulus persimilis+TX, Steinernema bibionis+TX,Steinernema carpocapsae + TX, Steinernema feltiae + TX, Steinernema glaseri + TX, Steinernema riobrave + TX, Steinernema riobravis + TX, Steinernema scapterisci + TX, Steinernema spp. species + TX, Trichogramma spp. species + TX, Typhlodromus occidentalis + TX, Verticillium lecanii (E)-Deca-5-en-1-ylacetate and (E)-Deca-5-en-1-ol +TX, (E)-Trideca-4-en-1-ylacetate +TX, (E)-6-methylhepta-2-en-4-ol +TX, (E,Z)-Tetradeca-4,10-dien-1-ylacetate +TX, (Z)-Dodeca-7-en-1-ylacetate +TX, (Z)-Dodeca-7-en-1-ylacetate +TX, (Z )-Hexadeca-11-Enal+TX, (Z)-Hexadeca-11-En-1-Ilacetate+TX, (Z)-Hexadeca-13-En-11-In-1-Ilacetate+TX, (Z)-Icosa-13-En-10-On+TX, (Z)-Tetradeca-7-En-1-Al+TX, (Z)-Tetradeca-9-En-1-All+TX, ( Z)-Tetradeca-9-ene-1-ylacetate+TX, (7E,9Z)-Dodeca-7,9-diene-1-ylacetate+TX, (9Z,11E)-Tetradeca-9,11-diene-1-ylacetate+TX, (9Z,12E)-Tetradeca-9,12-diene-1-ylacetate+TX, 14-Methyloctadeca-1-ene+TX,4-methylnonan-5-ol and 4-methylnonan-5-one + TX, α-multistriatin + TX, brevicomin + TX, kodrelle + TX, kodremon + TX, querelle + TX, dysparla + TX, dodeca-8-en-1-yl acetate + TX, dodeca-9-en-1-yl acetate + TX, dodeca-8 + TX, 10-dien-1-yl acetate + TX, dominicalla + TX, ethyl, 4-Methyloctanoate + TX, Eugenol + TX, Frontalin + TX, Grandlua + TX, Grandlua I + TX, Grandlua II + TX, Grandlua III + TX, Grandlua IV + TX, Hexalua + TX, Ipsdienol + TX, Ipsenol + TX, Japonila + TX, Lineatin + TX, Littlea + TX, Lupulua + TX, Medrua + TX, Megatomoic acid + TX, Methyleugenol + TX, Muscarua + TX, Octadeca-2,13-dien-1-yl acetate + TX, Octadeca-3,13-dien-1-yl Luacetate + TX, Olfura + TX, Orictalua + TX, Ostramon + TX, Sigura + TX, Solzidine + TX, Sulcatol + TX, Tetradeca-11-en-1-ylacetate + TX, Trimedolua + TX, Trimedolua A + TX, Trimedolua B1 + TX, Trimedolua B2 + TX, Trimedolua C + TX, Trunc-Call + TX, 2-(Octylthio)ethanol + TX, Butapyronoxyl + TX, Butoxy(Polypropylene Glycol) + TX, Dibutyladipate + TX, Dibutyl Phthalate + TX, Dibutylsuccinate + TX, Diethyltoluamide + TX, Dimethylcarbate + TX, Dimethylphthalate + TX, Ethylhexanediol + TX, Hexamide + TX, Methquine-butyl + TX, Methylneodecanamide + TX, Oxamate + TX, Picalidine + TX, 1-Dichloro-1-nitroethane + TX, 1,1-Dichloro-2,2-bis(4-ethylphenyl)ethane + TX, 1,2-Dichloropropane and 1,3-Dichloropropene + TX, 1-Bromo-2-chloroethane + TX, 2,2,2-Trichloro-1-(3,4-Dichloro (Lofyl)ethyl acetate + TX, 2,2-dichlorovinyl 2-ethylsulfinylethylmethyl phosphate + TX, 2-(1,3-dithiolan-2-yl)phenyldimethylcarbamate + TX, 2-(2-butoxyethoxy)ethylthiocyanate + TX, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenylmethylcarbamate + TX, 2-(4-chloro-3,5-xylyloxy)ethanol + TX, 2-chlorovinyl diethyl phosphate + TX, 2-imidazolidone + TX, 2-isovalerylindan-1,3-dione + TX,2-Methyl(prop-2-inyl)aminophenylmethylcarbamate + TX, 2-thiocyanatoethyl laurate + TX, 3-bromo-1-chloroprop-1-ene + TX, 3-methyl-1-phenylpyrazole-5-yldimethylcarbamate + TX, 4-methyl(prop-2-inyl)amino-3,5-xylylmethylcarbamate + TX, 5,5-dimethyl-3-oxocyclohexa-1-enyldimethylcarbamate + TX, acetylone + TX, acrylonitrile + TX, aldrin + TX, allosamidin + TX, alixicarb + TX, α-ecdysone + TX, aluminum phosphide + TX, aminocarb + TX, anabasine + TX, atidathion + TX, azamethiphos + TX, Bacillus thuringiensis thuringiensis)δ endotoxin + TX, barium hexafluorosilicate + TX, barium polysulfide + TX, bartholin + TX, Bayer 22 / 190 + TX, Bayer 22408 + TX, β-cyfluthrin + TX, β-cypermethrin + TX, bioetanomethrin + TX, biopermethrin + TX, bis(2-chloroethyl) ether + TX, sodium borate + TX, bromfenbinphos + TX, bromo-DDT + TX, bufencarb + TX, butacarb + TX, butathiophos + TX, butonate + TX, calcium arsenate + TX, calcium cyanide + TX, carbon disulfide + TX, carbon tetrachloride + TX, cartap hydrochloride + TX, sebadin + TX, chlorbicyclene + TX, chlordan + TX, Chlordecone + TX, Chloroform + TX, Chloropicrin + TX, Chlorphoxime + TX, Chlorprazophos + TX, Cis-resmethrin + TX, Cysmethrin + TX, Crocitrin + TX, Copper acetoarsenite + TX, Copper arsenate + TX, Copper oleate + TX, Cumithoate + TX, Cryolite + TX, CS708 + TX, Cyanophenphos + TX, Cyanophos + TX, Ciclethrin + TX, Cithioate + TX, d-Tetramethrin + TX, DAEP + TX, Dazomet + TX, Decarbofuran + TX, Diamidaphos + TX, Dicapton + TX, Dichlorophenthion + TX, Diclesil + TX, Dicyclanil + TX, Dieldrin + TX, Diethyl 5-methylpyrazole-3-yl phosphate + TX, Dirol + TX, Dimefluthrin + TX,Dimethane + TX, Dimethrin + TX, Dimethylvinphos + TX, Dimethilane + TX, Dinoprop + TX, Dinosam + TX, Dinoseb + TX, Diophenolane + TX, Dioxabenzophos + TX, Diticlophos + TX, DSP + TX, Ecdysterone + TX, EI 1642 + TX, EMPC + TX, EPBP + TX, Etaphos + TX, Ethiofencarb + TX, Ethyl formate + TX, Ethylene dibromide + TX, Dichloroethane + TX, Ethylene oxide + TX, EXD + TX, Fenchlorphos + TX, Phenetacarb + TX, Fenitrothion + TX, Phenoxacrim + TX, Fenpyritrin + TX, Fensulfothion + TX, Fenthion-ethyl + TX, Flucoflon + TX, Fosmethilane + TX, Fosspire + TX, Phos Thietane + TX, Frathiocarb + TX, Fretolin + TX, Guazatin + TX, Guazatin acetate + TX, Sodium tetrathiocarbonate + TX, Halfenprox + TX, HCH + TX, HEOD + TX, Heptachlor + TX, Heterophos + TX, HHDN + TX, Hydrogen cyanide + TX, Hikincarb + TX, IPSP + TX, Isazofos + TX, Isobenzane + TX, Isodrine + TX, Isofenphos + TX, Isolan + TX, Isoprothiolan + TX, Isoxa Thione + TX, Larval Hormone I + TX, Larval Hormone II + TX, Larval Hormone III + TX, Kereban + TX, Quinoprene + TX, Lead Arsenate + TX, Leptophos + TX, Lilimphos + TX, Litidathion + TX, m-Cumenyl Methylcarbamate + TX, Magnesium Phosphate + TX, Magidox + TX, Mecarfone + TX, Menazone + TX, Mercurous Chloride + TX, Mesulfe...

Images