Condensed bicyclic aromatic heterocyclic compounds having pesticidal activity

Abstract

Formula (I) JPEG2025520650000210.jpg52161(wherein the substituents are as defined in claim 1) The compounds of formula (I) and their agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides can be used as insecticides.

Description

Technical Field

[0001] The present invention relates to quinazoline compounds which are pesticidally active, in particular insecticidally active, to processes for their preparation, to compositions containing these compounds and to their use for controlling animal pests, including arthropods and in particular insects or representatives of the order Acarina (Acarina).

Background Art

[0002] WO 2021 / 083936, WO 2021 / 148639 and WO 2021 / 177160 describe certain quinazoline, quinazolinone and quinoline compounds.

Summary of the Invention

Means for Solving the Problems

[0003] Here, further novel pesticidally active quinazoline compounds have been found.

[0004] The present invention thus, in a first aspect, provides a compound of formula (I)

Chemical Formula

Chemical Formula

Mode for Carrying Out the Invention

[0005] Compounds of formula (I) having at least one basic centre can form, for example, acid addition salts with, for example, inorganic strong acids such as mineral acids, such as perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or hydrohalic acids, strong organic carboxylic acids such as C1-C4 alkane carboxylic acids which are unsubstituted or substituted, for example, by halogen, such as acetic acid, saturated or unsaturated dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, hydroxycarboxylic acids such as ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or acid addition salts with, for example, benzoic acid, or organic sulfonic acids such as C1-C4 alkane- or arylsulfonic acids which are unsubstituted or substituted, for example, by halogen, such as methane- or p-toluenesulfonic acid. Compounds of formula (I) having at least one acidic group can form, for example, salts with bases, 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 compounds of formula (I) according to the invention are in free form, in oxidized form as N-oxides or in salt form, for example in an agriculturally usable salt form.

[0007] N-oxides are oxidized forms of tertiary amines or oxidized forms of 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 compounds of formula (I) according to the invention also include hydrates which can be formed during salt formation.

[0009] As used herein, "C1-C n alkyl" refers to a saturated straight-chain or branched hydrocarbon group having 1 to n carbon atoms bonded through any of the carbon atoms, for example, methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl.

[0010] As used herein, "C1-C nThe term "haloalkyl" refers to a straight-chain or branched saturated alkyl group having 1 to n carbon atoms, bonded through any of the carbon atoms (as described above), and some or all of the hydrogen atoms in these groups may be substituted by fluorine, chlorine, bromine, and / or iodine, i.e., for example, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 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 group having 1, 2, 3, 4, or 5 fluorine atoms, for example, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl, or pentafluoroethyl.

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

[0012] As used herein, "C1-C n The term "cyanoalkyl" refers to a straight-chain or branched saturated C1-C n alkyl group having 1 to n carbon atoms (as described above), in which one of the hydrogen atoms in these groups is substituted with a cyano group, and examples include cyanomethyl, 2-cyanoethyl, 2-cyanopropyl, 3-cyanopropyl, 1-(cyanomethyl)-2-ethyl, 1-(methyl)-2-cyanoethyl, 4-cyanobutyl, and the like.

[0013] As used herein, the term "C3-C n "cycloalkyl" refers to a 3- to n-membered cycloalkyl group such as cyclopropane, cyclobutane, cyclopentane, and cyclohexane.

[0014] As used herein, the term "cyanoC3-C4 cycloalkyl" refers to a cyclopropane or cyclobutane group monosubstituted with cyano.

[0015] As used herein, "C3-C nThe term "cycloalkylcarbonyl" refers to a 3- to n-membered cycloalkyl group attached to a carbonyl (C=O) group, which carbonyl group is attached to the remainder of the molecule. Similarly, as used herein, "C1-C n alkylcarbonyl", "C1-C n alkoxycarbonyl", "phenyloxycarbonyl" and "benzyloxycarbonyl" refer to an alkyl, alkoxy, phenyloxy and benzyloxy group attached to a carbonyl (C=O) group, which carbonyl group is attached to the remainder of the molecule.

[0016] As used herein, the term "C3-C4 cycloalkyl-C1-C2 alkyl" refers to a 3- or 4-membered cycloalkyl group having a methylene or ethylene group, which methylene or ethylene group is attached 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 group and / or the alkyl group.

[0017] As used herein, the term "C3-C6 cycloalkyl C1-C4 haloalkoxy" refers to a 3- to 6-membered cycloalkyl group attached to a 1- to 4-membered haloalkoxy group, which haloalkoxy group is attached to the remainder of the molecule.

[0018] As used herein, the term "aminocarbonyl C1-C n alkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is substituted by a CONH2 group.

[0019] As used herein, the term "hydroxycarbonyl C1-C n alkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is substituted by a C(O)OH group.

[0020] As used herein, the term "C1-C n alkylsulfanyl" refers to C1-C attached via a sulfur atom nrefers to an alkyl moiety. Similarly, as used herein, "C1-C n haloalkylthio" or "C1-C n haloalkylsulfanyl" refers to a C1-C n haloalkyl moiety bonded through a sulfur atom. Similarly, "C3-C n cycloalkylsulfanyl" refers to a 3- to n-membered cycloalkyl moiety bonded through a sulfur atom.

[0021] As used herein, "C1-C n alkylsulfinyl" refers to a C1-C n alkyl moiety bonded through the sulfur atom of the S(=O) group. Similarly, as used herein, "C1-C n haloalkylsulfinyl" or "C1-C n haloalkylsulfinyl" refers to a C1-C n haloalkyl moiety bonded through the sulfur atom of the S(=O) group. Similarly, "C3-C n cycloalkylsulfinyl" refers to a 3- to n-membered cycloalkyl moiety bonded through the sulfur atom of the S(=O) group.

[0022] As used herein, "C1-C n alkylsulfonyl" refers to a C1-C n alkyl moiety bonded through the sulfur atom of the S(=O)2 group. Similarly, as used herein, "C1-C n haloalkylsulfonyl" or "C1-C n haloalkylsulfonyl" refers to a C1-C n haloalkyl moiety bonded through the sulfur atom of the S(=O)2 group. Similarly, "C3-C n cycloalkylsulfonyl" refers to a 3- to n-membered cycloalkyl moiety bonded through the sulfur atom of the S(=O)2 group.

[0023] As used herein, "trimethylsilyl C1-C nThe term "alkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is replaced by a -Si(CH3)3 group.

[0024] As used herein, "C2-C n The term "alkenyl" refers to a straight or branched alkenyl chain having 2 to n carbon atoms and one or two double bonds, such as ethenyl, prop-1-enyl, and but-2-enyl.

[0025] As used herein, "C2-C n The term "haloalkenyl" refers to a C2-C n alkenyl moiety substituted with one or more halo atoms, which may be the same or different.

[0026] As used herein, "C2-C n The term "alkynyl" refers to a straight or branched alkynyl chain having 2 to n carbon atoms and one triple bond, such as ethynyl, prop-2-ynyl, and but-3-ynyl.

[0027] As used herein, "C2-C n The term "haloalkynyl" refers to a C2-C n alkynyl moiety substituted with one or more halo atoms, which may be the same or different.

[0028] Halogen or "halo" generally refers to fluorine, chlorine, bromine, or iodine. This also applies to halogen in combination with other meanings such as haloalkyl.

[0029] As used herein, the term "heteroaryl" refers to a 5- or 6-membered aromatic monocyclic ring having 1 to 3 heteroatoms independently selected from N, O, and S. Examples are heteroaryls J-1 to J-41 shown in Scheme A below. Preferred heteroaryls are pyridyl, pyrimidyl, and pyrazolyl. Scheme A: Heteroaryls J-1 to J-41:

Chem.

[0030] R 4 and R 4a The pyridine, pyrimidine, pyrazine and pyridazine groups (unsubstituted or substituted) related to R and R are each attached to the remainder of the compound via a carbon atom in each ring.

[0031] As used herein, the term "control" refers to a reduction in the number of pests, the elimination of pests and / or the prevention of further damage by pests such that damage to plants or plant-derived products is reduced.

[0032] The wavy line, as used herein, represents, for example, the connection point / bonding point to the remainder of the compound at Q a -1 and Q b -1.

[0033] As used herein, the term "pest" refers to insects and mollusks found in agriculture, horticulture, forestry, the storage of plant-derived products (such as fruits, grains and lumber); and pests associated with damage to artificial structures. The term pest encompasses all stages in the life cycle of the pest.

[0034] As used herein, the term "effective amount" refers to the amount of a compound or a salt thereof that, upon single or multiple applications, brings about the desired effect.

[0035] The effective amount can be readily determined by one of ordinary skill in the art by observing the results obtained using known techniques and in similar situations. In determining the effective amount, a number of factors are considered, including, but not limited to, the type of plant or plant-derived product to which it is applied; the pest to be controlled and its life cycle; the particular compound being applied; the type of application; and other relevant circumstances.

[0036] As will be appreciated by those skilled in the art, the compounds of formula (I) have the following structure:

Chemical formula

[0037] The present invention contemplates both racemic compounds and individual enantiomers. Compounds having preferred stereochemistry are shown below. Particularly preferred compounds of the present invention are of formula (I’a):

Chemical formula

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

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

[0040] In embodiments of each aspect of the present invention, R is not hydrogen.

[0041] In embodiments of each aspect of the present invention, A.A 1 , A 2 and A 3 are, independently of each other, N or CR Y , provided that no more than two of the three are N; or B.A 1 and A 3 are N, and A 2 is CR Y ; or C.A 1 , A 2 and A 3 are, independently of each other, N or CH; or D.A 1 , A 2 and A 3 are, independently of each other, N or CH, provided that no more than two of the three are N; or E.A 1 is N, and A 2 and A 3 are CH; or F.A 1 and A 2 are CH, and A 3 is N; or G.A 1 and A 3 are N, and A 2 is CH; or H.A 1 =A 2 -A 3 together form NR-C(=O)-N; or I.A 1 =A 2 -A 3 together form NH-C(=O)-N; or In embodiments of each aspect of the present invention, A.A 4 is CR YY and A5 Is it N; or B.A 4 Is CR YY and A 5 Is CH; or C.A 4 Is CH, and A 5 Is it N; or D.A 4 Is N, and A 5 Is CH; or E.A 4 and A 5 are both CH.

[0042] In an embodiment of each aspect of the present invention, A.A 1 Is N, A 2 and A 3 Is CH, and A 4 and A 5 are both CH; or B.A 1 and A 2 Is CH, A 3 Is N, and A 4 and A 5 are both CH. C.A 1 and A 3 Is N, A 2 Is CH, and A 4 Is CR Y and A 5 Is CH; or D.A 1 and A 3 Is N, A 2 Is CH, and A 4 Is CH, and A 5 Is it N; or E.A 1 and A 3 Is N, A 2 Is CH, and A 4 Is N, and A 5 Is CH; or F.A 1 and A 3is N, and A 2 is CH, and A 4 is N or CH, and A 5 is CH; or G.A 1 and A 3 is N, and A 2 is CH, and A 4 is CH, and A 5 is N or CH; or H.A 1 and A 3 is N, and A 2 is CH, and A 4 and A 5 are both N; or I.A 1 and A 3 is N, and A 2 is CH, and A 4 and A 5 are both CH; or J.A 1 =A 2 -A 3 together are NH-C(=O)-N, and A 4 and A 5 are both CH.

[0043] A 1 =A 2 -A 3 In embodiments of each aspect of the present invention where =A and -A together are NR-C(=O)-N, R is A. hydrogen, methyl, ethyl, difluoroethyl or trifluoroethyl; or B. hydrogen; methyl, ethyl, 2,2-difluoroethyl or 2,2,2,-trifluoroethyl, or C. hydrogen; or D. methyl or 2,2,2,-trifluoroethyl; or E. methyl; or F. hydrogen or methyl is.

[0044] In preferred embodiments of each aspect of the present invention, A 1and A 3 is nitrogen, and A 2 , A 4 and A 5 is CH.

[0045] In embodiments of each aspect of the present invention, R 1 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- (wherein the C3-C4 cycloalkyl group is substituted with one or two halogen atoms), oxetan-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 cycloalkylC1-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 cycloalkylC1-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 cycloalkylC1-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; or J. hydrogen, methyl or cyclopropyl-methyl; or K. hydrogen or methyl: or L. hydrogen is.

[0046] In a preferred embodiment of each aspect of the present invention, R 1 is hydrogen, methyl or cyclopropyl-methyl, preferably R 1 is hydrogen or methyl; more preferably, R 1 is hydrogen.

[0047] In an embodiment of each aspect of the present invention, R2a 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 and J-41 (C3-C4 cycloalkyl, phenyl or heteroaryl are each independently substituted with 1-3 substituents R x respectively); OR 6 , piperidin-2-one-1-yl, pyridin-2-one-1-yl, R x azetidin-1-yl optionally substituted with R Z , pyrrolidin-1-yl, 1 or 2 substituents R x C3-C6 cycloalkyl C1-C4 alkyl substituted with R x , C3-C6 cycloalkyl C1-C3 alkoxy optionally substituted with R x , C1-C5 cyanoalkyl, C1-C5 cyanoalkoxy, 1-3 substituents R x C1-C4 alkylsulfanyl optionally substituted with 1-3 substituents R B. hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, C3-C6 cycloalkylcarbonyl, phenyl, pyrazolyl (C3-C4 cycloalkyl, phenyl, pyrazolyl are each independently substituted with 1-3 substituents R x respectively); OR 6 , piperidin-2-one-1-yl, pyridin-2-one-1-yl, R x azetidin-1-yl optionally substituted with R Z , pyrrolidin-1-yl, 1 or 2 substituents R xC3-C6 cycloalkyl C1-C3 alkoxy, C1-C5 cyanoalkyl, C1-C5 cyanoalkoxy, or 1-3 substituents R, which may each be optionally substituted x C1-C4 alkylsulfanyl, or 1-3 substituents R, which may each be optionally substituted x C1-C4 alkylsulfonyl or 1-3 substituents R, which may each be optionally substituted 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 (C3-C4 cycloalkyl, phenyl, pyrazolyl may each be independently substituted with 1-2 substituents R x ), OR 6 , R x Azetidin-1-yl, which may be optionally substituted with 1 or 2 substituents R Z C3-C6 cycloalkyl C1-C4 alkyl, which may be optionally substituted with 1 or 2 substituents R x C3-C6 cycloalkyl C1-C3 alkoxy, which may be optionally substituted with 1-3 substituents R x C1-C4 alkylsulfanyl, which may be optionally substituted with 1-3 substituents R x C1-C4 alkylsulfonyl or 1-3 substituents R, which may be optionally substituted 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, OR 6 , C3-C6 cycloalkyl C1-C4 alkyl, C3-C6 cycloalkyl C1-C4 alkyl substituted with 1 or 2 substituents R Z C1-C4 alkylsulfanyl, which may be substituted with 1-3 substituents Rx C1-C4 alkylsulfanyl, C1-C4 alkylsulfonyl, or 1-3 substituents R replaced by x C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, or 1-3 substituents R replaced by x C1-C4 alkylsulfinyl replaced by; or E. 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 independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkylcarbonyl, C3-C4 cycloalkylmethyl, oxo, C3-C4 cycloalkylmethyl substituted with 1-2 substituents independently selected from halogen, C1-C3 alkyl, and C1-C3 haloalkyl, C1-C2 alkylsulfanyl substituted with 1-3 halogens, or C1-C2 alkylsulfonyl substituted with 1-3 halogens; or F. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, cyclopropyl substituted with 1-2 substituents independently selected from halogen, methyl, and trifluoromethyl, cyclopropylcarbonyl, oxo, cyclopropylmethyl substituted with 1-2 substituents independently selected from halogen and trifluoromethyl, C1-C2 alkylsulfanyl substituted with 1-3 halogens, or C1-C2 alkylsulfonyl substituted with 1-3 halogens; or G. C3-C6 cycloalkyl substituted with 1 to 3 substituents independently selected from hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C6 cycloalkyl, C1-C3 alkyl, C1-C3 haloalkyl, cyano and halogen; cyclopropylcarbonyl; C3-C6 cycloalkyl C1-C4 alkyl substituted with 1 to 5 substituents independently selected from oxo, C1-C3 alkyl, C1-C3 haloalkyl, cyano and halogen; 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; or H. C3-C6 cycloalkyl substituted with 1 or 2 substituents independently selected from hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C6 cycloalkyl, C1-C3 alkyl, C1-C3 haloalkyl, cyano and halogen; C3-C4 cycloalkylcarbonyl; C3-C6 cycloalkyl C1-C4 alkyl substituted with 1 to 3 substituents independently selected from oxo, C1-C3 haloalkyl, cyano and halogen; 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; or I. Hydrogen, halogen, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkoxy, C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted with one or two substituents independently selected from C1-C3 haloalkyl, cyano and halogen, C3-C4 cycloalkylcarbonyl, C3-C6 cycloalkyl-C1-C4 alkyl, C3-C6 cycloalkyl-C1-C4 alkyl substituted with 1-3 substituents independently selected from oxo, C1-C3 haloalkyl, cyano and halogen, 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; or J. Hydrogen, halogen, C3-C4 cycloalkyl, C3-C4 cycloalkylcarbonyl, optionally substituted with one or two substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; 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. chlorine, bromine, iodine, trifluoromethylsulfonyl or trifluoromethyl; or P. chlorine, bromine, iodine, methyl, trifluoromethylsulfonyl or trifluoromethyl; or Q. chlorine, bromine, iodine, methyl or trifluoromethyl; or R. chlorine, bromine, iodine or trifluoromethyl is.

[0048] In a preferred embodiment of each aspect of the present invention, R 2a is chlorine, bromine, iodine or trifluoromethyl; preferably, R 2a is chlorine or trifluoromethyl.

[0049] In an embodiment of each aspect of the present invention, R 2b is A. hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, cyclopropylcarbonyl, C3-C6 cycloalkyl C1-C4 alkyl optionally substituted with 1 or 2 substituents R Z C1-C3 alkoxy, C1-C3 haloalkoxy or CN, C1-C4 alkylsulfanyl optionally substituted with 1-3 substituents R x C1-C4 alkylsulfonyl optionally substituted with 1-3 substituents R x or C1-C4 alkylsulfinyl optionally substituted with 1-3 substituents R x ; or B. hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl optionally substituted with 1-2 substituents selected from C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; or C. halogen, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl or C1-C3 haloalkoxy; or D. halogen, C1-C2 haloalkyl, C1-C2 haloalkylsulfanyl, C1-C2 haloalkylsulfonyl or C1-C2 haloalkoxy; or E. fluorine, chlorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethylsulfonyl; or F. fluorine, chlorine, bromine, iodine, trifluoromethylsulfanyl, trifluoromethylsulfonyl or trifluoromethyl; or G. chlorine, bromine, iodine, trifluoromethylsulfonyl or trifluoromethyl; or H. chlorine, bromine, iodine or trifluoromethyl; or I. chlorine or trifluoromethyl; or J. chlorine, bromine, iodine, trifluoromethyl, difluoromethylsulfonyl or trifluoromethylsulfonyl; or K. difluoromethylsulfonyl or trifluoromethylsulfonyl is.

[0050] In a preferred embodiment of each aspect of the present invention, R 2b is chlorine, bromine, iodine, trifluoromethyl, difluoromethylsulfonyl or trifluoromethylsulfonyl; preferably, R 2b is chlorine, bromine, iodine or trifluoromethyl. In an embodiment of each aspect of the present invention, R 2b is difluoromethylsulfonyl or trifluoromethylsulfonyl.

[0051] In an embodiment of each aspect of the present invention, A. R 2a and R 2b are independently selected from halogen, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl or C1-C3 haloalkoxy; or B.R 2a and R 2b is independently selected from fluorine, chlorine, bromine, iodine, trifluoromethylsulfanyl, trifluoromethylsulfonyl or trifluoromethyl; or C.R 2a and R 2b is independently selected from chlorine, bromine, iodine, trifluoromethylsulfonyl or trifluoromethyl; or D.R 2a is chlorine, bromine, iodine, methyl, trifluoromethylsulfonyl or trifluoromethyl; and R 2b is chlorine, bromine, iodine, trifluoromethylsulfonyl or trifluoromethyl; or E.R 2a is chlorine, bromine, iodine, methyl or trifluoromethyl; and R 2b is chlorine, bromine, iodine or trifluoromethyl; or F.R 2a and R 2b is selected to be different from chlorine, bromine, iodine, trifluoromethylsulfonyl or trifluoromethyl; or G.R 2a and R 2b is selected to be different from chlorine, bromine, iodine or trifluoromethyl; or H.R 2a is chlorine, bromine, iodine or trifluoromethyl, and R 2b is chlorine, bromine, iodine, trifluoromethyl, difluoromethylsulfonyl or trifluoromethylsulfonyl; or I.R 2a is chlorine or trifluoromethyl, and R 2b is chlorine, bromine, iodine or trifluoromethyl.

[0052] In a preferred embodiment of each aspect of the present invention, R 2a is chlorine, bromine, iodine or trifluoromethyl, and R 2bis chlorine, bromine, iodine, trifluoromethyl, difluoromethylsulfonyl or trifluoromethylsulfonyl; preferably, R 2a is chlorine, bromine, iodine or trifluoromethyl, and R 2b is chlorine, bromine, iodine or trifluoromethyl, or R 2a is chlorine or trifluoromethyl, and R 2b is difluoromethylsulfonyl or trifluoromethylsulfonyl. More preferably, R 2a is chlorine or trifluoromethyl, and R 2b is chlorine, bromine, iodine or trifluoromethyl.

[0053] In embodiments of each aspect of the present invention, R 3 is A. C1-C3 alkyl or C1-C3 haloalkyl; or B. methyl or trifluoromethyl; or C. methyl is.

[0054] In preferred embodiments of each aspect of the present invention, R 3 is methyl.

[0055] In embodiments of each aspect of the present invention, Q is A. Q a ; or B. Q b is.

[0056] In embodiments 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; D.Q a -1 is.

[0057]

Table 1

[0058] In the embodiments of each aspect of the present invention, Q b is A.Q b -1 to Q b selected from -13; or B.Q b -1 is.

[0059]

Table 2

[0060] In the preferred embodiments of each aspect of the present invention, Q is Q a and, more preferably, Q is Q a -1. In other preferred embodiments of each aspect of the present invention, Q is Q b and, more preferably, Q is Q b -1. In the preferred embodiments of the present invention, Q is Q a -1 or Q b -1. More preferably, Q is Q a -1.

[0061] In the embodiments of each aspect of the present invention, R 4 is A. pyrimidin-4-yl, pyrimidin-2-yl, pyrazin-2-yl, pyridazin-3-yl or thiazol-2-yl (each of which is, independently of one another, a single -C(O)NR 10 R 11 substituted with, and R 10 is hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C3-C4 halocycloalkyl or cyano C3-C4 cycloalkyl; and R11 is hydrogen, C1-C3 alkyl or C1-C3 haloalkyl); or B. pyrimidin-4-yl, pyrimidin-2-yl, pyrazin-2-yl, pyridazin-3-yl or thiazol-2-yl (each of which is, independently of one another, a single -C(O)NR 10 R 11 and is substituted with; R 10 is hydrogen, hydroxy, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, C3-C4 halocycloalkyl, cyano C3-C4 cycloalkyl, C3-C4 cycloalkyl C1-C3 cyanoalkyl, oxetan-3-yl, thietan-3-yl, 3-methylthietan-3-yl, 1,1-dioxothietan-3-yl or 3-methyl-1,1-dioxothietan-3-yl; and R 11 is hydrogen, C1-C3 alkyl or C1-C3 haloalkyl; or R 10 and R 11 together with the nitrogen to which they are attached form a pyrrolidin-1-yl, piperidin-1-yl or 4-morpholinyl group); or C. Q c -1 to Q c -6 and Q c -10:

Chemical formula

[0062] In embodiments of each aspect of the present invention, R 4a is A. pyrimidin-4-yl, pyrimidin-2-yl, pyrazin-2-yl, pyridazin-3-yl, thiazol-2-yl, N-linked pyrazol-1-yl or triazol-1-yl (each of which is, independently of one another, a single -C(O)NR 10 R 11 substituted; R 10 is hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C3-C4 halocycloalkyl or cyano C3-C4 cycloalkyl; and R 11 is hydrogen, C1-C3 alkyl or C1-C3 haloalkyl); or B. pyrimidin-4-yl, pyrimidin-2-yl, pyrazin-2-yl, pyridazin-3-yl or thiazol-2-yl (each of which is, independently of one another, a single -C(O)NR 10 R 11 substituted; R 10 is hydrogen, hydroxy, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, C3-C4 halocycloalkyl, cyano C3-C4 cycloalkyl, C3-C4 cycloalkyl C1-C3 cyanoalkyl, oxetan-3-yl, thietan-3-yl, 3-methylthietan-3-yl, 1,1-dioxothietan-3-yl or 3-methyl-1,1-dioxothietan-3-yl; and R 11 is hydrogen, C1-C3 alkyl or C1-C3 haloalkyl; or R 10 and R 11which, together with the nitrogen to which they are attached, form a pyrrolidin-1-yl, piperidin-1-yl or 4-morpholinyl group); or C. pyrimidin-4-yl, pyrimidin-2-yl, pyrazin-2-yl, pyridazin-3-yl or thiazol-2-yl (each of which, independently of one another, is mono - C(O)NR 10 R 11 substituted; R 10 is hydrogen, C1 - C3 alkyl, C1 - C3 cyanoalkyl, C1 - C3 haloalkyl, C3 - C4 cycloalkyl, C3 - C4 halocycloalkyl or cyano C3 - C4 cycloalkyl; and R 11 is hydrogen, C1 - C3 alkyl or C1 - C3 haloalkyl); or D. N - linked pyrazol - 1 - yl or triazol - 1 - yl (each of which, independently of one another, is mono - C(O)NR 10 R 11 substituted; R 10 is hydrogen, C1 - C3 alkyl, C1 - C3 cyanoalkyl, C1 - C3 haloalkyl, C3 - C4 cycloalkyl, C3 - C4 halocycloalkyl or cyano C3 - C4 cycloalkyl; and R 11 is hydrogen, C1 - C3 alkyl or C1 - C3 haloalkyl); or E. Q c -1 to Q c -8 and Q c -10:

Chemical formula

[0063] In embodiments of each aspect of the present invention, R 4 and R 4a are 4-cyano-pyrimidin-6-yl, which is Qc-10 below:

Chemical formula

[0064] In embodiments of each aspect of the present invention, R 4 and R 4a with respect to R 10 is A. hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C3-C4 halocycloalkyl or cyano C3-C4 cycloalkyl; or B. hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl or cyano C3-C4 cycloalkyl; or C. hydrogen, methyl, ethyl, cyanomethyl, difluoromethyl, trifluoromethyl, cyclopropyl or 1-cyanocyclopropyl; or D. hydrogen, methyl, ethyl, trifluoromethyl, cyclopropyl or 1-cyanocyclopropyl; or E. hydrogen, methyl, ethyl, cyclopropyl or 1-cyanocyclopropyl; or F. hydrogen, methyl, ethyl or cyclopropyl; or G. hydrogen, methyl or ethyl; or H. hydrogen, hydroxy, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, C3-C4 halocycloalkyl, cyano C3-C4 cycloalkyl, C3-C4 cycloalkyl C1-C3 cyanoalkyl, oxetan-3-yl, thietan-3-yl, 3-methylthietan-3-yl, 1,1-dioxothietan-3-yl or 3-methyl-1,1-dioxothietan-3-yl; or I. hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, cyanoethyl, methoxy, ethoxy, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-cyclopropyl-ethyl, oxetan-3-yl, thietan-3-yl, 3-methylthietan-3-yl, 1,1-dioxothietan-3-yl or 3-methyl-1,1-dioxothietan-3-yl; or J. Hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, cyanoethyl, methoxy, cyclopropyl, 1 - cyanocyclopropyl, 1 - cyano - 1 - cyclopropyl - ethyl, oxetan - 3 - yl, thietan - 3 - yl or 1,1 - dioxothietan - 3 - yl; or K. Hydrogen, hydroxy, methyl, ethyl, cyanomethyl, 2 - cyanoethyl, 1 - cyano - 1 - methyl - ethyl, methoxy, cyclopropyl, cyclopropylmethyl, 1 - cyanocyclopropyl, 1 - cyano - 1 - cyclopropyl - ethyl, oxetan - 3 - yl, thietan - 3 - yl, 3 - methylthietan - 3 - yl or 1,1 - dioxothietan - 3 - yl is.

[0065] In an embodiment of each aspect of the present invention, R 4 and R 4a with respect to R 11 is A. Hydrogen, C1 - C3 alkyl or C1 - C3 haloalkyl; or B. Hydrogen, methyl, ethyl, difluoromethyl or trifluoromethyl; or C. Hydrogen, methyl or trifluoromethyl; or D. Hydrogen, methyl or ethyl; or E. Hydrogen or methyl is.

[0066] In an embodiment of each aspect of the present invention, R 4 and R 4a with respect to R 10 and R 11 together with the nitrogen to which they are attached form a 4 - morpholinyl group such as a pyrrolidin - 1 - yl, piperidin - 1 - yl or 4 - morpholinyl group.

[0067] Preferably, in an embodiment of each aspect of the present invention, R 4 and R 4a are independently Q c -1 or Q c -6; R 10is hydrogen, methyl, ethyl, cyclopropyl or 1 - cyanocyclopropyl; and R 11 is hydrogen, methyl or ethyl. More preferably, in embodiments of each aspect of the present invention, R 4 and R 4a are independently Q c -1 or Q c -6; R 10 is hydrogen, methyl, ethyl or cyclopropyl; and R 11 is hydrogen, methyl or ethyl. Most preferably, in embodiments of each aspect of the present invention, R 4 and R 4a are independently Q c -1; R 10 is hydrogen, methyl or ethyl; and R 11 is hydrogen or methyl.

[0068] In embodiments of each aspect of the present invention, Q is Q a -1, and R 4 is Q c -1, Q c -2, Q c -3, Q c -4, Q c -5, Q c -6 or Q c -10, Q c -1 or Q c -6, etc., or Q c -1, Q c -3, Q c -4, Q c -6 or Q c -10, etc. Preferably, R 4 is Q c -1, Q c -2 or Q c -3. Most preferably, R 4 is Q c -1. In preferred embodiments, R 10is hydrogen, hydroxy, methyl, ethyl, cyanomethyl, 2-cyanoethyl, 1-cyano-1-methyl-ethyl, methoxy, cyclopropyl, cyclopropylmethyl, 1-cyanocyclopropyl, 1-cyano-1-cyclopropyl-ethyl, oxetan-3-yl, thietan-3-yl, 3-methylthietan-3-yl or 1,1-dioxothietan-3-yl, and R 11 is hydrogen, methyl or ethyl, preferably, R 11 is hydrogen or methyl. In other preferred embodiments, R 10 is hydrogen, methyl, ethyl, cyanomethyl, 2-cyanoethyl, 1-cyano-1-methyl-ethyl, cyclopropyl, cyclopropylmethyl, 1-cyanocyclopropyl or 1-cyano-1-cyclopropyl-ethyl, and R 11 is hydrogen, methyl or ethyl; preferably, R 11 is hydrogen or methyl. In other preferred embodiments, R 10 is hydrogen, methyl, ethyl; and R 11 is hydrogen or methyl.

[0069] In embodiments of each aspect of the present invention, Q is Q b -1, R 4a is Q c -1, and R 10 and R 11 are both hydrogen.

[0070] In embodiments of each aspect of the present invention, R 5 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 1-3 substituents selected from C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, CN or hydroxy; 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 It is.

[0071] In a preferred embodiment of each aspect of the present invention, R 5 is hydrogen.

[0072] In an embodiment of each aspect of the present invention, R 5a is 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 It is.

[0073] In an embodiment of each aspect of the present invention, R 5b is 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 It is.

[0074] In a preferred embodiment of each aspect of the present invention, R 5a and R 5b are hydrogen.

[0075] In embodiments of each aspect of the present invention, R 6 is A. phenyl, benzyl, heteroaryl or C3-C6 cycloalkyl (each of which may be optionally substituted with one substituent independently selected from R x ); or B. phenyl, benzyl, cyclopropyl or cyclopropyl substituted with one substituent selected from R x is

[0076] In embodiments of each aspect of the present invention, R x is A. halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; or B. F, Cl, Br, OCF2H, OCH3 or CN independently selected from

[0077] In embodiments of each aspect of the present invention, R Z is A. oxo, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; or B. oxo, F, Cl, Br, OCF2H, OCH3 or CN independently selected from

[0078] In embodiments of each aspect of the present invention, R Y is 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 is independently selected from

[0079] In an embodiment of each aspect of the present invention, R YY is 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 is independently selected from

[0080] The present invention thus provides compounds of formula (I) having all combinations / permutations of the substituents R, R 1 , R 2a , R 2b , R 3 , Q, A 1 , A 2 , A 3 , A 4 and A 5 For example, A 1 , A 2 and A 3 are of the first aspect (i.e., A 1 , A 2 and A 3 are, independently of each other, N or CR Y ); and R Y is of embodiment D (i.e., R Y is independently selected from hydrogen, methyl, trifluoromethyl and methoxy); A 4 and A 5 are of embodiment B (i.e., A 4 is CR YY , and A 5 is CH), R YYis of Embodiment B (i.e., R Y is hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen or cyclopropyl); R 1 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 2a is of Embodiment L (i.e., halogen, C1-C2 haloalkyl, C1-C2 haloalkylsulfanyl, C1-C2 haloalkylsulfonyl or C1-C2 haloalkoxy); R 2b is of Embodiment B (i.e., halogen, C1-C3 haloalkyl or C1-C3 haloalkoxy); R 3 is of Embodiment B (i.e., hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl optionally substituted with 1-2 substituents selected from C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN); Q is of Embodiment A (i.e., Q is Q a ), Q a can be of Embodiment B (i.e., Q a is Q a -1, Q a -6, Q a -7, Q a -10 and Q a -15); and R 4 is of Embodiment D (i.e., Q c -1, Q c -2, Qc -3, Q c -4, Q c -5 or Q c -6; R 10 is of Embodiment F [i.e., hydrogen, methyl, ethyl or cyclopropyl]; and R 11 is of Embodiment D [i.e., hydrogen, methyl or ethyl]) A compound of formula (I) is provided.

[0081] In embodiments of each aspect of the present invention, the compound of formula (I) is A 1 , A 2 and A 3 each independently of the others is N or CR Y (wherein R Y is hydrogen, methyl, trifluoromethyl and methoxy); A 4 is N or CH, and A 5 is CH; R 1 is hydrogen, methyl, propargyl or cyclopropyl-methyl; R 2a is 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 C1-C2 alkylsulfanyl substituted with 1-3 halogens, or C1-C2 alkylsulfonyl substituted with 1-3 halogens; R 2b is hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl optionally substituted with 1-2 substituents selected from C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; R 3 is methyl; and Q is Q a-1 to Q a -16 and Q b -1 to Q b selected from -13; R 4 (Q a -1 to Q a -16) as pyrimidin-4-yl, pyrimidin-2-yl, pyrazin-2-yl, pyridazin-3-yl or thiazol-2-yl (each of which, independently of one another, is a single -C(O)NR 10 R 11 substituted with; R 10 is hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl or cyano C3-C4 cycloalkyl; and R 11 is hydrogen, C1-C3 alkyl or C1-C3 haloalkyl) or; R 4a (Q b -1 to Q b -13) as pyrimidin-4-yl, pyrimidin-2-yl, pyrazin-2-yl, pyridazin-3-yl or thiazol-2-yl (each of which, independently of one another, is a single -C(O)NR 10 R 11 substituted with; R 10 is hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C3-C4 halocycloalkyl or cyano C3-C4 cycloalkyl; and R 11 is hydrogen, C1-C3 alkyl or C1-C3 haloalkyl).

[0082] In embodiments of each aspect of the present invention, the compound of formula (I) has A 1 =A 2 -A 3 (together) as NR-C(=O)-N (wherein R is hydrogen, methyl or 2,2,2-trifluoroethyl); A 4 has as N or CH, and A 5 has as CH; R 1 has as hydrogen, methyl, propargyl or cyclopropyl-methyl; R 2aselected from hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, halogen, methyl and trifluoromethyl; having cyclopropyl substituted with 1 to 2 substituents independently selected therefrom, cyclopropylcarbonyl, oxo, halogen and trifluoromethyl; having cyclopropylmethyl substituted with 1 to 2 substituents independently selected therefrom; or having C1-C2 alkylsulfanyl substituted with 1 to 3 halogens, or having C1-C2 alkylsulfonyl substituted with 1 to 3 halogens; R 2b selected from hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl; optionally substituted with 1 to 2 substituents selected therefrom; having C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; R 3 having methyl as; and having Q as Q a -1 to Q a -16 and Q b -1 to Q b -13; selected from R 4 (for Q a -1 to Q a -16) being

Chemical formula

Chemical formula

[0083] In embodiments of each aspect of the present invention, the compound of formula (I) is A 1 =A 2 -A 3 together having NR-C(=O)-N where R is hydrogen, methyl or 2,2,2-trifluoroethyl; A 4 having N or CH, and A 5 having as CH; R 1 having as hydrogen, methyl, propargyl or cyclopropyl-methyl; R 2a having as hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, halogen, methyl and cyclopropyl substituted with 1-2 substituents independently selected from trifluoromethyl, cyclopropylcarbonyl, oxo, halogen and cyclopropylmethyl substituted with 1-2 substituents independently selected from trifluoromethyl, or C1-C2 alkylsulfanyl substituted with 1-3 halogens, or C1-C2 alkylsulfonyl substituted with 1-3 halogens; R 2b having as hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl optionally substituted with 1-2 substituents selected from C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; R 3 having as methyl; and as Q, Q a -1 to Q a -16 and Q b -1 to Q b selected from -13; R 4 (for Q a -1 to Q a -16) having as pyrimidin-4-yl, pyrimidin-2-yl, pyrazin-2-yl, pyridazin-3-yl or thiazol-2-yl (each of which, independently of one another, a single -C(O)NR 10 R11 is replaced by R 10 is hydrogen, methyl, ethyl, cyanomethyl, difluoromethyl, trifluoromethyl, cyclopropyl, or 1-cyanocyclopropyl; and R 11 is hydrogen, methyl, ethyl, difluoromethyl or trifluoromethyl; or R 4a (Q b -1~Q b -13) as pyrimidin-4-yl, pyrimidin-2-yl, pyrazin-2-yl, pyridazin-3-yl, thiazol-2-yl, N-linked pyrazol-1-yl or triazol-1-yl (each of which may be independently a single -C(O)NR 10 R 11 is substituted with;R 10 is hydrogen, methyl, ethyl, cyanomethyl, difluoromethyl, trifluoromethyl, cyclopropyl, or 1-cyanocyclopropyl; and R 11 is hydrogen, methyl, ethyl, difluoromethyl or trifluoromethyl.

[0084] In an embodiment of each aspect of the invention, the compound of formula (I) is 1 , A 2 and A 3 Independently of each other as N or CR Y (where R Y are hydrogen, methyl, trifluoromethyl and methoxy; A 4 N or CH as A 5 as CH; R 1 R has hydrogen, methyl, propargyl or cyclopropyl-methyl; 2aselected independently from hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, halogen, methyl and trifluoromethyl, and having 1 to 2 substituents; cyclopropylmethyl optionally substituted with 1 to 2 substituents selected independently from cyclopropylcarbonyl, oxo, halogen and trifluoromethyl; or C1-C2 alkylsulfanyl substituted with 1 to 3 halogens; or C1-C2 alkylsulfonyl substituted with 1 to 3 halogens; R 2b selected independently from hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, and optionally having 1 to 2 substituents; C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; R 3 having methyl as; and Q as Q a -1 and Q b selected from -1, and R 4 as Q c -1, Q c -2, Q c -3, Q c -4, Q c -5 or Q c -6, or R 4a as Q c -1, Q c -2, Q c -3, Q c -4, Q c -5, Q c -6, Q c -7 or Q c -8,; R 10 is hydrogen, methyl, ethyl, trifluoromethyl, cyclopropyl or 1-cyanocyclopropyl; and R 11 is hydrogen, methyl, ethyl, difluoromethyl or trifluoromethyl; or Q has Q-1 to Q-18 shown in Table Z below.

[0085] In an embodiment of each aspect of the present invention, the compound of formula (I) is A 1 , A 2 and A 3 each independently has N or CH; A 4 and A 5 each has CH; R 1 has hydrogen, methyl, propargyl or cyclopropyl-methyl; R 2a is 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 C1-C2 alkylsulfanyl substituted with 1-3 halogens, or C1-C2 alkylsulfonyl substituted with 1-3 halogens; R 2b is hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl optionally substituted with 1-2 substituents selected from C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; R 3 has methyl; and Q is selected from Q a -1 and Q b -1; and R 4 is Q c -1, Q c -2, Q c -3, Q c -4, Q c -5 or Q c -6; or R 4a is Q c -1, Q c -2, Q c -3, Q c -4, Q c -5, Q c -6, Qc -7 or Q c -8; R 10 is hydrogen, methyl, ethyl, cyanomethyl, difluoromethyl, trifluoromethyl, cyclopropyl or 1 - cyanocyclopropyl; and R 11 is hydrogen, methyl or ethyl; or Q has Q - 1 to Q - 18 shown in Table Z below.

[0086] In embodiments of each aspect of the present invention, the compound of formula (I) has N or CH independently of each other as A 1 , A 2 and A 3 ; has CH as A 4 and A 5 respectively; has hydrogen, methyl, propargyl or cyclopropyl - methyl as R 1 ; has cyclopropyl substituted with 1 - 2 substituents independently selected from halogen, C1 - C3 haloalkyl, C1 - C3 haloalkoxy, cyclopropyl, halogen, methyl and trifluoromethyl, cyclopropylmethyl substituted with 1 - 2 substituents independently selected from cyclopropylcarbonyl, oxo, halogen and trifluoromethyl, or C1 - C2 alkylsulfanyl substituted with 1 - 3 halogens, or C1 - C2 alkylsulfonyl substituted with 1 - 3 halogens as R 2a ; has C3 - C4 cycloalkyl - C1 - C2 alkyl optionally substituted with 1 - 2 substituents selected from halogen, C3 - C4 cycloalkyl, cyclopropylcarbonyl, oxo, halogen, C1 - C3 alkyl and C1 - C3 haloalkyl, C1 - C3 haloalkyl, C1 - C3 haloalkylsulfanyl, C1 - C3 haloalkylsulfonyl, C1 - C3 alkoxy, C1 - C3 haloalkoxy or CN as R 2b ; has methyl as R 3 ; and is selected from Q a -1 and Q b -1 as Q, and has Q 4 -1 or Q c -6 as R c ; or R 4aas Q c -1, Q c -6, Q c -7 or Q c -8; and R 10 is hydrogen, methyl, ethyl or cyclopropyl; and R 11 is hydrogen or methyl; or as Q, has Q-1 to Q-18 shown in Table Z below.

[0087] In embodiments of each aspect of the present invention, the compound of formula (I) has A 1 =A 2 -A 3 (together) as NR-C(=O)-N (where R is hydrogen, methyl or 2,2,2-trifluoroethyl); A 4 has N or CH as, and A 5 has as CH; R 1 has as hydrogen, methyl, propargyl or cyclopropyl-methyl; R 2a has as, independently selected from hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, halogen, methyl and trifluoromethyl, cyclopropyl substituted with 1-2 substituents, cyclopropylcarbonyl, oxo, halogen and trifluoromethyl, cyclopropylmethyl substituted with 1-2 substituents independently selected from, or C1-C2 alkylsulfanyl substituted with 1-3 halogens, or C1-C2 alkylsulfonyl substituted with 1-3 halogens; R 2b has as, hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, optionally substituted with 1-2 substituents selected from C3-C4 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; R 3 has as methyl; and as Q, Q a -1 and Q b -1 selected from, and R4 or R 4a as Q c -1 or Q c has -6, and R 10 is hydrogen, methyl or ethyl; and R 11 is hydrogen or methyl; or as Q, has Q-1 to Q-18 shown in Table Z below.

[0088] In embodiments of each aspect of the present invention, the compound of formula (I) has N or CH independently of each other as A 1 , A 2 and A 3 ; has CH as A 4 and A 5 respectively; has hydrogen, methyl, propargyl or cyclopropyl-methyl as R 1 ; has halogen, C1-C3 haloalkyl or C1-C2 alkylsulfonyl substituted with 1 to 3 halogens as R 2a ; has halogen or C1-C3 haloalkyl as R 2b ; has methyl as R 3 ; and as Q, Q a -1 and Q b -1 are selected from, and R 4 or R 4a has Q c -1 as, and R 10 is hydrogen, methyl or ethyl; and R 11 is hydrogen or methyl.

[0089] In embodiments of each aspect of the present invention, the compound of formula (I) has A 1 and A 3 being N; A 2 being CH; A 4 and A 5 each having CH; R 1 being hydrogen or methyl; R 2a being chlorine, bromine, iodine, methyl or trifluoromethyl; R 2b being chlorine, bromine, iodine or trifluoromethyl; R 3 being methyl; and Q being Q a -1 or Qb is -1; R 4 is Q c -1, Q c -3, Q c -4; Q c -6 or Q c is -10; R 4a is Q c -1, Q c -3, Q c -4; Q c -6, Q c -7, Q c -8 or Q c is -10; R 10 is hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, cyanoethyl, methoxy, cyclopropyl, 1 - cyanocyclopropyl, 1 - cyano - 1 - cyclopropyl - ethyl, oxetan - 3 - yl, thietan - 3 - yl, 1,1 - dioxothietan - 3 - yl; and R 11 is hydrogen or methyl; or R 10 and R 11 together with the nitrogen to which they are attached, are pyrrolidin - 1 - yl, piperidin - 1 - yl or 4 - morpholinyl.

[0090] In a preferred embodiment of the present invention, A 1 and A 3 are nitrogen, A 2 , A 4 and A 5 are CH; R 1 is hydrogen, methyl or cyclopropyl - methyl; R 2a is chlorine, bromine, iodine or trifluoromethyl, and R 2b is chlorine, bromine, iodine, trifluoromethyl, difluoromethylsulfonyl or trifluoromethylsulfonyl; R 3 is methyl; Q is Q a -1 or Q b is -1, preferably, Q is Q a is -1.

[0091] In a preferred embodiment of the present invention, A 1 and A 3is nitrogen, A 2 , A 4 and A 5 are CH; R 1 is hydrogen, methyl or cyclopropyl-methyl; R 2a is chlorine, bromine, iodine or trifluoromethyl, and R 2b is chlorine, bromine, iodine, trifluoromethyl, difluoromethylsulfonyl or trifluoromethylsulfonyl; R 3 is methyl; Q is Q a -1; R 4 is Q c -1, Q c -2, Q c -3, Q c -4, Q c -5, Q c -6 or Q c -10, Q c -1 or Q c -6 etc., or Q c -1, Q c -3, Q c -4, Q c -6 or Q c -10 etc.; R 10 is hydrogen, hydroxy, methyl, ethyl, cyanomethyl, 2-cyanoethyl, 1-cyano-1-methyl-ethyl, methoxy, cyclopropyl, cyclopropylmethyl, 1-cyanocyclopropyl, 1-cyano-1-cyclopropyl-ethyl, oxetan-3-yl, thietan-3-yl, 3-methylthietan-3-yl or 1,1-dioxothietan-3-yl, and R 11 is hydrogen, methyl or ethyl, preferably, R 11 is hydrogen or methyl. Preferably, R 4 is Q c -1, Q c -2 or Q c -3; Most preferably, R 4 is Q c -1.

[0092] In another preferred embodiment of the present invention, A 1 and A 3 are nitrogen, A2 , A 4 and A 5 is CH; R 1 is hydrogen, methyl or cyclopropyl-methyl; R 2a is chlorine, bromine, iodine or trifluoromethyl, and R 2b is chlorine, bromine, iodine, trifluoromethyl, difluoromethylsulfonyl or trifluoromethylsulfonyl; R 3 is methyl; Q is Q b -1, R 4a is Q c -1, and R 10 and R 11 are both hydrogen. Preferably, R 1 is hydrogen or methyl; more preferably, R 1 is hydrogen. Preferably, R 2a is chlorine, bromine, iodine or trifluoromethyl, and R 2b is chlorine, bromine, iodine or trifluoromethyl, or R 2a is chlorine or trifluoromethyl, and R 2b is difluoromethylsulfonyl or trifluoromethylsulfonyl. More preferably, R 2a is chlorine or trifluoromethyl, and R 2b is chlorine, bromine, iodine or trifluoromethyl. Preferably, Q is Q a -1, R 10 is hydrogen, methyl, ethyl, cyanomethyl, 2-cyanoethyl, 1-cyano-1-methyl-ethyl, cyclopropyl, cyclopropylmethyl, 1-cyanocyclopropyl or 1-cyano-1-cyclopropyl-ethyl, and R 11 is hydrogen, methyl or ethyl; preferably, R 11 is hydrogen or methyl. In other preferred embodiments, R 10 is hydrogen, methyl, ethyl; and R 11 is hydrogen or methyl.

[0093] In an embodiment, the compound of formula (I) is of formula Iaa, Iab, Iac, Iad or Iae [Chemical formula] (wherein the asterisk indicates a stereocenter) and R 1 , R 2a , R 2b and R 3 are as defined in the first aspect, and Q1 corresponds to Q as defined in the first aspect, each having the corresponding embodiment as described above.

[0094] In an embodiment, compounds having the preferred stereochemistry shown in formula (I’a) may also be preferred for the compounds of formula Iaa, Iab and Iac. In a preferred embodiment, the following stereochemistry: [Chemical formula] (wherein R 1 , R 2a , R 2b , R 3 , Q1 (corresponding to Q in formula I) are as defined in the first aspect, and R is C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy) Compounds of formula I’ab and I’ae having the above, stereoisomers, enantiomers, tautomers and N-oxides of the compound of formula (I’ab), and their agrochemically acceptable salts are preferred.

[0095] In a second aspect, the present invention provides a composition comprising a compound of formula (I) as defined in the first aspect, one or more adjuvants and diluents, and optionally one or more other active ingredients.

[0096] In a third aspect, the present invention provides a method for controlling and preventing insects, mites, nematodes or mollusks, which comprises applying an insecticidally, acaricidally, nematocidally or molluscicidally effective amount of the compound as defined in the first aspect or the composition as defined in the second aspect to a pest, the habitat of the pest or a plant susceptible to attack by the pest.

[0097] In a fourth aspect, the present invention provides a method for protecting plant propagation material from attack by insects, mites, nematodes or molluscs, which comprises 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.

[0098] In a fifth aspect, the present invention provides plant propagation material such as seeds, which comprises, is treated with or is adhered to a compound of formula (I) as defined in the first aspect or a composition as defined in the second aspect.

[0099] In a further aspect, the present invention provides a method for controlling a parasite in or on an animal in need thereof, which comprises administering an effective amount of a compound of formula (I) as defined in the first aspect. The present invention further provides a method for controlling an ectoparasite on an animal in need thereof, which comprises administering an effective amount of a compound of formula I as defined in the first aspect. The present invention further provides a method for preventing and / or treating a disease infected by an ectoparasite, which comprises administering an effective amount of a compound of formula (I) as defined in the first aspect to an animal in need thereof.

[0100] The compounds of formula (I) can be prepared by those skilled in the art according to known methods. More specifically, the compounds and intermediates of formula I and I'a can thus be prepared as described below in the schemes and examples. The specific stereocenters are left unspecified for the sake of brevity and are not intended to limit the teachings of the schemes in any way.

[0101] The process for preparing the compounds of formula (I) according to the present invention is carried out by methods known to those skilled in the art.

[0102] The compounds of formula (I) can be prepared, for example, as shown in Scheme 1. Scheme 1: [Chemistry]

[0103] A compound of formula II, wherein A 1 A 2 A 3 A 4 A 5 R 2a and R 2b are as defined above for the compound of formula (I), and X 1 is a halogen or a leaving group such as a sulfonate, for example chloride), with a compound of formula III or a salt thereof (preferably a hydrohalide salt such as hydrochloride or hydrobromide or trifluoroacetate or any other equivalent salt) (wherein Q, R 1 and R 3 have the same meaning as defined above for the compound of formula (I)) to give a compound of formula (I), wherein A 1 A 2 A 3 A 4 A 5 R 1 R 2a R 2b R 3 and Q have the same meaning as defined 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, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, N,N-dimethylacetamide or N,N-dimethylformamide, in the temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C, in the presence or absence 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 sodium carbonate, potassium carbonate or cesium carbonate or an organic base such as triethylamine, diisopropylethylamine or pyridine.

[0104] A compound of formula II, wherein A 1 A 2 A 3 A 4 A5 , R 2a and R 2b is as defined above for the compound of formula (I), is known or can be prepared as described in, for example, WO 2021 / 083936 and WO 2021 / 177160, or they can be prepared by methods known to those skilled in the art.

[0105] Scheme 2: [Chemical formula] A compound of formula III or a salt thereof, wherein Q, R 1 and R 3 have the same meaning as defined above for the compound of formula (I), can be prepared, for example, as shown in Scheme 2. A compound of formula V, wherein R 3 and Q have the same meaning as defined above for the compound of formula (I), and X 2 is a leaving group such as a halogen, e.g., bromide, or a sulfonate, etc., of an amine of formula XIX or a salt thereof, wherein R 1 has the same meaning as defined above for the compound of formula (I), is treated with the compound of formula III or a salt thereof, wherein Q, R 1 and R 3 have the same meaning as defined 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, etc., within a temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C, with or without the addition of a base such as an inorganic base like sodium carbonate, potassium carbonate or cesium carbonate, or an organic base like triethylamine, diisopropylethylamine or pyridine, etc.

[0106] Alternatively, a compound of formula VII, wherein R 3 and Q have the same meaning as defined above for the compound of formula (I), of an amine of formula XIX or a salt thereof, wherein R 1(which has the same meaning as defined above for the compound of formula (I)) to give a compound of formula III or a salt thereof, wherein Q, R 1 and R 3 (which has the same meaning as defined above for the compound of formula (I)). This reaction is carried out, for example, in the presence or absence of a catalyst such as a hydrogenation catalyst like palladium on carbon, in the presence or absence of an acid such as acetic acid or a Lewis acid such as zinc bromide or titanium(IV) isopropoxide, in a solvent such as methanol or in the absence of a solvent, in the presence of a reducing agent such as hydrogen or a hydride such as sodium borohydride. This reaction can be carried out within a temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C. Such methods for the alkylation of amines and the reductive alkylation of amines and the ranges of conditions for carrying them out (for example, in the presence of NaBH(OAc)3 or NaBH3CN, in a suitable solvent, preferably acetic acid, at room temperature, as in WO 2002 / 088073; or alternatively, by the use of a combination of Ti(i-OiPr)4 and NaBH4 as described in Synthesis 2003(14), 2206) are well known to those skilled in the art. The amine of formula XIX or a salt thereof, wherein R 1 (which has the same meaning as defined above for the compound of formula (I)) is known or can be prepared by methods known to those skilled in the art.

[0107] Scheme 3:

Chemical Structure

[0108] Alternatively, the reaction of an amine of formula IVa with a compound of formula VII gives a compound of formula (I) (where R 1 is H, and A 1 , A 2 , A 3 , A 4 , A 5 , R 2a , R 2b , R 3 and Q have the same meanings as defined above for the compounds of formula (I)). This reaction is carried out, for example, in the presence or absence of a catalyst such as a hydrogenation catalyst like palladium on carbon, in the presence or absence of an acid such as acetic acid or a Lewis acid such as zinc bromide, in a solvent such as methanol or in the absence of a solvent, in the presence of a reducing agent such as a hydride like hydrogen or sodium borohydride. This reaction can be carried out within a temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C.

[0109] Such methods for the reductive alkylation of amines and the range of conditions for carrying them out are well known to those skilled in the art.

[0110] Scheme 4:

Chemical Structure

[0111] Alternatively, a compound of formula VII can be treated with a reducing agent, followed by reaction with a sulfonyl chloride such as methanesulfonyl chloride to give a compound of formula V (where the leaving group Q is a sulfonate such as mesylate). This reaction can be carried out in the presence or absence of a solvent, in the presence or absence of a base such as an inorganic base such as potassium carbonate or an organic base such as an amine base such as trimethylamine, and can be carried out in the temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C. Suitable reducing agents can be hydrides such as hydrogen or sodium borohydride, for example, in the presence or absence of a catalyst such as a hydrogenation catalyst such as palladium on carbon, in the presence or absence of an acid such as acetic acid or a Lewis acid such as zinc bromide, in the presence or absence of a solvent such as methanol. This reaction can be carried out in the temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C.

[0112] Such methods and the ranges of conditions for carrying out halogenation, reduction of carbonyl compounds and sulfonylation of alcohols 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.

[0113] Scheme 5:

Chemical Structure

[0114] The compound of formula (VI) wherein R 1 has the same meaning as defined above for the compound of formula (I), provided that R1 is not hydrogen, and X 3 is a leaving group such as a halogen or a sulfonate, for example chloride, bromide, iodide or mesylate, is known or they can be prepared by methods known to those skilled in the art.

[0115] Scheme 6:

Chemical formula

[0116] Compound X (wherein A 1 、A 2 、A 3 、A 4 、A 5 、R 2a 、R 2b and R 3 have the same meanings as defined above for the compounds of formula (I)) is followed by treatment with the known compound XIII (N,N-dimethylformamide dimethylacetal, DMF-DMA) to give the compound of formula XI (wherein A 1 、A 2 、A 3 、A 4 、A 5 、R 2a 、R 2b and R 3 have the same meanings as defined above for the compounds of formula (I)). This reaction can be carried out without a solvent or in a solvent, preferably in an organic solvent such as dichloromethane, tetrahydrofuran, 2-methyltetrahydrofuran or dioxane, in a temperature range of -100 to +300 °C, preferably ambient temperature to 100 °C or ambient temperature to 50 °C, in the absence of a base or in the presence of a base such as an inorganic base like sodium, potassium or cesium carbonate or an organic base like triethylamine, diisopropylethylamine or pyridine.

[0117] Compound XI (wherein A 1 、A 2 、A 3 、A 4 、A 5 、R 2a 、R 2b and R 3 have the same meanings as defined above for the compounds of formula (I)) is further reacted with a hydrazine compound of formula XII or a tautomer thereof or a salt thereof (wherein R 4 has the same meaning as defined above for the compounds of formula (I)) to give the compound of formula Ib (wherein A 1 、A 2 、A 3 、A 4 、A 5 、R2a , R 2b , R 3 and R 4 have the same meaning as defined above for the compounds of formula (I). This reaction can be carried out without a solvent or in a solvent, preferably in an organic solvent such as 1,4-dioxane or acetic acid, or in a solvent such as a mixture of 1,4-dioxane and acetic acid, within a temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C or ambient temperature to 80 °C. In this series of transformations, the intermediate compounds of formula X and formula XI can be used as crude products for subsequent steps, or they can be purified, for example, by chromatography and used in the next transformation in a purified form.

[0118] The compound of formula IX or a salt thereof (wherein R 3 has the same meaning as defined above for the compounds of formula (I)) is known or can be prepared by methods known to those skilled in the art. The hydrazine compound of formula XII or a tautomer or a salt thereof (wherein R 4 has the same meaning as defined above for the compounds of formula (I)) is known or can be prepared by methods known to those skilled in the art.

[0119] Formula Ik

Chemical formula

Chemical formula

Chemical formula

[0120] Scheme 7:

Chemical Structure

[0121] The compound of formula XIV is provided by the subsequent reaction of the intermediate of formula XVI with the compound of formula II. This reaction is carried out without using a solvent or in a solvent, preferably in a solvent such as an organic solvent like acetonitrile, within a temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C, in the presence or absence of a catalyst such as a metal catalyst like a palladium complex and with or without the addition of a base such as an inorganic base like potassium carbonate or an organic base like triethylamine.

[0122] Subsequently, the intermediate of formula XIV is reacted with the compound of formula XV to give the compound of formula Ic (where A 1, A 2 , A 3 , A 4 , A 5 , R 2a , R 2b , R 1 , R 3 and R 4a have the same meaning as described above for the compounds of formula (I), and R 4a -M1 in -M1 is, for example, a metal such as lithium or -MgCl or -ZnBr or -B(OH)2; or R 4a -M1 is a boronate such as the pinacol ester of boric acid or R 4a -Sn(n-Bu)3 etc. represents a stannane). Such conversions are known to those skilled in the art as Suzuki, Kumada, Negishi or Stille coupling reactions, respectively. Such reactions are carried out within a temperature range of -100 to +300 °C, preferably ambient temperature to 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 or an N-heterocyclic carbene (NHC) ligand or a phosphite ligand. This reaction can be carried out in the presence or absence of an additional metal catalyst such as a copper salt, for example CuI. This reaction is carried out in the presence or absence of a base which can be an inorganic base such as potassium carbonate or sodium hydroxide or cesium carbonate or an organic base such as an amine base like triethylamine. This reaction is carried out without using a solvent or in a solvent, preferably in a solvent. When the reaction mixture is heated, the reaction can be carried out under microwave irradiation or by conventional heating such as heating the reaction vessel in an oil bath.

[0123] By an alternative route, compound XVII can give intermediate XVIII in reaction with a compound of formula XV. This reaction is carried out under substantially the same range of conditions as described for the conversion of intermediate XIV to the compound of formula Ic.

[0124] Thereafter, intermediate XVIII gives a compound of formula Ic in reaction with amine IVa (where R 1 is hydrogen, and A 1, A 2 , A 3 , A 4 , A 5 , R 2a , R 2b , R 3 and R 4a have the same meaning as described above for the compounds of formula (I). This reaction is carried out under substantially the same conditions as described for the conversion of compound XVII to intermediate XVI in the presence of a reducing agent.

[0125] Furthermore, by an alternative route, the compound of intermediate formula XVIII can afford an intermediate of formula IIIa in reaction with an amine of formula XIX. This reaction is carried out under substantially the same conditions as described for the conversion of compound XVII to intermediate XVI in the presence of a reducing agent.

[0126] Thereafter, the intermediate of formula IIIa reacts with a compound of formula II to give a compound of formula Ic (wherein A 1 , A 2 , A 3 , A 4 , A 5 , R 2a , R 2b , R 1 , R 3 and R 4a have the same meaning as described above for the compounds of formula (I)). This reaction is carried out under substantially the same conditions as described for the conversion of intermediate XVI to intermediate XIV.

[0127] In these different multi-step sequences, the intermediate compounds of formula XIV, XVI, XVIII and IIIa can be used as crude products for their respective subsequent steps, or they can be purified, for example by chromatography, and used in 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.

[0128] Formula Id [Chemical formula] The compound of formula IIIb [Chemical formula] (wherein R 1 , R 3 , R 4a , R 5a and R 5b are as described in formula (I)) of an amine of formula II or a salt thereof [Chemical formula] (wherein A 1 , A 2 , A 3 , A 4 , A 5 , R 2a and R 2b are as described in formula (I), and X 1 is a leaving group such as a halogen such as chloride or a sulfonate) can be prepared by reaction with a compound of formula IIIb

[0129] Chemistry is described in more detail by Scheme 8 Scheme 8: [Chemical formula]

[0130] The reaction of a compound of formula II (wherein X 1 is a leaving group such as a halogen or a sulfonate, such as chloride) with a compound of formula IIIb to give a compound of formula Id (wherein A 1 , A 2 , A 3 , A 4 , A 5 , R 1 , R 2a , R 2b , R 3 , R 4a , R 5a and R 5b(which has the same meaning as described above for the compound of formula (I)) is provided. This reaction can be carried out without using a solvent or in a solvent, preferably in a solvent such as an organic solvent like acetonitrile, within a temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C, in the presence or absence of a catalyst such as a metal catalyst like a palladium complex and with or without the addition of a base such as an inorganic base like potassium carbonate or an organic base like triethylamine.

[0131] The formation of the compound of formula IIIb is described in Scheme 9. Scheme 9:

Chemical formula

[0132] The compound of formula IIIb can be prepared by treatment of a compound of formula XX (wherein R 3 , R 4a , R 5a and R 5b are as described in formula (I)) with a compound of formula IIIc (wherein R 1 is as defined in formula (I)) in the presence of, for example, NaBH(OAc)3 or NaBH3CN, in a suitable solvent, preferably acetic acid, at room temperature. Alternatively, other reagent systems for reductive amination can use a combination of Ti(i-OiPr)4 and NaBH4 (see Synthesis 2003(14), 2206).

[0133] The amine of formula IIIc can be obtained by the biocatalytic deracemization of the amine of formula IIId. This can be carried out, for example, in a suitable solvent such as acetonitrile or methyl tert-butyl ether, in the presence of an acyl donor such as ethyl methoxyacetate or vinyl acetate, at a temperature of 20 °C to 100 °C, using, for example, a lipase, such as Candida antarctica lipase B or Pseudomonas fluorescens lipase, finally in an immobilized form (e.g., Novozym® 435). Such processes are described, for example, in J. Org. Chem. 2007, 72, 6918 - 6923 or Adv. Synth. Catal. 2007, 349, 1481 - 1488. The stereochemical results expected from such enzymatic deracemization are known to those skilled in the art and are described in the literature such as J. Org. Chem. 1991, 56, 2656 - 2665 or J. Am. Chem. Soc. 2015, 137, 3996 - 4009.

[0134] In an alternative process, the compound of formula IIIc or a salt thereof (preferably a hydrohalide such as hydrochloride or hydrobromide or trifluoroacetate or any other equivalent salt etc.) can be obtained from the compound of formula XXII (wherein R 3 、R 4a 、R 5a and R 5b are as described in formula (I)) according to the synthesis described in Scheme 10. Scheme 10:

Chemical formula

[0135] The amine of formula IIIc or a salt thereof is the intermediate of formula XXII (wherein R 3 、R 4a 、R 5a and R 5bis as described in formula (I), and Z3 is, from -NPhth (N-phthalimide group) or -NBoc2 (N-bis(tert-butyloxycarbonyl) group), typically by treatment with hydrazine (preferably hydrazine hydrate or hydrazine monohydrate) in an alcohol solvent such as ethanol or isopropanol (where Z3 is -NPhth) or by treatment with an acid such as trifluoroacetic acid or hydrochloric acid in the presence of a suitable solvent such as dichloromethane, tetrahydrofuran or dioxane (where Z3 is -NBoc2), and is known to those skilled in the art and can be obtained under deprotection conditions described in documents such as Protective Groups in Organic Synthesis, 3rd Edition Theodora W. Green (The Rowland Institute for Science) and Peter G. M. Wuts (Pharmacia and Upjohn Company), John Wiley & Sons, Inc., New York, NY. 1999, ISBN 0-471-16019-9, etc.

[0136] Such an intermediate of formula XXII (where R 3 , R 4a , R 5a and R 5b are as described in formula (I), and Z3 is, from -NPhth (N-phthalimide group) or -NBoc2 (N-bis(tert-butyloxycarbonyl) group), is the alcohol of formula XXI (where R 3 , R 4a , R 5a and R 5bIt can be obtained by the Mitsunobu reaction, which involves treating the alcohol of formula XXI with an azodicarboxylate such as diethyl azodicarboxylate or diisopropyl azodicarboxylate in the presence of a phosphine such as triphenylphosphine or tributylphosphine and an amine such as phthalimide (HNPhth) or bis(tert-butoxycarbonyl)amine (HNBoc2), as described in formula (I). It is known to those skilled in the art that the Mitsunobu reaction proceeds with inversion of the stereocenter, for example, as described in Chem. Rev. 2009, 109, 2551 - 2651.

[0137] Alternatively, the amine of formula IIIc can be obtained by treating with triphenylphosphine and water (Staudinger reaction) or by hydrogenation using a palladium catalyst in the presence of hydrogen, etc., of the azide of formula XXIII (where R 3 、R 4a 、R 5a and R 5b are as described in formula (I)). The azide of formula XXIII can be obtained by treating the alcohol of formula XXI (where R 3 、R 4a 、R 5a and R 5b are as described in formula (I)) with an azidating reagent such as diphenylphosphoryl 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 proceed with inversion of the stereocenter and are described in the literature such as Adv. Synth. Catal. 2018, 360, 2157 - 2165.

[0138] The alcohol of formula XXI is a ketone of formula XXIV (where R 3 、R 4a 、R 5a and R 5bIt can be obtained by enantioselective reduction as described in formula (I). Such reduction can be carried out, for example, using a catalyst such as a ruthenium or rhodium catalyst together with a chiral ligand such as RuCl[(R,R)-TsDPEN](mesitylene) or RuBF4[(R,R)-TsDPEN](p-cymene) in the presence of a hydrogen donor system such as HCOOH / Et3N or HCO2NH4. Such processes are described, for example, in the literature such as J.Org.Chem.2017,82,5607.

[0139] Alternatively, the compound of formula IIIc can also be prepared as described in Scheme 11. Scheme 11:

Chemical formula

[0140] The amine of formula IIIc or its salt (preferably a hydrohalide such as hydrochloride or hydrobromide or trifluoroacetate or any other equivalent salt, etc.) can be prepared, for example, by deprotecting the amine of formula XXV using an acid such as trifluoroacetic acid or hydrochloric acid in the presence of a suitable solvent such as dichloromethane, tetrahydrofuran or dioxane, where R 3 , R 4a , R 5a and R 5b are as described in formula (I).

[0141] The amine of formula XXV can be obtained by condensation of the diamine of formula XXVII (where R 3 and R 4a are as described in formula (I)) in the diketone of formula XXVI (where R 5a and R 5b are as described in formula (I)). This condensation can be carried out in the presence of a suitable solvent such as ethanol or isopropanol and in the presence of an oxidizing agent such as air or DDQ.

[0142] The diketone of formula XXVI can be formed by the oxidation of the hydroxyketone of formula XXVII (wherein R 3 and R 4a are as described in formula (I)). This oxidation can involve, for example, SO3 - pyridine in the presence of a solvent such as dichloromethane or dimethyl sulfoxide DMSO or a mixture thereof, and a base such as triethylamine or alternatively sodium hypochlorite in the presence of a catalyst such as TEMPO / Bu4NHSO4. Examples of such oxidations can be found in the literature such as Synlett, 2014, 25, 596 or J. Am. Chem. Soc. 1990, 112, 5290 - 5313.

[0143] The hydroxyketone of formula XXVII can be synthesized by the crossed benzoin condensation between the aldehyde of formula XXIX (wherein R 4a is as described in formula (I)) and the aldehyde of formula XXVIII (wherein R 3 is as described in formula (I)).

[0144] The aldehyde of formula XXVIII is commercially available in chiral forms such as, for example, Boc - L - alaninal (CAS 79069 - 50 - 4) or tert - butyl N - [(1S)-1-(cyclopropylmethyl)-2 - oxo - ethyl]carbamate (CAS 881902 - 36 - 9). The crossed benzoin condensation is carried out in a suitable solvent such as DCM or THF in the presence of a base such as potassium tert - butoxide or N,N - isopropylethylamine, at a temperature from - 20 °C to the boiling point of the solvent, by employing an organic catalyst such as a triazolium salt or a thiazolium salt in the usual way. Examples of catalysts for such transformations are described in the literature such as J. Am. Chem. Soc. 2014, 136, 7539 - 7542 or Org. Lett. 2016, 18, 4518 - 4521.

[0145] Scheme 12:

Chemical Structure

[0146] The compound of formula XXX can be prepared by coupling of an amine of formula XXXIII and a compound of formula II (wherein A 1 A 2 A 3 A 4 A 5 R 2a R 2b and X 1 are as described in Scheme 1) under the conditions described in Scheme 1. Under the same conditions, when R 1 = H, the compound of formula XXX can be obtained directly from the compound of formula XXXIV.

[0147] The compound of formula XXXIII can be prepared, for example, in the presence of NaBH(OAc)3 or NaBH3CN, in a suitable solvent, preferably acetic acid, at room temperature, from a compound of formula XXXV (R 1It can be prepared by treatment of a compound of formula XXXIV as defined by formula I). Alternatively, other reagent systems for reductive amination use a combination of Ti(i-OiPr)4 and NaBH4 (see Synthesis 2003(14), 2206).

[0148] The amine of formula XXXIV can be prepared, for example, by a deracemization method involving the selective acylation of one enantiomer. Such an example is detailed by Scheme 13. Scheme 13: [Chemical Structure]

[0149] The amine of formula XXXIV is an amine of formula XXXIVa, where R 3 , R 5a and R 5b are as in formula (I), and X 07 is a leaving group such as bromine, chlorine or iodine, and can be obtained by biocatalytic deracemization. This can be carried out, for example, in a suitable solvent such as acetonitrile or methyl tert-butyl ether, in the presence of an acyl donor such as ethyl methoxyacetate or vinyl acetate, at a temperature of 20 °C to 100 °C, using, for example, a lipase, such as Candida antarctica lipase B or Pseudomonas fluorescens lipase, finally in an immobilized form (e.g., Novozym® 435). Such processes are described, for example, in J. Org. Chem. 2007, 72, 6918 - 6923 or Adv. Synth. Catal. 2007, 349, 1481 - 1488. The stereochemical results expected from such enzymatic deracemization are known to those skilled in the art and are described in documents such as J. Org. Chem. 1991, 56, 2656 - 2665 or J. Am. Chem. Soc. 2015, 137, 3996 - 4009.

[0150] Instead, the resolution of the amine of formula XXXIVa to give the amine of formula XXXIV can be achieved using an asymmetric auxiliary as described in Scheme 14. Scheme 14:

Chemical formula

[0151] The amine of formula XXXIV can be prepared from an intermediate of formula XXXVII (where R 3 , R 5a and R 5b are as in the compound of formula (I), X 07 is a leaving group such as bromine, chlorine or iodine, and X 12 * is an asymmetric auxiliary) by treatment with an acid such as HCl or a base such as NaOH. The asymmetric auxiliary of formula XXXVI is, for example, mandelic acid or (1R)-menthyl chloroformate. The intermediate of formula XXXVII can be formed by coupling an asymmetric auxiliary of formula XXXVI (where X0 is a leaving group such as chlorine) with an amine of formula XXXIVa according to the conditions detailed in Scheme 1. Examples of such deracemization processes are reported in the literature such as J. Org. Chem. 2007, 72, 485 - 493.

[0152] Alternatively, the amine of formula XXXIV or a salt thereof (preferably a hydrohalide such as hydrochloride or hydrobromide or trifluoroacetate or any other equivalent salt etc.) can be formed as described in Scheme 15. Scheme 15:

Chemical formula

[0153] The amine of formula XXXIV or a salt thereof is an intermediate of formula XXIIa (where R 3 , R 5a and R 5b are as described in formula (I), X 07is a leaving group of a halogen such as bromide or sulfonate, and Z3 is -NPhth (N-phthalimide group) or -NBoc2 (N-bis(tert-butyloxycarbonyl) group). It can be obtained under deprotection conditions known to those skilled in the art, for example, by treatment with hydrazine (preferably hydrazine hydrate or hydrazine monohydrate) in an alcohol solvent such as ethanol or isopropanol (where Z3 is -NPhth) or by treatment with an acid such as trifluoroacetic acid or hydrochloric acid in the presence of a suitable solvent such as dichloromethane, tetrahydrofuran or dioxane (where Z3 is -NBoc2), as described in documents such as Protective Groups in Organic Synthesis, 3rd Edition Theodora W. Green (The Rowland Institute for Science) and Peter G. M. Wuts (Pharmacia and Upjohn Company), John Wiley & Sons, Inc., New York, NY. 1999, ISBN 0-471-16019-9.

[0154] Such an intermediate of formula XXIIa (where R 3 、R 5a and R 5b are as described in formula (I), X 07 is a leaving group of a halogen such as bromide or sulfonate, and Z3 is -NPhth (N-phthalimide group) or -NBoc2 (N-bis(tert-butyloxycarbonyl) group).) involves the Mitsunobu reaction including the treatment of an alcohol of formula XXIa with an azodicarboxylate such as diethyl azodicarboxylate or diisopropyl azodicarboxylate in the presence of a phosphine such as triphenylphosphine or tributylphosphine and in the presence of an amine such as phthalimide (HNPhth) or bis(tert-butoxycarbonyl)amine (HNBoc2). The alcohol of formula XXIa (where R 3 、R 5a and R 5bis as described in formula (I), and X 07 (wherein X is a leaving group) can be obtained from. It is known to those skilled in the art that the Mitsunobu reaction proceeds with inversion of the stereocenter, as described, for example, in Chem. Rev. 2009, 109, 2551 - 2651.

[0155] Alternatively, the amine of formula XXXIV can be obtained by treatment with triphenylphosphine and water (the Staudinger reaction) or by hydrogenation using a palladium catalyst in the presence of hydrogen, etc., of the azide of formula XXIIIa (wherein R 3 , R 5a and R 5b are as described in formula (I), and X 07 is a leaving group such as a halogen or a sulfonate, e.g., bromide) by reduction. The azide of formula XXIIIa can be obtained by treating the alcohol of formula XXIa with an azidating reagent such as diphenylphosphoryl azide in the presence of a base such as DBU in a solvent such as toluene or THF. Such a process is known to those skilled in the art to proceed with inversion of the stereocenter and is described in the literature such as Adv. Synth. Catal. 2018, 360, 2157 - 2165.

[0156] The alcohol of formula XXIa can be obtained by the enantioselective reduction of the ketone of formula XXIVa (wherein R 3 , R 5a and R 5b are as described in formula (I), and X 07 is a leaving group such as a halogen or a sulfonate, e.g., bromide). Such a reduction can be carried out using a catalyst such as a ruthenium or rhodium catalyst together with a chiral ligand such as RuCl[(R,R)-TsDPEN](mesitylene) or RuBF4[(R,R)-TsDPEN](p-cymene) in the presence of a hydrogen donor system such as HCOOH / Et3N or HCO2NH4. Such a process is described in the literature such as J. Org. Chem. 2017, 82, 5607.

[0157] Formula II [Chemical formula] (wherein X 1 is a leaving group such as halogen or sulfonate, for example chloride) The compound of can be formed as shown in Schemes 16 to 18, for example.

[0158] Scheme 16: [Chemical formula] The compound of formula IIa (wherein R 2a , R 2b , A 4 and A 5 are as described in formula (I)) can be prepared according to reaction scheme 16. The compounds of formula XLII are known or they can be prepared by methods known to those skilled in the art. For example, as described in J. Org. Chem. 2018, 83, 930, for example, the compound of formula XL is reacted with an electrophilic iodination reagent such as N-iodosuccinimide in a solvent such as hexafluoroisopropanol to give the compound of formula XLI. Cyanation of the compound of formula XLI with copper(I) cyanide in a solvent such as DMF at a temperature such as 100 °C gives the compound of formula XLII (similar method to 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 gives the compound of formula XLIII (similar method to International Publication No. 2018 / 206539, page 80). The subsequent conversion of the compound of formula XLIII to the compound of formula IIa is achieved via a method known to those skilled in the art involving thionyl chloride at reflux in the presence of a catalyst such as N,N-dimethylformamide, similar to International Publication No. 2015 / 54572, page 263.

[0159] The compound of formula XLIII (wherein R 2a , A 4 and A 5is as described above in formula (I), R 2b is R x (wherein R x is selected independently from 1 to 3 substituents (more particularly 2 to 3 substituents) which are C1-C4 alkylsulfonyl (more particularly methylsulfonyl) substituted with halogen (more particularly fluorine)) is a compound of formula XLIIIa (wherein R 2a , A 4 and A 5 are as described in formula (I), and Gr is difluoromethyl or trifluoromethyl) can be represented by.

[0160] Scheme 16a: [Chemical formula] Such sulfone compounds of formula XLIIIa can optionally be obtained by the oxidation reaction of the corresponding sulfide compounds of formula XLIIIb or sulfoxide compounds of formula XLIIIb-1 in the presence of a catalyst such as ruthenium chloride, sodium tungstate or iron, manganese, cobalt and vanadium-based catalysts, for example together with other oxidants, including reagents such as meta-chloroperbenzoic acid (mCPBA), hydrogen peroxide, potassium peroxymonosulfate (oxone®), sodium periodate, sodium hypochlorite or tert-butyl hypochlorite (Scheme 16a). This oxidation reaction is generally carried out in the presence of a solvent such as aliphatic halogenated hydrocarbons (e.g., dichloromethane, chloroform or carbon tetrachloride), esters (e.g., ethyl acetate), alcohols (e.g., methanol or ethanol), acetonitrile, acetic acid or water; or mixtures thereof. Similarly, the sulfoxide compounds of formula XLIIIb-1 can be obtained via the oxidation of the sulfide compounds of formula XLIIIb. The amount of the oxidant used in this reaction generally produces 1 to 3 moles, preferably 1 to 1.2 moles of the sulfoxide compound of XLIIIb-1 based on 1 mole of the sulfide compound of XLIIIb, and preferably 2 to 2.2 moles of the oxidant based on 1 mole of the sulfide compound XLIIIb to produce the sulfone compound XLIIIa.

[0161] The compound of formula XLIIIb (wherein R 2a , A 4 and A 5 are as described above in formula (I) and Gr is trifluoromethyl) is in a solvent such as acetonitrile, dioxane, N,N-dimethylformamide or N,N-dimethylacetamide and at a temperature of 0 to 180 °C, preferably room temperature to 150 °C, with the compound of formula XLIIIc (wherein R 2a , A 4 and A 5 are as described above in formula (I) and R 2bcan be prepared by reacting it with a trifluoromethylthiolating reagent "CuS-Gr" such as copper(I) trifluoromethanethiolate (CAS 3872-23-9) or trifluoromethylthiolato(2,2-bipyridine)copper(I) (also known as (bpy)Cu(SCF3), CAS 1413732-47-4), where X is iodine or bromine. Such conditions are described in the literature such as J. Org. Chem. 1976, 41, 1644, or Synthesis 1975, 721 (CAS 3872-23-9) and Angew. Chem. Int. Ed. 2013, 52, 1548, or Tetrahedron, 2013, 69, 6046 (CAS 1413732-47-4).

[0162] A compound of formula XLIIIb, where R 2a , A 4 and A 5 are as described above in formula (I) and Gr is difluoromethyl), for example, in the presence of a base such as sodium carbonate or potassium carbonate, in a suitable solvent such as acetonitrile, Ν,Ν-dimethylformamide or N-methyl-2-pyrrolidone (NMP), at room temperature to the boiling point of the reaction mixture, from, for example, difluoroacetate XcCF2COONa or difluoromethyl(phosphonate) XcCF2P(O)(OEt)2 (where Xc can be chloro or bromo) generated by:CF2 carbene to a compound of formula XLIIId, where R 2a , A 4 and A 5 are as described above in formula (I)) can be obtained by treatment. Such methods are described in the literature such as Org. Lett. 15(19), 5036-5039; 2013, Tet 65(27), 5278-5283; 2009 or Chem. Commun. 53, 5706; 2017.

[0163] Alternatively, the compound of formula XLIIIb can be obtained, for example, as described in J. Fluor. Chem., 193, 113 - 117; 2017, by treating the compound of formula XLIIId with a difluoromethylsulfinate reagent in the presence of an oxidizing agent.

[0164] The compound of formula XLIIId (wherein R 2a , A 4 and A 5 are as described above in formula (I)) can be obtained by hydrolyzing the compound of formula XLIIIe (wherein R 2a , A 4 and A 5 are as described above in formula (I)) via basic or acidic hydrolysis conditions known to those skilled in the art (e.g., thioacetate hydrolysis by treatment with an aqueous acid solution such as aqueous HCl).

[0165] The compound of formula XLIIIe (wherein R 2a , A 4 and A 5 are as described above in formula (I)) can be obtained, for example, as described in J. Org. Chem. 21, 11464; 2017, by treating the compound of formula XLIIIc (wherein R 2a , A 4 and A 5 are as described in formula (I) and R 2b is iodine or bromine) with potassium thioacetate (KSAc) or sodium thioacetate under Ullmann cross - coupling copper - mediated reaction conditions.

[0166] Alternatively, the compound of formula XLIIId (wherein R 2a , A 4 and A 5is as described above in formula (I), for example, as described in Bioorg. Med. Chem. Lett. 23(13), 3947 - 3953; 2013 or International Publication No. 12 / 088190, in a suitable solvent such as Ν,Ν - dimethylformamide, N - methyl - 2 - pyrrolidone (NMP) or ethanol, at a temperature from room temperature to the boiling point of the solvent, with sodium sulfide or potassium sulfide or sodium hydrogen sulfide or potassium hydrogen sulfide (optionally as a hydrate salt) of the compound of formula XLIIIc (where R 2a , A 4 and A 5 are as described in formula (I), and R 2b is iodine or bromine) can be obtained by treatment.

[0167] The chemistry (Scheme 16a) shown above for the conversion of XLIIIc → XLIIId → XLIIIb can be carried out with some additional protection / deprotection steps as shown in Scheme 16b. Scheme 16b:

Chemical formula

[0168] The chemistry and conditions for the conversion of XLIIIf → XLIIIg → XLIIIh (Scheme 16b) are for the conversion of XLIIIc → XLIIId → XLIIIb (where the substituents Gr, R 2a , R 2b , A 4 and A 5The definition is the same as that detailed in Scheme 16a, and is the same as the above description regarding PG1 which is a protecting group such as, for example, a tetrahydropyranyl (THP) or tert-butyloxycarbonyl (Boc) group. Each of the protecting conditions (conversion of XLIIIc → XLIIIf) and the deprotecting conditions (conversion of XLIIIh → XLIIIb) are well-known to those skilled in the art and are described in documents such as, for example, Protective Groups in Organic Synthesis, 3rd Edition Theodora W. Green (The Rowland Institute for Science) and Peter G. M. Wuts (Pharmacia and Upjohn Company), John Wiley & Sons, Inc., New York, NY. 1999, ISBN 0-471-16019-9. For example, the THP protection of XLIIIc to produce XLIIIf (where PG1 is tetrahydropyranyl (THP)) can be achieved by treatment with 3,4-dihydro-2H-pyran in an inert solvent such as dimethyl sulfoxide, toluene or dioxane in the presence of a Lewis acid such as trifluoroacetic acid and at a temperature from room temperature to the boiling point of the reaction mixture. The deprotection of XLIIIh (where PG1 is tetrahydropyranyl (THP)) can be achieved by treatment with, for example, p-methoxybenzenesulfonic acid or p-toluenesulfonic acid (PTSA) optionally as a hydrate salt in an alcohol solvent such as methanol or ethanol, optionally in the presence of a co-solvent such as tetrahydrofuran, 2-methyltetrahydrofuran or dioxane and at a temperature of 0 to 80 °C, preferably at about room temperature.

[0169] Alternatively, a compound of formula XLIIIa (where R 2a , A 4 and A 5 are as described in formula (I) and Gr is difluoromethyl or trifluoromethyl) Scheme 16c:

Chemical formula

[0170] Similarly, the compound of formula XLIIIb-1, where R 2a , A 4 and A 5 are as described in formula (I) and Gr is difluoromethyl or trifluoromethyl, can be obtained via deprotection of the compound of formula XLIIIi-1, where R 2a , A 4 and A 5 are as described in formula (I), Gr is difluoromethyl or trifluoromethyl, and PG1 is a protecting group such as, for example, a tetrahydropyranyl (THP) or tert-butyloxycarbonyl (Boc) group).

[0171] The compound of formula XLIIIi, where R 2a , A 4 and A 5 are as described in formula (I), Gr is difluoromethyl or trifluoromethyl, and PG1 is a protecting group such as, for example, a tetrahydropyranyl (THP) or tert-butyloxycarbonyl (Boc) group), is the corresponding sulfide compound of formula XLIIIh or the sulfoxide compound of formula XLIIIi-1 under the conditions already detailed in Scheme 16a (conversion of XLIIIb → XLIIIa, respectively XLIIIb-1 → XLIIIa), where R 2a , A 4 and A 5is as described in formula (I), where Gr is difluoromethyl or trifluoromethyl, and PG1 is a protecting group such as, for example, a tetrahydropyranyl (THP) or tert-butyloxycarbonyl (Boc) group), and can be obtained by an oxidation reaction. Similarly, the sulfoxide compound of formula XLIIIi-1 can be obtained by the oxidation of the sulfide compound of formula XLIIIh (the conversion of XLIIIb to XLIIIb-1 in Scheme 16a).

[0172] Scheme 17:

Chemical formula

[0173] Scheme 18:

Chemical formula

[0174] Formula IVc [Chemical formula] The compound of can be prepared, for example, as shown in Scheme 19. Scheme 19: [Chemical formula]

[0175] The compound of formula IVc (where Z is H, C1-C3 alkyl, cyclopropyl, CF3, and R 2a , R 2b , A 4 and A 5 is as described in formula (I)) can be prepared according to reaction scheme 19. For example, as described in Eur. J. Med. Chem. 2017, 141, 446, the compound of formula XLII prepared as shown in Scheme 16 is reacted at a high temperature such as 180 °C in the presence of the compound of formula XLVIII to give an amine of formula IVc.

[0176] Alternatively, the compound of formula Iab can be prepared, for example, as shown in Scheme 20. Scheme 20: [Chemical formula]

[0177] The compound of formula Iab (wherein R 1 , R 2a , R 2b , R 3 , A 4 , A 5 , Q are as described in formula (I)) can be prepared according to Scheme 20, which is similar to the procedure on page 225 of WO 2010 / 093419. The compound of formula XLII prepared in Scheme 16 is treated with N,N-dimethylformamide dimethyl acetal at a high temperature, preferably 90 °C, to give the formamidine product of formula XLVIII. The compound of formula Iab is obtained by reaction with an amine of formula III in a suitable solvent, preferably acetic acid, at a high temperature, preferably 120 °C.

[0178] The compound of formula If

Chemical formula

Chemical formula

[0179] The compound of formula If (wherein R 1 , R 2a , R 2b , R 3 , A 4 , A 5 , Q are as described in formula (I)) can be prepared according to Scheme 21. Using the procedure shown in Scheme 1, the compound of formula IIb prepared in Scheme 17 (wherein R 2a , R 2b , A 4 and A 5 are as described in formula (I)) and an amine of formula III or a salt thereof (preferably a hydrohalide salt such as hydrochloride or hydrobromide or trifluoroacetate or any other equivalent salt, etc.) (wherein R 1 , R 3And Q is as described in formula (I), the reaction with which gives the compound of formula Ie. As described in Heterocycles 1996, 43, 2607, treatment of the compound of formula Ie under acidic conditions, at elevated temperature, preferably 70 - 80 °C, preferably with acetic acid gives the intermediate of formula LI. Methylation of the compound of formula LI to obtain the compound of formula If can be achieved 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, as is well known to those skilled in the art.

[0180] Compound of formula Ig

Chemical formula

Chemical formula

[0181] The compound of formula Ig (where R 1 , R 2a , R 2b , R 3 , A 4 , A 5, Q is as described in formula (I) and can be prepared according to Scheme 22. The compound of formula XLII prepared in Scheme 16 is treated with a diazotizing reagent, preferably isoamyl nitrite, at a high temperature, preferably 80 °C, in a diiodomethane solvent as described in J. Org. Chem. 1990, 55, 2543, to give an intermediate of formula LX. Reduction of the compound of formula LX is achieved in the presence of a selective reducing agent such as diisobutylaluminum hydride (DIBALH) at a low temperature, preferably -78 °C, in a solvent such as toluene, to give a compound of formula LXI. The subsequent Sonogashira coupling with trimethylsilylacetylene in a solvent such as triethylamine in the presence of a suitable palladium and copper catalyst, preferably bis(triphenylphosphine)palladium chloride and copper(I) iodide, gives a compound of formula LXII. Cyclization with ammonia in methanol gives a compound of formula LXIII. The procedure is similar to that described, for example, in Eur. J. Med. Chem. 2016, 118, 170. Treatment of the compound of formula LXIII with an oxidizing agent such as 3-chloro-perbenzoic acid or hydrogen peroxide in a solvent, preferably dichloromethane, gives the N-oxide of formula LXIV. Such oxidation is well known to those skilled in the art. Similar to the procedure described in International Publication No. 2016 / 123627, page 87, coupling of the compound of formula LXIV with an amine of formula III in the presence of a suitable activator such as bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP®), optionally in the presence of a base such as N,N-diisopropylethylamine, gives a compound of formula Ig.

[0182] Formula IId

Chemical Structure

Chemical Structure

[0183] The compound of formula IId (wherein R 2a , R 2b , A 4 , A 5 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 in the presence of a palladium catalyst, preferably Pd(PPh3)4, at an elevated temperature, preferably 105 °C, as described on page 57 of European Patent No. 1782811, to afford an intermediate of formula LXV. As in Bioorg. Med. Chem. Lett., 25, 919, treatment of the compound of formula LXV with aqueous sodium nitrite at low temperature, preferably 0-5 °C, in the presence of an acid such as hydrochloric acid or a sulfuric acid / acetic acid mixture affords a compound of formula LXVI. As is well known to those skilled in the art, the compound of formula IId is then optionally obtained via chlorination of the compound of formula LXVI using a chlorinating reagent such as POCl3 in the presence of an amine base such as N,N-diisopropylethylamine.

[0184] Formula IIe [Chemical formula] (wherein X 1 is a halogen or a sulfonate, such as a leaving group like chloride) The compound of can be prepared, for example, as shown in Scheme 24. Scheme 24: [Chemical formula]

[0185] The compound of formula IIe (wherein R 2a , R 2b , A 4 , A 5As described in formula (I), it can be prepared according to Scheme 24. As described in Tetrahedron Letters, 2015, 56, 5112, heating the compound of formula XL with ethyl 2-cyano-3-ethoxyacrylate at a high temperature, preferably 140 °C, gives the intermediate of formula LXVII. 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®), gives the compound of formula LXVIII. The subsequent conversion to the compound of formula IIe is achieved according to methods known to those skilled in the art, for example, in the presence of the catalyst N,N-dimethylformamide, with thionyl chloride at reflux, as described in US Patent Application Publication No. 2003 / 212276, page 15.

[0186] Formula Ih

Chemical formula

Chemical formula

[0187] The compound of formula Ih (where R 1 , R 2a , R 2b , R 3 , A 4 , A 5, Q is as described in formula (I) and can be prepared according to Scheme 25. Similar to International Publication No. 2011 / 4276, page 132, the compound of formula XLII prepared in Scheme 16 is heated with hydrogen peroxide as an aqueous solution or urea adduct in a methanol - water solvent in the presence of a base, preferably potassium carbonate, to give the intermediate of formula LXX. Similar to paragraph 133 of US Patent Application Publication No. 2014 / 0275072, treatment of the compound of formula LXX with aqueous sodium nitrite at low temperature, preferably 0 - 5 °C, in the presence of an acid such as hydrochloric acid or a sulfuric acid / acetic acid mixture gives the compound of formula LXXI. Similar to the method described in International Publication No. 2014 / 085528, page 55, coupling of the compound of formula LXXI with an amine of formula III in the presence of a suitable activator such as (benzotriazol - 1 - yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBoP®) and in the presence of a base such as N,N - diisopropylethylamine gives the compound of formula Ih.

[0188] Formula Ii

Chemical formula

Chemical formula

[0189] The compound of formula Ii, where R 1 , R 2a , R 2b , R 3 , A 4 , A 5, Q is as described in formula (I) can be prepared according to Scheme 26. Similar to WO 2018 / 34917, page 91, the compound of formula Iaa prepared according to Scheme 1, 5 or 6 is preferably treated with a fluorinating reagent such as 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) in a solvent such as acetonitrile to give the compound of formula Ii.

[0190] Formula Ij

Chemical Structure

Chemical Structure

[0191] The compound of formula Ij (where R 1 , R 2a , R 2b , R 3 , A 4 , A 5 , Q is as described in formula (I)) can be prepared according to Scheme 27. Similar to Nature Catalysis, 2020, 3, 107, the compound of formula Iaa prepared according to Scheme 1, 5 or 6 is treated with a chlorinating reagent such as N-chlorosuccinimide in the presence of catalytic dimethyl sulfoxide (DMSO), preferably in a solvent such as dichloromethane to give the compound of formula Ij.

[0192] Certain compounds of formula III or salts thereof (preferably hydrohalides such as hydrochloride or hydrobromide or any other equivalent salts etc.) (where R 1 , R 3 and Q have the same meaning as described above for the compounds of formula (I)) are known in the literature.

[0193] For example, a compound of formula IIIa or IIIb as defined above or a salt thereof (wherein R 1 , R 3 , R 4a , R 5a and R 5b are as described in formula (I)), in particular a compound of formula IIIa or IIIb as defined above or a salt thereof (wherein R 3 and R 4a are as described in formula (I), and R 1 , R 5a and R 5b are hydrogen) can be prepared in the same manner as described in WO 2021 / 069575.

Chemical formula

[0194] Similarly, a compound of formula IIIe or IIIf as defined above or a salt thereof (wherein R 1 , R 3 , R 4 and R 5 are as described in formula (I)), in particular a compound of formula IIIe or IIIf as defined above or a salt thereof (wherein R 3 and R 4 are as described in formula (I), R 1 is hydrogen, and R 5 is hydrogen, methyl or cyclopropyl) can be prepared, for example, in the same manner as described in WO 2021 / 099303, WO 2021 / 105091, WO 2021 / 165195 and WO 2021 / 224323.

[0195] Scheme 28:

Chemical formula

[0196] The compound of formula (IIIf - TH - 2) (wherein R 3 , R 10 and R 11 are as defined for the compound of formula (I), and X - is an anion) can be formed by treatment of a compound of formula (XXXVIIIa) (wherein R 3 , R 10 and R 11 are as defined for the compound of formula (I)) with an acid such as those listed above. This reaction can be carried out without using a solvent or in a solvent, for example, an organic solvent such as methanol, tetrahydrofuran, dichloromethane or dioxane or an inorganic solvent such as water or a mixture of such solvents. This reaction can be carried out within a temperature range of - 100 °C to 200 °C, more usually 0 °C to 150 °C, for example, at ambient temperature.

[0197] The compound of formula (XXXVIIIa) (wherein R 3 , R 10 and R 11 are as defined for the compound of formula (I)) is treated with an amine compound of formula HNR 10 R 11 or a salt thereof (wherein R 10 and R 11 are as defined for the compound of formula (I)) under standard amide bond-forming conditions known to those skilled in the art to give a compound of formula (XXXVIIIb) (wherein R 3It can be formed from (as defined for the compounds of formula (I)). Here, typically, the acid compound of formula (XXXVIIIb) is activated to its corresponding acid chloride with oxalyl chloride or thionyl chloride in an inert solvent such as dichloromethane (DCM) or tetrahydrofuran (THF) in the presence of a catalytic amount of N,N-dimethylformamide (DMF) at a temperature of 0 °C to 100 °C, preferably about 25 °C. Such methods are known to those skilled in the art and are described, for example, in Tetrahedron 2005, 61(46), 10827-10852. Alternatively, for example, it may be advantageous to carry out the reaction in the presence of a dehydrating reagent such as a peptide coupling reagent such as carbodiimide, HATU (1-[bis(dimethylamino)-methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, also known as hexafluorophosphate azabenzotriazole tetramethyluronium) or propanephosphonic acid cyclic anhydride (T3P®). Such amidation reactions can be carried out without using a solvent or in a solvent, preferably in an organic solvent such as acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, N,N-dimethylacetamide or N,N-dimethylformamide, in the temperature range of -100 to +300 °C, preferably ambient temperature to 200 °C, in the presence or absence of a catalyst such as an acylation catalyst such as 4-dimethylaminopyridine (DMAP) and with or without the addition of a base such as an inorganic base such as sodium carbonate, potassium carbonate or cesium carbonate or an organic base such as triethylamine, diisopropylethylamine or pyridine. The amine compound of formula HNR 10 R 11 (wherein R 10 =R 11 = hydrogen (i.e., HNR 10 R 11In a specific amidation reaction using ammonia (), it may be advantageous to use an ammonium salt (e.g., ammonium hydroxide or ammonium chloride) or an ammonia substitute such as a silica gel-supported ammonium salt (e.g., silica gel-supported ammonium chloride NH4Cl / SiO2 described in Tetrahedron Letters 2005, 46, 6879-6882).

[0198] The compound of formula (XXXVIIIb) (wherein R 3 is as defined for the compound of formula (I)) can be prepared by saponification of the compound of formula (XXXVIIIc) (wherein R 3 is as defined for the compound of formula (I) and Ra is C1-C6 alkyl) under conditions known to those skilled in the art (e.g., using aqueous sodium hydroxide, potassium hydroxide or lithium hydroxide in methanol, ethanol, tetrahydrofuran or dioxane at room temperature or up to reflux conditions).

[0199] Alternatively, the compound of formula (XXXVIIIa) (wherein R 3 , R 10 and R 11 are as defined for the compound of formula (I)) is optionally in the presence of a base such as an inorganic base such as sodium carbonate, potassium carbonate or cesium carbonate or an organic base such as triethylamine, diisopropylethylamine or pyridine, in a solvent such as an organic solvent such as methanol, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, dimethyl sulfoxide, N,N-dimethylacetamide or N,N-dimethylformamide, in the temperature range of -100 to +300 °C, preferably ambient temperature to 100 °C, optionally in a microwave, with an amine compound of formula HNR 10 R 11 or a salt thereof (wherein R 10 and R 11 are as defined for the compound of formula (I)), to give the compound of formula (XXXVIIIc) (wherein R 3is as defined for the compound of formula (I), and Ra is C1-C6 alkyl) can be formed directly from

[0200] A compound of formula (XXXVIIIc) wherein R 3 is as defined for the compound of formula (I), and Ra is C1-C6 alkyl) is a compound of formula (XXXVIIIe) or a tautomer or salt thereof (wherein Ra is C1-C6 alkyl) of a compound of formula (XXXVIIId) wherein R 3 is as defined for the compound of formula (I)) can be prepared by reaction with. This reaction can be carried out without a solvent or in a solvent, for example, in an organic solvent or a mixture of solvents such as dioxane and acetic acid as the solvent. This reaction can be carried out, for example, in the presence or absence of a desiccant such as in the presence of a molecular sieve, at a temperature of -100°C to 200°C, more usually 0°C to 150°C, for example 80°C.

[0201] A compound of formula (XXXVIIId) wherein R 3 is as defined for the compound of formula (I)) is known, for example, from WO 2021 / 083936 or WO 2021 / 165195, or they can be formed in the same manner as described therein. A compound of formula (XXXVIIIe) or a tautomer or salt thereof (wherein Ra is C1-C6 alkyl) is known or further commercially available, or they can be formed by known methods.

[0202] Scheme 29:

Chemical formula

[0203] The compound of formula (XXXIXe) or a tautomer or a salt thereof (wherein Ra is C1-C6 alkyl) is known or further commercially available, or they can be formed by known methods.

[0204] Scheme 29a:

Chemical formula

[0205] Compounds of formula (XXXVIIId-1) wherein R 1 and R 3 are as defined for the compounds of formula (I)) are either known or they can be formed in a similar manner to the descriptions found in, for example, WO 2021 / 083936 or WO 2021 / 165195.

[0206] Scheme 30:

Chemical formula

[0207] The compound of formula (XL-a) (wherein R 2a R 2b R 3 A 1 A 2 A 3 A 4 and A 5 are as defined for the compound of formula (I)) can be prepared by saponification of the compound of formula (XL-b) (wherein R 2a R 2b R 3 A 1 A 2 A 3 A 4 and A 5 are as defined for the compound of formula (I) and Ra is C1-C6 alkyl or benzyl) under conditions known to those skilled in the art (e.g., using aqueous sodium hydroxide, potassium hydroxide or lithium hydroxide in methanol, ethanol, tetrahydrofuran or dioxane at room temperature or up to reflux conditions).

[0208] Alternatively, the compound of formula (Im) (wherein R 2a R 2b R 3 A 1 A 2 A 3 A 4 A 5 R 10 and R 11is as defined for the compound of formula (I)) is optionally in the presence of a base such as an inorganic base such as sodium carbonate, potassium carbonate or cesium carbonate or an organic base such as triethylamine, diisopropylethylamine or pyridine, in a solvent such as an organic solvent such as methanol, acetonitrile, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, dimethyl sulfoxide, N,N-dimethylacetamide or N,N-dimethylformamide, at a temperature in the range of -100 to +300 °C, preferably ambient temperature to 100 °C, optionally in a microwave, of the amine compound of formula HNR 10 R 11 or a salt thereof (wherein R 10 and R 11 are as defined for the compound of formula (I)) by reaction with a compound of formula (XL-b) (wherein R 2a 、R 2b 、R 3 、A 1 、A 2 、A 3 、A 4 and A 5 are as defined for the compound of formula (I) and Ra is C1-C6 alkyl or benzyl) can be formed directly from.

[0209] The compound of formula (XL-b) (wherein R 2a 、R 2b 、R 3 、A 1 、A 2 、A 3 、A 4 and A 5 are as defined for the compound of formula (I) and Ra is C1-C6 alkyl or benzyl) is in the presence of an alcohol RaOH (where Ra is C1-C6 alkyl or benzyl) of a compound of formula (XL-c) (where R 2a 、R 2b 、R 3 、A 1 、A 2 、A 3 、A 4 and A 5is as defined for the compound of formula (I), and Xa is a halogen, preferably Br, Cl or I (more preferably Cl), and can be prepared by a carbonylation reaction. Typically, in such a carbonylation reaction, the compound of formula (XL-c) is reacted with carbon monoxide CO (usually under pressure within a range of, for example, 5 to 200 bar) in an alcohol RaOH solvent (optionally in the presence of an organic co-solvent) and at a temperature in the range of 0 to 250 °C, preferably room temperature to 200 °C, in the presence of a metal catalyst such as a palladium catalyst (e.g., palladium(II) acetate or [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) PdCl2(dppf)), optionally in the presence of a phosphine ligand, and preferably in the presence of a base such as triethylamine, diisopropylethylamine or pyridine.

[0210] The compound of formula (XL-c) (wherein R 2a 、R 2b 、R 3 、A 1 、A 2 、A 3 、A 4 and A 5 are as defined for the compound of formula (I), and Xa is a halogen, preferably Br, Cl or I (more preferably Cl), is prepared under the same conditions as described above in Scheme 1 from the compound of formula II (wherein R 2a 、R 2b 、A 1 、A 2 、A 3 、A 4 and A 5 are as defined for the compound of formula (I), and X 1 is a halogen or a leaving group such as a sulfonate, e.g., chloride) with a compound of formula (XL-d) or its free base (wherein R 3 is as defined for the compound of formula (I), Xa is a halogen, preferably Br, Cl or I (more preferably Cl), and X - is an anion as defined in Scheme 28).

[0211] The compound of formula (XL-d) or its free base (wherein R 3 is as defined for the compound of formula (I), Xa is a halogen, preferably Br, Cl or I (even more preferably Cl), and X - is an anion as defined in Scheme 28) can be prepared from the compound of formula (XL-e) (wherein R 3 is as defined for the compound of formula (I), Xa is a halogen, preferably Br, Cl or I (even more preferably Cl)) by treatment with an acid under the same conditions as described above in Scheme 28 (conversion from XXXVIIIa to IIIf-TH-2).

[0212] Certain compounds of formula (XL-e) (wherein R 3 is as defined for the compound of formula (I), Xa is a halogen, preferably Br, Cl or I (even more preferably Cl)) are known from, for example, WO 2021 / 224323 or WO 2021 / 165195, or they can be formed by known methods.

[0213] Scheme 30a:

Chemical Structure

[0214] The compound of formula (XL-c-1), wherein R 1 , R 2a , R 2b , R 3 , A 1 , A 2 , A 3 , A 4 and A 5 is as defined for the compound of formula (I), and Xa is halogen, preferably Br, Cl or I (more preferably Cl), and the compound of formula (XL-c), wherein R 2a , R 2b , R 3 , A 1 , A 2 , A 3 , A 4 and A 5 is as defined for the compound of formula (I), and Xa is halogen, preferably Br, Cl or I (more preferably Cl), and can be prepared by reacting with a compound of formula R 1 -X 3 (VI) (wherein R 1 has the same meaning as defined above for the compound of formula (I), provided that R 1 is not hydrogen, and X 3 is a leaving group such as halogen or sulfonate, for example chloride, bromide, iodide or mesylate).

[0215] Scheme 31:

Chemical formula

[0216] The compound of formula (XLI - c) (wherein R 1 and R 3 are as defined for the compound of formula (I), and Ra is C1 - C6 alkyl or benzyl) is the compound of formula (XLI - d) in the presence of an alcohol RaOH (wherein Ra is C1 - C6 alkyl or benzyl) (wherein R 1 and R 3is as defined for compounds of formula (I), and Xb is a halogen, preferably Br, Cl or I (even more preferably Br or Cl). Typically, in such carbonylation reactions, compounds of formula (XLI-d) are reacted with carbon monoxide CO (usually under pressure, for example in the range of 5 to 200 bar) in the presence of a metal catalyst, such as a palladium catalyst (e.g., palladium(II) acetate or [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)PdCl2(dppf)), optionally in the presence of a phosphine ligand, preferably in the presence of a base, such as triethylamine, diisopropylethylamine or pyridine, in an alcohol RaOH solvent (optionally in the presence of an organic co-solvent) and at a temperature in the range of 0 to 250°C, preferably room temperature to 200°C.

[0217] Scheme 32: [ka] A compound of formula (XLI-d) (wherein R 1 and R 3 is as defined for compounds of formula (I) and Xb is halogen, preferably Br, Cl or I (even more preferably Br or Cl)) is a compound of formula (XXXVIIId-1) of formula (XLI-e) or a tautomer or a salt thereof, where Xb is halogen, preferably Br, Cl or I (even more preferably Br or Cl) 1 and R 3 is as defined for compounds of formula (I) (Scheme 32). The reaction may be carried out neat or in a solvent, for example an organic solvent such as dioxane or acetic acid or a mixture thereof. The reaction may be carried out in the presence or absence of a drying agent, for example in the presence of molecular sieves, at a temperature between -100°C and 200°C, more usually between 0°C and 150°C, for example 80°C.

[0218] The compound of formula (XLI-e) or its tautomer or its salt (wherein Xb is halogen, preferably Br, Cl or I (more preferably Br or Cl)) is known or further commercially available, or they can be formed by known methods.

[0219] Scheme 33:

Chem.

[0220] The compound of formula (XLII-a) (where R 2a 、R 2b 、R 1 、R 3 、A 1 、A 2 、A 3 、A 4 and A 5 is as defined for the compounds of formula (I), and PG is benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl or 2,4-dimethoxybenzyl group) is in the presence of benzylamine, p-methoxybenzylamine, 3,4-dimethoxybenzylamine or 2,4-dimethoxybenzylamine, the compound of formula (XLII-b) (where R 2a 、R 2b 、R 1 、R 3 、A1 and A 2 and A 3 and A 4 and A 5 is prepared by an aminocarbonylation reaction as defined for the compound of formula (I), wherein Xd is halogen, preferably Br, Cl or I (more preferably Br). Typically, in such an aminocarbonylation reaction, the compound of formula (XLII-b) is reacted with carbon monoxide CO (usually under pressure within a range of, for example, 5 to 200 bar) in an inert solvent (such as toluene) in the presence of a metal catalyst such as a palladium catalyst (e.g., palladium(II) acetate, bis(benzonitrile)palladium(II) chloride or [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) PdCl2(dppf)), optionally in the presence of a phosphine ligand (such as xantphos), in the presence of the above benzylamine, preferably in the presence of a base such as triethylamine, diisopropylethylamine or pyridine, and at a temperature in the range of 0 to 250 °C, preferably room temperature to 200 °C.

[0221] The compound of formula (XLII-b), wherein R 2a and R 2b and R 1 and R 3 and A 1 and A 2 and A 3 and A 4 and A 5 is as defined for the compound of formula (I), and Xd is halogen, preferably Br, Cl or I (more preferably Br), is the compound of formula II, wherein R 2a and R 2b and A 1 and A 2 and A 3 and A 4 and A 5 is as defined for the compound of formula (I), and X 1 is a leaving group such as halogen or sulfonate, for example chloride, is the compound of formula (XLII-c) or its free base, wherein R 1 and R 3is as defined for the compound of formula (I), Xd is halogen, preferably Br, Cl or I (even more preferably Br), and X - (which is an anion as defined in Scheme 28) can be prepared by reacting under the same conditions as described above in Scheme 1.

[0222] A compound of formula (XLII-c) or its free base, wherein R 1 and R 3 is as defined for the compound of formula (I), Xd is halogen, preferably Br, Cl or I (even more preferably Br), and X - (which is an anion as defined in Scheme 28) is a compound of formula (XLII-d), wherein R 1 and R 3 is as defined for the compound of formula (I), Xd is halogen, preferably Br, Cl or I) can be prepared by treatment with an acid under the same conditions as described above in Scheme 28 (conversion from XXXVIIIa to IIIf-TH-2).

[0223] A compound of formula (XLII-d), wherein R 1 and R 3 is as defined for the compound of formula (I), Xd is halogen, preferably Br, Cl or I) can be prepared according to the description above in the present specification in Scheme 32 or, for example, under conditions similar to those found in WO 21 / 083936.

[0224] Depending on the method or reaction conditions, the reactants can be reacted in the presence of a base. Examples of suitable bases are alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamides, alkylenediamides, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxide and carbocyclic amines. Examples 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]undec-7-ene (DBU).

[0225] The reactants can be reacted with each other as such, 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, an excess base such as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline can also act as a solvent or diluent.

[0226] The reaction is advantageously carried out in a temperature range of about -80 °C to about +140 °C, preferably about -30 °C to about +100 °C, and in many cases in the range from ambient temperature to about +80 °C.

[0227] Depending on the reaction conditions suitable for each example and the selection of starting materials, for example, in one reaction step, it is possible to simply substitute one substituent with another substituent according to the present invention, or in the same reaction step, it is possible to substitute a plurality of substituents with other substituents according to the present invention.

[0228] The salts of the compounds of formula (I) can be prepared by methods known per se. Thus, for example, the acid addition salts of the compounds of formula (I) are obtained by treatment with a suitable acid or a suitable ion exchange reagent, and the salts with bases are obtained by treatment with a suitable base or a suitable ion exchange reagent.

[0229] The salts of the compounds of formula (I) can be converted in a conventional manner, for example, into the acid addition salts of the free compound I by treatment with a suitable basic compound or a suitable ion exchange reagent, and into the salts with bases by treatment with a suitable acid or a suitable ion exchange reagent.

[0230] Depending on the procedure or reaction conditions, the compounds of formula (I) having salt-forming properties are obtained in free form or in the form of salts. The salts of the compounds of formula (I) can be converted into other salts, acid addition salts, for example other acid addition salts, of the compounds of formula (I) in a manner known per se by treatment with suitable metal salts, such as the sodium, barium or silver salts of acids, for example the hydrochloride with silver acetate, in a suitable solvent in which the inorganic salts formed, such as silver chloride, are insoluble and thus precipitate from the reaction mixture.

[0231] Depending on the procedure or reaction conditions, the compounds of formula (I) having salt-forming properties are obtained in free form or in the form of salts.

[0232] The compounds of formula (I) and, where appropriate, their tautomers may exist, in each case in free form or in salt form, in the form of pure isomers, for example enantiomers and / or diastereomers, depending on the number of asymmetric carbon atoms present in the molecule, their absolute and relative configuration, and / or depending on the configuration of the non-aromatic double bonds present in the molecule, or as a mixture of isomers, for example a racemate, a mixture of diastereomers or a mixture of racemates, in one form of the possible isomers or as a mixture thereof. The invention relates to the pure isomers and also to all possible mixtures of isomers, and is to be understood in this sense above and below, even if the details of the stereochemistry are not specifically described in each case.

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

[0234] Mixtures of enantiomers such as racemates, obtained in a similar manner, can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, chromatography on a chiral adsorbent, for example high performance liquid chromatography (HPLC) on acetylcellulose using a suitable microorganism, cleavage by means of a specific immobilized enzyme via the formation of an inclusion compound using, for example, a chiral crown ether in which only one enantiomer is complexed, or conversion into diastereomeric salts, for example by reacting a basic end product racemate with an optically active acid such as camphoric acid, tartaric acid or malic acid or a sulfonic acid such as camphorsulfonic acid, separating the resulting mixture of diastereomers by fractional crystallization, for example based on different solubilities, to give a diastereomer from which the desired enantiomer can be liberated by the action of a suitable substance, for example a basic substance.

[0235] Pure diastereomers or enantiomers can be obtained according to the present invention not only by separating suitable mixtures of isomers, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the method according to the present invention using starting materials having stereochemical properties.

[0236] The N-oxide can be prepared by reacting a 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 oxidations are known from the literature, for example, J.Med.Chem., 32(12), 2561-73, 1989 or WO 2000 / 15615.

[0237] When the individual components have different biological activities, it is advantageous to isolate or synthesize the more biologically effective isomers, such as enantiomers or diastereomers, or mixtures of isomers, such as mixtures of enantiomers or diastereomers.

[0238] The compounds of formula (I) and, if appropriate, their tautomers can be obtained in each case in free form or in salt form, if appropriate in the form of hydrates, and / or can contain other solvents, for example solvents used for the crystallization of the compounds present in solid form.

[0239] The compounds of formula (I) according to Tables A-1 to A-71 below can be prepared according to the above methods. The following examples are intended to illustrate the present invention and show preferred compounds of formula (I) in the form of compounds of formula I-A.

Chemical formula

[0240] Table A-1 provides 38 compounds of formula I-A, A-1.001 to A-1.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is CF3, R2b is CF3, and Q is as defined in Table Z. For example, compound A-13.003 is [Chemical formula] as follows.

[0241] Table A-2 provides 38 compounds of formula I-A, A-2.001 to A-2.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is CF3, R 2b is Cl, and Q is as defined in Table Z.

[0242] Table A-3 provides 38 compounds of formula I-A, A-3.001 to A-3.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is CF3, R 2b is Br, and Q is as defined in Table Z.

[0243] Table A-4 provides 38 compounds of formula I-A, A-4.001 to A-4.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is Cl, R 2b is CF3, and Q is as defined in Table Z.

[0244] Table A-5 provides 38 compounds of formula I-A, A-5.001 to A-5.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2ais Cl, and R 2b is Cl, and Q is as defined in Table Z.

[0245] Table A-6 provides 38 compounds of formula I-A, A-6.001 to A-6.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is Cl, R 2b is Br, and Q is as defined in Table Z.

[0246] Table A-7 provides 38 compounds of formula I-A, A-7.001 to A-7.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is Br, R 2b is CF3, and Q is as defined in Table Z.

[0247] Table A-8 provides 38 compounds of formula I-A, A-8.001 to A-8.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is Br, R 2b is Cl, and Q is as defined in Table Z.

[0248] Table A-9 provides 38 compounds of formula I-A, A-9.001 to A-9.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is Br, R 2b is Br, and Q is as defined in Table Z.

[0249] Table A-10 provides 38 compounds of formula I-A, A-10.001 to A-10.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, R 2a is SO2-CF3, R 2b is CF3, and Q is as defined in Table Z.

[0250] Table A-11 provides 38 compounds of formula I-A, A-11.001 to A-11.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, R 2a is SO2-CF3, R 2b is Cl, and Q is as defined in Table Z.

[0251] Table A-12 provides 38 compounds of formula I-A, A-12.001 to A-12.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, R 2a is SO2-CF3, R 2b is Br, and Q is as defined in Table Z.

[0252] Table A-13 provides 38 compounds of formula I-A, A-13.001 to A-13.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, R 2a is CF3, R 2b is CF3, and Q is as defined in Table Z.

[0253] Table A-14 provides 38 compounds of formula I-A, A-14.001 to A-14.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, and R 2a is CF3, and R 2b is Cl, and Q is as defined in Table Z.

[0254] Table A-15 provides 38 compounds of formula I-A, A-15.001 to A-15.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, and R 2a is CF3, and R 2b is Br, and Q is as defined in Table Z.

[0255] Table A-16 provides 38 compounds of formula I-A, A-16.001 to A-16.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, and R 2a is Cl, R 2b is CF3, and Q is as defined in Table Z.

[0256] Table A-17 provides 38 compounds of formula I-A, A-17.001 to A-17.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, and R 2a is Cl, R 2b is Cl, and Q is as defined in Table Z.

[0257] Table A-18 provides 38 compounds of formula I-A, A-18.001 to A-18.038, where A 1is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is Cl, and R 2b is Br, and Q is as defined in Table Z.

[0258] Table A-19 provides 38 compounds of formula I-A, A-19.001 to A-19.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is Br, and R 2b is CF3, and Q is as defined in Table Z.

[0259] Table A-20 provides 38 compounds of formula I-A, A-20.001 to A-20.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is Br, and R 2b is Cl, and Q is as defined in Table Z.

[0260] Table A-21 provides 38 compounds of formula I-A, A-21.001 to A-21.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is Br, and R 2b is Br, and Q is as defined in Table Z.

[0261] Table A-22 provides 38 compounds of formula I-A, A-22.001 to A-22.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R1 is CH3, and R 2a is SO2-CF3, and R 2b is CF3, and Q is as defined in Table Z.

[0262] Table A-23 provides 38 compounds of formula I-A, A-23.001 to A-23.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is SO2-CF3, and R 2b is Cl, and Q is as defined in Table Z.

[0263] Table A-24 provides 38 compounds of formula I-A, A-24.001 to A-24.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is SO2-CF3, and R 2b is Br, and Q is as defined in Table Z.

[0264] Table A-25 provides 38 compounds of formula I-A, A-25.001 to A-25.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH2-cyclopropyl, and R 2a is CF3, and R 2b is CF3, and Q is as defined in Table Z.

[0265] Table A-26 provides 38 compounds of formula I-A, A-26.001 to A-26.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH2-cyclopropyl, and R2a is CF3, R 2b is Cl, and Q is as defined in Table Z.

[0266] Table A-27 provides 38 compounds of formula I-A, A-27.001 to A-27.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is CF3, R 2b is Br, and Q is as defined in Table Z.

[0267] Table A-28 provides 38 compounds of formula I-A, A-28.001 to A-28.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Cl, R 2b is CF3, and Q is as defined in Table Z.

[0268] Table A-29 provides 38 compounds of formula I-A, A-29.001 to A-29.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Cl, R 2b is Cl, and Q is as defined in Table Z.

[0269] Table A-30 provides 38 compounds of formula I-A, A-30.001 to A-30.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Cl, R2b is Br, and Q is as defined in Table Z.

[0270] Table A-31 provides 38 compounds of formula I-A, A-31.001 to A-31.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Br, R 2b is CF3, and Q is as defined in Table Z.

[0271] Table A-32 provides 38 compounds of formula I-A, A-32.001 to A-32.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Br, R 2b is Cl, and Q is as defined in Table Z.

[0272] Table A-33 provides 38 compounds of formula I-A, A-33.001 to A-33.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Br, R 2b is Br, and Q is as defined in Table Z.

[0273] Table A-34 provides 38 compounds of formula I-A, A-34.001 to A-34.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is SO2-CF3, R 2bis CF3, and Q is as defined in Table Z.

[0274] Table A-35 provides 38 compounds of formula I-A, A-35.001 to A-35.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is SO2-CF3, R 2b is Cl, and Q is as defined in Table Z.

[0275] Table A-36 provides 38 compounds of formula I-A, A-36.001 to A-36.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is SO2-CF3, R 2b is Br, and Q is as defined in Table Z.

[0276] Table A-37 provides 38 compounds of formula I-A, A-37.001 to A-37.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is CF3, R 2b is SO2-CF3, and Q is as defined in Table Z.

[0277] Table A-38 provides 38 compounds of formula I-A, A-38.001 to A-38.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is Cl, R 2bis SO2-CF3, and Q is as defined in Table Z.

[0278] Table A-39 provides 38 compounds of formula I-A, A-39.001 to A-39.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is Br, R 2b is SO2-CF3, and Q is as defined in Table Z.

[0279] Table A-40 provides 38 compounds of formula I-A, A-40.001 to A-40.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is Cl, R 2b is I, and Q is as defined in Table Z.

[0280] Table A-41 provides 38 compounds of formula I-A, A-41.001 to A-41.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is I, R 2b is Cl, and Q is as defined in Table Z.

[0281] Table A-42 provides 38 compounds of formula I-A, A-42.001 to A-42.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is H, R 2a is Br, R 2b is I, and Q is as defined in Table Z.

[0282] Table A-43 provides 38 compounds of formula I-A, A-43.001 to A-43.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, and R 2a is I, and R 2b is Br, and Q is as defined in Table Z.

[0283] Table A-44 provides 38 compounds of formula I-A, A-44.001 to A-44.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, and R 2a is CF3, and R 2b is I, and Q is as defined in Table Z.

[0284] Table A-45 provides 38 compounds of formula I-A, A-45.001 to A-45.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, and R 2a is I, and R 2b is CF3, and Q is as defined in Table Z.

[0285] Table A-46 provides 38 compounds of formula I-A, A-46.001 to A-46.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, and R 2a is CF3, and R 2b is SO2-CF3, and Q is as defined in Table Z.

[0286] Table A-47 provides 38 compounds of formula I-A, A-47.001 to A-47.038, where A1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is Cl, and R 2b is SO2-CF3, and Q is as defined in Table Z.

[0287] Table A-48 provides 38 compounds of formula I-A, A-48.001 to A-48.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is Br, and R 2b is SO2-CF3, and Q is as defined in Table Z.

[0288] Table A-49 provides 38 compounds of formula I-A, A-49.001 to A-49.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is Cl, and R 2b is I, and Q is as defined in Table Z.

[0289] Table A-50 provides 38 compounds of formula I-A, A-50.001 to A-50.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is I, and R 2b is Cl, and Q is as defined in Table Z.

[0290] Table A-51 provides 38 compounds of formula I-A, A-51.001 to A-51.038, where A 1 is N, and A 2 is CH, and A 3is N, and R 1 is CH3, and R 2a is Br, and R 2b is I, and Q is as defined in Table Z.

[0291] Table A-52 provides 38 compounds of formula I-A, A-52.001 to A-52.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is I, and R 2b is Br, and Q is as defined in Table Z.

[0292] Table A-53 provides 38 compounds of formula I-A, A-53.001 to A-53.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is CF3, and R 2b is I, and Q is as defined in Table Z.

[0293] Table A-54 provides 38 compounds of formula I-A, A-54.001 to A-54.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH3, and R 2a is I, and R 2b is CF3, and Q is as defined in Table Z.

[0294] Table A-55 provides 38 compounds of formula I-A, A-55.001 to A-55.038, where A 1 is N, and A 2 is CH, and A 3 is N, and R 1 is CH2-cyclopropyl, and R 2a is CF3, and R2b is SO2-CF3, and Q is as defined in Table Z.

[0295] Table A-56 provides 38 compounds of formula I-A, A-56.001 to A-56.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Cl, R 2b is SO2-CF3, and Q is as defined in Table Z.

[0296] Table A-57 provides 38 compounds of formula I-A, A-57.001 to A-57.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Br, R 2b is SO2-CF3, and Q is as defined in Table Z.

[0297] Table A-58 provides 38 compounds of formula I-A, A-58.001 to A-58.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Cl, R 2b is I, and Q is as defined in Table Z.

[0298] Table A-59 provides 38 compounds of formula I-A, A-59.001 to A-59.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is I, R 2bis Cl, and Q is as defined in Table Z.

[0299] Table A-60 provides 38 compounds of formula I-A, A-60.001 to A-60.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is Br, R 2b is I, and Q is as defined in Table Z.

[0300] Table A-61 provides 38 compounds of formula I-A, A-61.001 to A-61.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is I, R 2b is Br, and Q is as defined in Table Z.

[0301] Table A-62 provides 38 compounds of formula I-A, A-62.001 to A-62.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is CF3, R 2b is I, and Q is as defined in Table Z.

[0302] Table A-63 provides 38 compounds of formula I-A, A-63.001 to A-63.038, where A 1 is N, A 2 is CH, A 3 is N, R 1 is CH2-cyclopropyl, R 2a is I, R 2b is CF3, and Q is as defined in Table Z.

[0303] Table A-64 provides 38 compounds of formula I-A, A-64.001 to A-64.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, and R 2a is SO2-CHF2, and R 2b is Cl, and Q is as defined in Table Z.

[0304] Table A-65 provides 38 compounds of formula I-A, A-65.001 to A-65.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, and R 2a is SO2-CHF2, and R 2b is Br, and Q is as defined in Table Z.

[0305] Table A-66 provides 38 compounds of formula I-A, A-66.001 to A-66.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, and R 2a is SO2-CHF2, and R 2b is Cl, and Q is as defined in Table Z.

[0306] Table A-67 provides 38 compounds of formula I-A, A-67.001 to A-67.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, and R 2a is SO2-CHF2, and R 2b is Br, and Q is as defined in Table Z.

[0307] Table A-68 provides 38 compounds of formula I-A, A-68.001 to A-68.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, and R 2a is Cl, and R 2b is SO2-CHF2, and Q is as defined in Table Z.

[0308] Table A-69 provides 38 compounds of formula I-A, A-69.001 to A-69.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is H, and R 2a is Br, and R 2b is SO2-CHF2, and Q is as defined in Table Z.

[0309] Table A-70 provides 38 compounds of formula I-A, A-70.001 to A-70.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, and R 2a is Cl, and R 2b is SO2-CHF2, and Q is as defined in Table Z.

[0310] Table A-71 provides 38 compounds of formula I-A, A-71.001 to A-71.038, where A 1 is N, and A 2 is CH, and A 3 is N, R 1 is CH3, and R 2a is Br, and R 2b is SO2-CHF2, and Q is as defined in Table Z.

[0311]

Table 3-1

[0312]

Table 3-2

[0313]

Table 3-3

[0314] Specific intermediate compounds of Formulas II(i), III(i), IV(i), V(i), VII(i), XI(i), and XIV(i) or other intermediate compounds shown in Schemes 1-33 (some of which are novel) are also provided. For example, - Formula II(i)

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0315] [Table 4]

[0316] In particular, compounds of the following formula: - XL-Q ac1 -a, XL-Q ac1 -b and XL-Q ac1 -c: [Chemical formula] - XL-Q ac2 -a, XL-Q ac2 -b and XL-Q ac2 -c:

Chem.

Chem.

Chem.

[0317] - Formula XL-Q bc -a, XL-Q bc -b or XL-Q bc -c:

Chem.

[0318] - Formula XLIIIa(i), XLIIIb(i), XLIIIb-1(i), XLIIId(i) or XLIIIe(i):

Chemical formula

[0319] In a further aspect, the invention thus provides compounds of formula II(i), III(i), IV(i), V(i), VII(i), XI(i) and XIV(i) (wherein in each case, where applicable, A 1 , A 2 , A 3 , A 4 , A 5 , R 1 , R 2a and R 2b and Q are as defined in formula (I) in the first aspect; and for formula II(i), X 1provides (a halogen, preferably chloro or bromo). Further, the corresponding embodiments illustrated for formula (I) also apply to the compounds of formula II(i), III(i), IV(i), V(i), VII(i), XI(i) and XIV(i).

[0320] In a further aspect, the invention thus provides compounds of the formula XL-Q ac -a, XL-Q ac -b, XL-Q ac -c, XL-Q bc -a, XL-Q bc -b and XL-Q bc -c (wherein, in each case, where applicable, A 1 , A 2 , A 3 , A 4 , A 5 , R 1 , R 2a and R 2b and Q are as defined in formula (I) in the first aspect; and for the compounds of formula XL-Q ac -b, XL-Q ac -c, XL-Q bc -b and XL-Q bc -c, Ra is benzyl or C1-C6 alkyl, preferably Ra is methyl, and Xa is a halogen, for example Br, Cl or I, preferably Cl). Further, the corresponding embodiments illustrated for formula (I) also apply to the compounds of formula XL-Q ac -a, XL-Q ac -b, XL-Q ac -c, XL-Q bc -a, XL-Q bc -b and XL-Q bc -c.

[0321] In a further aspect, the invention thus provides compounds of the formula XLIIIa(i), XLIIIb(i), XLIIIb-1(i), XLIIId(i) or XLIIIe(i) (wherein, in each case, where applicable, A 4 , A 5 and R 2ais as defined in formula (I) in the first aspect; and Gr is difluoromethyl or trifluoromethyl). Further, the corresponding embodiments exemplified for formula (I) also apply to the compounds of formula XLIIIa(i), XLIIIb(i), XLIIIb-1(i), XLIIId(i) or XLIIIe(i).

[0322] The compounds of formula (I) according to the present invention are active ingredients that are prophylactically and / or therapeutically beneficial in the field of pest control even at low application rates, which have a very favorable biocidal spectrum and are well tolerated by warm-blooded animal species, fish and plants. The active ingredients according to the present invention act not only on normal sensitive animal pests such as representatives of insects or the order Acarina, but also on all or individual developmental stages of resistant animal pests. The insecticidal or acaricidal activity of the active ingredients according to the present invention may appear directly, i.e., immediately or only after some time has elapsed, for example as the destruction of pests occurring during molting or indirectly, for example as a reduced egg-laying and / or hatching rate.

[0323] Examples of the above animal pests are as follows: From the order Acarina, for example,[[]] From the genera Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp, Acarus siro, Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp., Bryobia spp, Calipitrimerus spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides spp, Eotetranychus spp, Eriophyes spp., Hemitarsonemus spp, Hyalomma spp., Ixodes spp., Olygonychus spp, Ornithodoros spp., Polyphagotarsone latus, Panonychus spp., Phyllocoptruta oleivora, Phytonemus spp, Polyphagotarsonemus spp, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Steneotarsonemus spp, Tarsonemus spp. and Tetranychus spp; From the order Anoplura, for example, Genus Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp. and Phylloxera spp.; From Coleoptera, for example, Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus spp., Aphodius spp, Astylus atromaculatus, Ataenius spp, Atomaria linearis, Chaetocnema tibialis, Cerotoma spp, Conoderus spp, Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp, Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna spp., Eremnus spp., Heteronychus arator, Hypothenemus hampei, Lagria vilosa, Leptinotarsa decemLineata, Lissorhoptrus spp., Liogenys spp, Maecolaspis spp, Maladera castanea, Megascelis spp, Melighetes aeneus, Melolontha spp., Myochrous armatus, Orycaephilus spp., Otiorhynchus spp., Phyllophaga spp, Phlyctinus spp., Popillia spp)、Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp., Scarabeidae, Sitophilus spp., Sitotroga spp., Somaticus spp, Sphenophorus spp, Sternechus subsignatus, Tenebrio spp., Tribolium spp. and Trogoderma spp.;. From Diptera, for example, Aedes spp., Anopheles spp, Antherigona soccata, Bactrocea oleae, Bibio hortulanus, Bradysia spp, Calliphora erythrocephala, Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus spp., Delia spp, Drosophila melanogaster, Fannia spp., Gastrophilus spp., Geomyza tripunctata, Glossina spp., Hypoderma spp., Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp., Orseolia spp., Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Rhagoletis spp, Rivelia quadrifasciata, Scatella spp, Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp. and Tipula spp.; from 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, Agonoscena targionii, Aleurodicus spp, Aleurocanthus spp, Aleurolobus barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca biguttula, Amritodus atkinsoni, Aonidiella spp., Aphididae, Aphis spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli, Bemisia spp, Brachycaudus spp, Brevicoryne brassicae, Cacopsylla spp, Cavariella aegopodii Scop., Ceroplaster spp)、Chrysomphalus aonidium, Chrysomphalus dictyospermi, Cicadella spp, Cofana spectra, Cryptomyzus spp, Cicadulina spp, Coccus hesperidum, Dalbulus maidis, Dialeurodes spp, Diaphorina citri, Diuraphis noxia, Dysaphis spp, Empoasca spp., Eriosoma larigerum, Erythroneura spp., Gascardia spp., Glycaspis brimblecombei, Hyadaphis pseudobrassicae, Hyalopterus spp, Hyperomyzus pallidus, Idioscopus clypealis, Jacobiasca lybica, Laodelphax spp., Lecanium corni, Lepidosaphes spp., Lopaphis erysimi, Lyogenys maidis, Macrosiphum spp., Mahanarva spp, Metcalfa pruinosa, Metopolophium dirhodum, Myndus crudus, Myzus spp)、Neotoxoptera 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., Pseudatomoscelis seriatus, Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp., Quesada gigas, Recilia dorsalis, Rhopalosiphum spp., Saissetia spp., Scaphoideus spp., Schizaphis spp., Sitobion spp)、Brown planthopper (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, Acromyrmex, Arge spp, Atta spp., Cephus spp., Diprion spp., Diprionidae, Gilpinia polytoma, Hoplocampa spp., Lasius spp., Monomorium pharaonis, Neodiprion spp., Pogonomyrmex spp, Slenopsis invicta, Solenopsis spp. and Vespa spp.; From the order Isoptera, for example, Coptotermes spp, Corniternes cumulans, Incisitermes spp, Macrotermes spp, Mastotermes spp, Microtermes spp, Reticulitermes spp.; Solenopsis geminate From the order Lepidoptera, for example, Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp., Argyresthia spp, Argyrotaenia spp., Autographa spp., Bucculatrix thurberiella, Busseola fusca, Cadra cautella, Carposina nipponensis, Chilo spp., Choristoneura spp., Chrysoteuchia topiaria, Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp., Cochylis spp., Coleophora spp., Colias lesbia, Cosmophila flava, Crambus spp, Crocidolomia binotalis, Cryptophlebia leucotreta, Cydalima perspectalis, 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)、Panolis flammea, Papaipema nebris, Pectinophora gossypiela, Perileucoptera coffeella, Pseudaletia unipuncta, Phthorimaea operculella, Pieris rapae, Pieris spp., Plutella xylostella, Prays spp., Pseudoplusia spp, Rachiplusia nu, Richia albicosta, Scirpophaga spp., Sesamia spp., Sparganothis spp., Spodoptera spp., Sylepta derogate, Synanthedon spp., Thaumetopoea spp., Tortrix spp., Trichoplusia ni, Tuta absoluta and Yponomeuta spp.;. From the order Mallophaga, for example, Damalinea spp. and Trichodectes spp.; From the order Orthoptera, for example, Cockroaches (Blatta spp.), German cockroaches (Blattella spp.), mole crickets (Gryllotalpa spp.), Madeira cockroach (Leucophaea maderae), locusts (Locusta spp.), six-spotted green tiger beetle (Neocurtilla hexadactyla), American cockroaches (Periplaneta spp.), mole crickets (Scapteriscus spp) and grasshoppers (Schistocerca spp.); From the order Psocoptera, for example, Booklice (Liposcelis spp.); From the order Siphonaptera, for example, Horn fleas (Ceratophyllus spp.), cat fleas (Ctenocephalides spp.) and oriental rat fleas (Xenopsylla cheopis); From the order Thysanoptera, for example, Bean thrips (Calliothrips phaseoli), flower thrips (Frankliniella spp.), sunflower thrips (Heliothrips spp), Hercinothrips spp., Parthenothrips spp, citrus thrips (Scirtothrips aurantii), soybean thrips (Sericothrips variabilis), Taeniothrips spp., thrips (Thrips spp); From the order Thysanura, for example, silverfish (Lepisma saccharina).

[0324] In a further aspect, the present invention relates to plant parasitic nematodes (endoparasitic, semi-endoparasitic and ectoparasitic nematodes), in particular root knot nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, Meloidogyne arenaria and other species of the genus Meloidogyne; cyst-forming nematodes, Globodera rostochiensis and other species of the genus Globodera; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii and other species of the genus Heterodera; seed gall nematodes, species of the genus Anguina; Aphelenchoides species, such as the stem nematode and the foliar nematode; sting nematodes, Belonolaimus longicaudatus and other species of the genus Belonolaimus; pine wood nematodes, Bursaphelenchus xylophilus and other species of the genus Bursaphelenchus; ring nematodes, Criconema species, Criconemella species, Criconemoides species, Mesocriconema species; stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci and other species of the genus Ditylenchus; needle nematodes, Dolichodorus species;Lacc nematodes, Heliocotylenchus multicinctus and other species of the genus Helicotylenchus; sheath and sheathoid nematodes, species of the genus Hemicycliophora and species of the genus Hemicriconemoides; species of the genus Hirshmanniella; spear nematodes, species of the genus Hoploaimus; false root-knot nematodes, species of the genus Nacobbus; needle nematodes, Longidorus elongatus and other species of the genus Longidorus; pin nematodes, species of the genus Pratylenchus; Pratylenchus neglectus, Pratylenchus penetrans, Pratylenchus curvitatus, Pratylenchus goodeyi and other species of the genus Pratylenchus; burrowing nematodes, Radopholus similis and other species of the genus Radopholus; false root-knot nematodes, Rotylenchus robustus, Rotylenchus reniformis and other species of the genus Rotylenchus; species of the genus Scutellonema; stubby-root nematodes, Trichodorus primitivus and other species of the genus Trichodorus, species of the genus Paratrichodorus;Damage to plants and parts thereof by plant parasitic nematodes such as Hirschmanniella spp., Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other species of the genus Tylenchorhynchus; Tylenchulus spp., species of the genus Tylenchulus; plant parasitic nematodes such as Longidorus spp., species of the genus Xiphinema; and other plant parasitic nematode species such as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp. and Quinisulcius spp. may also be related to a method for preventing such damage.;

[0325] The compounds of the present invention may also be active against mollusks. Examples thereof include, for example, Ampullariidae; Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus); Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba (G. trunculata); Helicelia (H. itala, H. obvia); Helicidae (Helicigona arbustorum); Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Lymnaea; Milax (M. gagates, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides.

[0326] The active ingredient according to the invention can be used to control, i.e. inhibit or destroy, pests of the above type which occur in particular in plants, in particular 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 optionally also later-formed plant organs remain protected from these pests.

[0327] Suitable target crops are in particular cereals such as wheat, barley, rye, oats, rice, maize or sorghum; beet such as sugar beet or fodder beet; fruits such as apples, pears, plums, peaches, almonds, cherries or soft fruits such as strawberries, raspberries or blackberries, i.e. pomaceous fruits, stone fruits or soft fruits; leguminous crops such as kidney beans, lentils, peas or soybeans; oil crops such as rapeseed, mustard, poppy, olive, sunflower, coconut, castor oil plant, cocoa or groundnut; cucurbitaceous plants such as pumpkins, cucumbers or melons; fibre plants such as cotton, flax, hemp or jute; citrus fruits such as oranges, lemons, grapefruits or tangerines; vegetables such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes or peppers; plants of the family Lauraceae such as avocado, cinnamon or camphor; and furthermore tobacco, nuts, coffee, aubergines, sugar cane, tea, pepper, grapes, hops, plants of the family Urticaceae and latex plants.

[0328] The compositions and / or methods of the invention can also be used in any ornamental and / or vegetable crops including flowers, shrubs, broad-leaved trees and evergreen trees.

[0329] For example, the present invention relates to the following ornamental species: species of Ageratum spp., Alonsoa spp., Anemone spp., Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster spp., Begonia spp. (e.g., B. elatior, B. semperflorens, B. tubereux), Bougainvillea spp., Brachycome spp., 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, Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia spp., Geranium gnaphalium, Gerbera spp., Gomphrena globosa, Heliotropium spp., Helianthus spp., Hibiscus spp.) species of the genus Hortensia (Hortensia spp.), species of the genus Hydrangea (Hydrangea spp.), Hypoestes phyllostachya, species of the genus Impatiens (Impatiens spp.) (Impatiens walleriana), species of the genus Iresines (Iresines spp.), species of the genus Kalanchoe (Kalanchoe spp.), Lantana camara, Lavatera trimestris, Leonotis leonurus, species of the genus Lilium (Lilium spp.), species of the genus Mesembryanthemum (Mesembryanthemum spp.), species of the genus Mimulus (Mimulus spp.), species of the genus Monarda (Monarda spp.), species of the genus Nemesia (Nemesia spp.), species of the genus Tagetes (Tagetes spp.), species of the genus Dianthus (Dianthus spp.) (carnation), species of the genus Canna (Canna spp.), species of the genus Oxalis (Oxalis spp.), species of the genus Bellis (Bellis spp.), species of the genus Pelargonium (Pelargonium spp.) (ivy geranium (P. peltatum), zonal geranium (P. zonale)), species of the genus Viola (Viola spp.) (pansy), species of the genus Petunia (Petunia spp.), species of the genus Phlox (Phlox spp.), species of the genus Plecthranthus (Plecthranthus spp.), species of the genus Poinsettia (Poinsettia spp.), species of the genus Parthenocissus (Parthenocissus spp.) (Virginia creeper (P. quinquefolia), Japanese ivy (P. tricuspidata)), species of the genus Primula (Primula spp.), species of the genus Ranunculus (Ranunculus spp.), species of the genus Rhododendron (Rhododendron spp.), species of the genus Rosa (Rosa spp.) (rose), species of the genus Rudbeckia (Rudbeckia spp.), species of the genus Saintpaulia (Saintpaulia spp.), species of the genus Salvia (Salvia spp.) can be used with any of Scaevola aemola, Schizanthus wisetonensis, Sedum spp., Solanum spp., Surfinia spp., Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp. and other flower bed plants.

[0330] For example, the present invention relates to the following vegetable species: species of the genus Allium (Allium spp.) (garlic (A. sativum), onion (A. cepa), shallot (A. oschaninii), leek (A. Porrum), scallion (A. ascalonicum), Welsh onion (A. fistulosum)), chervil (Anthriscus cerefolium), celery (Apium graveolus), asparagus (Asparagus officinalis), beet (Beta vulgarus), species of the genus Brassica (Brassica spp.) (cabbage (B. Oleracea), Chinese cabbage (B. Pekinensis), turnip (B. rapa)), capsicum (Capsicum annuum), chickpea (Cicer arietinum), endive (Cichorium endivia), species of the genus Cichorium (Cichorium spp.) (chicory (C. intybus), endive (C. endivia)), watermelon (Citrillus lanatus), species of the genus Cucumis (Cucumis spp.) (cucumber (C. sativus), melon (C. melo)), species of the genus Cucurbita (Cucurbita spp.) (summer squash (C. pepo), winter squash (C. maxima)), species of the genus Cyanara (Cyanara spp.) (artichoke (C. scolymus), cardoon (C. cardunculus)), carrot (Daucus carota), fennel (Foeniculum vulgare), species of the genus Hypericum, lettuce (Lactuca sativa), species of the genus Lycopersicon (Lycopersicon spp.) (tomato (L. esculentum), tomato (L. lycopersicum)), species of the genus Mentha, basil (Ocimum basilicum), parsley (Petroselinum crispum), species of the genus Phaseolus (Phaseolus spp.) (kidney bean (P. vulgaris), red bean (P.It can be used with any of coccineus), Pisum sativum, Raphanus sativus, Rheum rhaponticum, species of Rosmarinus, species of Salvia, Scorzonera hispanica, Solanum melongena, Spinacea oleracea, species of Valerianella (V. locusta, V. eriocarpa) and Vicia faba.

[0331] Preferred ornamental species include Saintpaulia, Begonia, Dahlia, Gerbera, Hydrangea, Kalmia, Rosa, Kalanchoe, Poinsettia, Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia, Sedum, Petunia, Viola, Primula, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Salvia, Hydrangea macrophylla, Rosemary, Sage, Valerianella locusta, Mint, Capsicum annuum, Tomato and Cucumber.

[0332] The active ingredient according to the present invention is particularly suitable for controlling Aphis craccivora, Diabrotica balteata, Heliothis virescens, Myzus persicae, Plutella xylostella and Spodoptera littoralis in cotton, vegetables, corn, rice and soybean crops. The active ingredient according to the present invention is further particularly suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatoes) and Chilo supressalis (preferably in rice).

[0333] The compound of formula (I) is particularly suitable for the following control. · One or more species of pests of the Hemiptera order, such as Bemisia tabaci, Aphis craccivora, Myzus persicae, Rhopalosiphum padi, Nilaparvata lugens and Euschistus heros (preferably in vegetables, soybeans and sugarcane); · One or more species of pests of the order Lepidoptera, such as Spodoptera littoralis, Spodoptera frugiperda, Plutella xylostella, Cnaphalocrocis medinalis, Cydia pomonella, Chrysodeixis includes, Chilo suppressalis, Elasmopalpus lignosellus, Pseudoplusia includens and Tuta absoluta (preferably those in vegetables and corn); · One or more species of pests of the order Thysanoptera, such as those of the family Thripidae, for example Thrips tabaci and Frankliniella occidentalis (preferably those in vegetables); and · Soil pests (such as those of the order Coleoptera), for example Diabrotica balteata, species of the genus Agriotes and Leptinotarsa decemLineata (preferably those in vegetables and corn).

[0334] It should be understood that the term "crop" also includes crops transformed by the use of recombinant DNA technology such that they are capable of synthesizing one or more selectively acting toxins, known, for example, from toxin-producing bacteria, in particular bacteria of the genus Bacillus.

[0335] Examples of toxins that can 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 or vegetative insecticidal proteins (Vip) derived from Bacillus thuringiensis, such as Vip1, Vip2, Vip3 or Vip3A; or insecticidal proteins of Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens or Xenorhabdus nematophilus, which are bacterial colony-forming nematodes; toxins produced by animals, such as scorpion toxins, spider-like toxins, bee toxins and other neurotoxins specific to insects; toxins produced by fungi, such as Streptomycetes toxins, plant lectins such as lectin, barley lectin or snowdrop lectin; lectins; protease inhibitors such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome-inactivating proteins (RIP) such as ricin, corn-RIP, abrin, luffin, saporin or bryodin; steroid-metabolizing enzymes such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers such as sodium channel or calcium channel blockers, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinase and glucanase.

[0336] With respect to the present invention, δ-endotoxins are understood, for example, to be Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C or vegetative insecticidal proteins (Vips), such as Vip1, Vip2, Vip3 or Vip3A, and also explicitly hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by new combinations of different domains of those proteins (see, for example, WO 02 / 15701). Truncated toxins, such as truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the natural toxin are replaced. In such amino acid substitutions, preferably a protease recognition sequence not occurring naturally is inserted into the toxin, for example, in the case of Cry3A055, a cathepsin-G-recognition sequence is inserted into the Cry3A toxin (see WO 03 / 018810).

[0337] Examples of such toxins or transgenic plants capable of synthesizing such toxins are disclosed, for example, in EP 0 374 753, WO 93 / 07278, WO 95 / 34656, EP 0 427 529, EP 451 878 and WO 03 / 052073.

[0338] Methods for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the abovementioned publications. CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95 / 34656, EP 0 367 474, EP 0 401 979 and WO 90 / 13651.

[0339] The toxins contained in transgenic plants confer resistance to pests on the plants. Such insects are found in insect taxa, but are particularly commonly found in beetles (Coleoptera), dipterous insects (Diptera) and moths (Lepidoptera).

[0340] Transgenic plants that encode insecticidal resistance and contain one or more genes that express one or more toxins are known, and some of them are commercially available. Examples of such plants are YieldGard® (maize variety expressing the Cry1Ab toxin); YieldGard Rootworm® (maize variety expressing the Cry3Bb1 toxin); YieldGard Plus® (maize variety expressing the Cry1Ab and Cry3Bb1 toxins); Starlink® (maize variety expressing the Cry9C toxin); Herculex I® (maize variety expressing the Cry1Fa2 toxin and the enzyme phosphinothricin N-acetyltransferase (PAT) to obtain resistance to the herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety expressing the Cry1Ac toxin); Bollgard I® (cotton variety expressing the Cry1Ac toxin); Bollgard II® (cotton variety expressing the Cry1Ac and Cry2Ab toxins); VipCot® (cotton variety expressing the Vip3A and Cry1Ab toxins); NewLeaf® (potato variety expressing the Cry3A toxin); NatureGard®, Agrisure® GT Advantage (GA21 glyphosate tolerance trait), Agrisure® CB Advantage (Bt11 European corn borer (CB) trait) and Protecta®.

[0341] Further examples of such transgenic crops are as follows: 1. Bt11 maize produced by Syngenta Seeds SAS (Chemin de l’Hobit 27, F-31 790 St. Sauveur, France), registration number C / FR / 96 / 05 / 10. A genetically modified maize that confers resistance to attack by European corn borers (Ostrinia nubilalis and Sesamia nonagrioides) through transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also expresses the enzyme PAT recombinantly to obtain resistance to the herbicide glufosinate ammonium.

[0342] 2. Bt176 maize produced by Syngenta Seeds SAS (Chemin de l’Hobit 27, F-31 790 St. Sauveur, France), registration number C / FR / 96 / 05 / 10. A genetically modified maize that confers resistance to attack by European corn borers (Ostrinia nubilalis and Sesamia nonagrioides) through transgenic expression of a Cry1Ab toxin. Bt176 maize also expresses the enzyme PAT recombinantly to obtain resistance to the herbicide glufosinate ammonium.

[0343] 3. MIR604 maize produced by Syngenta Seeds SAS (Chemin de l’Hobit 27, F-31 790 St. Sauveur, France), registration number C / FR / 96 / 05 / 10. A maize made insect-resistant through transgenic expression of a modified Cry3A toxin. This 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 No. WO 03 / 018810.

[0344] 4. MON 863 maize, registered number C / DE / 02 / 9, produced by Monsanto Europe S.A. (270-272 Avenue de Tervuren, B-1150 Brussels, Belgium). MON 863 expresses the Cry3Bb1 toxin and has resistance to certain Coleoptera insects.

[0345] 5. IPC 531 cotton, registered number C / ES / 96 / 02, produced by Monsanto Europe S.A. (270-272 Avenue de Tervuren, B-1150 Brussels, Belgium).

[0346] 6. 1507 maize, registered number C / NL / 00 / 10, produced by Pioneer Overseas Corporation (Avenue Tedesco, 7 B-1160 Brussels, Belgium). Genetically modified maize variety for the expression of the protein Cry1F to obtain resistance to certain Lepidoptera insects and the PAT protein to obtain resistance to the herbicide glufosinate ammonium.

[0347] 7. NK603×MON 810 maize, registered number C / GB / 02 / M3 / 03, produced by Monsanto Europe S.A. (270-272 Avenue de Tervuren, B-1150 Brussels, Belgium). Consists of a hybrid maize variety bred by the conventional method of crossing the genetically modified varieties NK603 and MON 810. NK603×MON 810 maize also expresses by genetic recombination the protein CP4 EPSPS obtained from the Agrobacterium sp. strain CP4, which confers 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.

[0348] Transgenic crops of insect-tolerant plants are also described in BATS (Zentrum fuer Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report 2003, (http: / / bats.ch).

[0349] The term "crop" is to be understood to include crops transformed by the use of recombinant DNA techniques such that they are able to synthesize, for example, so-called "pathogenesis-related proteins" (PRPs, see for example European Patent Application Publication No. 0392225), which are anti-pathogenic substances having a selective action. Examples of such anti-pathogenic substances and transgenic plants capable of synthesizing such anti-pathogenic 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 above publications.

[0350] Crops can also be improved to enhance resistance to fungal (e.g., Fusarium, anthracnose or Phytophthora), bacterial (e.g., Pseudomonas) or viral (e.g., potato leafroll virus, tomato yellow necrosis virus, cucumber mosaic virus) pathogens.

[0351] Crops include those having high resistance to nematodes such as soybean cyst nematode.

[0352] Crops that are resistant to abiotic stress include, for example, those having high resistance to drought, high salinity, high temperature, low temperature, frost or light by virtue of the expression of NF-YB or other proteins known in the art.

[0353] Examples of anti-pathogenic substances that can be expressed by such transgenic plants include, for example, ion channel blockers such as sodium channel or calcium channel blockers, such as viral KP1, KP4 or KP6 toxins; stilbene synthase; bibenzyl synthase; chitinase; glucanase; so-called "pathogenesis-related proteins" (PRPs; see, for example, European Patent Application Publication No. 0392225); anti-pathogenic 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" described in International Publication No. 03 / 000906).

[0354] A further field of use of the compositions according to the invention is the protection of stored products and storage rooms and raw materials (such as wood and textiles), floor coverings and buildings and the protection of humans, livestock and productive livestock from pests of the above type, especially in the field of hygiene.

[0355] The present invention provides a compound of the first aspect for use in therapy. The present invention provides a compound of the first aspect for use in controlling endoparasites in or on animals. The present invention further provides a compound of the first aspect for use in controlling ectoparasites on animals. The present invention further provides a compound of the first aspect for use in preventing and / or treating diseases infected by ectoparasites.

[0356] The present invention provides the use of a compound of the first aspect for the manufacture of a medicament for controlling endoparasites in or on animals. The present invention further provides the use of a compound of the first aspect for the manufacture of a medicament for controlling ectoparasites on animals. The present invention further provides the use of a compound of the first aspect for the manufacture of a medicament for preventing and / or treating diseases infected by ectoparasites.

[0357] The present invention provides the use of a compound of a first aspect in the control of parasites in or on an animal. The present invention further provides the use of a compound of a first aspect in the control of ectoparasites on an animal.

[0358] When used in relation to a parasite in or on an animal, the term "control" refers to the reduction in the number of pests or parasites, the extermination of pests or parasites and / or the prevention of further pest or parasite infestation.

[0359] When used in relation to a parasite in or on an animal, the term "treat" refers to the suppression, delay, arrest or regression of the progression or severity of an existing condition or disease.

[0360] When used in relation to a parasite in or on an animal, the term "prevent" refers to the avoidance of a condition or disease that is developing within the animal.

[0361] When used in relation to a parasite in or on an animal, the term "animal" can refer to mammals and non-mammals such as birds or fish. In the case of mammals, this can be a human or a non-human mammal. Non-human mammals include, but are not limited to, domestic animals and companion animals. Domestic animals include, but are not limited to, cows, camelids, pigs, sheep, goats and horses. Companion animals include, but are not limited to, dogs, cats and rabbits.

[0362] A "parasite" is a harmful organism that lives within or on a host animal and benefits from nutrients obtained at the expense of the host animal. An "endoparasite" is a parasite that lives inside the host animal. An "ectoparasite" is a parasite that lives on the host animal. Ectoparasites include, but are not limited to, mites, insects, and crustaceans (e.g., fish lice). The subclass Acari (or Acarina) includes ticks and mites. Ticks include, but are not limited to, members of the following genera: Rhipicaphalus, e.g., Rhipicaphalus (Boophilus) microplus and Rhipicephalus sanguineus; Amblyomma; Dermacentor; Haemaphysalis; Hyalomma; Ixodes; Rhipicentor; Margaropus; Argas; Otobius; and Ornithodoros. Mites include, but are not limited to, members of the following genera: Chorioptes, e.g., Chorioptes bovis; Psoroptes, e.g., Psoroptes ovis; Cheyletiella; Dermanyssus, e.g., Dermanyssus gallinae; Ornithonyssus; Demodex, e.g., Demodex canis; Sarcoptes, e.g., Sarcoptes scabiei; and Psorergates.Insects include, but are not limited to, members of the following orders: Siphonaptera, Diptera, Mallophaga, Lepidoptera, Coleoptera, and Homoptera. Members of the order Siphonaptera include, but are not limited to, Ctenocephalides felis and Ctenocephatides canis. Members of the order Diptera include, but are not limited to, species of the genus Musca; bot flies, such as Gasterophilus intestinalis and Oestrus ovis; horse flies; mosquitoes, such as species of the genus Haematopota and species of the genus Tabunus; species of the genus Haematobia, such as Haematobia irritans; species of the genus Stomoxys; species of the genus Lucilia; midges; and mosquitoes. Members of the order Mallophaga include, but are not limited to, sucking lice and biting lice, such as Bovicola Ovis and Bovicola Bovis.

[0363] When used in connection with a parasite in or on an animal, the term "effective amount" refers to the amount or dosage of a compound of the invention or a salt thereof which, upon single or multiple dosages to the animal, results in the desired effect in or on the animal. The effective amount can be readily determined by the attending diagnostician, as a person skilled in the art, by observing the use of known techniques and the results obtained in similar circumstances. In determining the effective amount, the attending diagnostician will consider a number of factors including, but not limited to, the mammalian species; its size, age and general health; the parasite to be controlled and the extent of the infestation; the particular disease or disorder involved; the involvement or severity of the disease or disorder; the response of the solid; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dosage regimen selected; the use of concomitant medications; and other relevant circumstances.

[0364] The compounds of the present invention can be administered to animals by any route having the desired effect, including but not limited to, topical, oral, parenteral, and subcutaneous routes. Topical administration is preferred. Formulations suitable for topical administration include, for example, solutions, emulsions, and suspensions, and can be in the form of pour-ons, spot-ons, spray-ons, spray races, or dips. Alternatively, the compounds of the present invention can be administered by ear tags or collars.

[0365] The salt forms of the compounds of the present invention include both pharmaceutically acceptable salts and veterinarily acceptable salts, which may differ from agrochemically acceptable salts. Pharmaceutically and veterinarily acceptable salts and general methodologies for their preparation are well known in the art. See, for example, Gould, P.L., “Salt selection for basic drugs”, International Journal of Pharmaceutics, 33:201-217 (1986); Bastin, R.J., et al. “Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities”, Organic Process Research and Development, 4:427-435 (2000); and Berge, S.M., et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Sciences, 66:1-19, (1977). Those skilled in the art of synthesis will understand that the compounds of the present invention can be readily converted to salts such as hydrochloride salts using techniques and conditions well known to those skilled in the art and isolated as such salts. 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 isolated as such salts.

[0366] The present invention also provides a method for controlling pests (such as mosquitoes and other disease vector animals; also see http: / / www.who.int / malaria / vector_control / irs / en / ). In one embodiment, the method for controlling pests includes applying the composition of the present invention to a target pest, its habitat, or a surface or substrate by brush application, roller application, spraying, coating, or dipping. As an example, IRS (indoor residual spraying) application to surfaces such as walls, ceilings, or floors is contemplated by the method of the present invention. In another embodiment, it is contemplated to apply such a composition to a substrate such as a non-woven or fabric material in the form of a net, clothing, bedding, curtain, and tent (or in a form that can be used in the manufacture thereof).

[0367] In one embodiment, the method for controlling such pests includes applying a pesticidally 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 residual pesticidal activity to the surface or substrate. Such application can be effected by brush application, roller application, spraying, coating, or dipping the pesticidal composition of the present invention. As an example, IRS application on a surface such as a wall, ceiling, or floor is contemplated by the method of the present invention so as to impart effective residual pesticidal activity to the surface. In another embodiment, it is contemplated to apply such a composition for residual control of pests on a substrate such as a fabric material in the form of a net, clothing, bedding, curtain, and tent (or in a form that can be used in the manufacture thereof).

[0368] The substrate comprising the nonwoven fabric, fabric or net to be treated can be made of natural fibers such as cotton, raffia, jute, linen, sisal, hemp or wool, or synthetic fibers such as polyamide, polyester, polypropylene, polyacrylonitrile. Polyester is particularly preferred. The methods of fabric treatment are known, for example, from WO 2008 / 151984, WO 2003 / 034823, US Patent No. 5,631,072, WO 2005 / 64072, WO 2006 / 128870, European Patent No. 1,724,392, WO 2005113886 or WO 2007 / 090739.

[0369] A further field of use of the composition according to the invention is the field of trunk injection / trunk treatment of all ornamental trees as well as trees bearing all kinds of fruit trees and nuts.

[0370] In the field of trunk injection / trunk treatment, the compounds according to the invention are particularly suitable against the above-mentioned wood-boring insects of the order Lepidoptera and Coleoptera, in particular the woodborers listed in Tables A and B below.

[0371] [Table 5]

[0372] [Table 6-1]

[0373] [Table 6-2]

[0374] The present invention can be used to control any insect pests that may be present in turfgrass, including, for example, beetles, grubs, billbugs, ground pearls, mole crickets, cutworms, mites, scale insects, chafers, sod webworms, chinch bugs, and earthworms. The present invention can also be used to control insect pests at various stages of the life cycle, including eggs, larvae, nymphs, and adults.

[0375] In particular, the present invention can be used to control insect pests that feed on the roots of turfgrass, including earthworms (Cyclocephala spp. (e.g., masked chafer, C. lurida), Rhizotrogus spp. (e.g., European chafer, R. majalis), Cotinus spp. (e.g., green June beetle, C. nitida), Popillia spp. (e.g., Japanese beetle, P. japonica), Phyllophaga spp. (e.g., May / June beetle), Ataenius spp. (e.g., Black turfgrass ataenius, A. spretulus), Maladera spp. (e.g., Asiatic garden beetle, M. castanea), and Tomarus spp., etc.), ground pearls (Margarodes spp.), mole crickets (tawny, southern, and short-winged; Scapteriscus spp., Gryllotalpa africana), and leatherjackets (European crane fly, Tipula spp.).

[0376] The present invention can also be used to control insect pests of turfgrass that live in straw, including fall armyworm (Spodoptera frugiperda and common armyworm (such as Pseudaletia unipuncta)), cutworms, billbugs (such as Sphenophorus spp., S. venatus verstitus, and S. parvulus), and sod webworms (such as Crambus spp. and tropical sod webworm, Herpetogramma phaeopteralis).

[0377] The present invention can also be used to control insect pests that inhabit the ground and feed on the leaves of turfgrass, including chinch bugs (such as Blissus insularis), mites of Bermudagrass (Eriophyes cynodoniensis), scale insects of Rhodesgrass (Antonina graminis), two-lined spittlebug (Propsapia bicincta), leafhoppers, cutworms (Noctuidae), and wheat aphids.

[0378] The present invention can also be used to control other pests of turfgrass, such as red imported fire ants (Solenopsis invicta) that create ant mounds in lawns.

[0379] In the field of hygiene, the composition according to the invention is effective against external parasites such as hard ticks, soft ticks, sarcoptic mites, chiggers, flies (stab flies and licking flies), parasitic fly larvae, lice, bed bugs, fleas and mosquitoes.

[0380] Examples of such parasites are as follows: Among the order Anoplurida, the genera Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp., and Solenopotes spp.

[0381] Among the order Mallophagida, the genera Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp., and Felicola spp.

[0382] Among the Diptera and its suborders Nematocerina and Brachycerina, for example, Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena spp., and Melophagus spp.

[0383] Among the Siphonapterida, for example, Pulex spp., Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp.

[0384] Among Heteropterida, for example, Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp.

[0385] Among Blattarida, for example, Blatta orientalis, Periplaneta americana, Blattela germanica, and Supella spp.

[0386] Among Acaria (Acarida), Metastigmata, and Mesostigmata, for example, Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp., and Varroa spp.

[0387] Among the mite order Actinedida (Prostigmata) and the tick order Acaridida (Astigmata), for example, the genus Acarapis spp., the genus Cheyletiella spp., the genus Ornithocheyletia spp., the genus Myobia spp., the genus Psorergates spp., the genus Demodex spp., the genus Trombicula spp., the genus Listrophorus spp., the genus Acarus spp., the genus Tyrophagus spp., the genus Caloglyphus spp., the genus Hypodectes spp., the genus Pterolichus spp., the genus Psoroptes spp., the genus Chorioptes spp., the genus Otodectes spp., the genus Sarcoptes spp., the genus Notoedres spp., the genus Knemidocoptes spp., the genus Cytodites spp. and the genus Laminosioptes spp.

[0388] The composition according to the present invention is also suitable for protecting materials such as wood, fabric, plastic, adhesive, glue, paint, paper and cardboard, leather, floor finish and building from insect parasitism.

[0389] The composition according to the present invention can be used, for example, against the following pests: Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, Ernobius mollis, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis, Xyleborus spec., Tryptodendron spec., Apate monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec.beetles such as

[0390] and Dinoderus minutus, as well as hymenopteran insects such as Sirex juvencus, Urocerus gigas, Urocerus gigas taignus, and Urocerus augur, and termites such as Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola, Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermes lucifugus, Mastotermes darwiniensis, Zootermopsis nevadensis, and Coptotermes formosanus, and silverfish such as Lepisma saccharina.

[0390] The compounds of formula I and Ia or salts thereof are particularly suitable for controlling one or more pests selected from the families: Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Delphacidae, Aphididae, Crambidae, Meloidogynidae and Heteroderidae. In a preferred embodiment of each aspect, compound TX (wherein the abbreviation "TX" means "one compound selected from the compounds defined in Tables A-1 to A-71 and compounds P1 to P85 of Table P (i.e., compounds P1 to P5, P6 to P17, P18 to P41 and P42 to P85)) controls one or more of the pests selected from the families: Plutellidae, Chrysomelidae, Thripidae, Pentatomidae, Delphacidae, Aphididae, Crambidae, Meloidogynidae and Heteroderidae.

[0391] The compounds of formula I and Ia or salts thereof are particularly suitable for controlling one or more pests selected from the species of the genus Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp. In a preferred embodiment of each aspect, compound TX (wherein the abbreviation "TX" means "one compound selected from the compounds defined in Tables A-1 to A-71 and compounds P1 to P85 of Table P (i.e., compounds P1 to P5, P6 to P17, P18 to P41 and P42 to P85)) controls one or more of the pests selected from the species of the genus Spodoptera spp, Plutella spp, Frankliniella spp, Thrips spp, Euschistus spp, Cydia spp, Nilaparvata spp, Myzus spp, Aphis spp, Diabrotica spp, Rhopalosiphum spp, Pseudoplusia spp and Chilo spp.

[0392] The compounds of formula I and Ia or salts thereof are particularly suitable for controlling one or more of Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum padi and Chilo suppressalis.

[0393] In a preferred embodiment of each aspect, the compound TX (where the abbreviation "TX" means "one compound selected from the compounds defined in Tables A-1 to A-71 and Compounds P1 to P85 in Table P (i.e., Compounds P1 to P5, P6 to P17, P18 to P41, and P42 to P85)) controls Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and one or more of Spodoptera littoralis + TX, Plutella xylostella + TX, etc., such as Chilo Suppressalis; Frankliniella occidentalis + TX, Thrips tabaci + TX, Euschistus heros + TX, Cydia pomonella + TX, Nilaparvata lugens + TX, Myzus persicae + TX, Chrysodeixis includens + TX, Aphis craccivora + TX, Diabrotica balteata + TX, Rhopalosiphum Padi + TX, and Chilo suppressalis + TX.

[0394] In embodiments of each aspect, one compound from Tables A-1 to A-71 and compounds P1 to P85 of Table P (i.e., compounds P1 to P5, P6 to P17, P18 to P41, and P42 to P85) are suitable for controlling Spodoptera littoralis, Plutella xylostella, Frankliniella occidentalis, Thrips tabaci, Euschistus heros, Cydia pomonella, Nilaparvata lugens, Myzus persicae, Chrysodeixis includens, Aphis craccivora, Diabrotica balteata, Rhopalosiphum Padia, and Chilo Suppressalis in cotton, vegetables, corn, cereals, rice, and soybean crops.

[0395] In embodiments, one compound from Tables A-1 to A-71 and compounds P1 to P85 of Table P (i.e., compounds P1 to P5, P6 to P17, P18 to P41, and P42 to P85) are suitable for controlling Mamestra (preferably in vegetables), Cydia pomonella (preferably in apples), Empoasca (preferably in vegetables, vineyards), Leptinotarsa (preferably in potatoes), and Chilo supressalis (preferably in rice).

[0396] The compounds according to the invention can have, inter alia, an advantageous level of biological activity for protecting plants against insects or excellent properties for use as agrochemical active ingredients (for example, high biological activity, advantageous activity spectrum, high safety profile (improved physicochemical properties or high biodegradability with respect to non-target organisms above and below ground (such as fish, birds and bees, etc.)) and can have any number of beneficial properties. In particular, it has surprisingly been found that compounds of a specific formula (I) can exhibit an advantageous safety profile with respect to non-target arthropods such as pollinators, especially honey bees, solitary bees and bumblebees. Most specifically, Apis mellifera.

[0397] The compounds according to the invention can be used as pesticidal agents in their unmodified form, but they are generally formulated into compositions using formulation aids such as carriers, solvents and surface-active substances in various ways. The formulations can be in various physical forms such as, for example, dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, expandable pellets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, oily flowables, aqueous dispersions, oily dispersions, suspoemulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (containing water or a water-miscible organic solvent as carrier), in the form of impregnated polymer films or other forms known, for example, from the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can be used directly or diluted before use. The dilution can be carried out, for example, with water, liquid fertilizers, trace elements, biological organisms, oils or solvents.

[0398] The complex can be prepared by mixing the active ingredient with a formulation aid, for example, to obtain the composition in the form of a fine solid, granules, solution, dispersion or emulsion. The active ingredient can also be formulated with other adjuvants such as fine solids, mineral oil, vegetable oil or animal oil, vegetable-modified oil or animal-modified oil, organic solvent, water, surfactants or combinations thereof.

[0399] The active ingredient can also be contained in extremely fine microcapsules. The microcapsules contain the active ingredient in a porous carrier. Thereby, the active ingredient can be released into the environment in a controlled amount (for example, sustained release). The microcapsules usually have a diameter of 0.1 to 500 microns. They contain the active ingredient in an amount of about 25 to 95% by weight based on the capsule weight. The active ingredient can be in the form of a solid mass, fine particles in a solid or liquid dispersion or in the form of a suitable solution. The encapsulating membrane can include, for example, natural or synthetic rubber, cellulose, styrene / butadiene copolymer, polyacrylonitrile, polyacrylate, polyester, polyamide, polyurethane, polyurea, chemically modified polymers and xanthan gum starch or other polymers known to those skilled in the art. Alternatively, extremely fine microcapsules can be formed by containing the active ingredient in the form of fine particles in a solid matrix of the base, but the microcapsules themselves are not encapsulated.

[0400] The compounding aids suitable for the preparation of the composition according to the present invention are known per se. As the liquid carrier, there are 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 esters of acetic acid, 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, alkyl pyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-Trichloroethane, 2-heptanone, α-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityloxide, 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, 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, high molecular weight alcohols such as N-methyl-2-pyrrolidone, etc. may be used.,

[0401] Suitable solid carriers are, for example, talc, titanium dioxide, phyllosilicate clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cotton hulls, wheat flour, soybean powder, pumice, wood flour, crushed walnut shells, lignin and similar substances.,

[0402] Most surfactants can be advantageously used in both solid and liquid formulations, especially those that can be diluted with a carrier before use. The surfactants can be anionic, cationic, nonionic or polymeric and can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surfactants include, for example, salts of alkyl sulfates such as diethanolammonium lauryl sulfate; salts of alkylaryl sulfonates such as calcium dodecylbenzenesulfonate; alkylphenol / alkylene oxide adducts such as nonylphenol ethoxylate; alcohol / alkylene oxide adducts such as tridecyl alcohol ethoxylate; soaps such as sodium stearate; salts of alkylnaphthalene sulfonates such as sodium dibutylnaphthalene sulfonate; dialkyl esters of sulfosuccinates such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters such as sorbitol oleate; quaternary amines such as lauryltrimethylammonium chloride; polyethylene glycol esters of fatty acids such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkyl phosphate esters; and further substances described, for example, in McCutcheon’s Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey (1981).

[0403] Further adjuvants that can be used in pesticidal formulations include crystallization inhibitors, viscosity modifiers, suspending agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, defoamers, complexing agents, neutralizing agents or pH adjusters and buffers, corrosion inhibitors, fragrances, wetting agents, uptake enhancers, trace elements, plasticizers, lubricants, lubricants, dispersants, thickeners, antifreeze agents, biocides and liquid and solid fertilizers.

[0404] The composition according to the present invention may contain an additive including vegetable oil or animal oil, mineral oil, alkyl esters of such oils, or a mixture of such oils and oil derivatives. The amount of the oil additive in the composition according to the present invention is generally 0.01 to 10% based on the mixture to be applied. For example, the oil additive may be added at a desired concentration into the spray tank after the spray mixture is prepared. Preferred oil additives include mineral oil or vegetable oils such as rapeseed oil, olive oil or sunflower oil, emulsified vegetable oils, alkyl esters of vegetable oils such as methyl derivatives, or animal oils such as fish oil or beef tallow. Preferred oil additives include alkyl esters of C8 - C 22 fatty acids, particularly C 12 -C 18 fatty acid methyl derivatives, 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 known from the Compendium of Herbicide Adjuvants, 10 th Edition, Southern Illinois University, 2010.

[0405] The composition of the present invention generally comprises 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 a formulation aid (which preferably contains 0 to 25% by weight of a surfactant). Commercial products may sometimes preferably be formulated as concentrates, but end users will usually utilize diluted formulations.

[0406] The application rates vary within a wide range and depend on the nature of the soil, the application method, the crop plants, the pests to be controlled, the main weather conditions, and other factors depending on the application method, the application time and the target crop. As per general guidelines, the compound may be applied in an amount of 1 to 2000 l / ha, particularly 10 to 1000 l / ha.

[0407] Preferred formulations may have the following composition (% by weight). Emulsifiable concentrate: Active ingredient: 1 - 95%, preferably 60 - 90% Surfactant: 1 - 30%, preferably 5 - 20% Liquid carrier: 1 - 80%, preferably 1 - 35%

[0408] Powder: Active ingredient: 0.1 - 10%, preferably 0.1 - 5% Solid carrier: 99.9 - 90%, preferably 99.9 - 99%

[0409] Suspension concentrate: Active ingredient: 5 - 75%, preferably 10 - 50% Water: 94 - 24%, preferably 88 - 30% Surfactant: 1 - 40%, preferably 2 - 30%

[0410] Wettable powder: Active ingredient: 0.5 - 90%, preferably 1 - 80% Surfactant: 0.5 - 20%, preferably 1 - 15% Solid carrier: 5 - 95%, preferably 15 - 90%

[0411] Granule: Active ingredient: 0.1 - 30%, preferably 0.1 - 15% Solid carrier: 99.5 - 70%, preferably 97 - 85%

Example

[0412] The following examples further illustrate the present invention but do not limit it.

[0413]

Table 7

[0414] The wettable powder can be obtained by thoroughly mixing the composite with the adjuvant, thoroughly grinding the mixture with a suitable mill, and diluting it with water to obtain a suspension of the desired concentration.

[0415]

Table 8

[0416] The composite is thoroughly mixed with an adjuvant, and the mixture is thoroughly ground in a suitable mill to obtain a powder that can be used directly for seed treatment.

[0417] [Table 9]

[0418] Emulsions of any required dilution that can be used for plant protection can be obtained from this concentrate by dilution with water.

[0419] [Table 10]

[0420] Ready-to-use powders are obtained by mixing the composite with a carrier and grinding this mixture in a suitable mill. Such powders can also be used for dry film coating of seeds.

[0421] [Table 11]

[0422] The composite is mixed and ground with an adjuvant, and this mixture is moistened with water. The mixture is extruded and then dried in an air stream.

[0423] [Table 12]

[0424] In a mixer, the finely ground composite is uniformly applied to kaolin moistened with polyethylene glycol. Coated granules that do not generate dust are thereby obtained.

[0425] [Table 13]

[0426] The finely ground composite is thoroughly mixed with an adjuvant to obtain a suspension concentrate, from which a suspension of any desired dilution can be obtained by diluting with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms by spraying, pouring or dipping.

[0427]

Table 14

[0428] The finely ground composite is thoroughly mixed with an adjuvant to obtain a suspension concentrate, from which a suspension of any desired dilution can be obtained by diluting with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against ectoparasitism by microorganisms by spraying, pouring or dipping.

[0429] Sustained-release capsule suspension 28 parts of the composite are mixed with 2 parts of an aromatic solvent and 7 parts of a toluene diisocyanate / polymethylene-polyphenyl isocyanate mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinyl alcohol, 0.05 part of a defoamer and 51.6 parts of water until the desired particle size is achieved. A mixture of 2.8 parts of 1,6-diaminohexane in 5.3 parts of water is added to this emulsion. The mixture is stirred until the polymerization reaction is complete. The resulting capsule suspension is stabilized by adding 0.25 part of a thickener and 3 parts of a dispersant. The capsule suspension formulation contains 28% active ingredient. The diameter of the medium-sized capsules is 8 - 15 microns. The resulting formulation is applied to the seeds as an aqueous suspension in an apparatus suitable for this purpose.

[0430] Examples of formulation types include emulsion concentrates (EC), suspension concentrates (SC), suspoemulsions (SE), capsule suspensions (CS), water-dispersible granules (WG), emulsifiable granules (EG), emulsions, oil-in-water (EO), emulsions, water-in-oil (EW), microemulsions (ME), oil dispersions (OD), oil miscible flowables (OF), oil miscible liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), technical concentrates (TK), dispersible concentrates (DC), wettable powders (WP), soluble granules (SG), or any technically preferred formulation in combination with an agriculturally acceptable adjuvant.

[0431] The activity of the compositions according to the invention can be considerably extended by adding other insecticidal, acaricidal and / or fungicidal active ingredients and can be adapted to general circumstances. Mixtures of the compounds of formula (I) with other insecticidal, acaricidal and / or fungicidal active ingredients may also be described as having synergistic activity in a broader sense and may have further unexpected advantages. For example, better tolerance by plants, reduced phytotoxicity, the fact that insects can be controlled at their different developmental stages or better behavior during their manufacture, for example during grinding or mixing, during their storage or during their use.

[0432] Suitable additives to the active ingredient in the present specification are, for example, active ingredients of the following types as representative examples: organophosphorus compounds, nitrophenol derivatives, thioureas, juvenile hormones, formamidines, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acyl ureas, pyridylmethyleneamino derivatives, macrolides, neonicotinoids and Bacillus thuringiensis preparations.

[0433] Preparation examples: “Mp” means melting point (°C). The free radical represents a methyl group. 11H NMR measurements were recorded on a Brucker 400 MHz spectrometer, and chemical shifts are reported in ppm relative to the TMS standard. Spectra were measured in a deuterated solvent as specified. Compounds were characterized using one of the following LCMS methods. The unique LCMS values obtained for each compound were the retention time (“Rt”, recorded in minutes) and the observed molecular ion (M+H) + or (M-H) - .

[0434] Method 1: Spectra were recorded on a mass spectrometer (SQD, SQDII or QDA single quadrupole mass spectrometer) manufactured by Waters Corporation, equipped with an electrospray source (polarity: positive and negative ions), capillary: 0.8 - 3.00 kV, cone: 5 - 30 V, source temperature: 120 - 150 °C, desolvation temperature: 350 - 600 °C, cone gas flow: 50 - 150 l / h, desolvation gas flow: 650 - 1000 l / h, mass range: 100 - 900 Da and an Acquity UPLC manufactured by Waters Corporation: 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 (ml / min) 0.85, gradient: isocratic 10% B for 0.2 minutes, then 10 - 100% B in 1.0 minute, isocratic 100% B for 0.2 minutes, 100 - 10% B in 0.05 minute, isocratic 10% B for 0.05 minute.

[0435] Method 2: The spectrum was recorded using an electrospray source (polarity: cations and anions, capillary: 3.00 kV, cone range: 41 V, extractor: 2.00 V, source temperature: 150 °C, desolvation temperature: 5000 °C, cone gas flow: 50 l / h, desolvation gas flow: 1000 l / h, mass range: 110 - 800 Da) and a Waters mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) equipped with an Acquity UPLC from Waters: binary pump, heated column compartment, diode-array detector and ELSD detector. Column: Waters UPLC HSS T3 C18, 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 rate (ml / min) 0.6.

[0436] Method 3: The spectrum was recorded using an electrospray source (polarity: anode and cathode switch), capillary: 0.8 - 3.00 kV, cone range: 25, source temperature: 120 - 150 °C, desolvation temperature: 500 - 600 °C, cone gas flow: 50 L / h, desolvation gas flow: 1000 L / h, mass range: 110 - 850 Da) and a Waters mass spectrometer (SQD2 or QDA single quadrupole mass spectrometer) equipped with an Acquity UPLC from Waters: quaternary solvent manager, heated column compartment, diode-array detector. Column: Acquity UPLC HSS T3 C18, 1.8 μm, 30 × 2.1 mm, temperature: 40 °C, DAD wavelength range (nm): 200 - 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH: gradient: 10% B for 0 minutes; 10 - 50% B for 0. - 0.2 minutes; 50 - 100% B for 0.2 - 0.6 minutes; 100% B for 0.6 - 1.3 minutes; 100 - 10% B for 1.3 - 1.4 minutes; 10% B for 1.4 - 1.6 minutes; flow rate (mL / min) 0.6.

[0437] Method 4: The spectrum was recorded using an electrospray source (polarity: anode and cathode polarity switch), capillary: 0.8 - 3.00 kV, cone range: 25, source temperature: 120 - 150 °C, desolvation temperature: 500 - 600 °C, cone gas flow: 50 L / h, desolvation gas flow: 1000 L / h, mass range: 110 - 850 Da) and a mass spectrometer (SQD2 or QDA single quadrupole mass spectrometer) from Waters equipped with an Acquity UPLC: Quaternary solvent manager, heated column compartment, and diode - array detector. Column: Acquity UPLC HSS T3 C18, 1.8 μm, 30 × 2.1 mm, temperature: 40 °C, DAD wavelength range (nm): 200 - 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH: gradient: 10% B for 0 minutes; 10% B for 0.0 - 0.5 minutes; 100% B for 0.5 - 2 minutes; 100% B for 2 - 3 minutes; 10% B for 3 - 3.5 minutes; 10% B for 3.5 - 4 minutes; flow rate (mL / min) 0.6.

[0438] Method 5: The spectrum was recorded using an electrospray source (polarity: cation or anion, capillary: 3.0 kV, cone: 30 V, extractor: 3.00 V, source temperature: 150 °C, desolvation temperature: 400 °C, cone gas flow: 60 L / hr, desolvation gas flow: 700 L / hr, mass range: 140 - 800 Da) and an ACQUITY mass spectrometer (QDa or SQDII single quadrupole mass spectrometer) from Waters Corporations equipped with a solvent degasser, binary pump, heated column compartment, and diode - array detector. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm, temperature: 60 °C, DAD wavelength range (nm): 210 - 400, solvent gradient: A = water / methanol 9:1 + 0.1% formic acid, B = acetonitrile + 0.1% formic acid, gradient: 0 - 100% B in 3.0 minutes; flow rate (ml / min) 0.75.

[0439] Example E1: Preparation of 2-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-ethyl-N-methyl-thiazole-5-carboxamide (Compound P6)

Chemical formula

Chemical formula

[0440] Step 2: Preparation of 2-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]thiazole-5-carboxylic acid (I-2) [Chem.] A mixture of methyl 2-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]thiazole-5-carboxylate (I-1) (3.7 g, 10 mmol) and lithium hydroxide (0.78 g, 31 mmol) in tetrahydrofuran (37 mL) and water (3.7 mL) was stirred at room temperature for 16 h, then diluted with EtOAc, water and 5% aqueous sodium dihydrogen phosphate (NaH2PO4) solution. The phases were separated, the aqueous layer was washed with EtOAc, cooled by adding crushed ice, and then acidified with 10% aqueous HCl. The precipitate formed was filtered, the solid was washed with water and dried. The solid was further washed with pentane and dried under reduced pressure to give 2-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]thiazole-5-carboxylic acid as an off-white solid. This material was used in the next step without further purification. LCMS (Method 2): retention time 1.03 min, m / z 284 [M+H-tBu] + 。

[0441] Step 3: Preparation of tert-butyl N-[(1S)-1-[2-[5-[ethyl(methyl)carbamoyl]thiazol-2-yl]-1,2,4-triazol-3-yl]ethyl]carbamate (I-3) [Chem.] A suspension of 2-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]thiazole-5-carboxylic acid (I-2) (0.5 g, 1.43 mmol) in EtOAc (11.8 mL) was treated with ethylmethylamine (0.19 mL, 2.21 mmol), N,N-diisopropylethylamine (0.76 mL, 4.42 mmol), and then propanephosphonic acid cyclic anhydride (T3P®, 50 wt% in ethyl acetate, 2.63 mL, 4.42 mmol). The reaction mixture was stirred at room temperature overnight. After dilution with water, the product was extracted with EtOAc (3 times), and the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by combiflash (gradient: ethyl acetate in cyclohexane) to give tert-butyl N-[(1S)-1-[2-[5-[ethyl(methyl)carbamoyl]thiazol-2-yl]-1,2,4-triazol-3-yl]ethyl]carbamate. LCMS (method 2): retention time 1.09 minutes, m / z 381 [M+H] + .

[0442] Step 4: Preparation of [(1S)-1-[2-[5-[ethyl(methyl)carbamoyl]thiazol-2-yl]-1,2,4-triazol-3-yl]ethyl]ammonium chloride (I-4) [Chemical formula] To a solution of tert-butyl N-[(1S)-1-[2-[5-[ethyl(methyl)carbamoyl]thiazol-2-yl]-1,2,4-triazol-3-yl]ethyl]carbamate (I-3) (0.43 g, 1.13 mmol) in 1,4-dioxane (3 mL) was added hydrochloric acid (4.0 M in 1,4-dioxane, 3 mL, 12 mmol). The reaction mixture was stirred at room temperature for 5 hours and then concentrated under reduced pressure until dry. The residue was triturated with TBME, and the solid formed was filtered and dried to give [(1S)-1-[2-[5-[ethyl(methyl)carbamoyl]thiazol-2-yl]-1,2,4-triazol-3-yl]ethyl]ammonium chloride as a white solid. LCMS (Method 2): retention time 0.17 minutes, m / z 281 [M+H] + (for the corresponding free base).

[0443] Step 5: Preparation of 2-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-ethyl-N-methyl-thiazole-5-carboxamide (Compound P6)

Chemical Structure

[0444] Example E2: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (Compound P5)

Chemical Structure

[0445] Example E3: Preparation of 6-[5-[(1S)-1-[(6,8-dibromoquinazolin-4-yl)-methyl-amino]ethyl]-1,2,4-triazol-1-yl]-N-methyl-pyrimidine-4-carboxamide (Compound P11)

Chemical formula

[0446] Example E4: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-(1-cyanocyclopropyl)pyrimidine-4-carboxamide (compound P22) [ka] Step 1: Preparation of [(1S)-1-[2-(6-chloropyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]ammonium chloride (I-17) [ka] A solution of tert-butyl N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (CAS 2694010-23-4, prepared as described in, for example, International Publication No. 21 / 165195) (20.0 g, 61.58 mmol) in 1,4-dioxane (200 mL) was added with hydrochloric acid solution (4 M in dioxane) (77.0 mL, 308 mmol) at room temperature. The reaction mixture was stirred at room temperature for 25 h, and the precipitate formed was isolated by filtration and the solid was dried under reduced pressure to give [(1S)-1-[2-(6-chloropyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]ammonium chloride (I-17) as a white solid. LCMS (Method 3): retention time 0.20 min, m / z 225 / 227 [M+H] + (for the corresponding free base).

[0447] Step 2: Preparation of 6-chloro-N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]-8-(trifluoromethyl)quinazolin-4-amine (I-18)

Chemical formula

[0448] Step 3: Preparation of methyl 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate (I-19)

Chemical formula

[0449] Similarly, methyl 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylate (I-22) can be obtained from intermediate (I-21) by the above protocol. LCMS (Method 3): retention time 1.21 minutes, m / z 493 / 495 [M+H] + 。

[0450] Step 4: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylic acid (I-20)

Chemical Structure

[0451] Similarly, 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylic acid (I-23) can be obtained from intermediate (I-22) by the above protocol. LCMS (Method 3): retention time 1.12 min, m / z 479 / 481 [M+H] + 。

[0452] Step 5: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-(1-cyanocyclopropyl)pyrimidine-4-carboxamide (Compound P22)

Chemical formula

[0453] Example E5: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-(thietan-3-yl)pyrimidine-4-carboxamide (Compound P25)

Chemical Structure

[0454] Similarly, 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-cyclopropyl-pyrimidine-4-carboxamide (Compound P23) can be obtained by the above protocol when thietan-3-ylammonium chloride is replaced with cyclopropanamine. LCMS (Method 3): retention time 1.24 min, m / z 504 / 506 [M+H] +。

[0455] Example E6: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-(1,1-dioxothietan-3-yl)pyrimidine-4-carboxamide (Compound P24)

Chemical formula

[0456] Example E7: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-methoxy-pyrimidine-4-carboxamide (Compound P28) [Chemical formula] Similarly, 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylic acid (I-20) (0.15 g, 0.323 mmol) in acetonitrile (3 mL), ammonium methoxy chloride (0.135 g, 1.614 mmol), 1-propanephosphonic acid cyclic anhydride (50% by mass in EtOAc, 0.2882 mL, 0.484 mmol), and triethylamine (0.197 g, 0.271 mL, 1.936 mmol) were used to obtain it according to the method of Step 5 of Example E4. After stirring at room temperature for 25 hours, the reaction mixture was diluted with aqueous NaHCO3 solution, stirring was continued for 20 minutes, the formed precipitate was isolated by filtration, the solid was washed with water, and dried under reduced pressure to obtain 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-methoxy-pyrimidine-4-carboxamide (Compound P28) as a white solid. LCMS (Method 3): Retention time 1.16 minutes, m / z 494 / 496 [M+H] + . 1 1H NMR (DMSO-d6) δ ppm: 12.53 (s, 1H), 9.28 (s, 1H), 9.16 (d, 1H), 8.97 (d, 1H), 8.40 (s, 1H), 8.37 (s, 1H), 8.28 (s, 1H), 8.24 (d, 1H), 6.55 (quartet, 1H), 3.75 (s, 3H), 1.76 (d, 3H).

[0457] Example E8: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-ethyl-N-methyl-pyrimidine-4-carboxamide (Compound P31)

Chemical formula

[0458] Similarly, [6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidin-4-yl]-morpholino-methanone (Compound P32) can be obtained by the above protocol when N-methylethanamine is replaced with morpholine. The crude product obtained after aqueous workup was purified by reverse-phase column chromatography (C18 column, H2O:ACN eluent). LCMS (Method 3): retention time 1.20 minutes, m / z 534 / 536 [M+H] + 。

[0459] Example E9: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-(cyanomethyl)pyrimidine-4-carboxamide (Compound P38)

Chemical Structure

[0460] Example E10: Preparation of 6-[5-[(1S)-1-[(8-chloro-6-iodoquinazolin-4-yl)amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile (Compound P18) [Chemical formula] A solution of 4,8-dichloro-6-iodoquinazoline (CAS 100948-96-7, prepared in the same manner as described, for example, in International Publication No. 2021 / 083936) (100 mg, 0.277 mmol, 90% by mass), [(1S)-1-[2-(6-cyanopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]ammonium 2,2,2-trifluoroacetate (I-13, CAS 2694010-00-7, prepared as described in International Publication No. 2021 / 165195) (101.3 mg, 0.277 mmol, 90% by mass) and triethylamine (0.194 mL, 0.141 g, 1.385 mmol) in tetrahydrofuran (2 mL) was heated in a microwave at 100 °C for 1 hour. The reaction mixture was cooled to room temperature and evaporated under reduced pressure. The residue was purified by combiflash (ethyl acetate in cyclohexane), and the resulting product was washed with TBME, filtered, and dried under high vacuum to obtain 6-[5-[(1S)-1-[(8-chloro-6-iodoquinazolin-4-yl)amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carbonitrile (Compound P18) as a white solid. LCMS (Method 3): retention time 1.13 minutes, m / z 504 / 506 [M+H] + . 11H NMR (400 MHz, DMSO-d6) δ ppm: 1.73 (d, 3H), 6.47 (quartet, 1H), 8.27 (d, 1H), 8.30 (s, 1H), 8.36 (s, 1H), 8.61 (d, 1H), 8.90 (d, 1H), 9.05 (d, 1H), 9.36 (d, 1H).

[0461] Example E11: Preparation of 6-[5-[(1S)-1-[(6-chloro-8-iodo-quinazolin-4-yl)-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (Compound P47)

Chemical Structure

[0462] Example E12: Preparation of 5-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrazine-2-carboxamide (Compound P21) [Chemical formula] A mixture of 4,6-dichloro-8-(trifluoromethyl)quinazoline (prepared as described in International Publication No. 21 / 083936) (100 mg, 0.374 mmol) and [(1S)-1-[2-(5-carbamoylpyrazin-2-yl)-1,2,4-triazol-3-yl]ethyl]ammonium chloride (I-16) (0.411 mmol) was added to ACN (2 mL) and triethylamine (1.87 mmol). The reaction mixture was stirred at 80 °C for 1 hour and then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate in cyclohexane) to obtain 5-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrazine-2-carboxamide (P21) as a pale yellow oil. LCMS (Method 4): retention time 1.74 minutes, m / z 464 / 466 [M+H] + .

[0463] Example E13: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-cyclopropyl-N-methyl-pyrimidine-4-carboxamide (Compound P63) [Chemical formula] 6-[5-[(1S)-1-[[6-Chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxylic acid (I-20) (200 mg, 0.43 mmol) and cyclopropyl(methyl)ammonium chloride (4.3 mmol) in acetonitrile (4 mL) were added with HATU (0.245 mmol) at room temperature, followed by triethylamine (1.29 mmol) at 0 - 5 °C. The reaction mixture was stirred at room temperature for 14 h, further stirred at 80 °C for 11 h, and then diluted with water and saturated aqueous sodium bicarbonate. The product was extracted with EtOAc, the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by reverse-phase combiflash using a C18 column (acetonitrile in water) to give 6-[5-[(1S)-1-[[6-chloro-8-(trifluoro-methyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-cyclopropyl-N-methyl-pyrimidine-4-carboxamide (P63) as a white solid. LCMS (method 3): retention time 1.11 min, m / z 518 / 520 [M+H] + 。 1 1H NMR (DMSO-d6) δ ppm: 9.22 (s, 1H), 9.15 (br d, 1H), 8.95 (m, 1H), 8.39 (s, 1H), 8.25 (s, 1H), 8.22 (m, 1H), 8.10 (s, 1H), 6.50 (quartet, 1H), 3.04 (s, 3H), 2.80 - 2.97 (m, 1H), 1.78 (br d, 3H), 0.40 - 0.59 (m, 4H).

[0464] Example E14: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethylsulfonyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (Compound P59)

Chem.

Chem.

[0465] Step 2: Preparation of 6-chloro-8-(trifluoromethylsulfonyl)quinazolin-4-ol (I-45)

Chem.

[0466] Step 3: Preparation of 4,6-dichloro-8-(trifluoromethylsulfonyl)quinazoline

Chemical Structure

[0467] Similarly, 4,6-dichloro-8-(difluoromethylsulfonyl)quinazoline can be obtained from 6-chloro-8-(difluoromethylsulfonyl)quinazolin-4-ol (I-44) by the above protocol. 1 H NMR (400 MHz, DMSO-d6) δ ppm 8.58 (s, 1H), 8.07 (d, 1H), 7.96 (d, 1H), 7.89 (t, 1H).

[0468] Step 4: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethylsulfonyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (Compound P59)

Chemical Structure

[0469] Similarly, 6-[5-[(1S)-1-[[6-chloro-8-(difluoromethylsulfonyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-4-carboxamide (Compound P84) can be obtained from 4,6-dichloro-8-(difluoromethylsulfonyl)quinazoline (1.0 equivalent) and [(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]ammonium chloride (I-12, 1.2 equivalents) in the presence of potassium carbonate (3.0 equivalents) in acetonitrile. The mixture was stirred at 0 °C to room temperature for 2 hours. Following standard workup, the crude material was purified by combiflash (ethyl acetate in cyclohexane), then by reverse-phase column chromatography (acetonitrile in water) to afford the desired Compound P84. 1 1H NMR (400 MHz, DMSO-d6) δ ppm 9.40 (d, 1H), 9.29 (s, 1H), 9.14 (d, 1H), 8.46 (br s, 1H), 8.42 (m, 2H), 8.40 (s, 1H), 8.28 (s, 1H), 8.13 (br s, 1H), 7.67 (t, 1H), 6.57 (quartet, 1H), 1.77 (d, 3H).

[0470] Example E15: Preparation of 6-[3-[1-[(6-chloro-8-iodo-quinazolin-4-yl)amino]ethyl]pyrazin-2-yl]pyrimidine-4-carboxamide (Compound P58)

Chemical Structure

Chemical Structure

[0471] Step 2: Preparation of 6-[3-(1,3-dioxoisoindolin-2-yl)but-1-ynyl]pyrimidine-4-carboxamide

Chemical Structure

[0472] Step 3: Preparation of 6-[3-(1,3-dioxoisoindolin-2-yl)-2-oxo-butyl]pyrimidine-4-carboxamide

Chemical Structure

[0473] Step 4: Preparation of 6-[3-(1,3-dioxoisoindolin-2-yl)-2-oxo-butanoyl]pyrimidine-4-carboxamide [Chemical formula] Selenium dioxide (1.1 g, 9.5 mmol) was added to 6-[3-(1,3-dioxoisoindolin-2-yl)-2-oxo-butyl]pyrimidine-4-carboxamide (prepared as described above) (1.6 g, 4.7 mmol) in tetrahydrofuran (32 mL) at room temperature. The reaction mixture was stirred at 65 °C for 16 hours, cooled to room temperature, and filtered through a celite bed. The filter cake was washed with EtOAc, and the filtrate was concentrated under reduced pressure to obtain crude 6-[3-(1,3-dioxoisoindolin-2-yl)-2-oxo-butanoyl]pyrimidine-4-carboxamide, which was used directly in the next step.

[0474] Step 5: Preparation of 6-[3-(1-aminoethyl)pyrazin-2-yl]pyrimidine-4-carboxamide [Chemical formula] A solution of ethanediamine (2.9 g, 48 mmol, 3.3 mL) in ethanol (17 mL) was added dropwise to a mixture of crude 6-[3-(1,3-dioxoisoindolin-2-yl)-2-oxo-butanoyl]pyrimidine-4-carboxamide (prepared as described above) (1.7 g) in ethanol (17 mL) at 0 °C. After the addition, the reaction mixture was stirred at room temperature for 24 hours, then diluted with water, and the product was extracted with 30% ACN in ethyl acetate. The combined organic layers were washed with water, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain crude 6-[3-(1-aminoethyl)pyrazin-2-yl]pyrimidine-4-carboxamide, which was used directly in the next step. LCMS (Method 3): Retention time 0.17 minutes, m / z 245 [M+H] + .

[0475] Step 6: Preparation of 6-[3-[1-[(6-chloro-8-iodo-quinazolin-4-yl)amino]ethyl]pyrazin-2-yl]pyrimidine-4-carboxamide (Compound P58)

Chem.

[0476] Example E16: Preparation of 2-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-5-carboxamide (Compound P68)

Chem.

Chem.

[0477] Step 2: Preparation of 2-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-[(4-methoxyphenyl)methyl]pyrimidine-5-carboxamide

Chem.

[0478] Step 3: Preparation of 2-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-5-carboxamide (Compound P68) [Chemical formula] A solution of 2-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]-N-[(4-methoxyphenyl)methyl]pyrimidine-5-carboxamide (prepared as described above) (0.15 g, 0.256 mmol) in acetonitrile (3.75 mL) was added to a solution of ammonium cerium(IV) nitrate (0.283 g, 0.513 mmol) in water (1 mL). The reaction mixture was stirred at room temperature for 16 h and then diluted with saturated aqueous sodium bicarbonate. The product was extracted several times with ethyl acetate, the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by combiflash (ethyl acetate in cyclohexane) to give 2-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyrimidine-5-carboxamide (P68) as a solid. LCMS (method 3): retention time 0.99 min, m / z 464 / 466 [M+H] + 。

[0479] Example E17: Preparation of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]methyl-amino]ethyl]-1,2,4-triazol-1-yl]-N-(2-cyanoethyl)pyrimidine-4-carboxamide (Compound P53)

Chem.

[0480]

Table 15-1

[0481]

Table 15-2

[0482]

Table 15-3

[0483]

Table 15-4

[0484]

Table 15-5

[0485]

Table 15-6

[0486]

Table 15-7

[0487]

Table 15-8

[0488]

Table 15-9

[0489]

Table 15-10

[0490]

Table 15-11

[0491]

Table 15-12

[0492]

Table 15-13

[0493]

Table 15-14

[0494]

Table 15-15

[0495]

Table 15-16

[0496]

Table 15-17

[0497]

Table 15-18

[0498]

Table 15-19

[0499]

Table 15-20

[0500]

Table 15-21

[0501] 1 Compounds P84 and P85 characterized by the measured 1H NMR values: P84: 1 1H NMR (400 MHz, DMSO-d6) δ ppm 9.40 (d, 1H), 9.29 (s, 1H), 9.14 (d, 1H), 8.46 (br s, 1H), 8.42 (m, 2H), 8.40 (s, 1H), 8.28 (s, 1H), 8.13 (br s, 1H), 7.67 (t, 1H), 6.57 (quartet, 1H), 1.77 (d, 3H). P85: 11H NMR (400 MHz, DMSO-d6) δ ppm 9.40 (d, 1H), 9.15 (d, 1H), 8.47 (s, 1H), 8.44 (d, 1H), 8.28 (s, 1H), 8.26 (br s, 1H), 8.22 (s, 1H), 7.79 (br s, 1H), 7.68 (t, 1H), 6.33 (quartet, 1H), 1.74 (d, 3H).

[0502] Preparation of Intermediate Example PI-1: Preparation of tert-Butyl N-[(1S)-1-[2-(5-Carbamoylthiazol-2-yl)-1,2,4-triazol-3-yl]ethyl]Carbamate (I-7)

Chemical Structure

[0503] Step 2: Preparation of tert-Butyl N-[(1S)-1-[2-(5-Carbamoylthiazol-2-yl)-1,2,4-triazol-3-yl]ethyl]Carbamate (I-7)

Chemical Structure

[0504] Example PI-2: Preparation of 6-chloro-N-[(1S)-1-[2-(6-chloropyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]-N-methyl-8-(trifluoromethyl)quinazolin-4-amine (I-21)

Chemical formula

[0505] Similarly, 6-chloro-N-[(1S)-1-[2-(6-iodopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]-N-methyl-8-(trifluoromethyl)quinazolin-4-amine (Compound I-39) can be obtained from 6-chloro-N-[(1S)-1-[2-(6-iodopyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]-8-(trifluoromethyl)quinazolin-4-amine (I-38) by the above protocol. LCMS (Method 4): retention time 2.32 min, m / z 561 / 563 [M+H] + 。

[0506] Example PI-3: Preparation of [(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]-methyl-ammonium chloride (I-29) [Chemical formula] Step 1: Preparation of tert-butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]-N-methyl-carbamate (I-28) [Chemical formula] To a solution of tert-butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]-N-methyl-carbamate (CAS 344609-43-4) (0.454 g, 2.24 mmol) in 2-methyltetrahydrofuran (4.5 mL) was added N,N-dimethylformamide dimethylacetal (2.69 mmol) at room temperature. The resulting reaction mixture was stirred at 40 °C for 1 hour and then concentrated under reduced pressure to give the crude intermediate tert-butyl N-[(1S)-2-[I-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]-N-methyl-carbamate (LCMS (Method 3): retention time 0.96 minutes, m / z 202 [M+H-tBu] + ).

[0507] 1,4-Dioxane (2.724 mL), acetic acid (2.724 mL) and 6-hydrazinopyrimidine-4-carboxamide (CAS 2283190-21-4) (0.34 g, 2.22 mmol) were added to this intermediate and the mixture was stirred at 80 °C for 16 hours and then concentrated under reduced pressure. The residue was purified by reverse-phase chromatography on a C18 column (acetonitrile in water) to give tert-butyl N-[(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]-N-methyl-carbamate (I-28). LCMS (Method 3): retention time 1.01 minutes, m / z 292 [M+H-tBu] + .

[0508] Step 2: Preparation of [(1S)-1-[2-(6-carbamoylpyrimidin-4-yl)-1,2,4-triazol-3-yl]ethyl]-methyl-ammonium chloride (I-29)

Chemical Structure

[0509] Example PI-4: Preparation of [(1S)-1-[2-(5-carbamoylpyridin-2-yl)-1,2,4-triazol-3-yl]ethyl]ammonium chloride (I-16)

Chemical Structure

Chemical Structure

[0510] 1,4-Dioxane (9.6 mL), acetic acid (9.6 mL) and 2-bromo-5-hydrazinylpyrazine (CAS 1001050-24-3) (1.6 g, 95%, 8.04 mmol) were added to this intermediate, and the mixture was stirred at 80 °C for 2 h, then cooled to room temperature and poured into water and EtOAc. The phases were separated, the aqueous layer was extracted with EtOAc, the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by combiflash (ethyl acetate in cyclohexane) to obtain tert-butyl N-[(1S)-1-[2-(5-bromopyrazin-2-yl)-1,2,4-triazol-3-yl]ethyl]carbamate as a gum. LCMS (Method 1): retention time 0.95 min, m / z 369 / 371 [M+H] + .

[0511] Step 2: Preparation of methyl 5-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1,2,4-triazol-1-yl]pyrazine-2-carboxylate (I-24) [Chemical formula] In a pressure vessel, 1,1'-bis(diphenylphosphino)ferrocene (dppf, 69.9 mg, 0.124 mmol) and bis(benzonitrile)palladium(II) chloride (24.2 mg, 0.0618 mmol) were dissolved in methanol (45.6 mL) under an argon atmosphere. N-[(1S)-1-[2-(5-bromopyrazin-2-yl)-1,2,4-triazol-3-yl]ethyl]carbamate (prepared as described above) (1140 mg, 3.09 mmol) and triethylamine (410 mg, 0.565 mL, 4.01 mmol) were added, and the mixture was flushed with an argon stream for 10 minutes and then with carbon monoxide. The reaction mixture was heated at 80 °C under a carbon monoxide pressure of 10 bar overnight. After cooling to room temperature, the pressure was carefully released and the vessel was flushed...

Claims

1. Equation (I) 【Chemistry 1】 (In the formula, A 1 A 2 and A 3 These are N or CR, independently of each other. Y is; or A 1 = A 2 -A 3 Together, they are NR-C(=O)-N; A 4 and A 5 are, independently of each other, N or CR YY ; Q is, 【Chemistry 2】 (In the formula, the dashed line indicates the connection of Q to the remainder of the compound in formula (I).) And; R is hydrogen, C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Alkoxy or C 1 ~C 3 It is a haloalkoxy; R 1 is hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Cyanoalkyl, aminocarbonyl C 1 ~C 6 Alkyl, hydroxycarbonyl C 1 ~C 6 Alkyl, C 1 ~C 6 Nitroalkyl, trimethylsilane C 1 ~C 6 Alkyl, C 1 ~C 3 Alkoxy-C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 2 ~C 6 Alkenil, C 2 ~C 6 Haloalkenil, C 2 ~C 6 Alkinyl, C 2 ~C 6 Haloalkynyl, C 3 ~C 4 Cycloalkyl C 1 ~C 2 Alkyl-, C 3 ~C 4 Cycloalkyl C 1 ~C 2 Alkyl-(where C 3 ~C 4 The cycloalkyl group is substituted with one or two halogen atoms), oxetane-3-yl-CH 2 -, C 1 ~C 6 Alkylcarbonyl, C 1 ~C 6 Alkoxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, benzyl, or halogen and C 1 ~C 6 Alkoxy and C 1 ~C 6 Benzyl substituted with one to three substituents independently selected from haloalkyl groups; R 2a and R 2b are each independently selected from one to three substituents selected from hydrogen, C 1 to C 3 alkyl, C 1 to C 3 haloalkyl, C 1 to C 3 haloalkylsulfanyl, C 1 to C 3 alkoxy, C 1 to C 3 haloalkoxy, halogen, NO 2 , SF 5 , CN, C(O)NH 2 , C(O)OH, C(S)NH 2 , C 3 to C 6 cycloalkyl, R x substituted C 3 to C 6 cycloalkyl, C 3 to C 6 cycloalkylcarbonyl, phenyl, R x substituted phenyl, heteroaryl, R x substituted heteroaryl; OR 6 , piperidin-2-one-1-yl, R x substituted piperidin-2-one-1-yl, pyridin-2-one-1-yl, R x substituted pyridin-2-one-1-yl, azetidin-1-yl, R x substituted azetidin-1-yl, pyrrolidin-1-yl, R x substituted pyrrolidin-1-yl, C 3 to C 6 cycloalkyl C 1 to C 4 alkyl, R Z substituted C 3 to C 6 cycloalkyl C 1 ~C 4 Alkyl; C 3 ~C 6 Cycloalkyl C 1 ~C 3 Alkoxy, R x C substituted with one or two substituents independently selected from 3 ~C 6 Cycloalkyl C 1 ~C 3 Alkoxy, C 1 ~C 5 Cyanoalkyl, C 1 ~C 5 Cyanoalkoxy, C 1 ~C 4 Alkyl sulfanyl, R x C substituted with 1 to 3 substituents independently selected from 1 ~C 4 Alkyl sulfanyl, C 1 ~C 4 Alkyl sulfonyl, R x C substituted with 1 to 3 substituents independently selected from 1 ~C 4 Alkyl sulfonyl, C 1 ~C 4 Alkyl sulfinyl and R x C substituted with 1 to 3 substituents independently selected from 1 ~C 4 Each alkylsulfinyl is independently selected; R 3 C 1 ~C 3 Alkyl or C 1 ~C 3 It is a haloalkyl; R 4 and R 4a Each is independently a single -C(O)NR 10 R 11 It is pyrimidinyl, pyrazinyl, pyridadinyl, or thiazolyl substituted with; or R 4a Each is a single -C(O)NR, independently of the others. 10 R 11 It is an N-linked pyrazolyl or N-linked triazolyl substituted with; or R 4 and R 4a It is 4-cyanopyrimidine-6-yl; R 10 is hydrogen, hydroxyl, C 1 ~C 3 Alkyl, C 1 ~C 3 Cyanoalkyl, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Alkoxy, C 3 ~C 4 Cycloalkyl, C 3 ~C 4 Halocycloalkyl, cyanoC 3 ~C 4 Cycloalkyl, C 3 ~C 4 Cycloalkyl C 1 ~C 3 These are cyanoalkyl, oxetan-3-yl, thietan-3-yl, 3-methylthietan-3-yl, 1,1-dioxothietan-3-yl or 3-methyl-1,1-dioxothietan-3-yl; and R 11 is hydrogen, C 1 ~C 3 Alkyl or C 1 ~C 3 It is haloalkyl; or R 10 and R 11 These, together with the nitrogen to which they are bonded, form pyrrolidine-1-yl, piperidine-1-yl, or 4-morpholinyl groups; R 5 is hydrogen, C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 3 ~C 4 Cycloalkyl, C 1 ~C 3 Alkoxy, C 3 ~C 4 Alkoxy C(O)-, (C 1 ~C 3 Alkyl(alkoxy) 2 CH-, halogen, CN, NH 2 C(O), amino(i.e., NH) 2 ), (C 1 ~C 3 Alkyl)amino, di(C) 1 ~C 3 Alkyl)amino, hydroxy, C 3 ~C 4 Halocycloalkyl, C 3 ~C 4 Cyanocycloalkyl, C 2 ~C 6 Alkenil, C 2 ~C 6 Haloalkenil, C 2 ~C 6 Alkinyl, C 2 ~C 6 Haloalkynyl, C 1 ~C 4 Haloalkylsulfanil, C 1 ~C 4 Haloalkylsulfinyl, C 1 ~C 4 Haloalkylsulfonyl, C 1 ~C 4 Alkyl sulfanyl, C 1 ~C 4 Alkyl sulfinyl, C 1 ~C 4 Alkyl sulfonyl, C 1 ~C 3 Alkoxy-C 1 ~C 3 Alkyl, C 1 ~C 3 Alkoxy-C 1 ~C 3 Alkoxy-C 1 ~C 3 Alkyl, (C 1 ~C 3 Alkyl) sulfonylamino, (C 1 ~C 3 Alkyl)sulfonyl (C 1 ~C 3 Alkyl)amino, (C 1 ~C 3 Alkyl)NHC(O), (C 1 ~C 3 Alkyl) 2 NC(O), (C 1 ~C 3 Cycloalkyl)NHC(O), (C 1 ~C 3 Cycloalkyl) (C 1 ~C 3 Alkyl)NC(O), (C 1 ~C 3 Alkyl)C(O)(C 1 ~C 3 (Alkyl) N, (C 1 ~C 3 Alkyl)C(O)NH, (C 1 ~C 3 Alkyl) C(O), (C 1 ~C 3 Alkoxy) C(O), HC(O), diphenylmethanymine, C 1 ~C 3 It is a haloalkoxy, phenyl, or five-membered aromatic heterocycle; or R 5 C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Alkoxy, C 3 ~C 4 Phenyl substituted with one to three substituents selected from cycloalkyl, halogen, CN, and hydroxyl; or R 5 C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Alkoxy, C 3 ~C 4 A five-membered aromatic heterocycle substituted with one to three substituents selected from cycloalkyl, halogen, CN, and hydroxyl; R 5a and R 5b These are, independently of each other, hydrogen, halogen, CN, and C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 3 ~C 4 Cycloalkyl, C 1 ~C 3 Alkoxy and C 1 ~C 3 Selected from haloalkoxys; R 6 is phenyl, benzyl, heteroaryl or C 3 ~C 6 It is cycloalkyl; or R 6 Each of them is independent of the others, R x Phenyl, benzyl, heteroaryl, or C11 are substituted with one to three substituents independently selected from the above. 3 ~C 6 It is cycloalkyl; R x is halogen, C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Alkoxy, C 1 ~C 3 Haloalkoxy, NO 2 SF 5 ,CN,C(O)NH 2 C(S)NH 2 , C 1 ~C 4 Haloalkylsulfanil, C 1 ~C 4 Haloalkylsulfinyl, C 1 ~C 4 Haloalkylsulfonyl, C 1 ~C 4 Alkyl sulfanyl, C 1 ~C 4 Alkyl sulfinyl and C 1 ~C 4 Independently selected from alkylsulfonyls; R Y is hydrogen, C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, hydroxy, C 1 ~C 3 Alkoxy, C 1 ~C 3 Selected from haloalkoxys, halogens, CN, and cyclopropyls; R YY is hydrogen, C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, hydroxy, C 1 ~C 3 Alkoxy, C 1 ~C 3 Selected from haloalkoxys, halogens, CN and cyclopropyl; and R Z These are oxo, halogen, and C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Alkoxy, C 1 ~C 3 (Selected from haloalkoxy and CN) A compound of the above formula (I) or an agriculturally acceptable salt, stereoisomer, enantiomer, tautomer, or N-oxide of the compound of formula (I).

2. A 1 and A 3 N is and A 2 CH is and A 4 CR Y and A 5 CH is; and R Y The compound according to claim 1, wherein is selected from hydrogen, methyl, trifluoromethyl, and methoxy.

3. R 1 The compound according to claim 1, wherein is hydrogen, methyl, ethyl, cyanomethyl, methoxymethyl, cyclopropyl-methyl, allyl, propargyl, benzyloxycarbonyl, or benzyl.

4. R 2a is halogen, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Haloalkylsulfanil, C 1 ~C 3 Haloalkoxy, C 3 ~C 6 Cycloalkyl, C 3 ~C 6 Cycloalkyl, C 1 ~C 3 C substituted with one or two substituents independently selected from haloalkyl, cyano, and halogen 3 ~C 6 Cycloalkyl, C 3 ~C 6 Cycloalkyl C 1 ~C 4 Alkyl, C 3 ~C 6 Cycloalkyl C 1 ~C 4 Alkyl, C 1 ~C 3 C substituted with 1 to 3 substituents independently selected from haloalkyl, cyano, and halogen 3 ~C 6 Cycloalkyl C 1 ~C 4 Alkyl, C 1 ~C 5 Cyanoalkyl, C 1 ~C 4 Alkyl sulfonyl, C 1 ~C 4 Haloalkylsulfonyl, C 1 ~C 4 Alkyl sulfinyl, C 1 ~C 4 Haloalkylsulfinyl, C 3 ~C 6 Cycloalkylsulfanyl, C 3 ~C 6 Cycloalkylsulfinyl or C 3 ~C 6 The compound according to claim 1, wherein it is a cycloalkylsulfonyl.

5. R 2b is halogen, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Haloalkylsulfanil, C 1 ~C 3 Haloalkylsulfonyl, C 1 ~C 3 Alkoxy, C 1 ~C 3 The compound according to claim 1, wherein the compound is a haloalkoxy or CN.

6. R 3 C 1 ~C 3 Alkyl or C 1 ~C 3 The compound according to claim 1, which is a haloalkyl.

7. Q is, Q a -1 to Q a - Selected from 16, and R 4 These are thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, 1,2,4-thiadiazole-3-yl, 1,3,4-thiadiazole-2-yl, or 1,2,4-thiadiazole-5-yl, each of which is independently unsubstituted or C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Alkoxy, C 3 ~C 4 Cycloalkyl, halo, hydroxyl, CN, C 1 ~C 6 Haloalkoxy, C 2 ~C 6 Haloalkenyloxy, C 2 ~C 6 Haloalkynyloxy, C 3 ~C 4 Halocycloalkoxy, NH 2 C(O)-, NH 2 C(S)-, (OH)N=C(NH 2 ) - and halogens, C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Alkoxy and C 1 ~C 3 The compound according to claim 1, wherein the compound is 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 a haloalkoxy.

8. Q is, Q b -1 to Q b - Selected from 13, and R 4a These are thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, 1,2,4-thiadiazole-3-yl, 1,3,4-thiadiazole-2-yl, or 1,2,4-thiadiazole-5-yl, each of which is independently unsubstituted or C 1 ~C 3 Alkyl, C 1 ~C 3 Haloalkyl, C 1 ~C 3 Alkoxy, C 3 ~C 4 Cycloalkyl, halogen, hydroxyl, cyano and C 1 ~C 3 The compound according to claim 1, which is substituted with one or two substituents independently selected from the haloalkoxy.

9. R 4 Q c -1, Q c -2, Q c -3, Q c -4, Q c -5, Q c -6 and Q c -10 is selected; or R 4a Q c -1, Q c -2, Q c -3, Q c -4, Q c -5, Q c -6, Q c -7, Q c -8 and Q c -10: 【Transformation 3】 (In the formula, R 10 is hydrogen, methyl, ethyl, cyanomethyl, difluoromethyl, trifluoromethyl, cyclopropyl or 1-cyanocyclopropyl; or R 10 is hydrogen, hydroxy, methyl, ethyl, trifluoromethyl, cyanoethyl, methoxy, ethoxy, cyclopropyl, 1-cyanocyclopropyl, 1-cyano-1-cyclopropyl-ethyl, oxetan-3-yl, thietan-3-yl, 3-methylthietan-3-yl, 1,1-dioxothietan-3-yl or 3-methyl-1,1-dioxothietan-3-yl; and R 11 (These are hydrogen, methyl, ethyl, difluoromethyl, or trifluoromethyl.) A compound according to claim 1, selected from the following.

10. The above formula (I) is a formula Iaa, Iab, Iac, Iad, or Iae, where an asterisk indicates the stereocenter: 【Chemistry 4】 (In the formula, R, R 1 , R 2a , R 2b and R 3 Q is as defined in claim 1, and 1 (This corresponds to Q as defined in claim 1) The compound according to claim 1, represented by [the given expression].

11. Q 1 Q a -1 and Q b -1: 【Transformation 5】 Selected from, R 4 and R 4a teeth, 【Transformation 6】 (In the formula, R 10 is hydrogen, methyl, ethyl, cyanomethyl, difluoromethyl, trifluoromethyl, cyclopropyl or 1-cyanocyclopropyl; and R 11 (These are hydrogen, methyl, ethyl, difluoromethyl, or trifluoromethyl.) A compound according to claim 10, independently selected from the above.

12. Q 1 Q a -1 and Q b -1: 【Transformation 7】 Selected from, R 4 and R 4a Q c The compound according to claim 10, wherein the value is -10.

13. A composition comprising a compound according to any one of claims 1 to 12, one or more auxiliary agents and diluents, and optionally one or more other active ingredients.

14. (i) A method for controlling and eliminating insects, mites, nematodes, or mollusks, comprising applying an insecticidal, acaricidal, nematodetic, or molluscicidal amount of a compound according to any one of claims 1 to 12 to a pest, a pest habitat, or a plant susceptible to attack by a pest; or (ii) A method for protecting plant propagation material from attack by insects, mites, nematodes or mollusks, comprising treating the propagation material or the area in which the propagation material is planted with an effective amount of the compound described in any one of claims 1 to 12; or (iii) A method for controlling a parasite in or on an animal in need thereof, comprising administering an effective amount of the compound described in any one of claims 1 to 12.

15. Plant propagation material, such as seeds, comprising, treated with, or attached to, the compound described in any one of claims 1 to 12.

16. Formula XL-Q ac -a, XL-Q ac -b or XL-Q ac -c: 【Transformation 8】 (In the formula, if applicable in each case, A 1 A 2 A 3 A 4 A 5 , R 2a and R 2b This is as defined in any one of claims 1 to 6, R 1 is hydrogen or methyl, R 3 It is methyl, Q c - COOH, Q c - COORa and Q c -Xa is, Table 1 And, Ra is benzyl or C 1 ~C 6 It is alkyl, preferably Ra is methyl, and Xa is a halogen, for example, Br, Cl, or I, preferably Cl. A compound of [this].

17. Formula XL-Q bc -a, XL-Q bc -b or XL-Q bc -c: 【Chemistry 9】 (In the formula, if applicable in each case, A 1 A 2 A 3 A 4 A 5 , R 2a and R 2b This is as defined in any one of claims 1 to 6, R 1 is hydrogen or methyl, R 3 It is methyl, Q c - COOH, Q c - COORa and Q c -Xa is Q as defined in claim 16. c1 -a, Q c1 -b and Q c1 -c, Ra is benzyl or C 1 ~C 6 It is alkyl, preferably Ra is methyl, and Xa is a halogen, for example, Br, Cl, or I, preferably Cl. A compound of [this].

18. Formulas XLIIIIa(i), XLIIIIb(i), XLIIIIb-1(i), XLIIIId(i), or XLIIIIe(i): 【Chemistry 10】 (In the formula, A 4 A 5 and R 2a (wherein Gr is difluoromethyl or trifluoromethyl, as defined in any one of claims 1, 2, and 4.) A compound of [this].

19. (i) A method for controlling and eliminating insects, mites, nematodes or mollusks, comprising applying an insecticidal, acaricidal, nematodetic or molluscicidal amount of the composition according to claim 13 to a pest, a habitat of a pest, or a plant susceptible to attack by a pest; or (ii) A method for protecting plant propagation material from attack by insects, mites, nematodes or mollusks, comprising treating the propagation material or the area in which the propagation material is planted with an effective amount of the composition according to claim 13; or (iii) A method for controlling a parasite in or on an animal in need thereof, comprising administering an effective amount of the composition according to claim 13.

20. Plant propagation material such as seeds, comprising, treated with, or attached to the composition described in Claim 13.

Images