Diazinone derivatives for the control of invertebrate pests

Abstract

The invention relates to heterocyclic compounds of formula (I) wherein the variables have the meanings as defined in the specification, to compositions comprising them, to active compound combinations comprising them, and to their use for protecting growing plants and animals from attack or infestation by invertebrate pests, furthermore, to seed comprising such compounds.

Description

[0001] 250083

[0002] 1

[0003] Diazinone compounds for the control of invertebrate pests

[0004] Description

[0005] The invention relates to compounds of formula I

[0006]

[0007] wherein

[0008] R1is H, OR10a, NR12R13, Ci-C6-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci- C6-alkyl-C3-C6-cycloalkyl, Ci-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkyl-Ci- C6-alkoxy, Ci-C6-alkoxy-C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C6-alkoxy, C2-C6- alkenyl-C3-C6-cycloalkyl, C2-C6-alkynyl-C3-C6-cycloalkyl, C3-C6-cycloalkyl-C2-C6- alkenyl, C3-C6-cycloalkyl-C2-C6-alkynyl, wherein the alkyl, alkoxy, alkenyl, alkynyl, and cycloalkyl moieties are unsubstituted or substituted with one or more R11; or C(O)R11a; R2is H, Ci-C3-alkyl, C2-C3-alkenyl, C3-C6-cycloalkyl, or C2-C3-alkynyl, wherein the alkyl, alkenyl, alkynyl and cycloalkyl moieties are unsubstituted or substituted with one or more halogen;

[0009] R3is independently halogen, CN, NO2, SF5, Ci-C6-alkyl, Ci-C6-alkoxy, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6- cycloalkyl, 3- to 6-membered heterocyclyl, wherein the alkyl, alkenyl, alkynyl, alkoxy, heterocyclyl and cycloalkyl moieties are unsubstituted or substituted with one or more R11; OR10a, NR12R13, C(O)NR12R13, C(O)OR10, C(O)R14, OS(O)2-R14, S(O)m-R14, - N=S(O)R12aR13a; or

[0010] two R3bound to two adjacent C-atoms can form a 4-, 5-, or 6-membered ring, which may contain one or two heteroatoms selected from N, O, and S as ring members, wherein the ring is unsubstituted or substituted with one or more halogen, CN, Ci-C3- alkyl, and / or Ci-C3-haloalkyl;

[0011] R4H, Ci-C3-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C3-C6-cycloalkyl-Ci-C2-alkyl, Ci-C2-alkyl- C3-C6-cycloalkyl, C3-C6-cycloalkyl, wherein the alkyl, alkenyl, alkynyl or cycloalkyl moieties are unsubstituted or substituted with one or more halogen, OH, Ci-C3-alkoxy, CN, or C(O)NH2; phenyl or 5- or 6-membered hetaryl, wherein the phenyl or hetaryl moiety are unsubstituted or substituted with one or more halogen, CN, C(O)NH2, Ci- C3-alkyl, Ci-C3-haloalkyl or Ci-C3-alkoxy, or Ci-C3-haloalkoxy;

[0012] HET is a group

[0013]

[0014] 250083

[0015] 2

[0016] wherein # is the bond to the CH(R2)amide spacer, and % is the bond to the diazinone ring;

[0017] R5a, R5bare independently from each other H, halogen, CN, Ci-C3-alkyl, Ci-C3-haloalkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C3-alkyl, Ci-C3-alkyl-C3-C6-cycloalkyl, Ci-C3- alkoxy, Ci-C3-haloalkoxy, C2-C3-alkenyl, or C2-C3-alkynyl;

[0018] R5cis H, halogen, CN, OR10a, NR12R13, C(O)NR12R13, C(O)OR10a, C(O)R14, S(O)m-R14, Ci- C3-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C3-alkyl, Ci-C3-alkyl-C3-C6-cycloalkyl, Ci-C3-alkoxy, C2-C3-alkenyl, C2-C3-alkynyl, -C(=NOCi-C4-alkyl)H, or -C(=NOCI-C4- alkyl)-Ci-C4-alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl and alkoxy are unsubstituted or substituted with one or more halogen and / or CN;

[0019] R6, R7are independently from each other H, halogen, CN, C(O)NH2, Ci-C3-alkyl, Ci-C3- haloalkyl, or C3-C6-cycloalkyl; or

[0020] R6and R7together with the carbon atom to which they are bound, form a 3-, 4-, 5-, or 6-membered saturated or partially, unsaturated carbocycle, wherein the carbocycle is unsubstituted or substituted with one or more halogen, cyano, Ci-C3-alkyl, or Ci-C3- haloalkyl; or form a 3-, 4-, 5-, or 6-membered saturated or partially unsaturated heterocycle, which may contain 1 or 2 heteroatoms or heteroatom-containing groups selected from N, O, S(O)m, and optionally one or two C(O) groups as ring members, wherein the heterocycle is unsubstituted or substituted with one or more halogen, cyano, Ci-C3-alkyl, or Ci-C3-haloalkyl; or

[0021] R6and R7together with the carbon atom to which they are bound form a C(O) group; R10is H, Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C4- cycloalkyl-Ci-C2-alkyl, C3-C4-halocycloalkyl-Ci-C2-alkyl, C(O)-Ci-C4-alkyl, C(O)-Ci- C4-haloalkyl, C(C)-C3-C4-cycloalkyl, C(C)-C3-C4-halocycloalkyl, SOm-Ci-C4-alkyl, SOm-Ci-C4-haloalkyl, SOm-C3-C6-cycloalkyl, or phenyl which is unsubstituted or substituted one or more with Ra;

[0022] R10ais H, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C4-cycloalkyl-Ci-C2-alkyl, C3-C4- halocycloalkyl-Ci-C2-alkyl, C(O)-Ci-C4-alkyl, C(C)-Ci-C4-haloalkyl, C(O)-C3-C4- cycloalkyl, C(C)-C3-C4-halocycloalkyl, SOm-Ci-C4-alkyl, SOm-Ci-C4-haloalkyl, SOm- C3-C6-cycloalkyl, or phenyl which is unsubstituted or substituted one or more with Ra; R11is halogen, CN, NO2, NR12R13, C(O)NH2, C(S)NH2, C(O)OH, OR10; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the heterocyclyl, hetaryl and phenyl moieties are unsubstituted or substituted with one or more halogen, Ci- C3-haloalkyl, and / or CN;

[0023] R11ais NR12R13, Ci-C6-alkyl, Ci-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C4-cycloalkyl- Ci-C2-alkyl, wherein the alkyl, alkoxy, alkenyl, alkynyl or cycloalkyl moiety is unsubstituted or substituted with one or more halogen; or 3- to 6-membered heterocyclyl, wherein the heterocyclyl moiety is unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN;

[0024] R12, R13are independently from each other H, Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-halo- alkoxy, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C(O)-Ci-C4-alkyl, C(C)-Ci-C4-haloalkyl, C(C)-C3-C4-cycloalkyl, C(C)-C3-C4-halocycloalkyl, C(O)NH-Ci-C4-alkyl, C(O)NH-Ci- C4-haloalkyl, C(O)N(Ci-C4-alkyl)-Ci-C4-alkyl, C(0)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(C)N(Ci-C4-haloalkyl)-Ci-C4-haloalkyl, C(C)NH-Ci-C4-alkoxy, C(C)NH-Ci-C4-halo- alkoxy, C(C)NH-Ci-C4-alkoxy-Ci-C4-alkyl, C(C)NH-Ci-C4-alkoxy-Ci-C4-haloalkyl;250083

[0025] 3

[0026] C(O)NH-phenyl, C(O)NH-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, C(O)NH-Ci-C4-alkyl-phenyl, C(O)NH-Ci-C4-alkyl-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN; S(0)m-Ci-C4-haloalkyl, S(0)m-C3-C4-cycloalkyl, S(0)m-C3-C4-halocycloalkyl; 3- to 6- membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN; or

[0027] R12and R13together with the atom / atoms to which they are bound, form a 3-, 4-, 5-, 6-, or 7-membered saturated, partially or fully unsaturated heterocycle, which heterocycle may additionally contain 1 or 2 heteroatoms or heteroatom-containing groups selected from N, O, S(O)m, and optionally one or two groups C(O) as ring members, and wherein the heterocycle moiety is unsubstituted or substituted with one or more Ra;

[0028] R12a, R13aare independently from each other Ci-C4-alkyl or C3-C6-cycloalkyl, which are unsubstituted or substituted with one or more halogen and / or CN; or R12aand R13atogether with the atom to which they are bound, form a 3-, 4-, 5-, 6-, or 7-membered saturated, partially or fully unsaturated heterocycle, wherein the heterocycle moiety may additionally contain 1 or 2 heteroatoms or heteroatom-containing groups selected from N, O, S(O)m, and optionally one or two groups C(O) as ring members, and wherein the heterocycle moiety is unsubstituted or substituted with one or more Ra; R14is H, Ci-C6-alkyl, C3-C6-cycloalkyl, wherein the alkyl and cycloalkyl moieties are unsubstituted or substituted with one or more R11; or 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more Ra;

[0029] Rais halogen, CN, NO2, OH, Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-haloalkyl, Ci-C4-alkoxy-Ci- C4-alkyl, Ci-C4-haloalkoxy, C3-C4-cycloalkyl, C3-C4-halocycloalkyl, S(O)m-Ci-C4-alkyl, S(0)m-Ci-C4-haloalkyl, S(0)m-C3-C4-cycloalkyl, or S(0)m-C3-C4-halocycloalkyl; m is 0, 1, or 2;

[0030] n is 0, 1, 2, or 3;

[0031] X is N, CH, orCR3;

[0032] Y is O, S, or N-RN;

[0033] RNis as defined for R4;

[0034] and the N-oxides, stereoisomers, tautomers, and agriculturally or veterinarily acceptable salts thereof.

[0035] The invention also provides agricultural compositions comprising at least one compound of formula I, a stereoisomer thereof and / or an agriculturally acceptable salt thereof and at least one liquid and / or solid carrier, especially at least one inert liquid and / or solid agriculturally acceptable carrier.

[0036] The invention also provides a veterinary composition comprising at least one compound of formula I, a stereoisomer thereof and / or a veterinarily acceptable salt thereof and at least one liquid and / or solid carrier, especially at least one inert veterinarily liquid and / or solid acceptable carrier.250083

[0037] 4

[0038] The invention also provides a method for controlling invertebrate pests which method comprises treating the pests, their food supply, their habitat or their breeding ground or a cultivated plant, plant propagation materials (such as seed), soil, area, material or environment in which the pests are growing or may grow, or the materials, cultivated plants, plant propagation materials (such as seed), soils, surfaces or spaces to be protected from pest attack or infestation with a pesticidally effective amount of a compound of formula I or a salt thereof as defined herein.

[0039] The invention also relates to plant propagation material, in particular seed, comprising at least one compound of formula I and / or an agriculturally acceptable salt thereof.

[0040] The invention further relates to a method for treating or protecting an animal from infestation or infection by parasites which comprises bringing the animal in contact with a parasiticidally effective amount of a compound of formula I or a veterinarily acceptable salt thereof. Bringing the animal in contact with the compound I, its salt orthe veterinary composition of the invention means applying or administering it to the animal.

[0041] WO2024133551, WO2023 / 072849, WO2021 / 069575, WO2021 / 259997, WO2021 / 037614 and WO2019 / 206799 describe structurally closely related active compounds, wherein the diazinone ring is designed differently. These compounds are mentioned to be useful for combating invertebrate pests.

[0042] Nevertheless, there remains a need for highly effective and versatile agents for combating invertebrate pests. It is therefore an object of the invention to provide compounds having a good pesticidal activity and showing a broad activity spectrum against a large number of different invertebrate pests, especially against difficult to control pests, such as insects.

[0043] It has been found that these objects can be achieved by compounds of formula I as depicted and defined below, and by their stereoisomers, salts, tautomers and N-oxides, in particular their agriculturally acceptable salts.

[0044] Formula I correspond to formulae I.A and LB.

[0045]

[0046] Different R1groups can be introduced as it has been shown in the literature, e.g., WO2019201835 for the HET: HB (triazole) case and W02020 / 070049 for the HET: HA (pyrazine) case. Different R2groups can be introduced as it has been shown in the literature, e.g., WO2019 / 202077. Different X and R3groups can be introduced as it has been shown in the literature, e.g., WO2021 / 069575 and WO2019 / 206799. Different R5aand R5bgroups could be introduced as it has been shown in the literature, e.g., WO2021 / 069575. Different R5cgroups could be introduced as it has been shown in the literature, e.g., W02020 / 094363, W02020 / 188014 and WO2021 / 13719.

[0047] The introduction of the diazinone moiety with the heteroatom Y in the ring, optionally carrying R4, R6and R7, is described in the following general synthesis schemes. The compound of formula I can be prepared from compounds I.A.1.1 which can be synthesized as described in, e.g., WO2021037614, WO2021170881 , WO2023104564 and WO2023037249.250083

[0048] 5

[0049]

[0050] Example 1: The Cl precursor I.A.1.1 can undergo a Pd-catalyzed cross-coupling reaction, using, e.g., Pd(PPh3)CI2with a metal M1substituted alkoxy-enol regent (M1can be e.g. SnBu3) to obtain the enol derivative I.A.I.2. This transformation is usually carried out at temperatures of from 0°C to 150°C, preferably from 80°C to 110°C, in an inert solvent. Suitable solvents are aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, preferably toluene. The reaction mixture can be worked up under acidic conditions to yield the methyl-ketone derivative I.A.I.3. Suitable acids and acidic catalysts are in general inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulphuric acid und perchloric acid, preferably hydrochloric acid. Optionally I.A.I.3 can be further functionalized with R6and / or R7in the alpha-position of the carbonyl-group using R6-Hal and / or R7-Hal (Hal = Cl, Br or I), a base in an organic solvent. This transformation is usually carried out at temperatures of from 0°C to 100°C, preferably from 25°C to 80°C. A workup between the introduction of R6and R7might be needed. Suitable solvents are halogenated hydrocarbons such as methylene chloride, chloroform, and chlorobenzene, preferably methylene chloride. Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, or, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride. Particular preference is given to sodium hydroxide or sodium hydride.

[0051]

[0052] Subsequently the alpha-position of the carbonyl group in I.A.I.3 can be brominated with a bromination agent such as, e.g., N-bromosuccinimide or Br2in an inert solvent to yield I.A.I.4. Suitable solvents are ethers such as diethylether, diisopropylether, tert. -butylmethylether (MTBE), dioxane, anisole, and tetrahydrofurane (THF), or, halogenated hydrocarbons such as methylene chloride, chloroform, and chlorobenzene, preferably THF or carbon tetrachloride.250083

[0053] 6

[0054]

[0055] In a following step I.A.1.4 can undergo a cyclization reaction with a hydrazino compound with R4as a residue, in case R4= H is aimed, a protecting group such as a Boc-protecting group, instead of R4, is necessary to perform the cyclization reaction. This transformation to yield I.A.1.5 is usually carried out at temperatures of from 0°C to 100°C, preferably from 25°C to 80°C. Suitable solvents are alcohols such as methanol (MeOH), ethanol (EtOH), n-propanol, isopropanol, n-butanol, and tert. -butanol, or, dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably, H2O, MeOH or DMF. In case of R4= H, a subsequent deprotection reaction, such as a Boc-deprotection reaction can yield I.A.1.5 with R4= H.

[0056]

[0057] 2) deprotection (only needed for the R4= H case)

[0058]

[0059] Example 2: To obtain the sulfur-compound I.A.1.6, the bromo-precursor I.A.1.4 can undergo an acid-catalyzed cyclization reaction with an aminocarbamothioic O-acid derivative in an inert solvent. This transformation is usually carried out at temperatures of from 0 °C to 100 °C, preferably from 25°C to 80 °C. Suitable solvents are ethers such as diethylether, diisopropylether, tert. -butylmethylether (MTBE), dioxane, anisole, and tetrahydrofurane (THF), or, dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), Preferably THF or DMF. Suitable acids and acidic catalysts are in general inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulphuric acid und perchloric acid, or, organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, toluene sulphonic acid, benzene sulphonic acid, camphor sulphonic acid, citric acid, and trifluoro acetic acid. Particular preference is given to hydrochloric acid or trifluoro acetic acid. The acids are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0060] <

[0061]

[0062] R4can be introduced subsequently with a nucleophilic substitution reaction with I.A.I.6 and an R4-Hal derivative (Hal = Cl, Br or I), a base in an inert solvent, to obtain I.A.I.7. This transformation250083

[0063] 7

[0064] is usually carried out at temperatures of from 0°C to 100°C, preferably from 0°C to 80°C. Suitable solvents are ethers such as diethylether, diisopropylether, tert. -butylmethylether (MTBE), dioxane, anisole, and tetrahydrofurane (THF) moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably THF or DMF. Suitable bases are, in general, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, or, organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to sodium hydride and triethylamine. The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0065]

[0066] Example 3: To obtain the aza-compound I.A.1.11 , the bromo-precursor I.A.I.4 can be converted to the alpha-amino compound I.A.I.8 using amination regents such as, e.g., hexamethylentetramine in the presence of a salt catalyst such as, e.g., Nal in an inert solvent. This transformation is usually carried out at temperatures of from -100 °C to 100 °C, preferably from 0°C to 60 °C. Suitable solvents are alcohols such as methanol (MeOH), ethanol (EtOH), n-propanol, isopropanol, n-butanol, and tert. -butanol, or, dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably MeOH, DMF or DMSO. Suitable acids and acidic catalysts are in general inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulphuric acid und perchloric acid, or, organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, toluene sulphonic acid, benzene sulphonic acid, camphor sulphonic acid, citric acid, and trifluoro acetic acid. Particular preference is given to hydrochloric acid. The acids are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0067]

[0068] The amino-precursor I.A.I.8 can undergo cyclization reaction with an hydrazinecarboxylic acid derivative (Aryl can be, e.g., phenyl, PG = protecting group = e.g. PMB group), a base and an inert solvent. This transformation is usually carried out at temperatures of from 25°C to 100 °C, preferably from 25°C to 80 °C to yield I. A.1.9. Suitable solvents are ethers such as diethylether, diisopropylether, tert. -butylmethylether (MTBE), dioxane, anisole, and tetrahydrofurane (THF), or,250083

[0069] 8

[0070] alcohols such as methanol (MeOH), ethanol (EtOH), n-propanol, isopropanol, n-butanol, and tert.-butanol, moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably MeOH, THF or DMF. Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to potassium carbonate and triethylamine. The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0071]

[0072] I.A.1.9 can undergo a nucleophilic substitution reaction with RN-Hal (Hal = Cl, Br or I), a base in an inert solvent to yield I. A.1.10. This transformation is usually carried out at temperatures of from 25°C to 100°C, preferably from 25°C to 80 °C. Suitable solvents are ethers such as diethylether, diisopropylether, tert. -butylmethylether (MTBE), dioxane, anisole, and tetrahydrofurane (THF) moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably THF, DMF or DMSO. Suitable bases are, in general, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to potassium carbonate or triethylamine. The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0073]

[0074] 250083

[0075] 9

[0076]

[0077] Subsequently the protecting group, e.g. a PMB-protecting group of I.A.1.10, can be cleaved off. This transformation is usually carried out at temperatures of from 0°C to 100 °C, preferably from 0°C to 80°C, in an inert solvent, in the presence of an acid or an oxidant, such as DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone). Suitable solvents are alcohols such as methanol (MeOH), ethanol (EtOH), n-propanol, isopropanol, n-butanol, and tert. -butanol, moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably MeOH, DMF or DMSO. Suitable acids and acidic catalysts are in general inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulphuric acid und perchloric acid, or, moreover organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, toluene sulphonic acid, benzene sulphonic acid, camphor sulphonic acid, citric acid, and trifluoro acetic acid. Preferably hydrochloric acid or trifluoro acetic acid. The acids are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent. Optionally the obtained NH group can be substituted with R4-Hal (Hal = Cl, Br or I), a base in an inert solvent, to obtain I.A.1.11. This transformation is usually carried out at temperatures of from 25°Cto 100°C, preferably from 25°C to 80°C. Suitable solvents are ethers such as diethylether, diisopropylether, tert. -butylmethylether (MTBE), dioxane, anisole, and tetrahydrofurane (THF) moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably THF or DMF. Suitable bases are, in general, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, or, organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to sodium hydride and triethylamine. The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0078] To obtain the I.B compound, as a first step, the protected hydrazine I.B.1.1 , which is commercially available or known by the literature, can be applied in a nucleophilic substitution reaction, with an aryl carbamate. This transformation is usually carried out at temperatures of from -100 °C to 50 °C, preferably at -60 °C - 0 °C in an inert solvent. Suitable solvents are halogenated hydrocarbons such as methylene chloride, chloroform, and chlorobenzene, or ethers such as diethylether, diisopropylether, tert. -butylmethylether, dioxane, anisole, and tetrahydrofuran (THF), preferably methylene chloride or THF. Subsequently the transformation of I.B.1.2 to I.B.1.3 can be done by applying an alpha-chlorinated-ortho-ester, e.g. 2-chloro- 1,1,1 -trimethoxyethane, under acidic conditions. This transformation is usually carried out at temperatures of from 0°C to 150°C, preferably at 25 °C, in an inert solvent, alcohols such as methanol (MeOH), ethanol (EtOH), n-propanol, isopropanol, n-butanol, and tert. -butanol, moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably MeOH or water. Suitable250083

[0079] 10

[0080] acids and acidic catalysts are in general organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, toluene sulphonic acid, benzene sulphonic acid, camphor sulphonic acid, citric acid, and trifluoro acetic acid (TFA). Particular preference is given to acetic acid. The acids are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0081]

[0082] The subsequent cyclization reaction to obtain LB.1.4 can be done in the following way. To obtain the aza-diazinone compound, H2N-RNcan react with LB.1.3 to obtain the cyclized product LB.1.4 (Y = N-RN), to obtain the oxa-diazinone compound, H2O and Nal can react with LB.1.3 to obtain the cyclized product LB.1.4 (Y = O) or to obtain the thia-diazinone compound, H2S and Nal can react with LB.1.3 to obtain the cyclized product LB.1.4 (Y = S) This transformation is usually carried out at temperatures of from 0°C to 150°C, preferably at 60 °C, in an inert solvent, alcohols such as methanol (MeOH), ethanol (EtOH), n-propanol, isopropanol, n-butanol, and tert. -butanol, moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably MeOH. Suitable bases are, in general, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, potassium carbonate or, organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to triethylamine for the Y = N-RNcase, potassium carbonate for the Y = O or S case. The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0083] As the next step, the methoxy group of LB.1.4 undergoes a nucleophilic substitution reaction to yield the hydrazino compound LB.1.5. This transformation is usually carried out at temperatures of from 0°C to 200°C, preferably at 120 °C, in an inert solvent, alcohols such as methanol (MeOH), ethanol (EtOH), n-propanol, isopropanol, n-butanol, and tert. -butanol, moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably MeOH.

[0084] 0u MDNPG'NAY

[0085] IB1 3 H2N-R or N Hydrazine hydrate H2O / H2S, J MeOH

[0086] Nal, base

[0087] I.B.I.4

[0088]

[0089] Subsequently, the hydrazine compound can undergo an acid-catalyzed cyclization reaction with LB.1.6, as is known in the literature (e.g. WO2019197468, WO2023072849). The amidine moiety bearing R5ccan undergo an acid catalyzed cyclization reaction with the hydrazine moiety of I.B.I.5 to obtain the triazole compound LB.1.7. This transformation is usually carried out at temperatures of from 0°C to 200°C, preferably at 50 °C, in an inert solvent. Suitable solvents are ethers such as diethylether, diisopropylether, tert. -butylmethylether (MTBE), dioxane, anisole, and250083

[0090] 11

[0091] tetrahydrofurane (THF) moreover such as methanol (MeOH), ethanol (EtOH), n-propanol, isopropanol, n-butanol, and tert. -butanol, moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably THF. Suitable acids and acidic catalysts are in general organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, toluene sulphonic acid, benzene sulphonic acid, camphor sulphonic acid, citric acid, and trifluoro acetic acid (TFA). Particular preference is given to acetic acid. The acids are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0092] In the next step, the protecting group PG, such a boc-protecting group, can be deprotected under mild acidic conditions to obtain I.B.I.8. This transformation is usually carried out at temperatures of from 0°C to 100°C, preferably from 25°C to 80°C. Suitable acids and acidic catalysts are in general trifluoro acetic acid (TFA) or trichloro acetic acid (TCIA), preferably TFA in an inert solvent or water. The acids are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0093] In the next step, R4can be introduced subsequently with a nucleophilic substitution reaction via an R4-Hal derivative (Hal = Cl, Br or I), a base in an inert solvent. This transformation is usually carried out at temperatures of from 0°C to 100°C, preferably from 0°C to 80°C. Suitable solvents are ethers such as diethylether, diisopropylether, tert. -butylmethylether (MTBE), dioxane, anisole, and tetrahydrofurane (THF) moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably THF or DMF. Suitable bases are, in general, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, or, organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to sodium hydride and triethylamine. The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.

[0094] In the next step PG2, such as a PMB group, can be removed under harsher conditions to obtain the amino compound I.B.I.9. This transformation is usually carried out at temperatures of from 0°C to 100 °C, preferably from 0°C to 80°C, in an inert solvent, in the presence of an acid or an oxidant, such as DDQ (2,3-dichloro-5,6-dicyano-1 ,4-benzoquinone). Suitable solvents are alcohols such as methanol (MeOH), ethanol (EtOH), n-propanol, isopropanol, n-butanol, and tert.-butanol, moreover dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably MeOH, DMF or DMSO. Suitable acids and acidic catalysts are in general inorganic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, sulphuric acid und perchloric acid, or, moreover organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, toluene sulphonic acid, benzene sulphonic acid, camphor sulphonic acid, citric acid, and trifluoro acetic acid. Preferably hydrochloric acid, trifluoro acetic acid or triflic acid. The acids are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.250083

[0095] 12

[0096]

[0097] As the last step the amino compound I.B.I.9 can be applied in a literature known amide coupling reaction with an carboxylic acid, e.g. HATU-based coupling reactions, or an carboxylic acid chloride counter part to obtain I.B.1.10. This transformation is usually carried out at temperatures of from 0°C to 100°C, preferably at 25 °C, in an inert solvent, in the presence of a base. Suitable solvents are dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), and dimethylacetamide (DMA), preferably DMF. Suitable bases are, in general, organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to N-ethyl-N-isopropyl-propan-2-amine.

[0098]

[0099] The starting materials required for preparing the compounds I are commercially available or known from literature [WO2021224323, WO2023285175, WO2021037614, WO2021170881 , WO2023104564 and WO2023037249],

[0100] The reaction mixtures are worked up in a customary manner, for example by mixing with water, separating the phases and, if appropriate, chromatographic purification of the crude products. Some of the intermediates and end products are obtained in the form of colorless or slightly brownish viscous oils which are purified or freed from volatile components under reduced pressure and at moderately elevated temperature. If the intermediates and end products are obtained as solids, purification can also be carried out by recrystallization or digestion.

[0101] If individual compounds I cannot be obtained by the routes described above, they can be prepared by derivatization of other compounds I.

[0102] However, if the synthesis yields mixtures of isomers, a separation is generally not necessarily required since in some cases the individual isomers can be interconverted during work-up for use or during application (for example under the action of light, acids or bases). Such conversions may also take place after use, for example in the treatment of plants in the treated plant, or in the harmful fungus / invertebrate pest to be controlled.

[0103] The organic moieties groups mentioned in the above definitions of the variables are - like the term halogen - collective terms for individual listings of the individual group members. The prefix Cn-Cmindicates in each case the possible number of carbon atoms in the group.250083

[0104] 13

[0105] The term “partially or fully substituted” by a radical means that in general the group is substituted with same or different radicals.

[0106] The term “halogen” denotes in each case fluorine, bromine, chlorine, or iodine, in particular fluorine, chlorine, or bromine.

[0107] The term "alkyl" as used herein and in the alkyl moieties of alkylamino, alkylcarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl and alkoxyalkyl denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, more preferably from 1 to 3 carbon atoms. Examples of an alkyl group are methyl (Me), ethyl (Et), n-propyl (n-Pr), iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n-pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1 -ethylpropyl, n-hexyl, 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, and 1-ethyl-2-methylpropyl.

[0108] The term "haloalkyl" as used herein and in the haloalkyl moieties of haloalkylcarbonyl, haloalkoxycarbonyl, haloalkylthio, haloalkylsulfonyl, haloalkylsulfinyl, haloalkoxy and haloalkoxyalkyl, denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms. Preferred haloalkyl moieties are selected from Ci-C4-haloalkyl, more preferably from Ci-C3-haloalkyl or Ci-C2-haloalkyl, in particular from Ci-C2-fluoroalkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, and the like.

[0109] The term "alkoxy" as used herein denotes in each case a straight-chain or branched alkyl group which is bonded via an oxygen atom and has usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms. Examples of an alkoxy group are methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy, tert. -butyloxy, and the like. The term "alkoxyalkyl" as used herein refers to alkyl usually comprising 1 to 10, frequently 1 to 4, preferably 1 to 2 carbon atoms, wherein 1 carbon atom carries an alkoxy radical usually comprising 1 to 4, preferably 1 or 2 carbon atoms as defined above. Examples are CH2OCH3, CH2-OC2H5, 2-(methoxy)ethyl, and 2-(ethoxy)ethyl.

[0110] The term "haloalkoxy" as used herein denotes in each case a straight-chain or branched alkoxy group having from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms, in particular fluorine atoms. Preferred haloalkoxy moieties include C1-C4-haloalkoxy, in particular Ci-C2-fluoroalkoxy, such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1 -fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoro-ethoxy, 2,2dichloro-2-fluorethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and the like.

[0111] The term "alkylthio "(alkylsulfanyl: S-alkyl)" as used herein refers to a straight-chain or branched saturated alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (= C1-C4-alkylthio), more preferably 1 to 3 carbon atoms, which is attached via a sulfur atom.

[0112] The term "haloalkylthio" as used herein refers to an alkylthio group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and / or iodine.250083

[0113] 14

[0114] The term "alkylsulfinyl" (alkylsulfoxyl: S(=O)-alkyl), as used herein refers to a straight-chain or branched saturated alkyl group (as mentioned above) having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (= Ci-C4-alkylsulfinyl), more preferably 1 to 3 carbon atoms bonded through the sulfur atom of the sulfinyl group at any position in the alkyl group.

[0115] The term "haloalkylsulfinyl" as used herein refers to an alkylsulfinyl group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and / or iodine.

[0116] The term "alkylsulfonyl" (S(=O)2-alkyl) as used herein refers to a straight-chain or branched saturated alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (= C1-C4-alkylsulfonyl), preferably 1 to 3 carbon atoms, which is bonded via the sulfur atom of the sulfonyl group at any position in the alkyl group.

[0117] The term "haloalkylsulfonyl" as used herein refers to an alkylsulfonyl group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and / or iodine.

[0118] The term "alkylcarbonyl" refers to an alkyl group as defined above, which is bonded via the carbon atom of a carbonyl group (C=O) to the remainder of the molecule.

[0119] The term "haloalkylcarbonyl" refers to an alkylcarbonyl group as mentioned above, wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and / or iodine. The term "alkoxycarbonyl" refers to an alkylcarbonyl group as defined above, which is bonded via an oxygen atom to the remainder of the molecule.

[0120] The term "haloalkoxycarbonyl” refers to an alkoxycarbonyl group as mentioned above, wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and / or iodine. The term "alkenyl" as used herein denotes in each case a singly unsaturated hydrocarbon radical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. vinyl, allyl (2-propen- 1-yl), 1-propen-1-yl, 2-propen-2-yl, methallyl (2-methylprop-2-en-1-yl), 2-buten-1-yl, 3-buten-1-yl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl, 2-ethylprop-2-en-1-yl and the like.

[0121] The term "haloalkenyl" as used herein refers to an alkenyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms.

[0122] The term "alkynyl" as used herein denotes in each case a singly unsaturated hydrocarbon radical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. ethynyl, propargyl (2-propyn-1-yl), 1-propyn-1-yl, 1-methylprop-2-yn-1-yl), 2-butyn-1-yl, 3-butyn-1-yl, 1-pentyn-1-yl, 3-pentyn-1-yl, 4-pentyn-1-yl, 1-methylbut-2-yn-1-yl, 1-ethylprop-2-yn-1-yl and the like.

[0123] The term "haloalkynyl" as used herein refers to an alkynyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms.

[0124] The term "cycloalkyl" as used herein and in the cycloalkyl moieties of cycloalkoxy and cycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 or from 3 to 6 carbon atoms, such as cyclopropyl (cC3H5), cyclobutyl (cC4H7), cyclopentyl (cC5H9), cyclohexyl (cC6Hn), cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl or cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0125] The term "cycloalkylalkyl" refers to a cycloalkyl group as defined above which is bonded via an alkylene group, such as a Ci-C5-alkyl group or a Ci-C4-alkyl group, in particular a methylene group CH2(=cycloalkylmethyl), to the remainder of the molecule.250083

[0126] 15

[0127] The term "halocycloalkyl" as used herein and in the halocycloalkyl moieties of halocycloalkoxy and halocycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 C atoms or 3 to 6 C atoms, wherein at least one, e.g. 1 , 2, 3, 4 or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine. Examples are 1- and 2-fluorocyclopropyl, 1,2-, 2,2- and 2,3-difluorocyclopropyl, 1 ,2,2-trifluorocyclopropyl, 2, 2,3,3-tetrafluorocyclpropyl, 1- and 2-chlorocyclopropyl, 1,2-, 2,2- and 2,3-dichlorocyclopropyl, 1,2,2-trichlorocyclopropyl, 2,2,3,3-tetrachlorocyclpropyl, 1-,2- and 3-fluorocyclopentyl, 1,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-difluorocyclopentyl, 1-,2- and 3-chlorocyclopentyl, 1,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-dichlorocyclopentyl and the like.

[0128] The term “halocycloalkenyl” as used herein and in the halocycloalkenyl moieties of halocycloalkenyloxy and halocycloalkenylthio denotes in each case a monocyclic singly unsaturated non-aromatic radical having usually from 3 to 10, e.g. 3 or 4 or from 5 to 10 carbon atoms, preferably from 3- to 8 carbon atoms, wherein at least one, e.g. 1, 2, 3, 4 or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine. Examples are 3,3-difluorocyclopropen-1-yl and 3,3-dichlorocyclopropen-1-yl.

[0129] The term "cycloalkenylalkyl" refers to a cycloalkenyl group as defined above which is bonded via an alkyl group, such as a Ci-C5-alkyl group or a Ci-C4-alkyl group, in particular a methylene group (= cycloalkenylmethyl), to the remainder of the molecule.

[0130] The term “carbocycle” or “carbocyclyl” includes in general a 3- to 12-membered, preferably a 3-to 8-membered or a 5- to 8-membered, more preferably a 5- or 6-membered mono-cyclic, non-aromatic ring comprising 3 to 12, preferably 3 to 8 or 5 to 8, more preferably 5 or 6 carbon atoms. Preferably, the term “carbocycle” covers cycloalkyl and cycloalkenyl groups as defined above. The term “heterocycle” or "heterocyclyl" includes in general 3- to 12-membered, preferably 3- to 6-membered, in particular 6-membered monocyclic heterocyclic non-aromatic radicals. The heterocyclic non-aromatic radicals usually comprise 1 , 2, 3, 4 or 5, preferably 1 , 2 or 3 heteroatoms selected from N, O, and S, wherein S-atoms as ring members may be present as S, SO, or SO2, and optionally one or two groups C(O) as ring members. Examples of 5- or 6-membered heterocyclic radicals comprise saturated or unsaturated, non-aromatic heterocyclic rings, such as oxiranyl, oxetanyl, thietanyl, thietanyl-S-oxid (S-oxothietanyl), thietanyl-S-dioxid (S-dioxothiethanyl), pyrrolidinyl, pyrrolinyl, pyrazolinyl, tetrahydrofuranyl, dihydrofuranyl, 1,3-dioxolanyl, thiolanyl, S-oxothiolanyl, S-dioxothiolanyl, dihydrothienyl, S-oxodihydrothienyl, S-dioxodihydrothienyl, oxazolidinyl, oxazolinyl, thiazolinyl, oxathiolanyl, piperidinyl, piperazinyl, pyranyl, dihydropyranyl, tetrahydropyranyl, 1,3- and 1 ,4-dioxanyl, thiopyranyl, S. oxothiopyranyl, S-dioxothiopyranyl, dihydrothiopyranyl, S-oxodihydrothiopyranyl, S-dioxodihydrothiopyranyl, tetrahydrothiopyranyl, S-oxotetrahydrothiopyranyl, S-dioxotetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, S-oxothiomorpholinyl, S-dioxothiomorpholinyl, thiazinyl and the like. Examples for heterocyclic ring also comprising 1 or 2 carbonyl groups as ring members comprise pyrrolidin- 2-onyl, pyrrolidin-2,5-dionyl, imidazolidin-2-onyl, oxazolidin-2-onyl, thiazolidin-2-onyl, and the like. The term "hetaryl" includes monocyclic 5- or 6-membered heteroaromatic radicals comprising as ring members 1, 2, 3 or 4 heteroatoms selected from N, O, and S. Examples of 5- or 6-membered heteroaromatic radicals include pyridyl, i.e. 2-, 3-, or 4-pyridyl, pyrimidinyl, i.e. 2-, 4- or 5-pyrimidinyl, pyrazinyl, pyridazinyl, i.e. 3- or4-pyridazinyl, thienyl, i.e. 2- or3-thienyl, furyl, i.e. 2-or 3-furyl, pyrrolyl, i.e. 2- or 3-pyrrolyl, oxazolyl, i.e. 2-, 3- or 5-oxazolyl, isoxazolyl, i.e. 3-, 4- or 5-isoxazolyl, thiazolyl, i.e. 2-, 3- or 5-thiazolyl, isothiazolyl, i.e. 3-, 4- or 5-isothiazolyl, pyrazolyl, i.e.

[0131] 1-, 3-, 4- or 5-pyrazolyl, i.e. 1-, 2-, 4- or 5-imidazolyl, oxadiazolyl, e.g. 2- or 5-[1 ,3,4]oxadiazolyl,250083

[0132] 16

[0133] 4- or 5-(1 ,2,3-oxadiazol)yl, 3- or 5-(1 ,2,4-oxadiazol)yl, 2- or 5-(1 , 3 ,4-th iad iazol)yl , thiadiazolyl, e.g.

[0134] 2- or 5-(1,3,4-thiadiazol)yl, 4- or 5-(1 ,2,3-thiadiazol)yl, 3- or 5-(1,2,4-thiadiazol)yl, triazolyl, e.g.

[0135] 1 H-, 2H- or 3H-1 ,2,3-triazol-4-yl, 2H-triazol-3-yl, 1 H-, 2H-, or 4H-1 ,2,4-triazolyl and tetrazolyl, i.e.

[0136] 1H- or 2H-tetrazolyl. The term "hetaryl" also includes bicyclic 8 to 10-membered heteroaromatic radicals comprising as ring members 1 , 2 or 3 heteroatoms selected from N, O, and S, wherein a 5- or 6-membered heteroaromatic ring is fused to a phenyl ring or to a 5- or 6-membered heteroaromatic radical. Examples of a 5- or 6-membered heteroaromatic ring fused to a phenyl ring or to a 5- or 6-membered heteroaromatic radical include benzofuranyl, benzothienyl, indolyl, indazolyl, benzimidazolyl, benzoxathiazolyl, benzoxadiazolyl, benzothiadiazolyl, benzoxazinyl, chinolinyl, isochinolinyl, purinyl, 1 ,8-naphthyridyl, pteridyl, pyrido[3,2-d]pyrimidyl or pyridoimidazolyl and the like. These fused hetaryl radicals may be bonded to the remainder of the molecule via any ring atom of 5- or 6-membered heteroaromatic ring or via a carbon atom of the fused phenyl moiety.

[0137] The terms "heterocyclylalkyl" and "hetarylalkyl" refer to heterocyclyl or hetaryl, respectively, as defined above which are bonded via a Ci-C5-alkyl group or a Ci-C4-alkyl group, in particular a methylene group (= heterocyclylmethyl or hetarylmethyl, resp.), to the remainder of the molecule. The term “arylalkyl” and "phenylalkyl" refer to aryl as defined above and phenyl, respectively, which are bonded via Ci-C5-alkyl group or a Ci-C4-alkyl group, in particular a methyl group (= arylmethyl or phenylmethyl), to the remainder of the molecule, examples including benzyl, 1-phenylethyl, 2-phenylethyl, 2-phenoxyethyl etc.

[0138] The terms “alkylene”, “cycloalkylene”, “heterocycloalkylene”, “alkenylene”, “cycloalkenylene”, “heterocycloalkenylene” and “alkynylene” refer to alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, heterocycloalkenyl and alkynyl as defined above, resp., which are bonded to the remainder of the molecule, via two atoms, preferably via two carbon atoms, of the respective group, so that they represent a linker between two moieties of the molecule.

[0139] It is understood that the various embodiments of compounds of formula I also include the N-oxide, stereoisomer, tautomer, agriculturally or veterinarily acceptable salt thereof.

[0140] In a particular embodiment, the variables of the compounds of the formula I have the following meanings, these meanings, both on their own and in combination with one another, being particular embodiments of the compounds of the formula I.

[0141] Embodiments and preferred compounds of the invention for use in pesticidal methods and for insecticidal application purposes are outlined in the following paragraphs.

[0142] With respect to the variables, the particularly preferred embodiments of the intermediates correspond to those of the compounds of the formula I.

[0143] In a preferred embodiment, the compounds I are present in form of a mixture of compounds I.S and I.R, wherein compound I.S with S-configuration of the carbon atom neighboring the nitrogen is present in an amount of more than 50% by weight, in particular of at least 70% by weight, more particularly of at least 85% by weight, more particularly of at least 90% by weight, more particularly of at least 95% by weight, specifically of at least 99% by weight, based on the total weight of250083

[0144] 17

[0145] compounds I.S and I.R. Compounds of formula I.S are a particularly preferred embodiment of the invention.

[0146]

[0147] In one particularly preferred embodiment of the invention, the method comprises the step of contacting the plant, parts of it, its propagation material, the pests, their food supply, habitat or breeding grounds with a pesticidally effective amount of a compound of formula I.S.

[0148] In various embodiments, R1is H, OH, Ci-C6-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, Ci-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkyl-Ci-C6-alkoxy, Ci-C6-alkoxy-C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C6-alkoxy, C2-C6-alkenyl-C3-C6-cycloalkyl, C2-C6-alkynyl-C3-C6-cycloalkyl, C3-C6-cycloalkyl-C2-C6-alkenyl, C3-C6-cycloalkyl-C2-C6-alkynyl, wherein the alkyl, alkoxy, alkenyl, alkynyl, and cycloalkyl moieties are unsubstituted or substituted with one or more halogen, CN, NO2, C(O)NH2; C(O)-Ci-C6-alkyl, C(O)-Ci-C6-alkoxy.

[0149] In various embodiments, R1is H, Ci-C6-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C4-alkyl, Ci-C4-alkyl-C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkyl-Ci-C6-alkoxy, wherein the alkyl, alkoxy, alkenyl, alkynyl and cycloalkyl moieties are unsubstituted or substituted with one or more halogen, preferably R1is H, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkyl-C3-C6-cycloalkyl, Ci-C4-alkyl-S-Ci-C4-alkyl, further preferably R1is H, CH3, CH2-cyclopropyl, or (CH2)2-S-CH3, more preferably R1is Hor CH3.

[0150] In various embodiments, R2is CH3.

[0151] In various embodiments, each R3is independently selected from halogen, CN, Ci-C4-alkyl, Ci-C4-alkoxy, C3-C6-cycloalkyl, S(O)m-Ci-C4-alkyl, OS(O)m-Ci-C4-alkyl, or S(O)m-phenyl, wherein the alkyl, alkoxy, cycloalkyl and phenyl moieties are unsubstituted or substituted with one or more CN or halogen.

[0152] In various embodiments two R3bound to two adjacent C-atoms can form a 4-, 5-, or 6-membered ring, which may contain one or two heteroatoms selected from N, O, and S as ring members, wherein the ring is unsubstituted or substituted with one or more halogen, CN, Ci-C3-alkyl, and / or Ci-C3-haloalkyl.

[0153] In various embodiments, each R3is independently selected from CF3, Cl, Br, SO2-CF3, O-SO2-CF3, SO-CF3, SO-CH3, C(CH3)2CN, 1-CN-CC3H4(CN-substituted cyclopropyl), OCHF2, and SO2-(4-F-phenyl). These R3substituents may be in the 3- and / or 5-positions. In various embodiments, n is 2 and one R3is CF3and the other is also CF3, or any one of Cl, Br, SO2-CF3, O-SO2-CF3, SO-250083

[0154] 18

[0155] CF3, SO-CH3, C(CH3)2CN, 1-CN-CC3H4(CN-substituted cyclopropyl), OCHF2, and SO2-(4-F-phenyl). In various embodiments, n is 2 and one R3is SO-CH3, SO-CF3, SO2-CF3or S02-(4-F-phenyl) and the other R3is Cl or Br. In one embodiment, one R3is 1-CN-cC3H4(CN-substituted cyclopropyl) and the other is OCHF2. In one embodiment, one R3is C(CH3)2CN and the other is Br.

[0156] In various embodiments, each R3is independently selected from halogen, CN, Ci-C4-alkyl, wherein alkyl is unsubstituted or substituted with one or more CN, Ci-C4-haloalkyl, Ci-C4-haloalkoxy, C3-C4-cycloalkyl, wherein cycloalkyl is unsubstituted or substituted with one or more CN or halogen, S(O)m-Ci-C4-alkyl, S(0)m-Ci-C4-haloalkyl, OS(O)m-Ci-C4-alkyl, OS(O)m-Ci-C4-haloalkyl, S(O)m-phenyl, wherein phenyl is unsubstituted or substituted with one or more halogen. In various embodiments, each R3is independently selected from F, Cl, Br, CF3, CCIF2, CF2CH3, CN, SCH3, OCH3, S-CH2-CN, S-CF3, SO2CF3, SOCF3, SO2(4-F-C6H4), SO2-(2-F-C6H4), SO2-(4-Br-C6H4), SO2-CH(CH3)2, SO2-CC3H5, SO2-CH3, O-SO2-CF3, 1-CN-CC3H4, C(CH3)2CN, 2-CI2-CC3H3, C(CH2)-CC3H5, CH(OCH3)-CC3H5, C(O)-CC3H5, CCH, C(CH3)3, CH(CI)2, CF2H, OCF3or OCF2H.

[0157] In various embodiments, each R3is independently selected from SCH3, S-CH2-CN, SO2CF3, SOCF3, SO2(4-F-C6H4), SO2-(2-F-C6H4), SO2-(4-Br-C6H4), SO2-CH(CH3)2, SO2-cC3H5, SO2-CH3, O-SO2-CF3, 1-CN-CC3H4, C(CH3)2CN, 2-CI2-CC3H3, C(CH2)-CC3H5, CH(OCH3)-CC3H5, C(O)-CC3H5, or CCH.

[0158] In various embodiments of (R3)n, index n is 2 and R3is in positions 3 and 5, preferably wherein R3is selected from 3,5-(CF3)2; 3-CF3, 5-CI; 3-(2-CI2-cC3H3), 5-CI; 3-(1-CN-cC3H4), 5-OCHF2; 3-C(CH2)-CC3H5, 5-CI; 3-S-CF3, 5-CN; 3-SO2-(2-F-C6H4), 5-CI; 3-SO2-(4-Br-C6H4), 5-CI; 3-CH(OCH3)-CC3H5, 5-CI; 3-CH(OCH3)-cC3H5, 5-CI; 3-C(O)-cC3H5, 5-CI; 3-SO2-CH(CH3)2, 5-CI; 3-SO2-(4-F-C6H4), 5-CI; 3-S(O)-CF3, 5-CI; 3-O-SO2-CF3, 5-CF3; 3-SO2-CF3, 5-CI; 3-C(CH3)2-CN, 5-Br; 3-SO2-CC3H5, 5-CI; 3-SO2-CH3, 5-CI; 3-O-CF3, 5-CI; 3-F, 5-OCH3; 3,5-Br2; 3-Br, 5-CI; 3-Br, 5-F; 3-F, 5-CCH; 3-Br, 5-CN; 3-CI, 5-CN; 3-F, 5-CN; 3-OCF3, 5-CN; 3-(1-CN-cC3H4), 5-Br; 3,5-CI2; 3-CI, 5-F; 3,5-F2; 3-OCF3, 5-Br; 3-OCF3, 5-F; 3-OCF2H, 5-CI; 3-OCF2H, 5-Br; 3-CF2H, 5-CI; 3-(1-CN-CC3H4), 5-OCF3; 3-CF3, 5-CN; 3-CF2H, 5-Br; 3-SCH3, 5-Br; 3-C(CH3)3, 5-CI; 3-OCF3, 5-OCF2H; 3-OCF2H, 5-CN; 3-CF2CH3, 5-F; 3-OCF2H, 5-OCF2H; 3-S-CH2-CN, 5-CI; 3-CI, 5-CH(CI)2; 3-CI, 5-CCIF2; or 3,5-(OCF3)2.

[0159] In various embodiments, at least one R3group in (R3)nis selected from R3d, wherein each R3dis independently Ci-C6-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, wherein alkyl, alkenyl, alkynyl, and cycloalkyl are unsubstituted or substituted with one or more R3a; NR12R13, C(O)NR12R13, C(O)OR10, C(O)R14, OS(O)2-R14and S(O)m-R14, wherein m is 1 or 2; and wherein each R3ais independently halogen, CN, NO2, OH.

[0160] In various embodiments, at least one R3group in (R3)nmay be selected from R3d, wherein each R3dis independently C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, wherein alkyl, alkenyl, alkynyl, and cycloalkyl are unsubstituted or substituted independently with one or more halogen, CN, NO2, or OH; Ci-C6-alkyl substituted with250083

[0161] 19

[0162] one or more CN, NO2, or OH; NR12R13, C(O)NR12bR13b, C(O)OR10b, C(O)R14, OS(O)2-R14and S(O)I-2-R14.

[0163] In various embodiments, at least one R3group in (R3)nmay be selected from R3d, wherein each R3dis independently NH2, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, wherein alkyl, alkenyl, alkynyl, and cycloalkyl are unsubstituted or substituted independently with one or more halogen or CN; Ci-C6-alkyl substituted with one or more CN; OS(O)2-Ci-C4-alkyl, OS(0)2-Ci-C4-haloalkyl; S(O)m-Ci-C4-alkyl, S(0)m-Ci-C4-haloalkyl, wherein m is 1 or 2.

[0164] In various embodiments where X is CR3, the R3substituents on the phenyl ring may, be selected from R3d, wherein each R3dis defined as above.

[0165] In various embodiments where X is N, the R3substituents on the hetaryl ring may, be selected from R3d, wherein each R3dis defined as above.

[0166] In various embodiments R3dis independently C4-C6-alkyl, C4-C6-alkoxy, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl or 3- to 6-membered heterocyclyl, wherein the alkyl, alkenyl, alkynyl, alkoxy, heterocyclyl and cycloalkyl moieties are unsubstituted or substituted with one or more R11.

[0167] In various embodiments R3dis independently, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, wherein alkyl, alkenyl, alkynyl, and cycloalkyl are unsubstituted or substituted independently with one or more halogen, CN, NO2, or OH.

[0168] In various embodiments R3dis independently, Ci-C3alkyl, Ci-C3alkoxy, Ci-C3-alkylthio, wherein alkyl and alkoxy are substituted with one or more R11b.

[0169] In various embodiments R3dis independently, Ci-C6-alkyl substituted with one or more CN, NO2, or OH.

[0170] In various embodiments R3dis independently, OR10a, NR12R13, C(O)NR12bR13b, C(S)NR12bR13b, C(O)OR10b, C(O)R14, OS(O)2-R14, S(O)I.2-R14, -N=S(O)R12aR13a.

[0171] In various embodiments R3dis independently, NR12R13, C(O)NR12bR13b, C(O)OR10b, C(O)R14, OS(O)2-R14and S(O)I.2-R14.

[0172] In various embodiments, at least one R3group in (R3)nis selected from R3d, if HET is HB.

[0173] In various embodiments, at least one R3group in (R3)nis selected from R3dif HET is HB, wherein each R3dis independently C4-C6-alkyl, C4-C6-alkoxy, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, 3- to 6-membered heterocyclyl, wherein the alkyl, alkenyl, alkynyl, alkoxy, heterocyclyl and cycloalkyl moieties are unsubstituted or substituted with one or more R11; Ci-C3alkyl, Ci-C3alkoxy, Ci-C3-alkylthio,250083

[0174] 20

[0175] wherein alkyl and alkoxy are substituted with one or more R11b; OR10a, NR12R13, C(O)NR12bR13b, C(S)NR12bR13b, C(O)OR10b, C(O)R14, OS(O)2-R14, S(O)I.2-R14, -N=S(O)R12aR13a; or two R3bound to two adjacent C-atoms can form a 4-, 5-, or 6-membered ring, which may contain one or two heteroatoms selected from N, O, and S as ring members, wherein the ring is unsubstituted or substituted with one or more halogen, CN, Ci-C3-alkyl, and / or Ci-C3-haloalkyl; In various embodiments, each R3dis independently C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, wherein alkyl, alkenyl, alkynyl, and cycloalkyl are unsubstituted or substituted independently with one or more halogen, CN, NO2, or OH; Ci-C6-alkyl substituted with one or more CN, NO2, or OH; NR12R13, C(O)NR12bR13b, C(O)OR10b, C(O)R14, OS(O)2-R14and S(O)m-R14wherein m is 1 or 2.

[0176] In various embodiments, each R3dis independently C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, wherein alkyl, alkenyl, alkynyl, and cycloalkyl are unsubstituted or substituted independently with one or more halogen, CN, NO2, or OH; Ci-C6-alkyl substituted with one or more CN, NO2, or OH; NR12R13, C(O)NR12bR13b, C(O)OR10b, C(O)R14, OS(O)2-R14and S(O)m-R14wherein m is 1 or 2.

[0177] In various embodiments, each R3dis independently NH2, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, wherein alkyl, alkenyl, alkynyl, and cycloalkyl are unsubstituted or substituted with one or more halogen or CN; Ci-C6-alkyl substituted with one or more CN; OS(O)2-Ci-C4-alkyl, OS(0)2-Ci-C4-haloalkyl; S(O)m-Ci-C4-alkyl, S(0)m-Ci-C4-haloalkyl, wherein m is 1 or 2.

[0178] In various embodiments, n is 2 and / or R3is in positions 3 and 5.

[0179] In various embodiments, R4is H, Ci-C3-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C3-C6-cycloalkyl-Ci-C2-alkyl, Ci-C2-alkyl-C3-C6-cycloalkyl, C3-C6-cycloalkyl, wherein the alkyl, alkenyl, alkynyl or cycloalkyl moieties are unsubstituted or substituted with one or more halogen, OH or Ci-C3-alkoxy, preferably R4is H, CH3or CH2CECH.

[0180] In various embodiments, R4is H, Ci-C3-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C3-C6-cycloalkyl-Ci-C2-alkyl, Ci-C2-alkyl-C3-C6-cycloalky, C3-C6-cycloalkyl, which are unsubstituted or substituted with one or more halogen, CN; preferably R4is H, CH3, CH2CH3, CH(CH3)2, CH2CH2CH3, cC3H5, CH2CN, CH2CECH, CH2OCH3, CHF2, CH2CF3, 1-CN-CC3H4, CH2CC3H5, C(H)=CH2, or CH2CH2CN, more preferably R4is H, CH3or CH2CECH.

[0181] In various embodiments, R4is H, C3-C4-alkenyl, C4-alkynyl, Ci-C2-alkyl-C3-C6-cycloalky, C3-C6-cycloalkyl, wherein the alkyl, alkenyl, alkynyl or cycloalkyl moieties are unsubstituted or substituted with one or more halogen, OH, Ci-C3-alkoxy.

[0182] In various embodiments, R5aand R5bare independently from each other H, halogen, CN, Ci-C3-alkyl, Ci-C3-haloalkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C3-alkyl, Ci-C3-alkyl-C3-C6-cycloalkyl, Ci-C3-alkoxy, Ci-C3-haloalkoxy, C2-C3-alkenyl, or C2-C3-alkynyl.250083

[0183] 21

[0184] In various embodiments, R5cis H, halogen, CN, OR10a, NR12R13, C(O)NR12R13, C(O)OR10a, C(O)R14, S(O)m-R14, Ci-C3-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C3-alkyl, Ci-C3-alkyl-C3-C6-cycloalkyl, Ci-C3-alkoxy, C2-C3-alkenyl, C2-C3-alkynyl, -C(=NOCi-C4-alkyl)H, or-C(=NOCi-C4-alkyl)-Ci-C4-alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl and alkoxy are unsubstituted or substituted with one or more halogen and / or CN.

[0185] In various embodiments, R5a, R5band R5care independently selected from H, halogen, CN, Ci-C3-alkyl or C3-C6-cycloalkyl, preferably R5a, R5band R5care H.

[0186] In various embodiments, R5ais selected from H, halogen, CN, Ci-C3-alkyl, Ci-C3-alkoxy, Ci-C3-haloalkyl, Ci-C3-haloalkoxy or C3-C6-cycloalkyl; preferably R5ais H.

[0187] In various embodiments, R5bis selected from H, halogen, CN, Ci-C3-alkyl, Ci-C3-alkoxy, Ci-C3-haloalkyl, Ci-C3-haloalkoxy or C3-C6-cycloalkyl; preferably R5bis H.

[0188] In various embodiments, R5cis selected from H, halogen, Ci-C3-alkyl, Ci-C3-alkoxy, Ci-C3-haloalkyl, Ci-C3-haloalkoxy or C3-C6-cycloalkyl; preferably R5cis H. In various embodiments, R5cis selected from H, halogen, Ci-C3-alkyl, Ci-C3-alkoxy, Ci-C3-haloalkyl, Ci-C3-haloalkoxy, C3-C6-cycloalkyl, NH2, NH-Ci-C3-alkyl; N-(Ci-C3-alkyl)2, NH-C(O)-Ci-C3-alkyl orS02-CH3; preferably R5cis H, CH3, c-Pr, Cl, Br, NH2, NH-CH3, N-(CH3)2or O-CH3.

[0189] In various embodiments, R5cis selected from H, halogen, CN, Ci-C3-alkyl, C3-C6-cycloalkyl, NH2, NHC(O)-Ci-C3-alkyl, NH(Ci-C3-alkyl), Ci-C4-haloalkyl, Ci-C3-alkoxy, or S-Ci-C3-alkyl; preferably wherein R5cis H, Cl, Br, I, CH3, CH2CH3, cyclopropyl, NH2, NHCH3, N(CH3)2, NHC(O)CH3, CF2H, CF3, OCH3.

[0190] In various embodiments, R6and R7are independently from each other H, halogen, CN, C(O)NH2, CH3, CH2CH3, CH(CH3)2or CH2CH2CH3; or R6and R7together with the carbon atom to which they are bound, form a cyclopropyl ring.

[0191] In various embodiments, R10bis Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C4-cycloalkyl-Ci-C2-alkyl, C3-C4-halocycloalkyl-Ci-C2-alkyl, C(O)-Ci-C4-alkyl, C(C)-Ci-C4-haloalkyl, C(C)-C3-C4-cycloalkyl, C(C)-C3-C4-halocycloalkyl, SOm-Ci-C4-alkyl, SOm-Ci-C4-haloalkyl, SOm-C3-C6-cycloalkyl, or phenyl which is unsubstituted or substituted with one or more Ra;

[0192] In various embodiments, R11bis CN, NO2, NR12R13, C(O)NH2, C(S)NH2, C(O)OH, OR10, Si(CH3)3; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the heterocyclyl, hetaryl and phenyl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN;

[0193] In various embodiments, R12b, R13bare independently from each other Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-haloalkoxy, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C(O)-Ci-C4-alkyl, C(O)-Ci-C4-haloalkyl, C(C)-C3-C4-cycloalkyl, C(C)-C3-C4-halocycloalkyl, C(O)NH-Ci-C4-alkyl, C(O)NH-Ci-C4-haloalkyl, C(O)N(Ci-C4-alkyl)-Ci-C4-alkyl, C(0)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(O)N(CI-C4-250083

[0194] 22

[0195] haloalkyl)-Ci-C4-haloalkyl, C(0)NH-Ci-C4-alkoxy, C(C)NH-Ci-C4-haloalkoxy, C(O)NH-CI-C4-alkoxy-Ci-C4-alkyl, C(0)NH-Ci-C4-alkoxy-Ci-C4-haloalkyl; C(O)NH-phenyl, C(O)NH-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, C(O)NH-Ci-C4-alkyl-phenyl, C(O)NH-Ci-C4-alkyl-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN; S(0)m-Ci-C4-haloalkyl, S(0)m-C3-C4-cycloalkyl, S(O)m-C3-C4-halocycloalkyl; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN; or R12band R13btogether with the atom(s) to which they are bound, form a 3-, 4-, 5-, 6-, or 7-membered saturated, partially or fully unsaturated heterocycle, which heterocycle may additionally contain 1 or 2 heteroatoms or heteroatomcontaining groups selected from N, O, S(O)m, and optionally one or two groups C(O) as ring members, and wherein the heterocycle moiety is unsubstituted or substituted with one or more Ra.

[0196] In various embodiments, the compounds are of formula I.A.N.1, I.A.N.Ia, I.A.N.2, or I.A.N.2a

[0197]

[0198] or the N-oxides, stereoisomers, and agriculturally or veterinarily acceptable salts thereof.

[0199] In various embodiments, the invention relates to compounds of Table I and II.

[0200] In particular with a view to their use, preference is given to the compounds of formula I compiled in the tables below. Each of the groups mentioned for a substituent in the tables is furthermore per se, independently of the combination in which it is mentioned, a particularly preferred aspect of the substituent in question.

[0201] Table 1 : Compounds of formula I.A.N.1 in which Y is O, R2is CH3, R4is H, R6is H, R7is H and the combination of R1and (R3)nfor a compound corresponds in each case to one row of Table A

[0202] Table 2 : Compounds of formula I.A.N.Ia in which Y is O, R2is CH3, R4is H, R6is H, R7is H and the combination of R1and (R3)nfor a compound corresponds in each case to one row of Table B250083

[0203] 23

[0204] Table 3 : Compounds of formula I.A.N.1 in which Y is N-CH3, R2is CH3, R4is H, R6is H, R7is H and the combination of R1and (R3)nfor a compound corresponds in each case to one row of Table A

[0205] Table 4 : Compounds of formula I.A.N.Ia in which Y is N-CH3, R2is CH3, R4is H, R6is H, R7is H and the combination of R1and (R3)nfor a compound corresponds in each case to one row of Table B

[0206] Table 5 : Compounds of formula I.A.N.1 in which R2is CH3, R4is H, R6is H, R7is H and the combination of R1, Y and (R3)nfor a compound corresponds in each case to one row of Table C Table 6 : Compounds of formula I.A.N.1 in which R2is CH3, R4is CH3, R6is H, R7is H and the combination of R1, Y and (R3)nfor a compound corresponds in each case to one row of Table C

[0207] Table A

[0208]

[0209]

[0210] BASF SE 1stDraft 250083IN01

[0211] 24

[0212] Table B Table C

[0213]

[0214]

[0215] As used herein, the term “compound(s) of the invention” or “compound(s) according to the invention” refers to the compound(s) of formula (I) as defined above, which are also referred to as “compound(s) of formula I” or “compound(s) I” or “formula I compound(s)”, and includes their salts, tautomers, stereoisomers, and N-oxides.

[0216] Mixtures

[0217] The invention also relates to a mixture of at least one compound of the invention with at least one mixing partner. Preferred are binary mixtures of one compound of the invention as component I with one mixing partner herein as component II. Preferred weight ratios for such binary mixtures are from 5000: 1 to 1 :5000, preferably from 1000: 1 to 1 : 1000, more preferably from 100: 1 to 1 : 100, particularly from 10:1 to 1:10. In such binary mixtures, components I and II may be used in equal amounts, or an excess of component I, or an excess of component II may be used.

[0218] Mixing partners can be selected from pesticides, in particular insecticides, nematicides, and acaricides, fungicides, herbicides, plant growth regulators, fertilizers. Preferred mixing partners are insecticides, nematicides, and fungicides.

[0219] The following list M of pesticides, grouped according to the Mode of Action Classification of the Insecticide Resistance Action Committee (IRAC), together with which the compounds of the invention can be used and with which potential synergistic effects might be produced, illustrates the possible combinations:

[0220] M.1 AChE inhibitors: aldicarb, alanycarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, trimethacarb, XMC, xylylcarb, triazamate; acephate, azamethiphos, azinphos-ethyl, azinphosmethyl, cadusafos, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorpyrifos, chlorpyrifosmethyl, coumaphos, cyanophos, demeton-S-methyl, diazinon, dichlorvos / DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, famphur, fenamiphos, fenitrothion, fenthion, fosthiazate, heptenophos, imicyafos, isofenphos, isopropyl O-(methoxyaminothio-phosphoryl) salicylate, isoxathion, malathion, mecarbam, methamidophos, methidathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion, parathion-methyl, phenthoate, phorate, phosalone, phosmet,Phosphamidon, phoxim, pirimiphos-methyl, profenofos, propetamphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, trichlorfon, vamidothion;

[0221] M.2. GABA-gated chloride channel antagonists: cyclodiene organochlorine compounds: endosulfan, chlordane; phenylpyrazoles: ethiprole, fipronil, flufiprole, pyrafluprole, pyriprole; M.3 Sodium channel modulators: pyrethroids: acrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin, bifenthrin, kappa-bifenthrin, bioallethrin, bioallethrin S-cylclopentenyl, bio-resmethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flucythrinate, flumethrin, tau-fluvalinate, halfenprox, heptafluthrin, imiprothrin, meperfluthrin.metofluthrin, momfluorothrin, epsilon-momfluorothrin, permethrin, phenothrin, prallethrin, profluthrin, pyrethrin (pyrethrum), resmethrin, silafluofen, tefluthrin, kappa-tefluthrin, tetramethylfluthrin, tetramethrin, tralomethrin, transfluthrin; sodium channel modulators, e.g.: DDT, methoxychlor;

[0222] M.4 nAChR agonists: neonicotinoids: acetamiprid, clothianidin, cycloxaprid, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam; 4,5-dihydro-N-nitro-1-(2-oxiranylmethyl)-1H-imidazol-2-amine, (2E-)-1-[(6-Chloropyridin-3-yl)methyl]-N'-nitro-2-pentylidenehydrazinecarbox-imidamide; 1-[(6-Chloropyridin-3-yl)methyl]-7-methyl-8-nitro-5-propoxy- 1,2, 3,5,6, 7-hexahydro-imidazo[1,2-a]pyridine; nicotine; sulfoxaflor; flupyradifurone; triflumezopyrim, fenmezoditiaz, flupyrimin, 1-[(2-chlorothiazol-5-yl)methyl]-3-(3,5-dimethylisoxazol-4-yl)pyrido[1,2-a]pyrimidine-2,4-dione;

[0223] M.5 Nicotinic acetylcholine receptor allosteric activators:spinosyns, e.g. spinosad or spineto-ram; M.6 Chloride channel activators from the class of avermectins and milbemycins, e.g. abamectin, emamectin benzoate, ivermectin, lepimectin, or milbemectin;

[0224] M.7 Juvenile hormone mimics, such as hydroprene, kino-prene, methoprene; fenoxycarb, or pyriproxyfen;

[0225] M.8 miscellaneous multi-site inhibitors: CH3Br, other alkyl halides, chloropicrin, sulfuryl fluoride, borax, tartar emetic;

[0226] M.9 Chordotonal organ TRPV channel modulators: afidopyropen, pymetrozine; pyrifluquinazon; M.10 Mite growth inhibitors: clofentezine, hexythiazox, diflovidazin, etoxazole;

[0227] M.11 Microbial disruptors of insect midgut membranes: bacillus thuringiensis, bacillus sphaericus, and insecticdal proteins they produce e.g.: bacillus thuringiensis subsp. israelensis, bacillus sphaericus, bacillus thuringiensis subsp. aizawai, bacillus thuringiensis subsp. kurstaki, bacillus thuringiensis subsp. tenebrionis, Bt crop proteins: CrylAb, CrylAc, CrylFa, Cry2Ab, mCry3A, Cry3Ab, Cry3Bb, Cry34 / 35Ab1;

[0228] M.12 Inhibitors of mitochondrial ATP synthase: diafenthiuron, organotin miticides, e.g.: azocyclotin, cyhexatin, fenbutatin oxide, propargite, tetradifon;

[0229] M.13 Uncouplers of oxidative phosphorylation via disruption of the proton gradient: chlorfenapyr, DNOC, sulfluramid;

[0230] M.14 nAChR channel blockers: nereistoxin analogues bensultap, cartap hydrochloride, thio-cyclam, thiosultap-sodium;

[0231] M.15 Inhibitors of the chitin biosynthesis type 0, e.g.: bistrifluron, chlorfluazuron, difluben-zuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, triflumuron;M.16 Inhibitors of the chitin biosynthesis type 1: buprofezin;

[0232] M.17 Moulting disruptors: Dipteran, cyromazine;

[0233] M.18 Ecdyson receptor agonists, e.g.: methoxyfenozide, tebufenozide, halofenozide, fufeno-zide, chromafenozide;

[0234] M.19 Octopamin receptor agonists: amitraz;

[0235] M.20 Mitochondrial complex III electron transport inhibitors: hydramethylnon, acequinocyl, fluacrypyrim; bifenazate;

[0236] M.21 METI acaricides and insecticides, e.g.: fenazaquin, fen pyroxi mate, pyrimidifen, pyrida-ben, tebufenpyrad, tolfenpyrad, rotenone;

[0237] M.22 Voltage-dependent sodium channel blockers: indoxacarb, metaflumizone, N-(3-chloro-2-methyl-phenyl)-2-[(4-chlorophenyl)[4-[methyl(methylsulfonyl)amino]phenyl]-methylene]-hydrazinecarboxamide, N-[4-chloro-2-[[(1,1-dimethylethyl)amino]carbonyl]-6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-(fluoromethoxy)-1H-pyrazole-5-carboxamide, 2-[2-(4-cyanophenyl)-1-[3-(trifluoromethyl)phenyl]ethylidene]-N-[4-(difluoromethoxy)phenyl]-hydrazinecarboxamide;

[0238] M.23 Inhibitors of the of acetyl CoA carboxylase, e.g.: spirodiclofen, spiromesifen, spirotetramat; spiropidion; spirobudifen, 11-(4-chloro-2,6-dimethylphenyl)-12-hydroxy-1 ,4-dioxa-9-azadispiro[4.2.4.2]tetradec-11-en-10-one, spidoxamat;

[0239] M.24 Mitochondrial complex IV electron transport inhibitors: e.g. aluminium phosphide, calcium phosphide, zinc phosphide, cyanide;

[0240] M.25 Mitochondrial complex II electron transport inhibitors, e.g.: cyenopyrafen, cyflumetofen, cyetpyrafen, pyflubumide;

[0241] M.28 Ryanodine receptor-modulators: chlorantraniliprole, cyantraniliprole, cyclaniliprole, flubendiamide, fluchlordiniliprole, (R)-3-chloro-N1-{2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoro-methyl)ethyl]phenyl}-N2-(1-methyl-2-methylsulfonylethyl)phthalamid, (S)-3-chloro-N1-{2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl}-N2-(1-methyl-2-methylsulfonylethyl)phthal-amide, methyl-2-[3,5-dibromo-2-({[3-bromo-1-(3-chlorpyridin-2-yl)-1H-pyrazol-5-yl]carbonyl}ami-no)benzoyl]-1,2-dimethylhydrazine-carboxylate; N-[2-(5-amino-1,3,4-thiadiazol-2-yl)-4-chloro-6-methyl-phenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide; 3-chloro-1-(3-chloro-2-pyridinyl)-N-[2,4-dichloro-6-[[(1-cyano-1-methylethyl)amino]carbonyl]phenyl]-1H-pyrazole-5-carboxamide; tetrachlorantraniliprole; tetraniliprole; tiorantraniliprole; N-[4-chloro-2-[[(1,1-dimethylethyl)amino]carbonyl]-6-methyl-phenyl]-1-(3-chloro-2-pyridinyl)-3-(fluoromethoxy)-1 H-pyrazole-5-carboxamide; cyhalodiamide; N-[2-(5-amino-1 ,3,4-thiadiazol-2-yl)-4-chloro-6-methylphenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide, pioxaniliprole; M.29: Chordotonal organ Modulators: flonicamid, flumetnicam;

[0242] M.30: broflanilide; fluxametamide, isocycloseram, piperflanilide;

[0243] M.33 acynonapyr;

[0244] M.UN. Unknown mode of action: afoxolaner, azadirachtin, amidoflumet, ben-zoximate, bromopropylate, chinomethionat, cryolite, cyproflanilid, dicloromezotiaz, dicofol, dimpropyridaz, flufenerim, flometoquin, fluensulfone, fluhexafon, fluopyram, fluralaner, metaldehyde, metoxadiazone, mivorilaner, modoflaner, piperonyl butoxide, pyridalyl, tioxazafen, trifluenfuronate, umifoxolaner, 11-(4-chloro-2,6-dimethylphenyl)-12-hydroxy-1 ,4-dioxa-9-azadispiro[4.2.4.2]-tetradec-11-en-10-one, 3-(4’-fluoro-2,4-dimethylbiphenyl-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4.5]dec-3-en-2-one, 1-[2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)sulfinyl]phenyl]-3-(trifluoromethyl)-1H-1,2,4-triazole-5-amine, actives on basis of bacillus firmus (Votivo, 1-1582); fluazaindolizine; N-[5-[[2-bromo-6-chloro-4-[1,2,2,3,3,3-hexafluoro-1-(trifluoromethyl)-propyl]phe-27

[0245] nyl]carbamoyl]-2-cyano-phenyl]-4-cyano-2-methyl-benzamide; 4-cyano-N-[2-cyano-5-[[2,6-dichloro-4-[1,2,2,3,3,3-hexafluoro-1-(trifluoromethyl)-propyl]phenyl]carbamoyl]phenyl]-2-methyl-benzamide; 4-cyano-N-[2-cyano-5-[[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoro-methyl)ethyl]phenyl]carbamoyl]phenyl]-2-methyl-benzamide; N-[5-[[2-bromo-6-chloro-4-[1, 2,2,2-tetrafluoro-1 -(trifluoromethyl) ethyl]phenyl]carbamoyl]-2-cyano-phenyl]-4-cyano-2-methyl-benzamide;

[0246] 1-[(6-chloro-3-pyridinyl)methyl]-1,2,3,5,6,7-hexahydro-5-methoxy-7-methyl-8-nitro-imidazo[1,2-a]pyridine; 1-[(6-chloropyridin-3-yl)methyl]-7-methyl-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridin-5-ol; 1-[(6-chloro-3-pyridinyl)methyl]-1,2,3,5,6,7-hexahydro-5-methoxy-7-methyl-8-nitro-imidazo[1,2-a]pyridine; 2-(3-pyridinyl)-N-(2-pyrimidinylmethyl )-2H-indazole-5-carboxamide; tyclopyrazoflor; sarolaner, lotilaner; N-[4-chloro-3-[[(phenylmethyl)amino]carbonyl]phenyl]-1-methyl-3-(1,1,2,2,2-pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide; N-[4-chloro-3-[[(phenylmethyl)amino]carbonyl]phenyl]-1 -methyl-3-(1, 1,2,2, 2-pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide; 2-(3-ethylsulfonyl-2-pyridyl)-3-methyl-6-(tri-fluoromethyl)imidazo[4,5-b]pyridine, 2-[3-ethylsulfonyl-5-(trifluoromethyl)-2-pyridyl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine; N-[4-chloro-3-(cyclopropylcarbamoyl)phenyl]-2-methyl-5-(1,1 ,2,2,2-pentafluoroethyl)-4-(trifluoromethyl)pyrazole-3-carboxamide, N-[4-chloro-3-[(1 -cyanocyclopropyl)carbamoyl]phenyl]-2-methyl-5-(1 , 1 ,2,2,2-pentafluoroethyl)-4-(trifluorome-thyl)pyrazole-3-carboxamide; benzpyrimoxan; tigolaner; oxazosulfyl; [(2S,3R,4R,5S,6S)-3,5-dimethoxy-6-methyl-4-propoxy-tetrahydropyran-2-yl] N-[4-[1-[4-(trifluoromethoxy)phenyl]- 1,2,4-triazol-3-yl]phenyl]carbamate; [(2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl] N-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]carbamate; [(2S,3R,4R,5S,6S)-3,5-dimethoxy-6-methyl-4-propoxy-tetrahydropyran-2-yl] N-[4-[1 -[4-(1 , 1 ,2,2,2-pentafluoroethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]carbamate; [(2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl] N-[4-[1-[4-(1 ,1 ,2,2,2-pentafluoroethoxy)phenyl]-1 ,2,4-triazol-3-yl]phenyl]carbamate; (2Z)-3-(2-isopropylphenyl)-2-[(E)-[4-[1-[4-(trifluorome-thoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylenehydrazono]thiazolidin-4-one, (2Z)-3-(2-isopropylphenyl)-2-[(E)-[4-[1 -[4-(1 , 1 ,2,2,2-pentafluoroethoxy)phenyl]-1 ,2,4-triazol-3-yl]phe-nyl]methylenehydrazono]thiazolidin-4-one, (2Z)-3-(2-isopropylphenyl)-2-[(E)-[4-[1 -[4-(1 , 1 ,2,2,2-pentafluoroethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylenehydrazono]thiazolidin-4-one; 2-(6-chloro-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-(6-bromo-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoro-methyl)imidazo[4,5-b]pyridine, 2-(3-ethylsulfonyl-6-iodo-imidazo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-(7-chloro-3-ethylsulfonyl-imidazo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-(7-chloro-3-ethylsulfonyl-imidazo[1,2-a]pyri-din-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 2-(3-ethylsulfonyl-7-iodo-imida-zo[1,2-a]pyridin-2-yl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 3-ethylsulfonyl-6-iodo-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridin-2-yl]imidazo[1,2-a]pyridine-8-carbonitrile, 2-[3-ethylsulfonyl-8-fluoro-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-methyl-6-(trifluoro-methyl)imidazo[4,5-b]pyridine, 2-[3-ethylsulfonyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-3-methyl-6-(trifluoromethylsulfinyl)imidazo[4,5-b]pyridine, 2-[3-ethylsulfonyl-7-(trifluoromethyl)imi-dazo[1,2-a]pyridin-2-yl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridine, 2-(6-bromo-3-ethyl-sulfonyl-imidazo[1,2-a]pyridin-2-yl)-6-(trifluoromethyl)pyrazolo[4,3-c]pyridine; N-[[2-fluoro-4-[(2S,3S)-2-hydroxy-3-(3,4,5-trichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]phenyl]methyl]cy-clopropanecarboxamide; sulfiflumin; flupentiofenox, N-[3-chloro-1-(3-pyridyl)pyrazol-4-yl]-2-me-250083

[0247] 28

[0248] thylsulfonyl-propanamide, cyclobutrifluram; N-[4-chloro-3-[(1-cyanocyclopro-pyl)carbamoyl]phenyl]-2-methyl-4-methylsulfonyl-5-(1 , 1 ,2,2,2-pentafluoroethyl)pyrazole-3-carboxamide, cyproflanilide, nicofluprole; 1 ,4-dimethyl-2-[2-(pyridin-3-yl)-2h-indazol-5-yl]-1 ,2,4-triazolidine-3, 5-dione, indazapyroxamet, tiapyrachlor, N-cyclopropyl-5-[(5S)-5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]isoquinoline-8-carboxamide, 5-[(5S)-5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-(pyrimidin-2-ylmethyl)iso-quinoline-8-carboxamide, N-[1-(2,6-difluorophenyl)pyrazol-3-yl]-2-(trifluoromethyl)benzamide, 5-((1R,3R)-3-(3,5-Bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane-1-carboxamido)-2-chloro-N-(3-(2,2-difluoroacetamido)-2,4-difluorophenyl)benzamide, 1-[6-(2,2-difluoro-7-methyl-[1,3]dioxolo[4,5-f]benzimidazol-6-yl)-5-ethylsulfonyl-3-pyridyl]cyclopropanecarbonitrile, 6-(5-cyclopropyl-3-ethylsulfonyl-2-pyridyl)-2,2-difluoro-7-methyl-[1,3]dioxolo[4,5-f]benzimidazole, Ledprona. Flupyroxystrobin, 3,5-bis(trifluoromethyl)-N-[(1S)-1-[1-[6-(trifluoromethyl)-4-pyrimidinyl]-1H-1,2,4-triazol-5-yl]ethyl]-benzamide, 2-(3-ethylsulfonyl-2-pyridyl)-5-(2,2,3,3,3-pentafluoropropoxy)pyrazine, 2-[3-ethylsulfonyl-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-yl]-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridine, 9-(methoxymethyl)-5-(3-pyridyl)-2-oxa-5,6,9,14-tetrazatricyclo[8.4.0.0A{3,7}]tetradeca-1 (10),3,6, 11,13-pentaen-8-one, bisulfufen, 2-[5-[(E)-2-chloro-3,3,3-trifluoro-prop-1-enyl]-1-methyl-imidazol-2-yl]-5-cyclopropyl-3-ethylsulfonyl-pyridine, cybenzoxasulfyl, isoflualanam;

[0249] Bentioflumin, Vadescana, (3Z)-1-[2-fluoro-4-[1-[4-(trifluoromethoxy)phenyl]-1 ,2,4-triazol-3-yl]phenyl]-3-[3-[5-methyl-2-(2,2,2-trifluoroethoxymethyl)phenyl]-4-oxo-thiazolidin-2-ylidene]urea, 1-[6-(2,2-difluoro-8-oxo-[1,3]dioxolo[4,5-g]chromen-7-yl)-5-ethylsulfonyl-3-pyridyl]cyclopropanecarbonitrile, 2-chloro-N-[(1S)-2-ethyl-1-methyl-butyl]furan-3-carboxamide, galquin, [5-cyclopropyl-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyridin-2-yl]-3-pyridyl]-ethyl-hydroxy-oxo-A6-sulfane, 4-[5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]- 2-methyl-N-[1-(2,2,2-trifluoroethylcarbamoyl)cyclopropyl]benzamide, 3-[3-ethylsulfonyl-7- (trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-7-(trifluoromethyl)chromen-4-one,

[0250] The commercially available compounds M listed above may be found in The Pesticide Man-ual, 18th Edition, C. MacBean, British Crop Protection Council (2018), or http: / / bcpcdata.com / pesticide-manual.html, http: / / www.alanwood.net / pesticides.

[0251] The active compounds described by IUPAC nomenclature are known from CN103814937; WO2013 / 003977, W02007 / 101369, WO2018 / 177970, CN10171577, CN102126994, W02007 / 101540, W02007 / 043677, WO2011 / 085575, W02008 / 134969, WO2012 / 034403, W02006 / 089633, W02008 / 067911 , W02006 / 043635, W02009 / 124707, WO2013 / 050317, WO2010 / 060379, WO2010 / 127926, WO2010 / 006713, WO2012 / 000896, W02007 / 101369, WO2012 / 143317, WO2015 / 038503, EP2910126, WO2015 / 059039, W02015 / 190316, WO2012 / 126766, W02009 / 102736, WO2013 / 116053, WO2018 / 052136, WO2015150252, W02020055955, WO2021158455, WO2013092350, WO201811111, EP3608311, WO2019236274, WO2013092350, WO 2018052136, W02009102736, WO2016174049, WO2012126766, CN106554335, WO2017054524, CN105153113, W02022072650; WO2018071327, W02022101502, WO2012158396, W02007079162, W02020013147, W02020097414, EP242081, WO2023058748, WO2017065228, EP3428166, WO2021029308, W02022009058, WO2017067500, W02020090585, WO2017146226, W02021043115, WO2023016278, W02021011722, WO2024126388, WO2024137594, EP4389739, WO2016096584, WO2024120137, WO2024188755, CN115925576, WO2024087613.250083

[0252] 29

[0253] The following list of fungicides, in conjunction with which the compounds of the invention can be used, illustrates the possible combinations:

[0254] A) Respiration (C)

[0255] complex III at Qosite (Qol, C3): azoxystrobin (A.1.1), bifemetstrobin (A.1.24), bifujunzhi (A.1.37), coumethoxystrobin (A.1.2), coumoxystrobin (A.1.3), dimoxystrobin (A.1.4), enestroburin (A.1.5), famoxadone (A.1.21), fenamidone (A.1.23), fenaminstrobin (A.1.6), flufenoxystrobin (A.1.7), fluoxastrobin (A.1.8), kresoxim-methyl (A.1.9), mandestrobin (A.1.10), metominostrobin (A.1.11), metyltetraprole (A.1.25; member of MoA subgroup A), orysastrobin (A.1.12), picoxy-strobin (A.1.13), pyraclostrobin (A.1.14), pyrametostrobin (A.1.15), pyraoxystrobin (A.1.16), pyribencarb (A.1.19), pyriminostrobin (A.1.36), triclopyricarb (A.1.20), trifloxystrobin (A.1.17), 2-(2-(3-(2,6-dichlorophenyl)-1-methyl-allylideneaminooxymethyl)-phenyl)-2-methoxyimino- / V-methyl-acetamide (A.1.18), methyl- / V-[2-[(1 ,4-dimethyl-5-phenyl-pyrazol-3-yl)oxylmethyl]-phenyl]- / V-methoxy-carbamate (A.1.22), (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]-oxy- 2-methoxyimino- / V,3-dimethyl-pent-3-enamide (A.1.34), (Z,2E)-5-[1-(4-chlorophenyl)pyrazol- 3-yl]oxy-2-methoxyimino- / V,3-dimethyl-pent-3-enamide (A.1.35), 2-(ortho-((2,5-dimethylphenyl-oxymethylen)phenyl)-3-methoxy-acrylic acid methylester (A.1.38), methyl (Z)-3-methoxy-2-[2-methyl-5-(3-propylpyrazol-1-yl)phenoxy]prop-2-enoate, methyl (Z)-2-[5-(3-isopropylpyrazol-1 -yl)-2-methyl-phenoxy]-3-methoxy-prop-2-enoate, methyl (Z)-3-methoxy-2-[2-methyl- 5-[3-(trifluoromethyl)pyrazol-1-yl]phenoxy]prop-2-enoate, methyl (Z)-3-methoxy-2-[2-methyl-5-(4-propyltriazol-2-yl)phenoxy]prop-2-enoate, methyl (Z)-3-methoxy-2-[2-methyl- 5-[4-(trifluoromethyl)triazol-2-yl]phenoxy]prop-2-enoate, methyl (Z)-2-[5-(4-isopropyltriazol-2-yl)- 2-methyl-phenoxy]-3-methoxy-prop-2-enoate, methyl (Z)-2-(5-cyclobutyl-2-methyl-phenoxy)- 3-methoxy-prop-2-enoate, methyl (Z)-2-(5-cyclopentyl-2-methyl-phenoxy)-3-methoxy-prop- 2-enoate, methyl (Z)-2-(5-cyclopropyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate, methyl (Z)-2-(5-cyclohexyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate, methyl (E)-3-methoxy-2-[(2-methyl-5-phenyl-phenyl)methyl]prop-2-enoate, methyl (E)-3-methoxy-2-[[5-[(E)- / V-methoxy-C-methyl-carbonimidoyl]-2,4-dimethyl-phenyl]methyl]prop-2-enoate; methyl (E)-2-[[5-(2-cyclopropylethynyl)-2,4-dimethyl-phenyl]methyl]-3-methoxy-prop-2-enoate; methyl (E)-3-methoxy-2-(2-phenyl-1 ,3-benzoxazol-4-yl)prop-2-enoate; methyl (E)-3-methoxy- 2-(2-phenyl-1 ,3-benzothiazol-4-yl)prop-2-enoate; methyl (E)-3-methoxy-2-(2-phenyl- 1 ,3-benzoxazol-7-yl)prop-2-enoate; methyl (Z)-2-[6-(2-cyclopropylethynyl)benzimidazol-1-yl]- 3-methoxy-prop-2-enoate; methyl (Z)-3-methoxy-2-(6-phenylbenzimidazol-1-yl)prop-2-enoate; methyl (Z)-2-(3-chloro-6-phenyl-indol-1-yl)-3-methoxy-prop-2-enoate; methyl (Z)-2-(2,3-dichloro- 6-phenyl-indol-1-yl)-3-methoxy-prop-2-enoate; methyl (Z)-3-methoxy-2-[6-[(E)-methoxyimino-methyl]indol-1-yl]prop-2-enoate; methyl (Z)-3-methoxy-2-[6-[(E)- / V-methoxy-C-methyl-carbonimidoyl]indol-1-yl]prop-2-enoate, methyl / V-[[5-[1-(2,6-difluoro-4-isopropyl-phenyl)pyrazol- 3-yl]-2-methyl-phenyl]methyl]carbamate, methyl / V-[[5-[1 -(4-cyclopropyl-2,6-difluoro-phenyl)-pyrazol-3-yl]-2-methyl-phenyl]methyl]carbamate, methyl A / -[[5- [ 1 -(4-chloro-2,6-difluoro-phenyl)pyrazol-3-yl]-2-methyl-phenyl]methyl]carbamate, methyl / V-[[5-[1-[2,6-difluoro- 4-(trifluoromethyl)phenyl]pyrazol-3-yl]-2-methyl-phenyl]methyl]carbamate;

[0256] complex III at Qi site (Qil, C4): cyazofamid (A.2.1), amisulbrom (A.2.2), [(6S,7R,8R)-8-benzyl-3-[(3-hydroxy-4-methoxy-pyridine-2-carbonyl)amino]-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl]-2-methylpropanoate (A.2.3), fenpicoxamid (A.2.4), florylpicoxamid (A.2.5), metarylpicoxamid (A.2.6);250083

[0257] 30

[0258] complex II (SDH I, C2): benodanil (A.3.1), benzovindiflupyr (A.3.2), bixafen (A.3.3), boscalid (A.3.4), carboxin (A.3.5), cyclobutrifluram (A.3.24), fenfuram (A.3.6), fluopyram (A.3.7), flutolanil (A.3.8), fluxapyroxad (A.3.9), furametpyr (A.3.10), inpyrfluxam (A.3.22), isofetamid (A.3.11), isoflucypram (A.3.31), isopyrazam (A.3.12), mepronil (A.3.13), oxycarboxin (A.3.14), penflufen (A.3.15), penthiopyrad (A.3.16), pydiflumetofen (A.3.17), pyrapropoyne (A.3.23), pyraziflumid (A.3.18), sedaxane (A.3.19), tecloftalam (A.3.20), thifluzamide (A.3.21), fluindapyr (A.3.28), / V-[2-[2-chloro-4-(trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-5-fluoro-1-methyl-pyrazole-4-carboxamide (A.3.29), methyl (E)-2-[2-[(5-cyano-2-methyl-phenoxy)methyl]phenyl]-3-methoxy-prop-2-enoate (A.3.30), 2-(difluoromethyl)- / V-(1 ,1 ,3-trimethyl-indan-4-yl)pyridine-3-carboxamide (A.3.32), 2-(difluoromethyl)- / V-[(3R)-1 ,1 ,3-trimethylindan-4-yl]pyridine-3-carboxamide (A.3.33), 2-(difluoromethyl)- / V-(3-ethyl-1,1-dimethyl-indan-4-yl)pyridine-3-carboxamide (A.3.34), 2-(difluoromethyl)- / V-[(3R)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide (A.3.35), 2-(difluoromethyl)- / V-(1 , 1 -dimethyl-3-propyl-indan-4-yl)pyridine-3-carboxamide (A.3.36), 2-(difluoromethyl)- / V-[(3R)-1,1-dimethyl-3-propyl-indan-4-yl]pyridine-3-carboxamide (A.3.37), 2-(difluoromethyl)- / V-(3-isobutyl-1,1-dimethyl-indan-4-yl)pyridine-3-carboxamide (A.3.38), 2-(difluoromethyl)- / V-[(3R)-3-isobutyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide (A.3.39);

[0259] complex I NADH oxido-reductase (C1): diflumetorim (A.4.1);

[0260] uncouplers (C5): binapacryl (A.4.2), dinobuton (A.4.3), dinocap (AAA), fluazinam (A.4.5), meptyldinocap (A.4.6), ferimzone (A.4.7);

[0261] inhibitors of ox. phosphorylation (C6): fentin salts, e.g. fentin-acetate (A.4.8), fentin chloride (A.4.9) or fentin hydroxide (A.4.10);

[0262] ATP transport: silthiofam (A.4.11);

[0263] quinone inside and outside inhibitor stigmatellin binding type (QioSI; C8): ametoctradin (A.5.1);

[0264] B) Sterol biosynthesis (G)

[0265] C14 demethylase (DMI, G1): triazoles: azaconazole (B.1.1), bitertanol (B.1.2), bromucon-azole (B.1.3), cyproconazole (B.1.4), difenoconazole (B.1.5), diniconazole (B.1.6), dinicon-azole-M (B.1.7), epoxiconazole (B.1.8), fenbuconazole (B.1.9), fluoxytioconazole (B.1.33), fluquinconazole (B.1.10), flusilazole (B.1.11), flutriafol (B.1.12), hexaconazole (B.1.13), imi-benconazole (B.1.14), ipconazole (B.1.15), ipfentrifluconazole (B.1.37), mefentrifluconazole (B.1.38), metconazole (B.1.17), myclobutanil (B.1.18), oxpoconazole (B.1.19), paclobutrazole (B.1.20), penconazole (B.1.21), propiconazole (B.1.22), prothioconazole (B.1.23), simeconazole (B.1.24), tebuconazole (B.1.25), tetraconazole (B.1.26), triadimefon (B.1.27), triadimenol (B.1.28), triticonazole (B.1.29), uniconazole (B.1.30), 2-(2,4-difluorophenyl)-1 ,1-difluoro- 3-(tetrazol-1-yl)-1-[5-[4-(2,2,2-trifluoroethoxy)phenyl]-2-pyridyl]propan-2-ol (B.1.31), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[4-(trifluoromethoxy)phenyl]- 2-pyridyl]propan-2-ol (B.1.32), 2-(chloromethyl)-2-methyl-5-(p-tolylmethyl)-1-(1 ,2,4-triazol- 1-ylmethyl)cyclopentanol (B.1.43), 4-[[6-[2-(2,4-difluorophenyl)-1 , 1 -difluoro-2-hydroxy 3-(1 ,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile (B.1.53), 2-[6-(4-bromophenoxy) 2-(trifluoromethyl)-3-pyridyl]-1-(1 ,2,4-triazol-1-yl)propan-2-ol (B.1.54), 2-[6-(4-chlorophenoxy) 2-(trifluoromethyl)-3-pyridyl]-1-(1 ,2,4-triazol-1-yl)propan-2-ol (B.1.55), (2R)-2-[4-(4-chlorophen oxy)-2-(trifluoromethyl)phenyl]-1-(1,2,4-triazol-1-yl)propan-2-ol, (2S)-2-[4-(4-chlorophenoxy) 2-(trifluoromethyl)phenyl]-1-(1,2,4-triazol-1-yl)propan-2-ol, methyl 2-[2-chloro 4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1 ,2,4-triazol-1-yl)propanoate (B.1.56), 2-[2-chloro 4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoic acid (B.1.57); imidazoles:250083

[0266] 31

[0267] imazalil (B.1.44), pefurazoate (B.1.45), prochloraz (B.1.46), triflumizole (B.1.47); pyrimidines, pyridines, piperazines: fenarimol (B.1.49), pyrifenox (B.1.50), triforine (B.1.51), [3-(4-chloro-2-fluoro-phenyl)-5-(2,4-difluorophenyl)isoxazol-4-yl]-(3-pyridyl)methanol (B.1.52);

[0268] delta14-reductase (G2): aldimorph (B.2.1), dodemorph (B.2.2), dodemorph-acetate (B.2.3), fenpropidin (B.2.6), fenpropimorph (B.2.4), piperalin (B.2.7), spiroxamine (B.2.8), tridemorph (B.2.5);

[0269] 3-keto reductase (G3): fenhexamid (B.3.1), fenpyrazamine (B.3.2);

[0270] other: chlorphenomizole (B.4.1);

[0271] C) Nucleic acids metabolism (A)

[0272] RNA polymerase I (A1): benalaxyl (C.1.1), benalaxyl-M (C.1.2), kiralaxyl (C.1.3), metalaxyl (C.1.4), metalaxyl-M (C.1.5), ofurace (C.1.6), oxadixyl (C.1.7);

[0273] adenosine deaminase (A2): bupirimate (C.2.4), 5-fluoro-2-(p-tolylmethoxy)pyrimidin-4-amine (C.2.6), 5-fluoro-2-(4-fluorophenylmethoxy)pyrimidin-4-amine (C.2.7), 5-fluoro-2-(4-chlorophenylmethoxy)pyrimidin-4-amine (C.2.8);

[0274] DNA / RNA synthesis (A3): 5-fluorocytosine (C.2.5), hymexazole (C.2.1), octhilinone (C.2.2), gyrase (A4): oxolinic acid (C.2.3);

[0275] dihydroorotate dehydrogenase (DHODH; A5): ipflufenoquin (C.5.1), quinofumelin (C.5.2), feneptamidoquin (C.5.3);

[0276] D) Cytoskeleton and motor protein (B)

[0277] tubulin polymerization (MBC; B1): benomyl (D.1.1), carbendazim (D.1.2), fuberidazole (D.1.3), pyridachlometyl (D.1.6), thiabendazole (D.1.4), thiophanate-methyl (D.1.5), / V-ethyl-2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]butanamide (D.1.8), / V-ethyl-2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methylsulfanyl-acetamide (D.1.9), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]- / V-(2-fluoroethyl)butanamide (D.1.10), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]- / V-(2-fluoroethyl)-2-methoxy-acetamide (D.1.11), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]- / V-propyl-butanamide (D.1.12), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methoxy- / V-propyl-acetamide (D.1.13) , 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methylsulfanyl- / V-propyl-acetamide (D.1.14), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]- / V-(2-fluoroethyl)-2-methylsulfanyl-acetamide (D.1.15), 4-(2-bromo-4-fluoro-phenyl)- / V-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3-amine (D.1.16), 4-(2-bromo-4-fluorophenyl)- / V-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1 / - / -pyrazol-5-amine, 4-(2-chloro-4,6-difluorophenyl)- / V-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1 / - / -pyrazol-5-amine, 4-(2-chloro-4-fluorophenyl)- / V-(2-fluoro-6-nitrophenyl)-3-ethyl-1-methyl-1 / - / -pyrazol-5-amine, 4-(2-chloro-4-fluorophenyl)- / V-(2-fluoro-4-methyl-6-nitrophenyl)-1,3-dimethyl-1 / - / -pyrazol- 5-amine, 4-(2-chloro-4-fluorophenyl)- / V-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1 / - / -pyrazol- 5-amine, 4-(2,4-difluorophenyl)- / V-(2-fluoro-6-nitrophenyl)-1,3-dimethyl-1 / - / -pyrazol-5-amine; tubulin polymerization (B2): diethofencarb (D.2.1),

[0278] tubulin polymersation (B3): ethaboxam (D.2.2), zoxamide (D.2.5);

[0279] cell division (B4): pencycuron (D.2.3);

[0280] spectrin-like proteins (B5): fluopicolide (D.2.4), fluopimomide (D.2.9); actin / myosin / fimbrin function (B6): metrafenone (D.2.6), phenamacril (D.2.8), pyriofenone (D.2.7);

[0281] E) Amino acids and protein synthesis (D)

[0282] methionine synthesis (D1): cyprodinil (E.1.1), mepanipyrim (E.1.2), pyrimethanil (E.1.3); ribosome, termination step (D2): blasticidin-S (E.2.1);250083

[0283] 32

[0284] ribosome initiation step (D3): kasugamycin (E.2.2), kasugamycin hydrochloride-hydrate (E.2.3);

[0285] ribosome initiation step (D4): streptomycin (E.2.5);

[0286] ribosome elongation step (D5): mildiomycin (E.2.4), oxytetracyclin (E.2.6);

[0287] F) Signal transduction

[0288] mechanism unknown (E1): proquinazid (F.2.2), quinoxyfen (F.2.1);

[0289] MAP / histidine kinase os-2 (E2): fludioxonil (F.1.5);

[0290] MAP / histidine kinase os-1 (E3): iprodione (F.1.2), procymidone (F.1.3), vinclozolin (F.1.4); G) Lipid synthesis or transport I membrane (F)

[0291] methyl transferase (F2): edifenphos (G.1.1), iprobenfos (G.1.2), isoprothiolane (G.1.4); pyrazophos (G.1.3);

[0292] cell peroxidation (F3): biphenyl (G.2.5), chloroneb (G.2.6), dicloran (G.2.1), etridiazole (G.2.7), quintozene (G.2.2), tecnazene (G.2.3), tolclofos-methyl (G.2.4);

[0293] cell membrane permeability (F4): propamocarb (G.4.1);

[0294] ergosterol binding (F8): natamycin;

[0295] oxysterol binding protein (F9): fluoxapiprolin (G.5.3), oxathiapiprolin (G.5.1), 4-[1-[2-[3-(di-fluoromethyl)-5-methyl-pyrazol-1-yl]acetyl]-4-piperidyl]- / V-tetralin-1-yl-pyridine-2-carboxamide (G.5.4), 4-[1 -[2-[3,5-bis(difluoromethyl)pyrazol-1 -yl]acetyl]-4-piperidyl]- / V-tetralin-1 -yl-pyridine- 2-carboxamide (G.5.5), 4-[1-[2-[3-(difluoromethyl)-5-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]- / V-tetralin-1-yl-pyridine-2-carboxamide (G.5.6), 4-[1-[2-[5-cyclopropyl-3-(difluoro-methyl)pyrazol-1-yl]acetyl]-4-piperidyl]- / V-tetralin-1-yl-pyridine-2-carboxamide (G.5.7), 4-[1-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]- / V-tetralin-1-yl-pyridine- 2-carboxamide (G.5.8), 4-[1-[2-[5-(difluoromethyl)-3-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-pi-peridyl]- / V-tetralin-1-yl-pyridine-2-carboxamide (G.5.9), 4-[1-[2-[3,5-bis(trifluoromethyl)pyrazol- 1-yl]acetyl]-4-piperidyl]- / V-tetralin-1-yl-pyridine-2-carboxamide (G.5.10), (4-[1-[2-[5-cyclopropyl- 3-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]- / V-tetralin-1-yl-pyridine-2-carboxamide (G.5.11), (1-(4-(4-(5-(2,6-dichlorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)- 2-((3-trifluoromethyl)pyrazin-2-yl)oxy)ethan-1-one, 1-(4-(4-(5-(2-chloro-6-fluorophenyl)- 4.5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin-1-yl)-2-((3-trifluoromethyl)pyridin-2-yl)oxy)ethan-1-one, tert-butyl 4-(4-(5-(2-bromo-6-fluorophenyl)-4,5-dihydroisoxazol-3-yl)thiazol-2-yl)piperidin- 1 -carboxylate, ((2-(3-(2-(1 -(2-(3,5-bis(trifluoromethyl)-1 H-pyrazol-1 -yl)acetyl)piperidin- 4-yl)thiazol-4-yl)-4,5-dihydroisoxazo-5-yl)-3-fluorophenyl)imino)dimethyl-A6-sulfanone,

[0296] ((2-(3-(2-(1-(2-(3,5-bis(difluoromethyl)-1 H-pyrazol-1 -yl)acetyl)piperidin-4-yl)thiazol-4-yl)-4,5-di-hydroisoxazo-5-yl)-3-fluorophenyl)imino)dimethyl-A6-sulfanone,

[0297] ((2-(3-(2-(1-(2-(3,5-bis(difluoromethyl)-1 H-pyrazol-1 -yl)acetyl)piperidin-4-yl)thiazol-4-yl)- 4.5-dihydroisoxazo-5-yl)-3-chorophenyl)imino)(isopropyl)(methyl)-A6-sulfanone,

[0298] ((2-(3-(2-(1-(2-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)acetyl)piperidin-4-yl)thiazol-4-yl)-4,5-di-hydroisoxazo-5-yl)-3-fluorophenyl)imino)(isopropyl)(methyl)-A6-sulfanone,

[0299] ((2-(3-(2-(1-(2-(3,5-bis(difluoromethyl)-1 H-pyrazol-1 -yl)acetyl)piperidin-4-yl)thiazol-4-yl)- 4.5-dihydroisoxazo-5-yl)-3-(trifluoromethyl)phenyl)imino)dimethyl-A6-sulfanone, ((3-fluoro- 2-(3-(2-(1-(2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetyl)piperidin-4-yl)thiazol-4-yl)- 4.5-dihydroisoxazo-5-yl)-phenyl)imino)dimethyl-A6-sulfanone;

[0300] H) Multi Site Activity (M)

[0301] inorganics (M01): Bordeaux mixture (H.1.1), copper (H.1.2), copper acetate (H.1.3), copper hydroxide (H.1.4), copper oxychloride (H.1.5), basic copper sulfate (H.1.6), sulfur (H.1.7);250083

[0302] 33

[0303] dithiocarbamates and relatives: ferbam (H.2.1), mancozeb (H.2.2), maneb (H.2.3), metam (H.2.4), metiram (H.2.5), propineb (H.2.6), thiram (H.2.7), zineb (H.2.8), ziram (H.2.9), zinc thiazole (H.2.10);

[0304] organochlorine compounds (M04, M05, M06, M08): anilazine (H.3.1), captafol (H.3.3), captan (H.3.4), chlorothalonil (H.3.2), dichlofluanid (H.3.6), dichlorophen (H.3.7), folpet (H.3.5), hexachlorobenzene (H.3.8), pentachlorphenole (H.3.9) and its salts, phthalide (H.3.10), tolylfluanid (H.3.11);

[0305] guanidines, quinones, quinoxalines, maleimides, thiocarbamates (M07, M09, M10, M11, M12): chinomethionat (H.4.13), dithianon (H.4.9), fluoroimide (H.4.11), guanidine (H.4.1), guazatine (H.4.4), guazatine-acetate (H.4.5), iminoctadine (H.4.6), iminoctadine-triacetate (H.4.7), iminoctadine-tris(albesilate) (H.4.8), methasulfocarb (H.4.12), 2,6-dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetraone (H.4.10),

[0306] I) Cell wall biosynthesis (H) and melanin synthesis in cell wall (I)

[0307] chitin synthase (H4): polyoxin B (1.1.2);

[0308] cellulose synthase (H5): benthiavalicarb (1.3.5), dimethomorph (1.3.1), flumorph (1.3.2), iprovalicarb (1.3.6), mandipropamid (1.3.3), pyrimorph (1.3.4), valifenalate (1.3.7);

[0309] reductase in melanin synthesis (MBI-R; 11) pyroquilon (1.2.1), tricyclazole (1.2.2); dehydratase in melanin synthesis (MBI-D, I2); carpropamid (1.2.3), dicyclomet (1.2.4), fenoxanil (1.2.5);

[0310] polyketide synthase in melanin synthesis (MBI-P, I3): tolprocarb (1.2.6);

[0311] J) Plant defence induction (P1 to P8)

[0312] salicylate-related (P01-P03, P08): acibenzolar-S-methyl (J.1.1), probenazole (J.1.2), isotianil (J.1.3), tiadinil (J.1.4), dichlobentiazox (J.1.13); phosphonates (P07): fosetyl (J.1.6), fosetyl-aluminum (J.1.7), phosphorous acid and its salts (J.1.8), calcium phosphonate (J.1.11), potassium phosphonate (J.1.12); others: potassium or sodium bicarbonate (J.1.9), 4-cyclopropyl- / V-(2,4-di-,methoxy-,phenyl)thiadiazole-5-carboxamide (J.1.10);

[0313] K) Unknown mode of action (U)

[0314] aminopyrifen (K.1.54), benziothiazolinone (K.1.48), bromothalonil (K.1.49), bronopol (K.1.1), cyflufenamid (K.1.3), cymoxanil (K.1.4), dazomet (K.1.5), debacarb (K.1.6), diclomezine (K.1.8), difenzoquat (K.1.9), difenzoquat-methylsulfate (K.1.10), diphenylamin (K.1.11), dodine, dodine free base (K.1.18), fenitropan (K.1.12), flufenoxadiazam (K.1.58) [MoA proposed: class II histone deacetylase inhibitor], flumetover (K.1.14), flumetylsulforim (K.1.60), flusulfamide (K.1.15), flutianil (K.1.16), harpin (K.1.17), nitrapyrin (K.1.19), nitrothal-isopropyl (K.1.20), oxinecopper (K.1.22), picarbutrazox (K.1.41), pyrisoxazole (K.1.37), seboctylamine (K.1.61), tebu-floquin (K.1.24), tecloftalam (K.1.25), triazoxide (K.1.26), validamycin (K.1.2); / V-(4-(4-chloro-3-trifluoromethyl-phenoxy)-2,5-dimethyl-phenyl)- / V-ethyl- / V-methyl formamidine (K.1.27), / V-(4-(4-fluoro-3-trifluoromethyl-phenoxy)-2,5-dimethyl-phenyl)- / V-ethyl- / V-methyl formamidine (K.1.28), / V-[4-[[3-[(4-chlorophenyl)methyl]-1,2,4-thiadiazol-5-yl]oxy]-2,5-dimethyl-phenyl]- / V-ethyl- / V-methyl-formamidine (K.1.29), / V-(5-bromo-6-indan-2-yloxy-2-methyl-3-pyridyl)- / V-ethyl- / V-methyl-formamidine (K.1.30), / V-[5-bromo-6-[1-(3,5-difluorophenyl)ethoxy]-2-methyl-3-pyridyl]- / V-ethyl- / V-methyl-formamidine (K.1.31), / V-[5-bromo-6-(4-isopropylcyclohexoxy)-2-methyl-3-pyridyl]- / V-ethyl- / V-methyl-formamidine (K.1.32), / V-[5-bromo-2-methyl-6-(1-phenylethoxy)-3-pyridyl]- / V-ethyl- / V-methyl-formamidine (K.1.33), / V-(2-methyl-5-trifluoromethyl-4-(3-trimethylsilanyl-propoxy)-phenyl)- / V-ethyl- / V-methyl formamidine (K.1.34), / V-(5-difluoromethyl-2-methyl-4-(3-trimethylsilanyl-propoxy)-phenyl)- / V-ethyl- / V-methyl250083

[0315] 34

[0316] formamidine (K.1.35), 2-(4-chloro-phenyl)- / V-[4-(3,4-dimethoxy-phenyl)-isoxazol-5-yl]-2-prop-2-ynyloxy-acetamide (K.1.36), 3-[5-(4-methylphenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine (K.1.38), 5-chloro-1-(4,6-dimethoxy-pyrimidin-2-yl)-2-methyl-1 / - / -benzoimidazole (K.1.39), ethyl (Z)-3-amino-2-cyano-3-phenyl-prop-2-enoate (K.1.40), pentyl / V-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate (K.1.42), but-3-ynyl / V-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate (K.1.43), 2-(6-benzyl-2-pyridyl)quinazoline (K.1.50), 2-[6-(3-fluoro-4-methoxy-phenyl)-5-methyl- 2-pyridyl]quinazoline (K.1.51), / V-(2,5-dimethyl-4-phenoxy-phenyl)- / V-ethyl- / V-methyl-formamidine (K.1.53), / V-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]- / V-ethyl- / V-methyl-formamidine (K.1.56), / V'-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]- / V-ethyl- / V-methyl-formamidine (K.1.57), / V-methyl-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol- 3-yl]benzenecarbothioamide (K.1.59), / V-methoxy- / V-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide (K.1.61), / V-((4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol- 3-yl]phenyl)methyl)propanamide (K.1.62), 3,3,3-trifluoro- / V-[[3-fluoro-4-[5-(trifluoromethyl)- 1.2.4-oxadiazol-3-yl]phenyl]methyl]propanamide (K.1.63), 3,3,3-trifluoro- / V-[[2-fluoro-4-[5-(tri-fluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide (K.1.64), / V-[2,3-difluoro- 4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]benzyl]butanamide (K.1.65), / V-[[2,3-difluoro- 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-3,3,3-trifluoro-propanamide (K.1.66), 1 -methoxy- 1-methyl-3-[[4-[5-(trifluoromethyl)-1, 2, 4-oxadiazol-3-yl]phenyl]methyl]urea (K.1.67), 1 , 1 -diethyl-3-[[4-[5-[trifluoromethyl]- 1 ,2,4-oxadiazol-3-yl]phenyl]methyl]urea (K.1.68), / V,2-dimethoxy- / V-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide (K.1.69), / V-ethyl-2-methyl- / V-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]meth-yl]propanamide (K.1.70), 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]-phenyl]methyl]urea (K.1.71), 1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]pyr-rolidin-2-one (K.1.72), 1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]piperidin- 2-one (K.1.73), 4-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]morpholin-3-one (K.1.74), 4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin- 3-one (K.1.75), 2-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one (K.1.76), 5,5-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one (K.1.77), 3,3-dimethyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phen-yl]methyl]piperidin-2-one (K.1.78), 2-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]meth-yl]oxazinan-3-one (K.1.79), 1-[[3-fluoro-4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]-methyl]azepan-2-one (K.1.80), 4,4-dimethyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]-phenyl]methyl]pyrrolidin-2-one (K.1.81), 5-methyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]pyrrolidin-2-one (K.1.82), ethyl 1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol- 3-yl]phenyl]methyl]pyrazole-4-carboxylate (K.1.83), / V-methyl-1-[[4-[5-(trifluoromethyl)- 1.2.4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxamide (K.1.84), / V, / V-dimethyl- 1-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl]-1 / - / -1,2,4-triazol-3-amine (K.1.85), / V-methoxy- / V-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole- 4-carboxamide (K.1.86), propyl-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]-pyrazole-4-carboxamide (K.1.87), / V-methoxy-1-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxamide (K.1.88), / V-allyl- / V-[[4-[5-(trifluoromethyl)- 1.2.4-oxadiazol-3-yl]phenyl]methyl]propanamide (K.1.89), 3-ethyl-1-methoxy-1-[[4-[5-(tri-fluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]urea (K.1.90), 1 ,3-dimethoxy-1-[[4-[5-(tri-fluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]methyl]urea (K.1.91), / V-allyl- / V-[[4-[5-(trifluoromethyl)-250083

[0317] 35

[0318] 1,2,4-oxadiazol-3-yl]phenyl]methyl]acetamide (K.1.92), / V-[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]benzyl]cyclopropanecarboxamide (K.1.93), 1-methyl-3-[[4-[5-(trifluoromethyl)-1 ,2,4-oxadi-azol-3-yl]phenyl]methyl]urea (K.1.94), / V'-[2-chloro-4-(2-fluorophenoxy)-5-methyl-phenyl]- / V-ethyl- / V-methyl-formamidine (K.1.95), / V-[2-chloro-4-[(4-methoxy-phenyl)methyl]-5-methyl-phenyl]- / V-ethyl- / V-methyl-formamidine (K.1.96), / V'-[2-chloro-4-[(4-cyano-phenyl)methyl]-5-methyl-phenyl]- / V-ethyl- / V-methyl-formamidine (K.1.97), / V'-[2,5-dimethyl-4-(o-tolylmethyl)phenyl]- / V-ethyl-N-methyl-formamidine (K.1.98), 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)- / V-[2-(2,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (K.1.99), 3-(3-bromo-2-fluoro-phenoxy)-6-chloro- / V-[2-(2-chloro-4-methyl-phenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (K.1.100), 6-chloro- / V-[2-(2-chloro-4-methyl-phenyl)- 2.2-difluoro-ethyl]-3-(3-cyclopropyl-2-fluoro-phenoxy)-5-methyl-pyridazine-4-carboxamide (K.1.101), 6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)- / V-[2-(3,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (K.1.102), 6-chloro-3-(3-chloro-2-fluoro-phenoxy)- / V-[2-(2,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide (K.1.103), / V-[2-(2-bromo-4-methyl-phenyl)-2,2-difluoro-ethyl]-6-chloro-3-(3-cyclopropyl-2-fluoro-phenoxy)- 5-methyl-pyridazine-4-carboxamide (K.1.104), 2-[cyano-(2,6-difluoro-4-pyridyl)amino]-5-methyl- / V-spiro[3.4]octan-3-yl-thiazole-4-carboxamide, 2-[acetyl-(2,6-difluoro-4-pyridyl)amino]- / V-(2,2-dimethylcyclobutyl)-5-methyl-thiazole-4-carboxamide, 2-[(2,6-difluoro-4-pyridyl)- (2-methoxyacetyl)amino]- / V-(2,2-dimethylcyclobutyl)-5-methyl-thiazole-4-carboxamide, 2-[cyano-(2,6-difluoro-4-pyridyl)amino]- / V-(2,2-dimethylcyclobutyl)-5-methyl-thiazole-4-carboxamide, / V-[1-[[3 2-(5-fluoro-2-methoxy-phenyl)-2-hydroxy-ethyl]-5-[(Z)- / V-isopropoxy-C-methyl-carbon-imidoyl]-2,6-dioxo-pyrimidin-1-yl]methyl]-2-methyl-propyl]-2-methyl-propanamide,

[0319] / V-[1-[[3 2-(5-fluoro-2-methoxy-phenyl)-2-hydroxy-ethyl]-5-[(Z)- / V-isopropoxy-C-methyl-carbonimidoyl]-2,6-dioxo-pyrimidin-1-yl]methyl]-2-methyl-propyl]-2,2-dimethyl-propanamide, / V-[2-[3-[2-(5-fluoro-2-methoxy-phenyl)-2-hydroxy-ethyl]-5-[(Z)- / V-isopropoxy-C-methyl-carbonimidoyl]-2,6-dioxo-pyrimidin-1-yl]-1-methyl-ethyl]-2-methyl-propanamide,

[0320] / V-[2-[3-[2-hydroxy-2-(2-methoxyphenyl)ethyl]-5-[(Z)- / V-isopropoxy-C-methyl-carbonimidoyl]-2,6-dioxo-pyrimidin-1-yl]-1-methyl-ethyl]-2-methyl-propanamide, / V-[2-[3-[2-(2-cyanoethoxy)-2-(5-fluoro-2-methoxy-phenyl)ethyl]-5-[(Z)- / V-isopropoxy-C-methyl-carbonimidoyl]-2,6-dioxo-pyrimidin-1-yl]-1-methyl-ethyl]-2-methyl-propanamide, rac-3-[3-(3-chloro-2-fluoro-phenoxy)- 6-methyl-pyridazin-4-yl]-5-[(2-chloro-4-methyl-phenyl)methyl]-5,6-dihydro-4 / - / -1,2,4-oxadiazine, (5S)-3-[3-(3-chloro-2-fluoro-phenoxy)-6-methyl-pyridazin-4-yl]-5-[(2-chloro-4-methyl-phenyl)methyl]-5,6-dihydro-4H-1,2,4-oxadiazine, (5R)-3-[3-(3-chloro-2-fluoro-phenoxy)-6-methyl-pyridazin-4-yl]-5-[(2-chloro-4-methyl-phenyl)methyl]-5,6-dihydro-4 / - / -1,2,4-oxadiazine, 2-(4-fluorophenoxy)-1-[4-[5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl]phenyl]ethanone, 2-[(6-fluoro- 3-pyridyl)oxy]-1-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethanone, 2-(4-fluoroanilino)-1-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethenone, ethyl 1-[[4-[[2-(trifluoromethyl)- 1.3-dioxolan-2-yl]methoxy]phenyl]methyl]-1H-pyrazole-4-carboxylate, ethyl 1-[[4-[[(1Z)-2-ethoxy- 3.3.3-trifluoro-1-propen-1-yl]oxy]phenyl]methyl]-1 / - / -pyrazole-4-carboxylate;

[0321] The fungicides described by common names, their preparation and their activity e.g. against harmful fungi is known (cf.: http: / / www.alanwood.net / pesticides / ); these substances are commercially available.

[0322] The active substances, their preparation and their activity e.g. against fungi is known (www.bcpcpesticidecompendium.bcpc.org / ); many of them are commercially available. Compounds defined by IUPAC nomenclature, their preparation and pesticidal activity are also250083

[0323] 36

[0324] known (e.g. Can. J. Plant Sci. 48(6), 587-94, 1968; EP-141 317; EP-152031; EP-226917; EP-243970; EP-256503; EP-428941; EP-532022; EP-1 028 125; EP-1 035 122; EP-1 201 648; EP-1 122244, JP2002316902; DE19650197; DE10021412; DE102005009458; US 3,296,272; US 3,325,503; WO 98 / 46608; WO 99 / 14187; WO 99 / 24413; WO 99 / 27783; WO 00 / 29404; WO 00 / 46148; WO 00 / 65913; WO 01 / 54501; WO 01 / 56358; WO 02 / 22583; WO 02 / 40431; WO 03 / 10149; WO 03 / 11853; WO 03 / 14103; WO 03 / 16286; WO 03 / 53145; WO 03 / 61388; WO 03 / 66609; WO 03 / 74491; WO 04 / 49804; WO 04 / 83193; WO 05 / 120234; WO 05 / 123689; WO 05 / 123690; WO 05 / 63721; WO 05 / 87772; WO 05 / 87773; WO 06 / 15866; WO 06 / 87325; WO 06 / 87343; WO 07 / 82098; WO 07 / 90624, WO 10 / 139271, WO 11 / 028657, WO 12 / 168188, WO 07 / 006670, WO 11 / 77514; WO 13 / 047749, WO 10 / 069882, WO 13 / 047441, WO 03 / 16303, WO 09 / 90181, WO 13 / 007767, WO 13 / 010862, WO 13 / 127704, WO 13 / 024009, WO 13 / 24010, WO 13 / 047441, WO 13 / 162072, WO 13 / 092224, WO 11 / 135833, ON 1907024, ON 1456054, ON 103387541, ON 1309897, WO 12 / 84812, ON 1907024, WO 09094442, WO 14 / 60177, WO 13 / 116251, WO 08 / 013622, WO 15 / 65922, WO 94 / 01546, EP 2865265, WO 07 / 129454, WO 12 / 165511, WO 11 / 081174, WO 13 / 47441, WO 16 / 156241, WO 16 / 162265, WO 23 / 99460, WO 21 / 244950, WO 21 / 244951, WO 22 / 130188, WO 22 / 243810, WO 21 / 255070, WO 21 / 176057, WO 21 / 153754, JP2023064110, JP2022153603, JP2022046550, JP2022031355, WO 22 / 249074, WO 23 / 046861, WO 18 / 177894, WO 20 / 212513, WO 20 / 097012, US 2023 / 0069915.

[0325] Suitable mixing partners for the compounds of the invention also include biopesticides.

[0326] Biopesticides have been defined as a form of pesticides based on micro-organisms (bacteria, fungi, viruses, nematodes, etc.) or natural products (compounds, e.g. metabolites, proteins, or extracts from biological or other natural sources) (U.S. Environmental Protection Agency: http: / / www.epa.gov / pesticides / biopesticides / ). Biopesticides fall into two major classes, microbial and biochemical pesticides:

[0327] (1) Microbial pesticides consist of bacteria, fungi or viruses (and often include the metabolites that bacteria and fungi produce). Entomopathogenic nematodes are also classified as microbial pesticides, even though they are multi-cellular.

[0328] (2) Biochemical pesticides are naturally occurring substances or or structurally-similar and functionally identical to a naturally-occurring substance and extracts from biological sources that control pests or provide other crop protection uses as defined below, but have non-toxic mode of actions (e.g. growth or developmental regulation, attractants, repellents or defence activators (e.g. induced resistance) and are relatively non-toxic to mammals.

[0329] The following list of biopesticides, in conjunction with which the compounds of the invention can be used, illustrates the possible combinations:

[0330] L) Biopesticides

[0331] L1) Microbial pesticides with fungicidal, bactericidal, viricidal and / or plant defense activator activity: Ampelomyces quisqualis, Aspergillus flavus, Aureobasidium pullulans, Bacillus altitudinis, B. amyloliquefaciens, B. amyloliquefaciens ssp. plantarum (also referred to as B. velezensis), B. megaterium, B. mojavensis, B. mycoides, B. pumilus, B. simplex, B. solisalsi, B. subtilis, B. subtilis var. amyloliquefaciens, B. velezensis, Candida oleophila, C. saitoana, Clavibacter michiganensis (bacteriophages), Coniothyrium minitans, Cryphonectria parasitica, Cryptococcus albidus, Dilophosphora alopecuri, Fusarium oxysporum, Clonostachys rosea f. catenulate (also named Gliocladium catenulatum), Gliocladium roseum, Lysobacter antibioticus,250083

[0332] 37

[0333] L enzymogenes, Metschnikowia fructicola, Microdochium dimerum, Microsphaeropsis ochracea, Muscodor albus, Paenibacillus alvei, Paenibacillus epiphyticus, P. polymyxa, Pantoea vagans, Penicillium bilaiae, Phlebiopsis gigantea, Pseudomonas sp., Pseudomonas chloraphis, Pseudo-zyma flocculosa, Pichia anomala, Pythium oligandrum, Sphaerodes mycoparasitica, Streptomyces griseoviridis, S. lydicus, S. violaceusniger, Talaromyces flavus, Trichoderma asperelloides, T. asperellum, T. atroviride, T. fertile, T. gamsii, T. harmatum, T. harzianum, T. polysporum, T. stromaticum, T. virens, T. viride, Typhula phacorrhiza, Ulocladium oudemansii, Verticillium dahliae, zucchini yellow mosaic virus (avirulent strain);

[0334] L2) Biochemical pesticides with fungicidal, bactericidal, viricidal and / or plant defense activator activity: harpin protein, plant oils (BM3): tea tree oil, orange oil (L.2.1), eugenol, limonene (L.2.2), geraniol (L.2.3), thymol (L.2.4); Reynoutria sachalinensis extract, aureobasidin (in particular aureobasidin A (L.2.5)), ambruticin (L.2.6), bafilomycin (L.2.7) (in particular bafilomycin A1, B1 and C1), chlorflavonin (L.2.8), cinnamaldehyde (L.2.9), natamycin (L.2.10; F8);

[0335] L3) Microbial pesticides with insecticidal, acaricidal, molluscidal and / or nematicidal activity: Agrobacterium radiobacter, Bacillus cereus, B. firmus, B. thuringiensis, B. thuringiensis ssp. aizawai, B. t. ssp. israelensis, B. t. ssp. galleriae, B. t. ssp. kurstaki, B. t. ssp. tenebrionis, Beauveria bassiana, B. brongniartii, Burkholderia spp., Chromobacterium subtsugae, Cydia pomonella granulovirus (CpGV), Cryptophlebia leucotreta granulovirus (CrleGV), Flavobacterium spp., Helicoverpa armigera nucleopolyhedrovirus (HearNPV), Helicoverpa zea nucleopolyhedrovirus (HzNPV), Helicoverpa zea single capsid nucleopolyhedrovirus (HzSNPV), Heterorhabditis bacteriophora, Isaria fumosorosea, Lecanicillium longisporum, L. muscarium, Metarhizium anisopliae, M. anisopliae var. anisopliae, M. anisopliae var. acridum, Nomuraea rileyi, Paecilomyces fumosoroseus, P. lilacinus, Paenibacillus popilliae, Pasteuria spp., P. nishizawae, P. penetrans, P. ramosa, P. thornea, P. usgae, Pseudomonas fluorescens, Spodoptera littoralis nucleopolyhedrovirus (SpliNPV), Steinernema carpocapsae, S. feltiae, S. kraussei, Streptomyces galbus, S. microflavus- L4) Biochemical pesticides with insecticidal, acaricidal, molluscidal, pheromone and / or nematicidal activity: L-carvone, citral, (E,Z)-7,9-dodecadien-1-yl acetate, ethyl formate, (E,Z)-2,4-ethyl decadienoate (pear ester), (Z,Z,E)-7,11,13-hexadecatrienal, heptyl butyrate, isopropyl myristate, lavanulyl senecioate, cis-jasmone, 2-methyl-1 -butanol, methyl eugenol, methyl jasmonate, (E,Z)-2,13-octadecadien-1-ol, (E,Z)-2,13-octadecadien-1-ol acetate, (E,Z)-3,13-octadecadien-1-ol, (R)-1-octen-3-ol, pentatermanone, (E,Z,Z)-3,8,11 -tetradecatrienyl acetate, (Z,E)-9,12-tetradecadien-1-yl acetate, (Z)-7-tetradecen-2-one, (Z)-9-tetradecen-1-yl acetate, (Z)-11-tetradecenal, (Z)-11-tetradecen-1-ol, extract of Chenopodium ambrosiodes, Neem oil, Quillay extract;

[0336] L5) Microbial pesticides with plant stress reducing, plant growth regulator, plant growth promoting and / or yield enhancing activity: Azospirillum amazonense, A. brasilense, A. lipoferum, A. irakense, A. halopraeferens, Bradyrhizobium spp., B. elkanii, B. japonicum, B. liaoningense, B. lupini, Delftia acidovorans, Glomus intraradices, Mesorhizobium spp., Rhizobium leguminosarum bv. phaseoli, R. I. bv. tri foil! , R. I. bv. viciae, R. tropic!, Sinorhizobium meliloti. The biopesticides from group L1) and / or L2) may also have insecticidal, acaricidal, molluscidal, pheromone, nematicidal, plant stress reducing, plant growth regulator, plant growth promoting and / or yield enhancing activity. The biopesticides from group L3) and / or L4) may also have fungicidal, bactericidal, viricidal, plant defense activator, plant stress reducing, plant growth regulator, plant growth promoting and / or yield enhancing activity. The biopesticides from group250083

[0337] 38

[0338] L5) may also have fungicidal, bactericidal, viricidal, plant defense activator, insecticidal, acaricidal, molluscidal, pheromone and / or nematicidal activity.

[0339] Many of these biopesticides have been deposited under deposition numbers mentioned herein (the prefices e.g. ATCC or DSM referto the acronym of the respective culture collection, for details see e.g. here: http: / / www. wfcc.info / ccinfo / collection / by_acronym / ), are referred to in literature, registered and / or are commercially available: mixtures of Aureobasidium pullulans DSM 14940 and DSM 14941 isolated in 1989 in Konstanz, Germany (e.g. blastospores in BlossomProtect® from bio-ferm GmbH, Austria), Azospirillum brasilense Sp245 originally isolated in wheat reagion of South Brazil (Passo Fundo) at least prior to 1980 (BR 11005; e.g. GELFIX® Gram neas from BASF Agricultural Specialties Ltd., Brazil), A. brasilense strains Ab-V5 and Ab-V6 (e.g. in AzoMax from Novozymes BioAg Produtos papra Agricultura Ltda., Quattro Barras, Brazil or Simbiose-Malz® from Simbiose-Agro, Brazil; Plant Soil 331, 413-425, 2010), Bacillus amyloliquefaciens strain AP-188 (NRRL B-50615 and B-50331; US8,445,255); B. amylo-liquefaciens ssp. plantarum strains formerly also sometimes referred to as B. subtilis, recently together with B. methylotrophicus, and B. velezensis classified as B. velezensis (Int. J. Syst. Evol. Microbiol. 66, 1212-1217, 2016): B. a. ssp. plantarum or B. velezensis D747 isolated from air in Kikugawashi, Japan (US 20130236522 A1; FERM BP 8234; e.g. Double Nickel™ 55 WDG from Certis LLC, USA), B. a. ssp. plantarum or B. velezensis FZB24 isolated from soil in Brandenburg, Germany (also called SB3615; DSM 96-2; J. Plant Dis. Prot. 105, 181-197, 1998; e.g. Taegro® from Novozyme Biologicals, Inc., USA), B. a. ssp. plantarum or B. velezensis FZB42 isolated from soil in Brandenburg, Germany (DSM 23117; J. Plant Dis. Prot. 105, 181-197, 1998; e.g. RhizoVital® 42 from AbiTEP GmbH, Germany), B. a. ssp. plantarum or B. vele-zensis MBI600 isolated from faba bean in Sutton Bonington, Nottinghamshire, U.K. at least before 1988 (also called 1430; NRRL B 50595; US 2012 / 0149571 A1; e.g. Integral® from BASF Corp., USA), B. a. ssp. plantarum or B. velezensis QST-713 isolated from peach orchard in 1995 in California, U.S.A. (NRRL B 21661 ; e.g. Serenade® MAX from Bayer Crop Science LP, USA), B. a. ssp. plantarum or B. velezensis TJ1000 isolated in 1992 in South Dakoda, U.S.A, (also called 1BE; ATCC BAA-390; CA 2471555 A1; e.g. QuickRoots™ from TJ Technologies, Watertown, SD, USA); B. firmus CNCM 1-1582, a variant of parental strain EIP-N1 (CNCM 1-1556) isolated from soil of central plain area of Israel (WO 2009 / 126473, US6,406,690; e.g. Votivo® from Bayer CropScience LP, USA), B. pumilus GHA 180 isolated from apple tree rhizo-sphere in Mexico (IDAC 260707-01 ; e.g. PROMIX® BXfrom Premier Horticulture, Quebec, Canada), B. pumilus INR-7 otherwise referred to as BU F22 and BU-F33 isolated at least be-fore 1993 from cucumber infested by Erwinia tracheiphila (NRRL B-50185, NRRL B-50153; US 8,445,255), B. pumilus KFP9F isolated from the rhizosphere of grasses in South Africa at least before 2008 (NRRL B-50754; WO 2014 / 029697; e.g. BAC-UP or FUSION-P from BASF Agricultural Specialities (Pty) Ltd., South Africa), B. pumilus QST 2808 was isolated from soil collected in Pohnpei, Federated States of Micronesia, in 1998 (NRRL B 30087; e.g. Sonata® or Ballad® Plus from Bayer Crop Science LP, USA), B. simplex ABU 288 (NRRL B-50304; US8,445,255), B. subtilis FB17 also called UD 1022 or UD10-22 isolated from red beet roots in North America (ATCC PTA-11857; System. Appl. Microbiol. 27, 372-379, 2004; US2010 / 0260735; WO 2011 / 109395); B. thuringiensis ssp. aizawai ABTS-1857 isolated from soil taken from a lawn in Ephraim, Wisconsin, U.S.A., in 1987 (also called ABG 6346; ATCC SD-1372; e.g. XenTari® from BioFa AG, Munsingen, Germany), B. t. ssp. kurstaki ABTS-351 identical to HD-1 isolated in 1967 from diseased Pink Bollworm black larvae in Brownsville, Texas, U.S.A. (ATCC SD-1275; e.g. Dipel® DF from Valent BioSciences, IL, USA), B. t. ssp. kurstaki SB4250083

[0340] 39

[0341] isolated from E. saccharina larval cadavers (NRRL B-50753; e.g. Beta Pro® from BASF Agricultural Specialities (Pty) Ltd., South Africa), B. t. ssp. tenebrionis NB-176-1, a mutant of strain NB-125, a wild type strain isolated in 1982 from a dead pupa of the beetle Tenebrio molitor (DSM 5480; EP 585215 B1 ; e.g. Novodor® from Valent BioSciences, Switzerland), Beauveria bassiana GHA (ATCC 74250; e.g. BotaniGard® 22WGP from Laverlam Int. Corp., USA), B. bassiana JW-1 (ATCC 74040; e.g. Naturalis® from CBC (Europe) S.r.l., Italy), B. bassiana PPRI 5339 isolated from the larva of the tortoise beetle Conchyloctenia punctata (NRRL 50757; e.g. BroadBand® from BASF Agricultural Specialities (Pty) Ltd., South Africa), Bradyrhizobium elkanii strains SEMIA 5019 (also called 29W) isolated in Rio de Janeiro, Brazil and SEMIA 587 isolated in 1967 in the State of Rio Grande do Sul, from an area previously inoculated with a North American isolate, and used in commercial inoculants since 1968 (Appl. Environ. Microbiol. 73(8), 2635, 2007; e.g. GELFIX 5 from BASF Agricultural Specialties Ltd., Brazil), B. japonicum 532c isolated from Wisconsin field in U.S.A. (Nitragin 61A152; Can. J. Plant. Sci. 70, 661-666, 1990; e.g. in Rhizoflo®, Histick®, Hicoat® Super from BASF Agricultural Specialties Ltd., Canada), B. japonicum E-109 variant of strain USDA 138 (INTA E109, SEMIA 5085; Eur. J. Soil Biol. 45, 28-35, 2009; Biol. Fertil. Soils 47, 81-89, 2011); B. japonicum strains deposited at SEMIA known from Appl. Environ. Microbiol. 73(8), 2635, 2007: SEMIA 5079 isolated from soil in Cerrados region, Brazil by Embrapa-Cerrados used in commercial inoculants since 1992 (CPAC 15; e.g. GELFIX 5 or ADHERE 60 from BASF Agricultural Specialties Ltd., Brazil), B. japonicum SEMIA 5080 obtained under lab condtions by Embrapa-Cerrados in Brazil and used in commercial inoculants since 1992, being a natural variant of SEMIA 586 (CB1809) originally isolated in U.S.A. (CPAC 7; e.g. GELFIX 5 or ADHERE 60 from BASF Agricultural Specialties Ltd., Brazil); Burkholderia sp. A396 isolated from soil in Nikko, Japan, in 2008 (NRRL B-50319; WO 2013 / 032693; Marrone Bio Innovations, Inc., USA), Coniothyrium minitans CON / M / 91-08 isolated from oilseed rape (WO 1996 / 021358; DSM 9660; e.g. Contans® WG, Intercept® WG from Bayer CropScience AG, Germany), harpin (alpha-beta) protein (Science 257, 85-88, 1992; e.g. Messenger™ or HARP-N Tek from Plant Health Care pic, U.K.), Helicoverpa armigera nucleopolyhedrovirus (HearNPV) (J. Invertebrate Pathol. 107, 112-126, 2011; e.g. Helicovex® from Adermatt Biocontrol, Switzerland; Diplomata® from Koppert, Brazil; Vivus® Max from AgBiTech Pty Ltd., Queensland, Australia), Helicoverpa zea single capsid nucleopolyhedrovirus (HzSNPV) (e.g. Gemstar® from Certis LLC, USA), Helicoverpa zea nucleopolyhedrovirus ABA-NPV-U (e.g. Heligen® from AgBiTech Pty Ltd., Queensland, Australia), Heterorhabditis bacteriophora (e.g. Nemasys® G from BASF Agricultural Specialities Limited, UK), Isaria fumosorosea Apopka-97 isolated from mealy bug on gynura in Apopka, Florida, U.S.A. (ATCC 20874; Biocontrol Science Technol. 22(7), 747-761, 2012; e.g. PFR-97™ or PreFeRal® from Certis LLC, USA), Metarhizium anisopliae var. anisopliae F52 also called 275 or V275 isolated from codling moth in Austria (DSM 3884, ATCC 90448; e.g. Met52® Novozymes Biologicals BioAg Group, Canada), Metschnikowia fructicola 277 isolated from grapes in the central part of Israel (US 6,994,849; NRRL Y-30752; e.g. formerly Shemer® from Agrogreen, Israel), Paecilomyces ilacinus 251 isolated from infected nematode eggs in the Philippines (AGAL 89 / 030550; WQ1991 / 02051 ; Crop Protection 27, 352-361, 2008; e.g. BioAct®from Bayer CropScience AG, Germany and MeloCon® from Certis, USA), Paenibacillus alvei NAS6G6 isolated from the rhizosphere of grasses in South Africa at least before 2008 (WO 2014 / 029697; NRRL B-50755; e.g. BAC-UP from BASF Agricultural Specialities (Pty) Ltd., South Africa), Paenibacillus strains isolated from soil samples from a variety of European locations including250083

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[0343] Germany: P. epiphyticus Lu17015 (WO 2016 / 020371; DSM 26971), P. polymyxa ssp. plantarum Lu16774 (WO 2016 / 020371; DSM 26969), P. p. ssp. plantarum strain Lu17007 (WO 2016 / 020371; DSM 26970); Pasteuria nishizawae Pn1 isolated from a soybean field in the mid-20005 in Illinois, U.S.A. (ATCC SD 5833; Federal Register 76(22), 5808, February 2, 2011; e.g. Clariva™ PN from Syngenta Crop Protection, LLC, USA), Penicillium bilaiae (also called P. bilaii) strains ATCC 18309 (= ATCC 74319), ATCC 20851 and / or ATCC 22348 (=ATCC 74318) originally isolated from soil in Alberta, Canada (Fertilizer Res. 39, 97-103, 1994; Can. J. Plant Sci.

[0344] 78(1), 91-102, 1998; US 5,026,417, WO 1995 / 017806; e.g. Jump Start®, Provide® from Novozymes Biologicals BioAg Group, Canada), Reynoutria sachalinensis extract (EP 0307510 B1 ; e.g. Regalia® SC from Marrone BioInnovations, Davis, CA, USA or Milsana® from BioFa AG, Germany), Steinernema carpocapsae (e.g. Millenium® from BASF Agricultural Specialities Limited, UK), S. feltiae (e.g. Nemashield® from BioWorks, Inc., USA; Nemasys® from BASF Agricultural Specialities Limited, UK), Streptomyces microflavus NRRL B-50550 (WO 2014 / 124369; Bayer CropScience, Germany), Trichoderma asperelloides JM41R isolated in South Africa (NRRL 50759; also referred to as T. fertile; e.g. Trichoplus® from BASF Agricultural Specialities (Pty) Ltd., South Africa), T. harzianum T-22 also called KRL-AG2 (ATCC 20847; BioControl 57, 687-696, 2012; e.g. Plantshield® from BioWorks Inc., USA or SabrEx™ from Advanced Biological Marketing Inc., Van Wert, OH, USA).

[0345] According to the invention, the solid material (dry matter) of the biopesticides (with the ex-ception of oils e.g. Neem oil) are considered as active components (e.g. to be obtained after drying or evaporation of the extraction or suspension medium in case of liquid formulations of the microbial pesticides).

[0346] In accordance with the invention, the weight ratios and percentages used herein for a biological extract e.g. Quillay extract are based on the total weight of the dry content (solid material) of the respective extract(s).

[0347] The total weight ratios of compositions comprising at least one microbial pesticide in the form of viable microbial cells including dormant forms, can be determined using the amount of CFU of the respective microorganism to calculate the total weight of the respective active component with the following equation that 1x1010CFU equals one gram of total weight of the respective active component. Colony forming unit is measure of viable microbial cells, in particular fungal and bacterial cells. In addition, here “CFU” may also be understood as the number of (juvenile) individual nematodes in case of (entomopathogenic) nematode biopesticides, e.g. Steinernema feltiae.

[0348] When mixtures comprising microbial pesticides are employed in crop protection, the application rates range from 1x106to 5x1016(or more) CFU / ha, preferably from 1x108to 1x1013CFU / ha, and even more preferably from 1x109to 5x1015CFU / ha and in particular from 1x1012to 5x1014CFU / ha. In the case of nematodes as microbial pesticides (e.g. Steinernema feltiae), the application rates regularly range from 1x105to 1x1012(or more), preferably from 1x108to 1x1011, more preferably from 5x108to 1x1010individuals (e.g. in the form of eggs, juvenile or any other live stages, preferably in an infetive juvenile stage) per ha.

[0349] When mixtures comprising microbial pesticides are employed in seed treatment, the application rates generally range from 1x106to 1x1012(or more) CFU / seed, preferably from 1x106to 1x109CFU / seed. Furthermore, the application rates with respect to seed treatment generally range from 1x107to 1x1014(or more) CFU per 100 kg of seed, preferably from 1x109to 1x1012CFU per 100 kg of seed.250083

[0350] 41

[0351] Formulations

[0352] The invention also relates to agrochemical compositions comprising an auxiliary and at least one compound of the invention or a mixture thereof.

[0353] An agrochemical composition comprises a pesticidally effective amount of a compound of the invention or a mixture thereof.

[0354] The compounds of the invention or the mixtures thereof can be converted into customary types of agro-chemical compositions, e.g. solutions, emulsions, suspensions, dusts, powders, pastes, granules, pressings, capsules, and mixtures thereof. Examples for composition types are suspensions (e.g. SC, OD, FS), emulsifiable concentrates (e.g. EC), emulsions (e.g. EW, EO, ES, ME), capsules (e.g. CS, ZC), pastes, pastilles, wettable powders or dusts (e.g. WP, SP, WS, DP, DS), pressings (e.g. BR, TB, DT), granules (e.g. WG, SG, GR, FG, GG, MG), insecticidal articles (e.g. LN), as well as gel formulations for the treatment of plant propagation materials e.g. seeds (e.g. GF). These and further compositions types are defined in the “Catalogue of pesticide formulation types and international coding system”, Technical Monograph No. 2, 6th Ed. May 2008, CropLife International.

[0355] The compositions are prepared in a known manner, e.g. described by Mollet and Grubemann, Formulation technology, Wiley VCH, Weinheim, 2001; or Knowles, New developments in crop protection product formulation, Agrow Reports DS243, T&F Informa, London, 2005.

[0356] Examples for suitable auxiliaries are solvents, liquid carriers, solid carriers or fillers, surfactants, dispersants, emulsifiers, wetters, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesion agents, thickeners, humectants, repellents, attractants, feeding stimulants, compatibilizers, bactericides, anti-freezing agents, anti-foaming agents, colorants, tackifiers and binders.

[0357] Suitable solvents and liquid carriers are water and organic solvents, e.g. mineral oil fractions of medium to high boiling point, e.g. kerosene, diesel oil; oils of vegetable or animal origin; hydrocarbons, e.g. toluene, paraffin, tetrahydronaphthalene, alkylated naphthalenes; alcohols, e.g. ethanol, propanol, butanol, benzylalcohol, cyclohexanol; glycols; DMSO; ketones, e.g. cyclohexanone; esters, e.g. lactates, carbonates, fatty acid esters, gamma-butyrolactone; fatty acids; phosphonates; amines; amides, e.g. N-methylpyrrolidone, fatty acid dimethylamides; and mixtures thereof.

[0358] Suitable solid carriers or fillers are mineral earths, e.g. silicates, silica gels, talc, kaolins, limestone, lime, chalk, clays, dolomite, diatomaceous earth, bentonite, CaSO4, MgSO4, MgO; polysaccharide powders, e.g. cellulose, starch; fertilizers, e.g. (NH4)2SO4, (NH4)3PO4, NH4NO3, ureas; products of vegetable origin, e.g. cereal meal, tree bark meal, wood meal, nutshell meal, and mixtures thereof.

[0359] Suitable surfactants are surface-active compounds, e.g. anionic, cationic, nonionic and amphoteric surfactants, block polymers, polyelectrolytes, and mixtures thereof. Such surfactants can be used as emusifier, dispersant, solubilizer, wetter, penetration enhancer, protective col-loid, or adjuvant. Examples of surfactants are listed in McCutcheon’s, Vol.1: Emulsifiers & Detergents, McCutcheon’s Directories, Glen Rock, USA, 2008 (International or North American Ed.).

[0360] Suitable anionic surfactants are alkali, alkaline earth or ammonium salts of sulfonates, sulfates, phosphates, carboxylates, and mixtures thereof. Examples of sulfonates are alkylarylsulfonates, diphenylsulfonates, alpha-olefin sulfonates, lignine sulfonates, sulfonates of fatty acids and oils, sulfonates of ethoxylated alkylphenols, sulfonates of alkoxylated arylphenols, sulfonates of250083

[0361] 42

[0362] condensed naphthalenes, sulfonates of dodecyl- and tridecylbenzenes, sulfonates of naphthalenes and alkylnaphthalenes, sulfosuccinates or sulfosuccinamates. Examples of sulfates are sulfates of fatty acids and oils, of ethoxylated alkylphenols, of alcohols, of ethoxylated alcohols, or of fatty acid esters. Examples of phosphates are phosphate esters. Examples of carboxylates are alkyl carboxylates, and carboxylated alcohol or alkylphenol ethoxylates.

[0363] Suitable nonionic surfactants are alkoxylates, N-subsituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants, and mixtures thereof. Examples of alkoxylates are compounds e.g. alcohols, alkylphenols, amines, amides, arylphenols, fatty acids or fatty acid esters which have been alkoxylated with 1 to 50 equivalents. Ethylene oxide and / or propylene oxide may be employed for the alkoxylation, preferably ethylene oxide. Examples of N-subsititued fatty acid amides are fatty acid glucamides or fatty acid alkanola-mides. Examples of esters are fatty acid esters, glycerol esters or monoglycerides. Examples of sugar-based surfactants are sorbitans, ethoxylated sorbitans, sucrose and glucose esters or alkylpolyglucosides. Examples of polymeric surfactants are homo- or copolymers of vinylpyrrolidone, vinylalcohols, or vinylacetate.

[0364] Suitable cationic surfactants are quaternary surfactants, e.g. quaternary ammonium compounds with one or two hydrophobic groups, or salts of long-chain primary amines. Suitable amphoteric surfactants are alkylbetains and imidazolines. Suitable block polymers are block polymers of the A-B or A-B-A type comprising blocks of polyethylene oxide and polypropylene oxide, or of the A-B-C type comprising alkanol, polyethylene oxide and polypropylene oxide. Suitable polyelectrolytes are polyacids or polybases. Examples of polyacids are alkali salts of polyacrylic acid or polyacid comb polymers. Examples of polybases are polyvinylamines, or polyethyleneamines.

[0365] Suitable adjuvants are compounds, which have a neglectable or even no pesticidal activity themselves, and which improve the biological performance of the compounds of the invention on the target. Examples are surfactants, mineral or vegetable oils, and other auxilaries. Further examples are listed by Knowles, Adjuvants and additives, Agrow Reports DS256, T&F Informa UK, 2006, chapter 5.

[0366] Suitable thickeners are polysaccharides (e.g. xanthan gum, carboxymethylcellulose), inorganic clays (organically modified or unmodified), polycarboxylates, and silicates.

[0367] Suitable bactericides are bronopol and isothiazolinone derivatives e.g. alkylisothiazolinones and benzisothiazolinones.

[0368] Suitable anti-freezing agents are ethylene glycol, propylene glycol, urea, and glycerin.

[0369] Suitable anti-foaming agents are silicones, long chain alcohols, and salts of fatty acids.

[0370] Suitable colorants (e.g. in red, blue, or green) are pigments of low water solubility and water-soluble dyes. Examples are inorganic colorants (e.g. iron oxide, titan oxide, iron hexacyanoferrate) and organic colorants (e.g. alizarin-, azo-, and phthalocyanine colorants). Suitable tackifiers or binders are polyvinylpyrrolidons, polyvinylacetates, polyvinyl alcohols, polyacrylates, biological or synthetic waxes, and cellulose ethers.

[0371] Examples for composition types and their preparation are:

[0372] i) Water-soluble concentrates (SL, LS)

[0373] 10-60 wt% of a compound I according to the invention and 5-15 wt% wetting agent (e.g. alcohol alkoxylates) are dissolved in water and / or in a water-soluble solvent (e.g. alcohols) up to 100 wt%. The active substance dissolves upon dilution with water.

[0374] ii) Dispersible concentrates (DC)250083

[0375] 43

[0376] 5-25 wt% of a compound I according to the invention and 1-10 wt% dispersant (e.g. polyvinylpyrrolidone) are dissolved in up to 100 wt% organic solvent (e.g. cyclohexanone). Dilution with water gives a dispersion.

[0377] iii) Emulsifiable concentrates (EC)

[0378] 15-70 wt% of a compound I according to the invention and 5-10 wt% emulsifiers (e.g. calcium dodecylbenzenesulfonate and castor oil ethoxylate) are dissolved in up to 100 wt% waterinsoluble organic solvent (e.g. aromatic hydrocarbon). Dilution with water gives an emulsion. iv) Emulsions (EW, EO, ES)

[0379] 5-40 wt% of a compound I according to the invention and 1-10 wt% emulsifiers (e.g. calcium dodecylbenzenesulfonate and castor oil ethoxylate) are dissolved in 20-40 wt% water-insoluble organic solvent (e.g. aromatic hydrocarbon). This mixture is introduced into up to 100 wt% water by means of an emulsifying machine and made into a homogeneous emulsion. Dilution with water gives an emulsion.

[0380] v) Suspensions (SC, OD, FS)

[0381] In an agitated ball mill, 20-60 wt% of a compound I according to the invention are comminuted with addition of 2-10 wt% dispersants and wetting agents (e.g. sodium lignosulfonate and alcohol ethoxylate), 0,1-2 wt% thickener (e.g. xanthan gum) and up to 100 wt% water to give a fine active substance suspension. Dilution with water gives a stable suspension of the active sub-stance. For FS type composition up to 40 wt% binder (e.g. polyvinylalcohol) is added.

[0382] vi) Water-dispersible granules and water-soluble granules (WG, SG)

[0383] 50-80 wt% of a compound I according to the invention are ground finely with addition of up to 100 wt% dispersants and wetting agents (e.g. sodium lignosulfonate and alcohol ethoxylate) and prepared as water-dispersible or water-soluble granules by means of technical appliances (e.g. extrusion, spray tower, fluidized bed). Dilution with water gives a stable dispersion or solution of the active substance.

[0384] vii) Water-dispersible powders and water-soluble powders (WP, SP, WS)

[0385] 50-80 wt% of a compound I according to the invention are ground in a rotor-stator mill with addition of 1-5 wt% dispersants (e.g. sodium lignosulfonate), 1-3 wt% wetting agents (e.g. alcohol ethoxylate) and up to 100 wt% solid carrier, e.g. silica gel. Dilution with water gives a stable dispersion or solution of the active substance.

[0386] viii) Gel (GW, GF)

[0387] In an agitated ball mill, 5-25 wt% of a compound I according to the invention are comminuted with addition of 3-10 wt% dispersants (e.g. sodium lignosulfonate), 1-5 wt% thickener (e.g. carboxymethylcellulose) and up to 100 wt% water to give a fine suspension of the active substance. Dilution with water gives a stable suspension of the active substance.

[0388] ix) Microemulsion (ME)

[0389] 5-20 wt% of a compound I according to the invention are added to 5-30 wt% organic solvent blend (e.g. fatty acid dimethylamide and cyclohexanone), 10-25 wt% surfactant blend (e.g. alcohol ethoxylate and arylphenol ethoxylate), and water up to 100 %. This mixture is stirred for 1 h to produce spontaneously a thermodynamically stable microemulsion.

[0390] x) Microcapsules (CS)

[0391] An oil phase comprising 5-50 wt% of a compound I according to the invention, 0-40 wt% water insoluble organic solvent (e.g. aromatic hydrocarbon), 2-15 wt% acrylic monomers (e.g. methylmethacrylate, methacrylic acid and a di- or triacrylate) are dispersed into an aqueous solution of a protective colloid (e.g. polyvinyl alcohol). Radical polymerization initiated by a radical250083

[0392] 44

[0393] initiator results in the formation of poly(meth)acrylate microcapsules. Alternatively, an oil phase comprising 5-50 wt% of a compound I according to the invention, 0-40 wt% water insoluble organic solvent (e.g. aromatic hydrocarbon), and an isocyanate monomer (e.g. di-phenylme-thene-4,4’-diisocyanatae) are dispersed into an aqueous solution of a protective colloid (e.g. polyvinyl alcohol). The addition of a polyamine (e.g. hexamethylenediamine) results in the for-ation of a polyurea microcapsule. The monomers amount to 1-10 wt%. The wt% relate to the total CS composition.

[0394] xi) Dustable powders (DP, DS)

[0395] 1-10 wt% of a compound I according to the invention are ground finely and mixed intimately with up to 100 wt% solid carrier, e.g. finely divided kaolin.

[0396] xii) Granules (GR, FG)

[0397] 0.5-30 wt% of a compound I according to the invention is ground finely and associated with up to 100 wt% solid carrier (e.g. silicate). Granulation is achieved by extrusion, spray-drying or the fluidized bed.

[0398] xiii) Ultra-low volume liquids (UL)

[0399] 1-50 wt% of a compound I according to the invention are dissolved in up to 100 wt% organic solvent, e.g. aromatic hydrocarbon.

[0400] The compositions types i) to xi) may optionally comprise further auxiliaries, e.g. 0.1-1 wt% bactericides, 5-15 wt% anti-freezing agents, 0.1-1 wt% anti-foaming agents, and 0.1-1 wt% colorants.

[0401] The agrochemical compositions generally comprise between 0.01 and 95%, preferably be-tween 0.1 and 90%, and most preferably between 0.5 and 75%, by weight of active substance. The active substances are employed in a purity of from 90% to 100%, preferably from 95% to 100% (according to NMR spectrum).

[0402] Various types of oils, wetters, adjuvants, fertilizer, or micronutrients, and other pesticides (e.g. herbicides, insecticides, fungicides, growth regulators, safeners) may be added to the active substances or the compositions comprising them as premix or, if appropriate not until immediately prior to use (tank mix). These agents can be admixed with the compositions according to the invention in a weight ratio of 1 : 100 to 100: 1 , preferably 1 : 10 to 10:1.

[0403] The user applies the composition according to the invention usually from a predosage device, a knapsack sprayer, a spray tank, a spray plane, or an irrigation system. Usually, the agro-chemical composition is made up with water, buffer, and / or further auxiliaries to the desired application concentration and the ready-to-use spray liquor or the agrochemical composition according to the invention is thus obtained. Usually, 20 to 2000 liters, preferably 50 to 400 liters, of the ready-to-use spray liquor are applied per hectare of agricultural useful area.

[0404] According to one embodiment, individual components of the composition of the invention e.g. parts of a kit or parts of a binary or ternary mixture may be mixed by the user himself in a spray tank and further auxiliaries may be added, if appropriate.

[0405] In a further embodiment, either individual components of the composition according to the invention or partially premixed components, e.g. components comprising compounds of the invention and / or mixing partners as defined above, may be mixed by the user in a spray tank and further auxiliaries and additives may be added.

[0406] In a further embodiment, either individual components of the composition according to the invention or partially premixed components, e.g. components comprising compounds of the250083

[0407] 45

[0408] invention and / or mixing partners as defined above, can be applied jointly (e.g. after tank mix) or consecutively.

[0409] Application methods

[0410] The compounds of the invention are suitable for use in protecting crops, plants, plant propagation materials, e.g. seeds, or soil or water, in which the plants are growing, from attack or infestation by animal pests. Therefore, the invention also relates to a plant protection method, which comprises contacting crops, plants, plant propagation materials, e.g. seeds, or soil or water, in which the plants are growing, to be protected from attack or infestation by animal pests, with a pesticidally effective amount of a compound of the invention.

[0411] The compounds of the invention are also suitable for use in combating or controlling animal pests. Therefore, the invention also relates to a method of combating or controlling animal pests, which comprises contacting the animal pests, their habitat, breeding ground, or food supply, or the crops, plants, plant propagation materials, e.g. seeds, or soil, or the area, material or environment in which the animal pests are growing or may grow, with a pesticidally effective amount of a compound of the invention.

[0412] The compounds of the invention are effective through both contact and ingestion. Further-more, the compounds of the invention can be applied to any and all developmental stages, e.g. egg, larva, pupa, and adult.

[0413] The compounds of the invention can be applied as such or in form of compositions comprising them as defined above. Furthermore, the compounds of the invention can be applied together with a mixing partner or in form of compositions comprising said mixtures. The components of said mixture can be applied simultaneously, jointly or separately, or in succession, that is immediately one after another and thereby creating the mixture “in situ” on the desired location, e.g. the plant, the sequence, in the case of separate application, generally not having any effect on the result of the control measures.

[0414] The application can be carried out both before and after the infestation of the crops, plants, plant propagation materials, e.g. seeds, soil, or the area, material or environment by the pests.

[0415] Suitable application methods include i.a. soil treatment, seed treatment, in furrow application, and foliar application. Soil treatment methods include drenching the soil, drip irrigation (drip application onto the soil), dipping roots, tubers or bulbs, or soil injection. Seed treatment techniques include seed dressing, seed coating, seed dusting, seed soaking, and seed pelleting. In furrow applications typically include the steps of making a furrow in cultivated land, seeding the furrow with seeds, applying the pesticidally active compound to the furrow, and closing the furrow. Foliar application refers to the application of the pesticidally active compound to plant foliage, e.g. through spray equipment. For foliar applications, it can be advantageous to modify the behavior of the pests by use of pheromones in combination with the compounds of the invention. Suitable pheromones for specific crops and pests are known and publicly available from databases of pheromones and semiochemicals, e.g. http: / / www.pherobase.com.

[0416] As used herein, the term "contacting" includes both direct contact (applying the com-pounds / compositions directly on the animal pest or plant - typically to the foliage, stem or roots of the plant) and indirect contact (applying the compounds / compositions to the locus, i.e. habitat, breeding ground, plant, seed, soil, area, material, or environment in which a pest is growing or may grow, of the animal pest or plant).250083

[0417] 46

[0418] The term “animal pest” includes arthropods, gastropods, and nematodes. Preferred animal pests according to the invention are arthropods, preferably insects and arachnids, in particular insects. Insects, which are of particular relevance for crops, are typically referred to as crop insect pests. The term "crop" refers to both, growing and harvested crops.

[0419] The term “plant” includes cereals, e.g. durum and other wheat, rye, barley, triticale, oats, rice, or maize (fodder maize and sugar maize I sweet and field corn); beet, e.g. sugar beet, or fodder beet; fruits, e.g. pomes, stone fruits, or soft fruits, e.g. apples, pears, plums, peaches, nectarines, almonds, cherries, papayas, strawberries, raspberries, blackberries or gooseberries; leguminous plants, e.g. beans, lentils, peas, alfalfa, or soybeans; oil plants, e.g. rapeseed (oilseed rape), turnip rape, mustard, olives, sunflowers, coconut, cocoa beans, castor oil plants, oil palms, ground nuts, or soybeans; cucurbits, e.g. squashes, pumpkins, cucumber or melons; fiber plants, e.g. cotton, flax, hemp, or jute; citrus fruit, e.g. oranges, lemons, grapefruits or mandarins; vegetables, e.g. eggplant, spinach, lettuce (e.g. iceberg lettuce), chicory, cabbage, asparagus, cabbages, carrots, onions, garlic, leeks, tomatoes, potatoes, cucurbits or sweet peppers; lauraceous plants, e.g. avocados, cinnamon, or camphor; energy and raw material plants, e.g. corn, soybean, rapeseed, sugar cane or oil palm; tobacco; nuts, e.g. walnuts; pistachios; coffee; tea; bananas; vines; hop; sweet leaf (Stevia); natural rubber plants or ornamental and forestry plants, shrubs, broad-leaved trees or evergreens, eucalyptus; turf; lawn; grass. Preferred plants include potatoes sugar beets, tobacco, wheat, rye, barley, oats, rice, corn, cotton, soybeans, rapeseed, legumes, sunflowers, coffee, or sugar cane; fruits; vines; ornamentals; or vegetables, e.g. cucumbers, tomatoes, beans or squashes.

[0420] The term "cultivated plants" is to be understood as including plants which have been modified by mutagenesis or genetic engineering in order to provide a new trait to a plant or to modify an already present trait.

[0421] Mutagenesis includes techniques of random mutagenesis using X-rays or mutagenic chemicals, but also techniques of targeted mutagenesis, in order to create mutations at a specific locus of a plant genome. Targeted mutagenesis techniques frequently use oligonucleotides or proteins like CRISPR / Cas, zinc-finger nucleases, TALENs or meganucleases to achieve the targeting effect. Genetic engineering usually uses recombinant DNA techniques to create modifications in a plant genome which under natural circumstances cannot readily be obtained by cross breeding, mutagenesis or natural recombination. Typically, one or more genes are integrated into the genome of a plant in order to add a trait or improve a trait. These integrated genes are also referred to as transgenes in the art, while plant comprising such transgenes are referred to as transgenic plants. The process of plant transformation usually produces several transformation events, which differ in the genomic locus in which a transgene has been integrated. Plants comprising a specific transgene on a specific genomic locus are usually described as comprising a specific “event”, which is referred to by a specific event name. Traits which have been introduced in plants or have been modified include in particular herbicide tolerance, insect resistance, increased yield and tolerance to abiotic conditions, like drought.

[0422] Herbicide tolerance has been created by using mutagenesis as well as using genetic engineering. Plants which have been rendered tolerant to ALS inhibitor herbicides by conventional methods of mutagenesis and breeding comprise plant varieties commercially available under the name Clearfield®.250083

[0423] 47

[0424] Herbicide tolerance has been created to glyphosate, glufosinate, 2,4-D, dicamba, oxynil herbicides, like bromoxynil and ioxynil, sulfonylurea herbicides, ALS inhibitor herbicides and HPPD inhibitors, like isoxaflutole and mesotrione.

[0425] Transgenes which have been used to provide herbicide tolerance traits comprise: for tolerance to glyphosate: cp4 epsps, epsps grg23ace5, mepsps, 2mepsps, gat4601 , gat4621 and goxv247, for tolerance to glufosinate: pat and bar, for tolerance to 2,4-D: aad-1 and aad-12, for tolerance to dicamba: dmo, for tolerance to oxynil herbicies: bxn, for tolerance to sulfonylurea herbicides: zm-hra, csr1-2, gm-hra, S4-HrA, for tolerance to ALS inhibitor herbicides: csr1-2, for tolerance to HPPD inhibitor herbicides: hppdPF, W336 and avhppd-03.

[0426] Transgenic corn events comprising herbicide tolerance genes are e.g., but not excluding others, DAS40278, MON801 , MON802, MON809, MON810, MON832, MON87411 , MON87419, MON87427, MON88017, MON89034, NK603, GA21 , MZHG0JG, HCEM485, VCO-01981-5, 676, 678, 680, 33121 , 4114, 59122, 98140, Bt10, Bt176, CBH-351 , DBT418, DLL25, MS3, MS6, MZIR098, T25, TC1507 and TC6275.

[0427] Transgenic soybean events comprising herbicide tolerance genes are e.g., but not excluding others, GTS 40-3-2, MON87705, MON87708, MON87712, MON87769, MON89788, A2704-12, A2704-21 , A5547-127, A5547-35, DP356043, DAS44406-6, DAS68416-4, DAS-81419-2, GU262, SYHT0H2, W62, W98, FG72 and CV127.

[0428] Transgenic cotton events comprising herbicide tolerance genes are e.g., but not excluding others, 19-51a, 31707, 42317, 81910, 281-24-236, 3006-210-23, BXN10211 , BXN10215, BXN10222, BXN10224, MON1445, MON1698, MON88701 , MON88913, GHB119, GHB614, LLCotton25, T303-3 and T304-40.

[0429] Transgenic canola events comprising herbicide tolerance genes are e.g., but not excluding others, MON88302, HCR-1, HCN10, HCN28, HCN92, MS1 , MS8, PHYU, PHY23, PHY35, PHY36, RF1 , RF2 and RF3.

[0430] Insect resistance has mainly been created by transferring bacterial genes for insecticidal pro-teins to plants. Transgenes which have most frequently been used are toxin genes of Bacillus spec, and synthetic variants thereof, like cry1A, cry 1 Ab, cry1 Ab-Ac, cry 1 Ac, cry1A.1O5, cry1F, cry1Fa2, cry2Ab2, cry2Ae, mcry3A, ecry3.1Ab, cry3Bb1 , cry34Ab1 , cry35Ab1 , cry9C, vip3A(a), vip3Aa20. However, also genes of plant origin have been transferred to other plants. In particular genes coding for protease inhibitors, like CpTI and pin 11. A further approach uses transgenes in order to produce double stranded RNA in plants to target and downregulate in-sect genes. An example for such a transgene is dvsnf7.

[0431] Transgenic corn events comprising genes for insecticidal proteins or double stranded RNA are e.g., but not excluding others, Bt10, Bt11 , Bt176, MON801 , MON802, MON809, MON810, MON863, MON87411 , MON88017, MON89034, 33121 , 4114, 5307, 59122, TC1507, TC6275, CBH-351 , MIR162, DBT418 and MZIR098.

[0432] Transgenic soybean events comprising genes for insecticidal proteins are e.g., but not excluding others, MON87701 , MON87751 and DAS-81419.

[0433] Transgenic cotton events comprising genes for insecticidal proteins are e.g., but not excluding others, SGK321 , MON531 , MON757, MON1076, MON15985, 31707, 31803, 31807, 31808, 42317, BNLA-601 , Eventl, COT67B, COT102, T303-3, T304-40, GFM Cry1A, GK12, MLS 9124, 281-24-236, 3006-210-23, GHB119 and SGK321.250083

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[0435] Increased yield has been created by increasing ear biomass using the transgene athb17, be-ing present in corn event MON87403, or by enhancing photosynthesis using the transgene bbx32, being present in the soybean event MON87712.

[0436] Cultivated plants comprising a modified oil content have been created by using the transgenes: gm-fad2-1, Pj.D6D, Nc.Fad3, fad2-1A and fatb1-A. Soybean events comprising at least one of these genes are: 260-05, MON87705 and MON87769.

[0437] Tolerance to abiotic conditions, in particular to tolerance to drought, has been created by using the transgene cspB, comprised by the corn event MON87460 and by using the transgene Hahb-4, comprised by soybean event IND-00410-5.

[0438] Traits are frequently combined by combining genes in a transformation event or by combining different events during the breeding process. Preferred combination of traits are herbicide tolerance to different groups of herbicides, insect tolerance to different kind of insects, in particular tolerance to lepidopteran and coleopteran insects, herbicide tolerance with one or several types of insect resistance, herbicide tolerance with increased yield as well as a combination of herbicide tolerance and tolerance to abiotic conditions.

[0439] Plants comprising singular or stacked traits as well as the genes and events providing these traits are known (http: / / www.isaaa.org / gmapprovaldatabase) and (http: / / cera-gmc.org / GMCropDatabase).

[0440] Further information on specific events and methods to detect them can be found for canola events MS1, MS8, RF3, GT73, MON88302, KK179 in W001 / 031042, W001 / 041558, W001 / 041558, W002 / 036831, WO11 / 153186, W013 / 003558, for cotton events MON1445, MON15985, MON531 (MON15985), LLCotton25, MON88913, COT102, 281-24-236, 3006-210-23, COT67B, GHB614, T304-40, GHB119, MON88701, 81910 in WO02 / 034946, W002 / 100163, W002 / 100163, W003 / 013224, WO04 / 072235, WO04 / 039986, WO05 / 103266, WO05 / 103266, WO06 / 128573, W007 / 017186, W008 / 122406, W008 / 151780, WO12 / 134808, WO13 / 112527, for corn events GA21, MON810, DLL25, TC1507, MON863, MIR604, LY038, MON88017, 3272, 59122, NK603, MIR162, MON89034, 98140, 32138, MON87460, 5307, 4114, MON87427, DAS40278, MON87411, 33121, MON87403, MON87419 in W098 / 044140, US02 / 102582, US03 / 126634, WO04 / 099447, W004 / 011601, WO05 / 103301, W005 / 061720, W005 / 059103, WO06 / 098952, WO06 / 039376, US2007 / 292854, W007 / 142840, W007 / 140256, WO08 / 112019, W009 / 103049, WO09 / 111263, W010 / 077816, WO11 / 084621, WO11 / 062904, WO11 / 022469, WO13 / 169923, WO14 / 116854, WO15 / 053998, WO15 / 142571, for potato events E12, F10, J3, J55, V11, X17, Y9 in WO14 / 178910, WO14 / 178913, WO14 / 178941, WO14 / 179276, WO16 / 183445, WO17 / 062831, WO17 / 062825, for rice events LLRICE06, LLRICE601, LLRICE62 in WG00 / 026345, WG00 / 026356, WG00 / 026345 for soybean events H7-1, MON89788, A2704-12, A5547-127, DP305423, DP356043, MON87701, MON87769, CV127, MON87705, DAS68416-4, MON87708, MON87712, SYHT0H2, DAS81419, DAS81419 x DAS44406-6, MON87751 in WO04 / 074492, WO06 / 130436, WO06 / 108674, WO06 / 108675, WO08 / 054747, W008 / 002872, WO09 / 064652, W009 / 102873, W010 / 080829, W010 / 037016, W011 / 066384, W011 / 034704, W012 / 051199, W012 / 082548, W013 / 016527, WO13 / 016516, WO14 / 201235.

[0441] The use of compositions according to the invention on cultivated plants may result in effects which are specific to a cultivated plant comprising a certain gene or event. These effects may comprise enhanced yield, enhanced resistance or tolerance to insects, nematodes, fungal, bacterial,250083

[0442] 49

[0443] mycoplasma, viral or viroid pathogens as well as early vigor, early or delayed ripening, cold or heat tolerance as well as changed amino acid or fatty acid spectrum or content.

[0444] It has been found that the pesticidal activity of the compounds of the invention may be enhanced by the insecticidal trait of a modified plant. Furthermore, it has been found that the compounds of the invention are suitable for preventing insects to become resistant to the insecticidal trait or for combating pests, which already have become resistant to the insecticidal trait of a modified plant. Moreover, the compounds of the invention are suitable for combating pests, against which the insecticidal trait is not effective, so that a complementary insecticidal activity can advantageously be used.

[0445] The term "plant propagation material" refers to all the generative parts of the plant e.g. seeds and vegetative plant material e.g. cuttings and tubers (e.g. potatoes), which can be used for the multiplication of the plant. This includes seeds, roots, fruits, tubers, bulbs, rhizomes, shoots, sprouts and other parts of plants. Seedlings and young plants, which are to be trans-planted after germination or after emergence from soil, may also be included. These plant propagation materials may be treated prophylactically with a plant protection compound either at or before planting or transplanting.

[0446] The term “seed” embraces seeds and plant propagules of all kinds including but not limited to true seeds, seed pieces, suckers, corms, bulbs, fruit, tubers, grains, cuttings, cut shoots and the like, and means in a preferred embodiment true seeds.

[0447] In general, "pesticidally effective amount" means the amount of active ingredient needed to achieve an observable effect on growth, including the effects of necrosis, death, retardation, prevention, and removal, destruction, or otherwise diminishing the occurrence and activity of the target organism. The pesticidally effective amount can vary for the various compounds / compositions used in the invention. A pesticidally effective amount of the compositions will also vary according to the prevailing conditions e.g. desired pesticidal effect and duration, weather, target species, locus, mode of application.

[0448] In the case of soil treatment, in furrow application or of application to the pests dwelling place or nest, the quantity of active ingredient ranges from 0.0001 to 500 g per 100 m2, preferably from 0.001 to 20 g per 100 m2.

[0449] For use in treating crop plants, e.g. by foliar application, the rate of application of the active ingredients of this invention may be in the range of 0.0001 g to 4000 g per hectare, e.g. from 1 g to 2 kg per hectare or from 1 g to 750 g per hectare, desirably from 1 g to 100 g per hectare, more desirably from 10 g to 50 g per hectare, e.g., 10 to 20 g per hectare, 20 to 30 g per hec-tare, 30 to 40 g per hectare, or 40 to 50 g per hectare.

[0450] The compounds of the invention are particularly suitable for use in the treatment of seeds in order to protect the seeds from insect pests, in particular from soil-living insect pests, and the resulting seedling’s roots and shoots against soil pests and foliar insects. The invention therefore also relates to a method for the protection of seeds from insects, in particular from soil insects, and of the seedling's roots and shoots from insects, in particular from soil and foliar insects, said method comprising treating the seeds before sowing and / or after pregermination with a compound of the invention. The protection of the seedling's roots and shoots is preferred. More preferred is the protection of seedling’s shoots from piercing and sucking insects, chewing insects and nematodes.The term “seed treatment” comprises e.g. seed dressing, seed coating, seed dusting, seed soaking, seed pelleting, and in-furrow application methods. Preferably, the seed treatment application of the active compound is carried out by spraying or by dusting the seeds before sowing of the plants and before emergence of the plants.

[0451] The invention also comprises seeds coated with or containing the active compound. The term "coated with and / or containing" generally signifies that the active ingredient is for the most part on the surface of the propagation product at the time of application, although a greater or lesser part of the ingredient may penetrate into the propagation product, depending on the method of application. When the said propagation product is (re)planted, it may absorb the active ingredient. Suitable seed is e.g. seed of cereals, root crops, oil crops, vegetables, spices, ornamentals, e.g. seed of durum and other wheat, barley, oats, rye, maize (fodder maize and sugar maize I sweet and field corn), soybeans, oil crops, crucifers, cotton, sunflowers, bananas, rice, oilseed rape, turnip rape, sugarbeet, fodder beet, eggplants, potatoes, grass, lawn, turf, fodder grass, tomatoes, leeks, pumpkin / squash, cabbage, iceberg lettuce, pepper, cucumbers, melons, Brassica species, melons, beans, peas, garlic, onions, carrots, tuberous plants e.g. potatoes, sugarcane, tobacco, grapes, petunias, geranium / pelargoniums, pansies and impatiens.

[0452] In addition, the active compound may also be used for the treatment of seeds from plants, which have been modified by mutagenisis or genetic engineering, and which e.g. tolerate the action of herbicides or fungicides or insecticides.

[0453] Conventional seed treatment formulations include e.g. flowable concentrates FS, solutions LS, suspoemulsions (SE), powders for dry treatment DS, water dispersible powders for slurry treatment WS, water-soluble powders SS and emulsion ES and EC and gel formulation GF. These formulations can be applied to the seed diluted or undiluted. Application to the seeds is carried out before sowing, either directly on the seeds or after having pregerminated the latter. Preferably, the formulations are applied such that germination is not included.

[0454] The active substance concentrations in ready-to-use formulations, which may be obtained after two-to-tenfold dilution, are preferably from 0.01 to 60% by weight, more preferably from 0.1 to 40% by weight.

[0455] In a preferred embodiment a FS formulation is used for seed treatment. Typically, a FS formulation may comprise 1-800 g / l of active ingredient, 1-200 g / l Surfactant, 0 to 200 g / l antifreezing agent, 0 to 400 g / l of binder, 0 to 200 g / l of a pigment and up to 1 liter of a solvent, preferably water.

[0456] Especially preferred FS formulations of the compounds of the invention for seed treatment usually comprise from 0.1 to 80% by weight (1 to 800 g / l) of the active ingredient, from 0.1 to 20% by weight (1 to 200 g / l) of at least one surfactant, e.g. 0.05 to 5% by weight of a wetter and from 0.5 to 15% by weight of a dispersing agent, up to 20% by weight, e.g. from 5 to 20% of an anti-freeze agent, from 0 to 15% by weight, e.g. 1 to 15% by weight of a pigment and / or a dye, from 0 to 40% by weight, e.g. 1 to 40% by weight of a binder (sticker / adhesion agent), optionally up to 5% by weight, e.g. from 0.1 to 5% by weight of a thickener, optionally from 0.1 to 2% of an anti-foam agent, and optionally a preservative e.g. a biocide, antioxidant or the like, e.g. in an amount from 0.01 to 1% by weight and a filler / vehicle up to 100% by weight.

[0457] In the treatment of seed, the application rates of the compounds of the invention are generally from 0.1 g to 10 kg per 100 kg of seed, preferably from 1 g to 5 kg per 100 kg of seed, more preferably from 1 g to 1000 g per 100 kg of seed and in particular from 1 g to 200 g per 100 kg of seed, e.g. from 1 g to 100 g or from 5 g to 100 g per 100 kg of seed.The invention therefore also relates to seed comprising a compound of the invention, or an agriculturally useful salt thereof, as defined herein. The amount of the compound of the invention or the agriculturally useful salt thereof will in general vary from 0.1 g to 10 kg per 100 kg of seed, preferably from 1 g to 5 kg per 100 kg of seed, in particular from 1 g to 1000 g per 100 kg of seed. For specific crops e.g. lettuce the rate can be higher.

[0458] The compounds of the invention may also be used for improving the health of a plant. Therefore, the invention also relates to a method for improving plant health by treating a plant, plant propagation material and / or the locus where the plant is growing or is to grow with an effective and non-phytotoxic amount of a compound of the invention.

[0459] As used herein “an effective and non-phytotoxic amount” means that the compound is used in a quantity which allows to obtain the desired effect but which does not give rise to any phytotoxic symptom on the treated plant or on the plant grown from the treated propagule or treated soil. "Plant health" is defined as a condition of the plant and / or its products which is determined by several aspects alone or in combination with each other e.g. yield (e.g. increased biomass and / or increased content of valuable ingredients), quality (e.g. improved content or composition of certain ingredients or shelf life), plant vigour (e.g. improved plant growth and / or greener leaves (“greening effect”), tolerance to abiotic (e.g. drought) and / or biotic stress (e.g. disease) and production efficiency (e.g., harvesting efficiency, processability).

[0460] The above identified indicators for the health condition of a plant may be interdependent and may result from each other. Each indicator is defined in the art and can be determined by methods known to a skilled person.

[0461] The compounds of the invention are also suitable for use against non-crop insect pests. For use against said non-crop pests, compounds of the invention can be used as bait composition, gel, general insect spray, aerosol, as ultra-low volume application and bed net (impregnated or surface applied). Furthermore, drenching and rodding methods can be used.

[0462] As used herein, the term “non-crop insect pest” refers to pests, which are particularly relevant for non-crop targets, e.g. ants, termites, wasps, flies, ticks, mosquitoes, bed bugs, crickets, or cockroaches.

[0463] The bait can be a liquid, a solid or a semisolid preparation (e.g. a gel). The bait employed in the composition is a product, which is sufficiently attractive to incite insects e.g. ants, termites, wasps, flies, mosquitoes, crickets etc. or cockroaches to eat it. The attractiveness can be manipulated by using feeding stimulants or sex pheromones. Food stimulants are preferably chosen from animal and / or plant proteins (meat-, fish- or blood meal, insect parts, egg yolk), from fats and oils of animal and / or plant origin, or mono-, oligo- or polyorganosaccharides, especially from sucrose, lactose, fructose, dextrose, glucose, starch, pectin or even molasses or honey. Fresh or decaying parts of fruits, crops, plants, animals, insects or specific parts thereof can also serve as a feeding stimulant. Sex pheromones are known to be more insect specific. Specific pheromones are known (http: / / www.pherobase.com).

[0464] For use in bait compositions, the typical content of active ingredient is from 0.001 wt% to 15 wt%, desirably from 0.001 wt% to 5 wt% of active compound.

[0465] Formulations of the compounds of the invention as aerosols (e.g in spray cans), oil sprays or pump sprays are highly suitable for professional or non-professional users for controlling pests e.g. flies, fleas, ticks, bed bugs, mosquitoes or cockroaches. Aerosol recipes are preferably52

[0466] composed of the active compound, solvents, furthermore auxiliaries e.g. emulsifiers, perfume oils, if appropriate stabilizers, and, if required, propellants.

[0467] The oil spray formulations differ from the aerosol recipes in that no propellants are used.

[0468] For use in spray compositions, the content of active ingredient is from 0.001 to 80 wt%, preferably from 0.01 to 50 wt% and most preferably from 0.01 to 15 wt%.

[0469] The compounds of the invention and its respective compositions can also be used in mosquito and fumigating coils, smoke cartridges, vaporizer plates or long-term vaporizers and also in moth papers, moth pads or other heat-independent vaporizer systems.

[0470] Methods to control infectious diseases transmitted by insects (e.g. malaria, dengue and yellow fever, lymphatic filariasis, and leishmaniasis) with compounds of the invention and its re-spective compositions also comprise treating surfaces of huts and houses, air spraying and impregnation of curtains, tents, clothing items, bed nets, tsetse-flytrap. Insecticidal compositions for application to fibers, fabric, knitgoods, nonwovens, netting material or foils and tarpaulins preferably comprise a mixture including the insecticide, optionally a repellent and at least one binder.

[0471] The compounds of the invention and its compositions can be used for protecting wooden materials e.g. trees, board fences, sleepers, frames, artistic artifacts, etc. and buildings, but also construction materials, furniture, leathers, fibers, vinyl articles, electric wires and cables etc. from ants, termites and / or wood or textile destroying beetles, and for controlling ants and termites from doing harm to crops or human beings (e.g. when the pests invade into houses and public facilities or nest in yards, orchards or parks).

[0472] Customary application rates in the protection of materials are, e.g., from 0.001 g to 2000 g or from 0.01 g to 1000 g of active compound per m2treated material, desirably from 0.1 g to 50 g per m2. Insecticidal compositions for use in the impregnation of materials typically contain from 0.001 to 95 wt%, preferably from 0.1 to 45 wt%, and more preferably from 1 to 25 wt% of at least one repellent and / or insecticide.

[0473] Digital application

[0474] The compounds of the invention and the compositions containing them may be applied in combination with, or by utilizing smart agricultural technologies, such as precision agriculture, remote and proximate imaging and image recognition, or smart agricultural site management programs. These smart agricultural technologies typically include models, e.g. computer programs, that support the user by considering information from a wide variety of sources to increase the quality and yield of harvested material, reduce damage by pests including the prediction of pest pressure and smart application of crop protection products, secure environ-mental protection, support quick and reliable agronomic decision making, reduce usage of fertilizers and crop protection products, reduce product residues in consumables increase spatial and temporal precision of agronomical measures, automate processes, and enable traceability of measures. Commercially available systems which include agronomic models are e.g. FieldScripts™ from The Climate Corporation, Xarvio™ from BASF, AGLogic™ from John Deere, etc.

[0475] Information input for these models include but is not limited to soil data, information on the plants that are currently growing or that may grow at the area of interest including crop plants and / or unwanted vegetation, weather information, information on the location of the area and directly derivable information thereof, information on pest pressure, information on beneficial organisms, and / or historic information of any of the aforementioned.250083

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[0477] The information usable for precision agriculture may be based on input by at least one user, be accessible from external data sources and databases, or be based on sensor data. Data sources typically includes proximate-detection systems like soil-borne sensors and remote sensing as may be achieved by imaging with unmanned airborne vehicles like drones, or satellites. Sensors may be included in an Internet-of-Things system and may be directly or indirectly connected to the processing unit, e.g. via a wireless network and / or cloud applications. The information is typically taken into account by at least one processing unit and used to provide recommendations and generate control signals.

[0478] Typical technologies that are used in smart agricultural technologies include self-steering ro-bots (such as tractors, harvesters, drones), artificial intelligence (e.g. machine learning), imaging technologies (e.g. image segmentation technologies), big data analysis, and model generation, cloud computing, and machine-to-machine communication.

[0479] Precision agriculture such as precision farming is characterized by spatially and / or temporally resolved, targeted application of active ingredients like pesticides, plant-growth-regulators, fertilizers, and / or water including the variation of application rates over the agronomic site, zone or spot application, and of the spatially and / or temporally resolved, targeted planting or seeding of desired plant propagation material to a agronomic site. Precision farming typically includes the use of geo-positioning technologies like GPS for gaining information on the location and boundaries of the area of interest, the utilized application equipment, sensing equipment and recorded data, and to control the actions of farm vehicles such as spraying. By combining geopositioning data with (digital) maps, it is possible to (semi)-automate agricultural measures at the site of interest, e.g. by using (semi)-autonomous spraying or seeding equipment.

[0480] Precision farming may typically include the application of smart spraying equipment, e.g. spot spraying, and precision spraying at a farm, e.g. by irrigation systems, tractors, robots, helicopters, airplanes, unmanned aerial vehicles, such as drones. Such equipment usually includes input sensors (such as e.g. a camera) and a processing unit configured to analyze the input data and configured to provide a recommendation or decision based on the analysis of the input data to apply the compounds of the invention or compositions comprising them to the agronomic site, e.g. the soil, the crop plants, or to control pests in a specific and precise manner. For example, pests may be detected, identified, and / or classified from imagery acquired by a camera. Such identification and / classification can make use of image processing algorithms, which may utilize artificial intelligence (e.g. machine learning algorithms), or decision trees. In this manner, the compounds or compositions described herein can be applied only at the required location, point in time and dose rate.

[0481] Pests

[0482] The compounds of the invention are especially suitable for efficiently combating animal pests e.g. arthropods, gastropods and nematodes including:

[0483] insects from the order of Lepidoptera, e.g. Achroia grisella, Acleris spp. e.g. A. fimbriana, A. gloverana, A. variana; Acrolepiopsis assectella, Acronicta major, Adoxophyes spp. e.g. A. cyrtosema, A. orana; Aedia leucomelas, Agrotis spp. e.g. A. exclamationis, A. fucosa, A. ipsilon, A. orthogoma, A. segetum, A. subterranea; Alabama argillacea, Aleurodicus dispersus, Alsophila pometaria, Ampelophaga rubiginosa, Amyelois transitella, Anacampsis sarcitella, Anagasta kuehniella, Anarsia lineatella, Anisota senatoria, Antheraea pernyi, Anticarsia (=Thermesia) spp. e.g. A. gemmatalis; Apamea spp., Aproaerema modicella, Archips spp. e.g. A. argyrospila, A.250083

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[0485] fuscocupreanus, A. rosana, A. xyloseanus; Argyresthia conjugella, Argyroploce spp., Argyrotaenia spp. e.g. A. velutinana; Athetis mindara, Austroasca viridigrisea, Autographa gamma, Autographa nigrisigna, Barathra brassicae, Bedellia spp., Bonagota salubricola, Borbo cinnara, Bucculatrix thurberiella, Bupalus piniarius, Busseola spp., Cacoecia spp. e.g. C. murinana, C. podana; Cactoblastis cactorum, Cadra cautella, Calingo braziliensis, Caloptilis theivora, Capua reticulana, Carposina spp. e.g. C. niponensis, C. sasakii; Cephus spp., Chaetocnema aridula, Cheimatobia brumata, Chilo spp. e.g. C. Indicus, C. suppressalis, C. partellus; Choreutis pariana, Choristoneura spp. e.g. C. conflictana, C. fumiferana, C. longicellana, C. murinana, C. occidentalis, C. rosaceana; Chrysodeixis (=Pseudoplusia) spp., e.g. C. eriosoma, C. includens; Cirphis unipuncta, Clysia ambiguella, Cnaphalocerus spp., Cnaphalocrocis medinalis, Cnephasia spp., Cochylis hospes, Coleophora spp., Colias eurytheme, Conopomorpha spp., Conotrachelus spp., Copitarsia spp., Corcyra cephalonica, Crambus caliginosellus, Crambus teterrellus, Crocidosema (=Epinotia) aporema, Cydalima (=Diaphania) perspectalis, Cydia (=Carpocapsa) spp., e.g. C. pomonella, C. latiferreana; Dalaca noctuides, Datana integerrima, Dasychira pinicola, Dendrolimus spp., e.g. D. pini, D. spectabilis, D. sibiricus; Desmia funeralis, Diaphania spp., e.g. D. nitidalis, D. hyalinata; Diatraea grandiosella, Diatraea saccharalis, Diphthera festiva, Earias spp. e.g. E. insulana, E. vittella; Ecdytolopha aurantianu, Egira (=Xylomyges) curialis, Elasmopalpus lignosellus, Eldana saccharina, Endopiza viteana, Ennomos subsignaria, Eoreuma loftini, Ephestia spp., e.g. E. cautella, E. elutella, E. kuehniella; Epinotia aporema, Epiphyas postvittana, Erannis tiliaria, Erionota thrax, Etiella spp., Eulia spp., Eupoecilia ambiguella, Euproctis chrysorrhoea, Euxoa spp., Evetria bouliana, Faronta albilinea, Feltia spp. e.g. F. subterranean; Galleria mellonella, Gracillaria spp., Grapholita spp. e.g. G. funebrana, G. molesta, G. inopinata; Halysidota spp., Harrisina americana, Hedylepta spp., Helicoverpa spp. e.g. H. armigera (=Heliothis armigera), H. zea (=Heliothis zea); Heliothis spp. e.g. H. assulta, H. subflexa, H. virescens; Hellula spp. e.g. H. undalis, H. rogatalis; Helocoverpa gelotopoeon, Hemileuca oliviae, Herpetogramma licarsisalis, Hibernia defoliaria, Hofmannophila pseudospretella, Homoeosoma electellum, Homona magnanima, Hypena scabra, Hyphantria cunea, Hyponomeuta padella, Hyponomeuta malinellus, Kakivoria flavofasciata, Keiferia lycopersicella, Lambdina fiscellaria fiscellaria, Lambdina fiscellaria lugubrosa, Lamprosema indicata, Laspeyresia molesta, Leguminivora glycinivorella, Lerodea eufala, Leucinodes orbonalis, Leucoma salicis, Leucoptera spp. e.g. L. coffeella, L. scitella; Leuminivora lycinivorella, Lithocolletis blancardella, Lithophane antennata, Llattia octo (=Amyna axis), Lobesia botrana, Lophocampa spp., Loxagrotis albicosta, Loxostege spp. e.g. L. sticticalis, L. cereralis; Lymantria spp., e.g. L. dispar, L. monacha; Lyonetia clerkella, Lyonetia prunifoliella, Malacosoma spp., e.g. M. americanum, M. californicum, M. constrictum, M. neu-stria; Mamestra spp., e.g. M. brassicae, M. configurata; Mamstra brassicae, Manduca spp. e.g. M. quinquemaculata, M. sexta; Marasmia spp, Marmara spp., Maruca testulalis, Megalopyge lanata, Melanchra picta, Melanitis leda, Mocis spp., e.g. M. lapites, M. repanda; Mocis latipes, Monochroa fragariae, Mythimna separata, Nemapogon cloacella, Neoleucinodes elegantalis, Nepytia spp., Nymphula spp., Oiketicus spp., Omiodes indicata, Omphisa anastomosalis, Operophtera brumata, Orgyia pseudotsugata, Oria spp., Orthaga thyrisalis, Ostrinia spp. e.g. O. nubilalis; Oulema oryzae, Paleacrita vernata, Panolis flammea, Parnara spp., Papaipema nebris, Papilio cresphontes, Paramyelois transitella, Paranthrene regalis, Paysandisia archon, Pectinophora spp. e.g. P. gossypiella; Peridroma saucia, Perileucoptera spp., e.g. P. coffeella; Phalera bucephala, Phryganidia californica, Phthorimaea spp. e.g. P. operculella; Phyllocnistis250083

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[0487] citrella, Phyllonorycterspp. e.g. P. blancardella, P. crataegella, P. issikii, P. ringoniella; Pieris spp. e.g. P. brassicae, P. rapae, P. napi; Pilocrocis tripunctata, Plathypena scabra, Platynota spp. e.g. P. flavedana, P. idaeusalis, P. stultana; Platyptilia carduidactyla, Plebejus argus, Plo-dia interpunctella, Plusia spp, Plutella maculipennis, Plutella xylostella, Pontia protodica, Prays spp., Prodenia spp., Proxenus lepigone, Pseudaletia spp. e.g. P. sequax, P. unipuncta; Pyrausta nubilalis, Rachiplusia nu, Richia albicosta, Rhizobius ventralis, Rhyacionia frustrana, Sabulodes aegrotata, Schizura concinna, Schoenobius spp., Schreckensteinia festaliella, Scirpophaga spp. e.g. S. incertulas, S. innotata; Scotia segetum, Sesamia spp. e.g. S. inferens, Seudyra subflava, Sitotroga cerealella, Sparganothis pilleriana, Spilonota lechriaspis, S. ocelli-na, Spodoptera (=Lamphygma) spp. e.g. S. cosmoides, S. eridania, S. exigua, S. frugiperda, S. latisfascia, S. littoralis, S. litura, S. omithogalli; Stigmella spp., Stomopteryx subsecivella, Strymon bazochii, Sylepta derogata, Synanthedon spp. e.g. S. exitiosa, Tecia solanivora, Telehin licus, Thaumatopoea pityocampa, Thaumatotibia (=Cryptophlebia) leucotreta, Thaumetopoea pityocampa, Thecla spp., Theresimima ampelophaga, Thyrinteina spp, Tildenia inconspicuella, Tinea spp. e.g. T. cloacella, T. pellionella; Tineola bisselliella, Tortrix spp. e.g. T. viridana; Trichophaga tapetzella, Trichoplusia spp. e.g. T. ni; Tuta (=Scrobipalpula) absoluta, Udea spp. e.g. U. rubigalis, U. rubigalis; Virachola spp., Yponomeuta padella, and Zeiraphera canadensis; insects from the order of Coleoptera, e.g. Acalymma vittatum, Acanthoscehdes obtectus, Adoretus spp., Agelastica alni, Agrilus spp. e.g. A. anxius, A. planipennis, A. sinuatus; Agriotes spp. e.g. A. fuscicollis, A. lineatus, A. obscurus; Alphitobius diaperinus, Amphimallus solstitialis, Anisandrus dispar, Anisoplia austriaca, Anobium punctatum, Anomala corpulenta, Anomala rufocuprea, Anoplophora spp. e.g. A. glabripennis; Anthonomus spp. e.g. A. eugenii, A. grandis, A. pomorum; Anthrenus spp., Aphthona euphoridae, Apion spp., Apogonia spp., Athous haemorrhoidalis, Atomaria spp. e.g. A. linearis; Attagenus spp., Aulacophora femoralis, Blastophagus piniperda, Blitophaga undata, Bruchidius obtectus, Bruchus spp. e.g. B. lentis, B. pisorum, B. rufimanus; Byctiscus betulae, Callidiellum rufipenne, Callopistria floridensis, Callosobruchus chinensis, Cameraria ohridella, Cassida nebulosa, Cerotoma trifurcata, Cetonia aurata, Ceuthorhynchus spp. e.g. C. assimilis, C. napi; Chaetocnema tibialis, Cleonus mendicus, Conoderus spp. e.g. C. vespertinus; Conotrachelus nenuphar, Cosmopolites spp., Costelytra zealandica, Crioceris asparagi, Cryptolestes ferrugineus, Cryptorhynchus lapathi, Ctenicera spp. e.g. C. destructor; Curculio spp., Cylindrocopturus spp., Cyclocephala spp., Dac-tylispa balyi, Dectes texanus, Dermestes spp., Diabrotica spp. e.g. D. undecimpunctata, D. speciosa, D. longicornis, D. semipunctata, D. virgifera; Diaprepes abbreviates, Dichocrocis spp., Dicladispa armigera, Diloboderus abderus, Diocalandra frumenti (Diocalandra stigmaticollis), Enaphalodes rufulus, Epilachna spp. e.g. E. varivestis, E. vigintioctomaculata; Epitrix spp. e.g. E. hirtipennis, E. similaris; Eutheola humilis, Eutinobothrus brasiliensis, Faustinus cubae, Gibbium psylloides, Gnathocerus cornutus, Hellula undalis, Heteronychus arator, Hylamorpha elegans, Hylobius abietis, Hylotrupes bajulus, Hypera spp., e.g. H. brunneipennis, H. postica; Hypomeces squamosus, Hypothenemus spp., Ips typographus, Lachnosterna consanguinea, Lasioderma serricorne, Latheticus oryzae, Lathridius spp., Lerna spp. e.g. L. bilineata, L. melanopus; Leptinotarsa spp. e.g. L. decemlineata; Leptispa pygmaea, Limonius californi-cus, Lissorhoptrus oryzophilus, Lixus spp., Luperodes spp., Lyctus spp. e.g. L. bruneus; Liogenys fuscus, Macrodactylus spp. e.g. M. subspinosus; Maladera matrida, Megaplatypus mutates, Megascelis spp., Melanotus communis, Meligethes spp. e.g. M. aeneus; Melolontha spp. e.g. M. hippocastani, M. melolontha; Metamasius hemipterus, Microtheca spp., Migdolus spp. e.g. M.250083

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[0489] fryanus, Monochamus spp. e.g. M. alternatus; Naupactus xanthographus, Niptus hololeucus, Oberia brevis, Oemona hirta, Oryctes rhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorrhynchus sulcatus, Otiorrhynchus ovatus, Otiorrhynchus sulcatus, Oulema melanopus, Oulema oryzae, Oxycetonia jucunda, Phaedon spp. e.g. P. brassicae, P. cochleariae; Phoracantha recurva, Phyllobius pyri, Phyllopertha horticola, Phyllophaga spp. e.g. P. helleri; Phyllotreta spp. e.g. P. chrysocephala, P. nemorum, P. striolata, P. vittula; Phyllopertha horticola, Popillia japonica, Premnotrypes spp., Psacothea hilaris, Psylliodes chrysocephala, Prostephanus truncates, Psylliodes spp., Ptinus spp., Pulga saltona, Rhizopertha dominica, Rhynchophorus spp. e.g. R. billineatus, R. ferrugineus, R. palmarum, R. phoenicis, R. vulneratus; Saperda Candida, Scolytus schevyrewi, Scyphophorus acupunctatus, Sitona lineatus, Sitophilus spp. e.g. S. granaria, S. oryzae, S. zeamais; Sphenophorus spp. e.g. S. levis; Stegobium paniceum, Sternechus spp. e.g. S. subsignatus; Strophomorphus ctenotus, Symphyletes spp., Tanymecus spp., Tenebrio molitor, Tenebrioides mauretanicus, Tribolium spp. e.g. T. castaneum; Trogoderma spp., Tychius spp., Xylotrechus spp. e.g. X. pyrrhoderus; and, Zabrus spp. e.g. Z. tenebrioides;

[0490] insects from the order of Diptera e.g. Aedes spp. e.g. A. aegypti, A. albopictus, A. vexans; Anastrepha ludens, Anopheles spp. e.g. A. albimanus, A. crucians, A. freeborni, A. gambiae, A. leucosphyrus, A. maculipennis, A. minimus, A. quadrimaculatus, A. sinensis; Bactrocera invadens, Bibio hortulanus, Calliphora erythrocephala, Calliphora vicina, Ceratitis capitata, Chrysomyia spp. e.g. C. bezziana, C. hominivorax, C. macellaria; Chrysops atlanticus, Chrysops discalis, Chrysops silacea, Cochliomyia spp. e.g. C. hominivorax; Contarinia spp. e.g. C. sorghicola; Cordylobia anthropophaga, Culex spp. e.g. C. nigripalpus, C. pipiens, C. quinquefasciatus, C. tarsalis, C. tritaeniorhynchus; Culicoides furens, Culiseta inornata, Culiseta melanura, Cuterebra spp., Dacus cucurbitae, Dacus oleae, Dasineura brassicae, Dasineura oxycoccana, Delia spp. e.g. D. antique, D. coarctata, D. platura, D. radicum; Dermatobia hominis, Drosophila spp. e.g. D. suzukii, Fannia spp. e.g. F. canicularis; Gastraphilus spp. e.g. G. intestinalis; Geomyza tipunctata, Glossina spp. e.g. G. fuscipes, G. morsitans, G. palpalis, G. tachinoides; Haematobia irritans, Haplodiplosis equestris, Hippelates spp., Hylemyia spp. e.g. H. platura; Hypoderma spp. e.g. H. lineata; Hyppobosca spp., Hydrellia philippina, Leptoconops torrens, Liriomyza spp. e.g. L. sativae, L. trifolii; Lucilia spp. e.g. L. caprina, L. cuprina, L. sericata; Lycoria pectoralis, Mansonia titillanus, Mayetiola spp. e.g. M. destructor; Musca spp. e.g. M. autumnalis, M. domestica; Muscina stabulans, Oestrus spp. e.g. O. ovis; Opomyza florum, Oscinella spp. e.g. O. frit; Orseolia oryzae, Pegomya hysocyami, Phlebotomus argentipes, Phorbia spp. e.g. P. antiqua, P. brassicae, P. coarctata; Phytomyza gymnostoma, Prosimulium mixtum, Psila rosae, Psorophora columbiae, Psorophora discolor, Rhagoletis spp. e.g. R. cerasi, R. cingulate, R. indifferens, R. mendax, R. pomonella; Rivellia quadrifasciata, Sarcophaga spp. e.g. S. haemorrhoidalis; Simulium vittatum, Sitodiplosis mosellana, Stomoxys spp. e.g. S. calcitrans; Tabanus spp. e.g. T. atratus, T. bovinus, T. lineola, T. similis; Tannia spp., Thecodiplo-sis japonensis, Tipula oleracea, Tipula paludosa, Wohlfahrtia spp, and Zaprionus indianus; insects from the order of Thysanoptera e.g., Baliothrips biformis, Dichromothrips corbetti, Dichromothrips ssp., Echinothrips americanus, Enneothrips flavens, Frankliniella spp. e.g. F. fusca, F. occidentalis, F. tritici; Heliothrips spp., Hercinothrips femoralis, Kakothrips spp., Microcephalothrips abdominalis, Neohydatothrips samayunkur, Pezothrips kellyanus, Rhipiphorothrips cruentatus, Scirtothrips spp. e.g. S. citri, S. dorsalis, S. perseae;250083

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[0492] Stenchaetothrips spp, Taeniothrips cardamoni, Taeniothrips inconsequens, Thrips spp. e.g. T. imagines, T. hawaiiensis, T. oryzae, T. palmi, T. parvispinus, T. tabaci;

[0493] insects from the order of Hemiptera e.g., Acizzia jamatonica, Acrosternum spp., e.g. A. hilare; Acyrthosipon spp., e.g. A. onobrychis, A. pisum; Adelges laricis, Adelges tsugae, Adelphocoris spp., e.g. A. rapidus, A. superbus; Aeneolamia spp., Agonoscena spp., Aulacorthum solani, Aleurocanthus woglumi, Aleurodes spp., Aleurodicus disperses, Aleurolobus barodensis, Aleurothrixus spp., Amrasca spp., Anasa tristis, Antestiopsis spp., Anuraphis cardui, Aonidiella spp., Aphanostigma piri, Aphidula nasturtii, Aphis spp. e.g. A. craccivora, A. fabae, A. forbesi, A. gossypii, A. grossulariae, A. maidiradicis, A. pomi, A. sambuci, A. schneideri, A. spiraecola; Arboridia apicalis, Arilus critatus, Aspidiella spp., Aspidiotus spp., Atanus spp., Aulacaspis yasumatsui, Aulacorthum solani, Bactericera cockerelli (Paratrioza cockerelli), Bemisia spp. e.g. B. argentifolii, B. tabaci (Aleurodes tabaci); Blissus spp. e.g. B. leucopterus; Brachycaudus spp. e.g. B. cardui, B. helichrysi, B. persicae, B. prunicola; Brachycolus spp., Brachycorynella as-paragi, Brevicoryne brassicae, Cacopsylla spp. e.g. C. fulguralis, C. pyricola (Psylla piri); Calligypona marginata, Calocoris spp., Campylomma livida, Capitophorus horni, Carneocephala fulgida, Cavelerius spp., Ceraplastes spp., Ceratovacuna lanigera, Ceroplastes ceriferus, Cerosipha gossypii, Chaetosiphon fragaefolii, Chionaspis tegalensis, Chlorita onukii, Chromaphis juglandicola, Chrysomphalus ficus, Cicadulina mbila, Cimex spp. e.g. C. hemipterus, C. lectularius; Circulifer tenellus, Coccomytilus halli, Coccus spp. e.g. C. hesperidum, C. pseudomagnoliarum; Corythucha arcuata, Creontiades dilutus, Cryptomyzus ribis, Chrysomphalus aonidum, Cryptomyzus ribis, Ctenarytaina spatulata, Cyrtopeltis notatus, Dalbulus spp., Dasynus piperis, Dialeurodes spp. e.g. D. citrifolii; Dalbulus maidis, Diaphorina spp. e.g. D. citri; Diaspis spp. e.g. D. bromeliae; Dichelops furcatus, Diconocoris hewetti, Doralis spp., Dreyfusia nordmannianae, Dreyfusia piceae, Drosicha spp., Dysaphis spp. e.g. D. plantaginea, D. pyri, D. radicola; Dysaulacorthum pseudosolani, Dysdercus spp. e.g. D. cingulatus, D. intermedius; Dysmicoccus spp., Edessa spp., Geocoris spp., Empoasca spp. e.g. E. fabae, E. solana; Epidiaspis leperii, Eriosoma spp. e.g. E. lanigerum, E. pyricola; Erythroneura spp., Eurygaster spp. e.g. E. integriceps; Euscelis bilobatus, Euschistus spp. e.g. E. heros, E. impictiventris, E. servus; Fiorinia theae, Geococcus coffeae, Glycaspis brimblecombei, Halyomorpha spp. e.g. H. halys; Heliopeltis spp., Homalodisca vitripennis (=H. coagulata), Horcias nobilellus, Hyalopterus pruni, Hyperomyzus lactucae, Icerya spp. e.g. I. purchase; Idiocerus spp., Idioscopus spp., Laodelphax striatellus, Lecanium spp., Lecanoideus floccissimus, Lepidosaphes spp. e.g. L. ulmi; Leptocorisa spp., Leptoglossus phyllopus, Lipaphis erysimi, Lygus spp. e.g. L. hesperus, L. lineolaris, L. praten-sis; Maconellicoccus hirsutus, Marchalina hellenica, Macropes excavatus, Macrosiphum spp. e.g. M. rosae, M. avenae, M. euphorbiae; Macrosteles quadrilineatus, Mahanarva fimbriolata, Megacopta cribraria, Megoura viciae, Melanaphis pyrarius, Melanaphis sacchari, Melanocallis (=Tinocallis) caryaefoliae, Metcafiella spp., Metopolophium dirhodum, Monellia costalis, Mo-nelliopsis pecanis, Myzocallis coryli, Murgantia spp., Myzus spp. e.g. M. ascalonicus, M. cerasi, M. nicotianae, M. persicae, M. varians; Nasonovia ribisnigri, Neotoxoptera formosana, Neomegalotomus spp, Nephotettix spp. e.g. N. malayanus, N. nigropictus, N. parvus, N. vires-cens; Nezara spp. e.g. N. viridula; Nilaparvata lugens, Nysius huttoni, Oebalus spp. e.g. O. pugnax; Oncometopia spp., Orthezia praelonga, Oxycaraenus hyalinipennis, Parabemisia myricae, Parlatoria spp., Parthenolecanium spp. e.g. P. corni, P. persicae; Pemphigus spp. e.g. P. bursarius, P. populivenae; Peregrinus maidis, Perkinsiella saccharicida, Phenacoccus spp. e.g. P. aceris, P. gossypii; Phloeomyzus250083

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[0495] passerinii, Phorodon humuli, Phylloxera spp. e.g. P. devastatrix, Piesma quadrata, Piezodorus spp. e.g. P. guildinii; Pinnaspis aspidistrae, Pianococcus spp. e.g. P. citri, P. ficus; Prosapia bicincta, Protopulvinaria pyriformis, Psallus seriatus, Pseudacysta persea, Pseudaulacaspis pentagona, Pseudococcus spp. e.g. P. comstocki; Psylla spp. e.g. P. mali; Pteromalus spp., Pulvinaria amygdali, Pyrilla spp., Quadraspidiotus spp., e.g. Q. perniciosus; Quesada gigas, Rastrococcus spp., Reduvius senilis, Rhizoecus americanus, Rhodnius spp., Rhopalomyzus ascalonicus, Rhopalosiphum spp. e.g. R. pseudobrassicas, R. insertum, R. maidis, R. padi; Sagatodes spp., Sahlbergella singulars, Saissetia spp., Sappaphis mala, Sappaphis mali, Scaptocoris spp., Scaphoideus titanus, Schizaphis graminum, Schizoneura lanuginosa, Scotinophora spp., Selenaspidus articulatus, Sitobion avenae, Sogata spp., Sogatella furcifera, Solubea insularis, Spissistilus festinus (=Stictocephala festina), Stephanitis nashi, Stephanitis pyrioides, Stephanitis takeyai, Tenalaphara malayensis, Tetraleurodes perseae, Therioaphis maculate, Thyanta spp. e.g. T. accerra, T. perditor; Tibraca spp., Tomaspis spp., Toxoptera spp. e.g. T. aurantii; Trialeurodes spp. e.g. T. abutilonea, T. ricini, T. vaporariorum; Triatoma spp., Trioza spp., Typhlocyba spp., Unaspis spp. e.g. U. citri, U. yanonensis; and Viteus vitifolii, Insects from the order Hymenoptera e.g. Acanthomyops interjectus, Athalia rosae, Atta spp. e.g. A. capiguara, A. cephalotes, A. cephalotes, A. laevigata, A. robusta, A. sexdens, A. texana, Bombus spp., Brachymyrmex spp., Camponotus spp. e.g. C. floridanus, C. pennsylvanicus, C. modoc; Cardiocondyla nuda, Chalibion sp, Crematogasterspp., Dasymutilla occidentalis, Diprion spp., Dolichovespula maculata, Dorymyrmex spp., Dryocosmus kuriphilus, Formica spp., Hoplocampa spp. e.g. H. minuta, H. testudinea; Iridomyrmex humilis, Lasius spp. e.g. L. niger, Linepithema humile, Liometopum spp., Leptocybe invasa, Monomorium spp. e.g. M. pharaonis, Monomorium, Nylandria fulva, Pachycondyla chinensis, Paratrechina longicornis, Paravespula spp., e.g. P. germanica, P. pennsylvanica, P. vulgaris; Pheidole spp. e.g. P. megacephala; Pogonomyrmex spp. e.g. P. barbatus, P. californicus, Polistes rubiginosa, Prenolepis impairs, Pseudomyrmex gracilis, Schelipron spp., Sirex cyaneus, Solenopsis spp. e.g. S. geminata, S.invicta, S. molesta, S. richteri, S. xyloni, Sphecius speciosus, Sphex spp., Tapinoma spp. e.g. T. melanocephalum, T. sessile; Tetramorium spp., e.g. T. caespitum, T. bicarinatum, Vespa spp., e.g. V. crabro; Vespula spp., e.g. V. squamosal; Wasmannia auropunctata, Xylocopa sp;

[0496] Insects from the order Orthoptera e.g. Acheta domesticus, Calliptamus italicus, Chortoicetes terminifera, Ceuthophilus spp., Diastrammena asynamora, Dociostaurus maroccanus, Gryllotalpa spp. e.g. G. africana, G. gryllotalpa; Gryllus spp., Hieroglyphus daganensis, Kraussaria angulifera, Locusta spp. e.g. L. migratoria, L. pardalina; Melanoplus spp. e.g. M. bivittatus, M. femurrubrum, M. mexicanus, M. sanguinipes, M. spretus; Nomadacris septemfasciata, Oedaleus senegalensis, Scapteriscus spp., Schistocerca spp. e.g. S. americana, S. gregaria, Stemopelmatus spp., Tachycines asynamorus, and Zonozerus variegatus;

[0497] Pests from the Class Arachnida e.g. Acari.e.g. of the families Argasidae, Ixodidae and Sar-coptidae, e.g. Amblyomma spp. (e.g. A. americanum, A. variegatum, A. maculatum), Argas spp. e.g. A. persicu), Boophilus spp. e.g. B. annulatus, B. decoloratus, B. microplus, Dermacentor spp. e.g. D.silvarum, D. andersoni, D. variabilis, Hyalomma spp. e.g. H. truncatum, Ixodes spp. e.g. I. ricinus, I. rubicundus, I. scapularis, I. holocyclus, I. pacificus, Rhipicephalus sanguineus, Ornithodorus spp. e.g. O. moubata, O. hermsi, O. turicata, Ornithonyssus bacoti, Otobius megnini, Dermanyssus gallinae, Psoroptes spp. e.g. P. ovis, Rhipicephalus spp. e.g. R. sanguineus, R. appendiculatus, Rhipicephalus evertsi, Rhizoglyphus spp., Sarcoptes spp. e.g. S. Scabiei; and Family Eriophyidae including Aceria spp. e.g. A. sheldoni, A. anthocoptes, Acallitus250083

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[0499] spp., Aculops spp. e.g. A. lycopersici, A. pelekassi; Aculus spp. e.g. A. schlechtendali; Colomerus vitis, Epitrimerus pyri, Phyllocoptruta oleivora; Eriophytes ribis and Eriophyes spp. e.g. Eriophyes sheldoni; Family Tarsonemidae including Hemitarsonemus spp., Phytonemus pallidus and Polyphagotarsonemus latus, Stenotarsonemus spp. Steneotarsonemus spinki; Family Tenuipalpidae including Brevipalpus spp. e.g. B. phoenicis; Family Tetranychidae including Eotetranychus spp., Eutetranychus spp., Oligonychus spp., Petrobia latens, Tetranychus spp. e.g. T. cinnabarinus, T. evansi, T. kanzawai, T, pacificus, T. phaseulus, T. telarius and T. urticae; Bryobia praetiosa; Panonychus spp. e.g. P. ulmi, P. citri; Metatetranychus spp. and Oligonychus spp. e.g. O. pratensis, O. perseae, Vasates lycopersici; Raoiella indica, Family Carpoglyphidae including Carpoglyphus spp.; Penthaleidae spp. e.g. Halotydeus destructor; Family Demodicidae with species e.g. Demodex spp.; Family Trombicidea including Trombicula spp.; Family Macronyssidae including Ornothonyssus spp.; Family Pyemotidae including Pyemotes tritici; Tyrophagus putrescentiae; Family Acaridae includ-ing Acarus siro; Family Araneida including Latrodectus mactans, Eratigena agrestis, Cheiracanthium sp, Lycosa sp Achaearanea tepidariorum and Loxosceles reclusa;

[0500] Pests from the Phylum Nematoda, e.g. plant parasitic nematodes e.g. root-knot nematodes, Meloidogyne spp. e.g. M. hapla, M. incognita, M. javanica; cyst-forming nematodes, Globodera spp. e.g. G. rostochiensis; Heterodera spp. e.g. H. avenae, H. glycines, H. schachtii, H. trifolii; Seed gall nematodes, Anguina spp.; Stem and foliar nematodes, Aphelenchoides spp. e.g. A. besseyi; Sting nematodes, Belonolaimus spp. e.g. B. longicaudatus; Pine nematodes, Bursaphelenchus spp. e.g. B. lignicolus, B. xylophilus; Ring nematodes, Criconema spp., Criconemella spp. e.g. C. xenoplax and C. ornata; and, Criconemoides spp. e.g. Criconemoides informis; Mesocriconema spp.; Stem and bulb nematodes, Ditylenchus spp. e.g. D. destructor, D. dipsaci; Awl nematodes, Dolichodorus spp.; Spiral nematodes, Heliocotylenchus multicinctus; Sheath and sheathoid nematodes, Hemicycliophora spp. and Hemicriconemoides spp.; Hirshmanniella spp.; Lance nematodes, Hoploaimus spp.; False rootknot nematodes, Nacobbus spp.; Needle nematodes, Longidorus spp. e.g. L. elongatus; Lesion nematodes, Pratylenchus spp. e.g. P. brachyurus, P. neglectus, P. penetrans, P. curvitatus, P. goodeyi; Burrowing nematodes, Radopholus spp. e.g. R. similis; Rhadopholus spp.; Rhodopholus spp.; Reniform nematodes, Rotylenchus spp. e.g. R. robustus, R. reniformis; Scutellonema spp.; Stubby-root nematode, Trichodorus spp. e.g. T. obtusus, T. primitivus; Paratrichodorus spp. e.g. P. minor; Stunt nematodes, Tylenchorhynchus spp. e.g. T. claytoni, T. dubius; Citrus nematodes, Tylenchulus spp. e.g. T. semipenetrans; Dagger nematodes, Xiphinema spp.; and other plant parasitic nematode species;

[0501] Insects from the order Blattodea e.g. Macrotermes spp. e.g. M. natalensis; Cornitermes cu-mulans, Procornitermes spp., Globitermes sulfureus, Neocapritermes spp. e.g. N. opacus, N. parvus; Odontotermes spp., Nasutitermes spp. e.g. N. corniger; Coptotermes spp. e.g. C. for-mosanus, C. gestroi, C. acinaciformis; Reticulitermes spp. e.g. R. hesperus, R. tibialis, R. speratus, R. flavipes, R. grassei, R. lucifugus, R. virginicus; Heterotermes spp. e.g. H. aureus, H. longiceps, H. tenuis; Cryptotermes spp. e.g. C. brevis, C. cavifrons; Incisitermes spp. e.g. I. minor, I. snyderi; Marginitermes hubbardi, Kalotermes flavicollis, Neotermes spp. e.g. N. cas-taneus, Zootermopsis spp. e.g. Z. angusticollis, Z. nevadensis, Mastotermes spp. e.g. M. dar-winiensis; Blatta spp. e.g. B. orientalis, B. lateralis; Blattella spp. e.g. B. asahinae, B. germanica; Rhyparobia maderae, Panchlora nivea, Periplaneta spp. e.g. P. americana, P. australasiae, P. brunnea, P.250083

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[0503] fuliginosa, P. japonica; Supella longipalpa, Parcoblatta pennsylvanica, Eurycotis floridana, Pycnoscelus surinamensis,

[0504] Insects from the order Siphonoptera e.g. Cediopsylla simples, Ceratophyllus spp., Ctenoce-phalides spp. e.g. C. felis, C. canis, Xenopsylla cheopis, Pulex irritans, Trichodectes canis, Tunga penetrans, and Nosopsyllus fasciatus,

[0505] Insects from the order Thysanura e.g. Lepisma saccharina, Ctenolepisma urbana, and Thermobia domestica,

[0506] Pests from the class Chilopoda e.g. Geophilus spp., Scutigera spp. e.g. Scutigera coleoptrata; Pests from the class Diplopoda e.g. Blaniulus guttulatus, Julus spp., Narceus spp.,

[0507] Pests from the class Symphyla e.g. Scutigerella immaculata,

[0508] Insects from the order Dermaptera, e.g. Forficula auricularia,

[0509] Insects from the order Collembola, e.g. Onychiurus spp., e.g. Onychiurus armatus,

[0510] Pests from the order Isopoda, e.g. Armadillidium vulgare, Oniscus asellus, Porcellio scaber, Insects from the order Phthiraptera, e.g. Damalinia spp., Pediculus spp. e.g. Pediculus hu-manus capitis, Pediculus humanus corporis, Pediculus humanus humanus; Pthirus pubis, Haematopinus spp. e.g. Haematopinus eurysternus, Haematopinus suis; Linognathus spp. e.g. Linognathus vituli; Bovicola bovis, Menopon gallinae, Menacanthus stramineus and Solenopotes capillatus, Trichodectes spp.,

[0511] Further pest species which may be controlled by compounds I include: from the Phylum Mollusca, class Bivalvia, e.g., Dreissena spp.; class Gastropoda, e.g., Arion spp., Biomphalaria spp., Bulinus spp., Deroceras spp., Galba spp., Lymnaea spp., Oncomelania spp., Pomacea canaliclata, Succinea spp.; from the class of the helminths, e.g., Ancylostoma duodenale, Ancylostoma ceylanicum, Acylostoma braziliensis, Ancylostoma spp., Ascaris lubricoides, Ascaris spp., Brugia malayi, Brugia timori, Bunostomum spp., Chabertia spp., Clonorchis spp., Cooperia spp., Dicrocoelium spp., Dictyocaulus filaria, Diphyllobothrium latum, Dracunculus medinensis, Echinococcus granulosus, Echinococcus multilocularis, Enterobius vermicularis, Faciola spp., Haemonchus spp. e.g. Haemonchus contortus; Heterakis spp., Hymenolepis nana, Hyostrongulus spp., Loa Loa, Nematodirus spp., Oesophagostomum spp., Opisthorchis spp., Onchocerca volvulus, Ostertagia spp., Paragonimus spp., Schistosomen spp., Strongyloides fuel-leborni, Strongyloides stercora lis, Stronyloides spp., Taenia saginata, Taenia solium, Trichinella spiralis, Trichinella nativa, Trichinella britovi, Trichinella nelsoni, Trichinella pseudopsiralis, Trichostrongulus spp., Trichuris trichuria, Wuchereria bancrofti.

[0512] The compounds of the invention are particularly suitable for efficiently combating

[0513] insects from the sub-order of Auchenorrhyncha, e.g. Amrasca biguttula, Empoasca spp., Nephotettix virescens, Sogatella furcifera, Mahanarva spp., Laodelphax striatellus, Nilapar-vata lugens, Diaphorina citri, Lycorma delicatula, Pentastiridus leporinus;

[0514] Lepidoptera, e.g. Helicoverpa spp., Heliothis virescens, Lobesia botrana, Ostrinia nubilalis, Plutella xylostella, Pseudoplusia includens, Scirpophaga incertulas, Spodoptera spp., Trichoplusia ni, Tuta absoluta, Cnaphalocrocis medialis, Cydia pomonella, Chilo suppressalis, Anticarsia gemmatalis, Agrotis ipsilon, Chrysodeixis includens;

[0515] True bugs, e.g. Lygus spp., Stink bugs such as Euschistus spp., Halyomorpha halys, Nezara viridula, Piezodorus guildinii, Dichelops furcatus;

[0516] Thrips, e.g. Frankliniella spp., Thrips spp., Dichromothrips corbettii;

[0517] Aphids, e.g. Acyrthosiphon pisum, Aphis spp., Myzus persicae, Rhopalosiphum spp., Schi-zaphis graminum, Megoura viciae;250083

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[0519] Whiteflies, e.g. Trialeurodes vaporariorum, Bemisia spp.;

[0520] Coleoptera, e.g. Phyllotreta spp., Melanotus spp., Meligethes aeneus, Leptinotarsa decimlineata, Ceutorhynchus spp., Diabrotica spp., Anthonomus grandis, Atomaria linearia, Agriotes spp., Epilachna spp.;

[0521] Flies, e.g. Delia spp., Ceratitis capitate, Bactrocera spp., Liriomyza spp.;

[0522] Coccoidea, e.g. Aonidiella aurantia, Ferrisia virgate;

[0523] Anthropods of class Arachnida (Mites), e.g. Penthaleus major, Tetranychus spp.;

[0524] Nematodes, e.g. Heterodera glycines, Meloidogyne sp., Pratylenchus spp., Caenorhabditis elegans.

[0525] Animal health

[0526] The compounds of the invention are suitable for use in treating or protecting animals against infestation or infection by parasites. Therefore, the invention also relates to the use of a compound of the invention for the manufacture of a medicament for the treatment or protection of animals against infestation or infection by parasites. Furthermore, the invention relates to a method of treating or protecting animals against infestation and infection by parasites, which comprises orally, topically or parenterally administering or applying to the animals a parasiticidally effective amount of a compound of the invention.

[0527] The invention also relates to the non-therapeutic use of compounds of the invention for treating or protecting animals against infestation and infection by parasites. Moreover, the invention relates to a non-therapeutic method of treating or protecting animals against infestation and infection by parasites, which comprises applying to a locus a parasiticidally effective amount of a compound of the invention.

[0528] The compounds of the invention are further suitable for use in combating or controlling parasites in and on animals. Furthermore, the invention relates to a method of combating or con-trolling parasites in and on animals, which comprises contacting the parasites with a parasitically effective amount of a compound of the invention.

[0529] The invention also relates to the non-therapeutic use of compounds of the invention for controlling or combating parasites. Moreover, the invention relates to a non-therapeutic method of combating or controlling parasites, which comprises applying to a locus a parasiticidally effective amount of a compound of the invention.

[0530] The compounds of the invention can be effective through both contact (via soil, glass, wall, bed net, carpet, blankets or animal parts) and ingestion (e.g. baits). Furthermore, the compounds of the invention can be applied to any and all developmental stages.

[0531] The compounds of the invention can be applied as such or in form of compositions comprising the compounds of the invention.

[0532] The compounds of the invention can also be applied together with a mixing partner, which acts against pathogenic parasites, e.g. with synthetic coccidiosis compounds, polyetherantibiotics e.g. Amprolium, Robenidin, Toltrazuril, Monensin, Salinomycin, Maduramicin, Lasalocid, Narasin or Semduramicin, or with other mixing partners as defined above, or in form of compositions comprising said mixtures.

[0533] The compounds of the invention and compositions comprising them can be applied orally, parenterally or topically, e.g. dermally. The compounds of the invention can be systemically or non-systemically effective.250083

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[0535] The application can be carried out prophylactically, therapeutically or non-therapeutically. Furthermore, the application can be carried out preventively to places at which occurrence of the parasites is expected.

[0536] As used herein, the term "contacting" includes both direct contact (applying the com-pounds / compositions directly on the parasite, including the application directly on the animal or excluding the application directly on the animal, e.g. at its locus for the latter) and indirect contact (applying the compounds / compositions to the locus of the parasite). The contact of the parasite through application to its locus is an example of a non-therapeutic use of the compounds of the invention.

[0537] The term "locus" means the habitat, food supply, breeding ground, area, material or environment in which a parasite is growing or may grow outside of the animal.

[0538] As used herein, the term “parasites” includes endo- and ectoparasites. In some embodiments of the invention, endoparasites can be preferred. In other embodiments, ectoparasites can be preferred. Infestations in warm-blooded animals and fish include lice, biting lice, ticks, nasal bots, keds, biting flies, muscoid flies, flies, myiasitic fly larvae, chiggers, gnats, mosquitoes and fleas. The compounds of the invention are especially useful for combating parasites of the following orders and species, respectively:

[0539] fleas (Siphonaptera), e.g. Ctenocephalides felis, C. canis, Xenopsylla cheopis, Pulex irri-tans, Tunga penetrans, and Nosopsyllus fasciatus; cockroaches (Blattaria - Blattodea), e.g. Blattella germanica, B. asahinae, Periplaneta americana, P. japonica, P. brunnea, P. fuligginosa, P. australasiae, and Blatta orientalis; flies, mosquitoes (Diptera), e.g. Aedes aegypti, A. albopictus, A. vexans, Anastrepha ludens, Anopheles maculipennis, A. crucians, A. albimanus, A. gambiae, A. freeborni, A. leucosphyrus, A. minimus, A. quadrimaculatus, Calliphora vicina, Chrysomya bezziana, C. hominivorax, C. macellaria, Chrysops discalis, C. silacea, C. atlanticus, Cochliomyia hominivorax, Cordylobia anthropophaga, Culicoides furens, Culex pipiens, C. nigripalpus, C. quinquefasciatus, C. tarsalis, Culiseta inornata, C. melanura, Dermatobia hominis, Fannia canicularis, Gasterophilus intestinalis, Glossina morsitans, G. palpalis, G. fuscipes, G. tachinoides, Haematobia irritans, Haplodiplosis equestris, Hippelates spp., Hypoderma line-ata, Leptoconops torrens, Lucilia caprina, L. cuprina, L. sericata, Lycoria pectoralis, Mansonia spp., Musca domestica, M. stabulans, Oestrus ovis, Phlebotomus argentipes, Psorophora columbiae, P. discolor, Prosimulium mixtum, Sarcophaga spp., S. haemorrhoidalis, Simulium vittatum, Stomoxys calcitrans, Tabanus bovinus, T. atratus, T. lineola, and T. similis; lice (Phthiraptera), e.g. Pediculus humanus capitis, P. humanus humanus, Pthirus pubis, Haematopinus eurysternus, H. suis, Linognathus vituli, Bovicola bovis, Menopon gallinae, Menacanthus stramineus, and Solenopotes capillatus; ticks and parasitic mites (Parasitiformes): ticks (Ixodida), e.g. Ixodes scapularis, I. holocyclus, I. pacificus, Rhiphicephalus sanguineus, Dermacentor andersoni, D. variabilis, Amblyomma americanum, A. maculatum, Ornithodorus hermsi, O. turicata and parasitic mites (Mesostigmata), e.g. Ornithonyssus bacoti, Dermanyssus gallinae; Actinedida (Prostigmata) and Acaridida (Astigmata), e.g. Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergates spp., Demo-dexspp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp., and Laminosioptes spp; Bugs (Het-eropterida): Cimex lectularius, C. hemipterus, Reduvius senilis, Triatoma spp., Rhodnius ssp., Panstrongylus ssp., and Arilus critatus; Anoplurida, e.g. Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp., and Solenopotes spp.;250083

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[0541] Mallophagida (suborders Arnblycerina and Ischnocerina), e.g. Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Trichodectes spp., and Felicola spp.; Roundworms Nematoda: Wipeworms and Trichinosis (Trichosyringida), e.g. Trichinellidae (Trichinella spp.), (Trichuridae) Trichuris spp., Capillaria spp.; Rhabditida, e.g. Rhabditis spp., Strongyloides spp., Helicephalobus spp.; Strongylida, e.g. Strongylus spp., Ancylostoma spp., Necator americanus, Bunostomum spp. (Hookworm), Trichostrongylus spp., Haemonchus contortus, Ostertagia spp., Cooperia spp., Nematodirus spp., Dictyocaulus spp., Cyathostoma spp., Oesophagostomum spp., Stephanurus dentatus, Ollulanus spp., Chabertia spp., Stephanurus dentatus, Syngamus trachea, Ancylostoma spp., Uncinaria spp., Globocephalus spp., Necator spp., Metastrongylus spp., Muellerius capillaris, Protostrongylus spp., Angiostrongylus spp., Parelaphostrongylus spp., Aleurostrongylus abstrusus, and Dioctophyma renale; Intestinal roundworms (Ascaridida), e.g. Ascaris lumbricoides, Ascaris suum, Ascaridia galli, Parascaris equorum, Enterobius vermicularis (Threadworm), Toxocara canis, Toxascaris leonine, Skrjabinema spp., and Oxyuris equi; Camallanida, e.g. Dracunculus medinensis (guinea worm); Spirurida, e.g. Thelazia spp., Wuchereria spp., Brugia spp., Onchocerca spp., Dirofilari spp. a, Dipetalonema spp., Setaria spp., Elaeophora spp., Spirocerca lupi, and Habronema spp.; Thorny headed worms (Acanthocephala), e.g. Acanthocephalus spp., Macracanthorhynchus hirudinaceus and Oncicola spp.; Planarians (Plathelminthes): Flukes (Trematoda), e.g. Faciola spp., Fascioloides magna, Paragonimus spp., Dicrocoelium spp., Fasciolopsis buski, Clonorchis sinensis, Schistosoma spp., Trichobilharzia spp., Alaria alata, Paragonimus spp., and Nanocyetes spp.; Cercomeromorpha, in particular Cestoda (Tapeworms), e.g. Diphyllo-bothrium spp., Tenia spp., Echinococcus spp., Dipylidium caninum, Multiceps spp., Hymenolepis spp., Mesocestoides spp., Vampirolepis spp., Moniezia spp., Anoplocephala spp., Sirometra spp., Anoplocephala spp., and Hymenolepis spp..

[0542] The term “animal” includes warm-blooded animals (including humans) and fish. Preferred are mammals, e.g. cattle, sheep, swine, camels, deer, horses, pigs, poultry, rabbits, goats, dogs and cats, water buffalo, donkeys, fallow deer and reindeer, and also in fur-bearing animals e.g. mink, chinchilla and raccoon, birds e.g. hens, geese, turkeys and ducks and fish e.g. fresh- and saltwater fish e.g. trout, carp and eels. Particularly preferred are domestic animals, e.g. dogs or cats. Generally, "parasiticidally effective amount" means the amount of active ingredient needed to achieve an observable effect on growth, including the effects of necrosis, death, retardation, prevention, and removal, destruction, or otherwise diminishing the occurrence and activity of the target organism. The parasiticidally effective amount can vary for the various compounds / compositions used in the invention. A parasiticidally effective amount of the compositions will also vary according to the prevailing conditions e.g. desired parasiticidal effect and duration, target species, mode of application.

[0543] Generally, it is favorable to apply the compounds of the invention in total amounts of 0.5 mg / kg to 100 mg / kg per day, preferably 1 mg / kg to 50 mg / kg per day.

[0544] For oral administration to warm-blooded animals, the compounds I may be formulated as animal feeds, animal feed premixes, animal feed concentrates, pills, solutions, pastes, suspensions, drenches, gels, tablets, boluses and capsules. In addition, the compounds I may be ad-ministered to the animals in their drinking water. For oral administration, the dosage form chosen should provide the animal with 0.01 mg / kg to 100 mg / kg of animal body weight per day of the compounds I, preferably with 0.5 mg / kg to 100 mg / kg of animal body weight per day.250083

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[0546] Alternatively, the compounds I may be administered to animals parenterally, e.g., by intraruminal, intramuscular, intravenous or subcutaneous injection. The compounds I may be dispersed or dissolved in a physiologically acceptable carrier for subcutaneous injection. Alternatively, the compounds I may be formulated into an implant for subcutaneous administration. In addition the compounds I may be transdermally administered to animals. For parenteral administration, the dosage form chosen should provide the animal with 0.01 mg / kg to 100 mg / kg of animal body weight per day of the compounds I.

[0547] The compounds I may also be applied topically to the animals in the form of dips, dusts, powders, collars, medallions, sprays, shampoos, spot-on and pour-on formulations and in ointments or oil-in-water or water-in-oil emulsions. For topical application, dips and sprays usually contain 0.5 ppm to 5,000 ppm and preferably 1 ppm to 3,000 ppm of the compounds I. In addition, the compounds I may be formulated as ear tags for animals, particularly quadrupeds e.g. cattle and sheep. Suitable preparations are:

[0548] - Solutions e.g. oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, pouring-on formulations, gels;

[0549] - Emulsions and suspensions for oral or dermal administration; semi-solid preparations;

[0550] - Formulations in which the active compound is processed in an ointment base or in an oil-in-water or water-in-oil emulsion base;

[0551] - Solid preparations e.g. powders, premixes or concentrates, granules, pellets, tablets, boluses, capsules; aerosols and inhalants, and active compound-containing shaped articles.

[0552] Compositions suitable for injection are prepared by dissolving the active ingredient in a suit-able solvent and optionally adding further auxiliaries e.g. acids, bases, buffer salts, preservatives, and solubilizers. Suitable auxiliaries for injection solutions are known in the art. The solutions are filtered and filled sterile.

[0553] Oral solutions are administered directly. Concentrates are administered orally after prior dilution to the use concentration. Oral solutions and concentrates are prepared according to the state of the art and as described above for injection solutions, sterile procedures not being necessary. Solutions for use on the skin are trickled on, spread on, rubbed in, sprinkled on or sprayed on. Solutions for use on the skin are prepared according to the state of the art and according to what is described above for injection solutions, sterile procedures not being necessary.

[0554] Gels are applied to or spread on the skin or introduced into body cavities. Gels are prepared by treating solutions which have been prepared as described in the case of the injection solutions with sufficient thickener that a clear material having an ointment-like consistency results. Suitable thickeners are known in the art.

[0555] Pour-on formulations are poured or sprayed onto limited areas of the skin, the active compound penetrating the skin and acting systemically. Pour-on formulations are prepared by dis-solving, suspending or emulsifying the active compound in suitable skin-compatible solvents or solvent mixtures. If appropriate, other auxiliaries e.g. colorants, bioabsorption-promoting substances, antioxidants, light stabilizers, adhesives are added. Suitable such auxiliaries are known in the art. Emulsions can be administered orally, dermally or as injections. Emulsions are either of the water-in-oil type or of the oil-in-water type. They are prepared by dissolving the active com-pound either in the hydrophobic or in the hydrophilic phase and homogenizing this with the solvent of the other phase with the aid of suitable emulsifiers and, if appropriate, other auxiliaries e.g. colorants, absorption-promoting substances, preservatives, antioxidants, light stabilizers, viscosity-250083

[0556] 65

[0557] enhancing substances. Suitable hydrophobic phases (oils), suitable hydrophilic phases, suitable emulsifiers, and suitable further auxiliaries for emulsions are known in the art.

[0558] Suspensions can be administered orally or topically / dermally. They are prepared by suspending the active compound in a suspending agent, if appropriate with addition of other auxiliaries e.g. wetting agents, colorants, bioabsorption-promoting substances, preservatives, antioxidants, light stabilizers. Suitable suspending agents, and suitable other auxiliaries for suspensions including wetting agents are known in the art.

[0559] Semi-solid preparations can be administered orally or topically / dermally. They differ from the suspensions and emulsions described above only by their higher viscosity.

[0560] For the production of solid preparations, the active compound is mixed with suitable excipients, if appropriate with addition of auxiliaries, and brought into the desired form. Suitable auxiliaries for this purpose are known in the art.

[0561] The compositions which can be used in the invention can comprise generally from about 0.001 to 95% of the compound of the invention.

[0562] Ready-to-use preparations contain the compounds acting against parasites, preferably ectoparasites, in concentrations of 10 ppm to 80% by weight, preferably from 0.1 to 65% by weight, more preferably from 1 to 50% by weight, most preferably from 5 to 40% by weight. Preparations which are diluted before use contain the compounds acting against ectoparasites in concentrations of 0.5 to 90% by weight, preferably of 1 to 50% by weight.

[0563] Furthermore, the preparations comprise the compounds of formula I against endoparasites in concentrations of 10 ppm to 2% by weight, preferably of 0.05 to 0.9% by weight, very particularly preferably of 0.005 to 0.25% by weight.

[0564] Topical application may be conducted with compound-containing shaped articles e.g. collars, medallions, ear tags, bands for fixing at body parts, and adhesive strips and foils.

[0565] Generally it is favorable to apply solid formulations which release compounds of the invention in total amounts of 10 mg / kg to 300 mg / kg, preferably 20 mg / kg to 200 mg / kg, most preferably 25 mg / kg to 160 mg / kg body weight of the treated animal in the course of three weeks.

[0566] A. Preparation Examples

[0567] The compounds were characterized by melting point determination, by NMR spectroscopy or by the mass-to-charge ratio ([m / z]) and retention time (RT; [min.]), as determined by mass spectrometry (MS) coupled with HPLC analysis (HPLC-MS = high performance liquid chromatography-coupled mass spectrometry), LC analysis (LC-MS = liquid chromatography-coupled mass spectrometry) or chiral SFC (SFC = supercritical fluid chromatography).

[0568] Method A: Agilent 1200 & G6130A; Column: XBridge, C-18, 5 pm, 4.6*50mm; Mobile Phase: A: 0.05% TFA; B: ACN; Temperature: 40°C; Flow: 2.0 mL / min; MS: ESI positive; Mass range (m / z): 100-1000.

[0569] Method B: Agilent 1200 & G6130A; Column: Diamonsil Plus, C-18, 5 pm, 30*4.6 mm; Mobile Phase: A: 0.05% TFA; B: ACN; Temperature: 40°C; Flow: 2.0 mL / min; MS: ESI positive; Mass range (m / z): 100-1000.

[0570] Method C: Agilent 1200 & G6130A, Column: Poroshell 120 EC-C18, C-18, 4 pm, 150*4.6 mm; Mobile Phase: A: 0.05% TFA; B: ACN; Temperature: 40°C; Flow: 2.0 mL / min; MS: ESI positive; Mass range (m / z): 100-1000.

[0571] Method D: LC: Shimadzu LC-30AD, ESI; Column: Kinetex EVO C18.5pm 2.1x30mm; Mobile phase: A: water + 0.04% TFA; B: ACN + 0.02% TFA; Temperature: 40°C; Gradient: 5% B to 100%250083

[0572] 66

[0573] B in 2.5 min; 100% B to 5% B in 0.02min; 5% B for 0.5min; Flow: 0.8ml_ / min; MS: ESI positive; Mass range: 100-2000.

[0574] Method E: Agilent 1200 & G6130A, Column: Poroshell 120 EC-C18, C-18, 2,7 pm, 4.6*30mm; Mobile Phase: A: 0.05% TFA; B: ACN; Temperature: 40°C; Flow: 1.5 mL / min; MS: ESI positive; Mass range (m / z): 100-1000.

[0575] Intermediate 1 : Synthesis of tert-butyl / V-[(5-bromo-2,4-dimethoxy-phenyl)methyl]- / V-[1-[3-[3-[(4-methoxyphenyl)methyl]-2-oxo-6 / - / -1,3,4-oxadiazin-5-yl]pyrazin-2-yl]ethyl]carbamate (lnt-1):

[0576] Step 1: A mixture of tert-butyl / V-[1-(3-chloropyrazin-2-yl)ethyl]- / V-[(2,4-dimethoxyphenyl)methyl]carbamate (synthesized as described in WO2025131957) (10.0 g, 24.5 mmol), Pd(PPh3)2CI2( 1.7 g, 2.5 mmol) and tributyl(1-ethoxyethenyl)stannane (13.3 g, 36.8 mmol) in Toluene (100 mL) under N2was stirred at 110 °C for 16 hrs. The mixture was concentrated. The residue was purified by column chromatography on silica gel (PE / EtOAc = 5 / 1) to afford the compound tert-Butyl (2,4-dimethoxybenzyl)(1-(3-(1-ethoxyvinyl)pyrazin-2-yl)ethyl)carbamate (10.0 g, 92% yield) as yellow oil. LC-MS (ES) m / z = 444.2 (M+H)+

[0577] Step 2: To a mixture of tert-Butyl (2,4-dimethoxybenzyl)(1-(3-(1-ethoxyvinyl)pyrazin-2-yl)ethyl)carbamate (11.9 g, 26.8 mol) in THF (100 mL) and H2O (10 mL) was added NBS (11.9 g, 67.0 mmol). The mixture was stirred at 25 °C for 2 hrs. The mixture was quenched with sat. Na2S2O3(50 mL) and diluted with NaHCO3(50 mL), extracted with EtOAc (100 mL *2). The organic layer was dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (PE / EtOAc = 2 / 1) to afford the compound tert-Butyl (5-bromo-2,4-dimethoxybenzyl)(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)carbamate (9.0 g, 59% yield) as yellow oil. LC-MS (ES) m / z = 595.9 (M+Na)+

[0578] Step 3: A mixture of tert-Butyl (5-bromo-2,4-dimethoxybenzyl)(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)carbamate (5.4 g, 9.5 mmol) and tert-butyl / V-amino- / V-[(4-methoxyphenyl)methyl]carbamate (3.6 g, 0.4 mmol) in AcOH (50 mL) was stirred at 25 °C for 5 hrs. The mixture was concentrated. The residue was purified by column chromatography on silica gel (PE / EtOAc = 2 / 1) to afford the compound tert-butyl (5-bromo-2,4-dimethoxybenzyl)(1-(3-(3-(4-methoxybenzyl)-2-oxo-3,6-dihydro-2 / - / -1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)carbamate (2.0 g, 31% yield) as a yellow solid. LC-MS (ES) m / z = 570.1 (M+H-100)+ 1H NMR (400 MHz, CDCI3) 68.51-8.31 (m, 2H), 7.43-7.32 (m, 2H), 7.26-7.17 (m, 1H), 6.93-6.86 (m, 2H), 6.47-5.94 (m, 2H), 5.41-4.44 (m, 6H), 3.89-3.76 (m, 9H), 1.39-1.07 (m, 12H).

[0579] Due to the potential for degradation of the amine intermediates, these intermediates can be stored in the form of protected intermediates. Prior to their use in the subsequent nucleophilic substitution reaction or amide coupling reaction, they can be deprotected in the following, generally applicible, way. The respective ammonium salts can be converted into the respective amines by adding a base after the reaction.

[0580] A mixture of tert-butyl (5-bromo-2,4-dimethoxybenzyl)(1-(3-(3-(4-methoxybenzyl)-2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)carbamate (64 mg, 0.10 mmol) in TFA (1 mL) and TfOH (0.1 mL) was stirred at 20 °C for 1 hr. The mixture was concentrated to afford the crude compound 5-[3-(1-aminoethyl)pyrazin-2-yl]-3,6-dihydro-1 ,3,4-oxadiazin-2-one (31 mg, 97% yield) as yellow oil. LC-MS (ES) m / z = 221.9 (M+H)+250083

[0581] 67

[0582] Amine intermediate compound:

[0583] 5-[3-(1-aminoethyl)pyrazin-2-yl]-3,6-dihydro-1,3,4-oxadiazin-2-one (lnt-1 a)

[0584] Example 1: Synthesis of N-(1-(3-(3-methyl-2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-1):

[0585] Step 1: A mixture of N-[1-(3-chloropyrazin-2-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (10 g, 25.1 mmol), tributyl(1-ethoxyethenyl)stannane (13.6 g, 37.7 mmol) and Pd(PPh3)2CI2(1.76 g, 2.51 mmol) in toluene (100 mL) stirred under N2at 25 °C. The reaction mixture was stirred at 110 °C for 12 hours. The mixture was concentrated and purified by column chromatography on silica gel (PE / EtOAc = 20 / 1) to afford N-(1-(3-(1-ethoxyvinyl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (10.68 g, 93% yield) as a yellow solid. LC-MS (ES) m / z = 434.3 (M+H)+.

[0586] Step 2: To a solution of N-(1-(3-(1-ethoxyvinyl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (650 mg, 1.49 mmol) in THF (10 mL) was added H2O (1 mL) and NBS (292 mg, 1.64 mmol) at 25 °C. The reaction mixture was stirred at 25 °C for 2 hours. The mixture was diluted with water (30 mL), then extracted with EtOAc (30 mL * 3). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated to afford the crude product N-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (600 mg, 74% yield) as a yellow solid. LC-MS (ES) m / z = 483.8 (M+H)+.

[0587] Step 3 : To a solution of N-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (200 mg, 0.41 mmol) in AcOH (5 mL) was added (tert-butoxy)-N-methylcarbohydrazide (181 mg, 1.24 mmol). Then the mixture was stirred at 30 °C for 12 hours. The mixture was diluted with water (30 mL), then extracted with EtOAc (30 mL * 3). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by a silica gel column chromatography (PE / EtOAc = 20 / 1-5 / 1) to afford the desired product N-(1-(3-(3-methyl-2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (117.8 mg, 46% yield) as a white solid. LC-MS (ES) m / z = 476.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 59.51 (d, J = 6.8 Hz, 1H), 8.69 (d, J = 2.4 Hz, 1H), 8.63 (d, J = 2.4 Hz, 1H), 8.52 (s, 2H), 8.30 (s, 1H), 5.96-5.92 (m, 1H), 5.50-5.36 (m, 2H), 3.40 (s, 3H), 1.59 (d, J = 6.8 Hz, 3H).

[0588] Example 2: Synthesis of N-(1-(3-(2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-2)

[0589] To a solution of N-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1.0 g, 2.7 mmol) and [(methoxymethanethioyl)amino]amine (0.34 g, 3.2 mmol) in MeCN (5.0 mL) was added TFA (1 mL). Then the mixture was stirred at 70 °C for 6 hours. The mixture was diluted with water (30 mL), then extracted with EtOAc (30 mL * 3). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by a silica gel column chromatography (PE / EtOAc = 5 / 1 -1 / 1) to afford N-(1-(3-(2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-2) (0.6 g, 59% yield) as a white solid. LC-MS (ES) m / z = 478.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 5 11.91 (s, 1H), 9.53 (d, J = 6.8 Hz, 1H), 8.69 (s, 1H), 8.64 (s, 1H), 8.53 (s, 2H), 8.30 (s, 1H), 5.89-5.86 (m, 1H), 4.43-4.27 (m, 2H), 1.59 (d, J = 6.8 Hz, 3H).250083

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[0591] Example 3: Synthesis of N-(1-(3-(3-methyl-2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-3)

[0592] To a solution of N-(1-(3-(2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-2) (200 mg, 0.54 mmol) in DMF (4 mL) was added K2CO3(149.7 mg, 1.08 mmol) and Mel (115.3 mg, 0.81 mmol) at 25 °C. The reaction mixture was stirred at 30 °C for 12 hours. The mixture was diluted with water (30 mL), then extracted with EtOAc (30 mL * 3). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by a silica gel column chromatography (PE / EtOAc = 5 / 1 -2 / 1) to afford the desired product (120 mg, 58% yield) as a yellow solid. LC-MS (ES) m / z = 492.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 69.52 (d, J = 6.8 Hz, 1H), 8.71 (d, J = 2.4 Hz, 1H), 8.66 (d, J = 2.4 Hz, 1H), 8.51 (s, 2H), 8.30 (s, 1H), 5.89-5.85 (m, 1H), 4.45-4.29 (m, 2H), 3.44 (s, 3H), 1.61 (d, J = 6.8 Hz, 3H).

[0593] Example 4 : Synthesis of 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-(1-(3-(3-methyl-2-oxo-3,6-dihydro-2H-1 ,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)benzamide (I-4) :

[0594] Step 1 : A solution of tert-butyl N-[1-(3-chloropyrazin-2-yl)ethyl]carbamate (1 g, 3.88 mmol) in HCI / EA (10 mL) was stirred at room temperature for 3 hours. The mixture was concentrated to afford the crude product 1-(3-chloropyrazin-2-yl)ethan-1 -amine (0.66 g, 100% yield) as a white solid. LC-MS (ES) m / z = 158.1 (M+H)+.

[0595] Step 2 : A solution of 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzoic acid (100 mg, 0.3949 mmol), 1-(3-chloropyrazin-2-yl)ethan-1 -amine (68 mg, 0.43 mmol), HATU (225 mg, 0.59 mmol) and DIEA (153 mg, 1.18 mmol) was stirred at room temperature for 1 hour. The mixture was diluted with water (5 mL) and extracted with EA (5 mL * 2). The combined organic layers were washed with brine (5 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (PE / EtOAc = 3 / 1) to afford the product N-(1-(3-chloropyrazin-2-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzamide (120 mg, 62% yield) as a white solid. LC-MS (ES) m / z = 393.1 (M+H)+.

[0596] Step 3 : A solution of N-(1-(3-chloropyrazin-2-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzamide (1.3 g, 0.0033 mol), tributyl(1-ethoxyethenyl)stannane (1.79 g, 4.95 mmol) and Pd(PPh3)2CI2(0.23 g, 0.33 mmol) in toluene (15 mL) under nitrogen was stirred at 110 °C for 3 hours. The mixture was diluted with water (20 mL), extracted with EA (20 mL * 2), washed with brine (30 mL). The organic layer was concentrated. The residue was purified by chromatography on silica gel (PE / EtOAc = 4 / 1) to afford 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-(1-(3-(1-ethoxyvinyl)pyrazin-2-yl)ethyl)benzamide (1.0 g, 67% yield) as a yellow oil. LC-MS (ES) m / z = 429.5 (M+H)+.

[0597] Step 4 : A solution of 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-(1-(3-(1-ethoxyvinyl)pyrazin-2-yl)ethyl)benzamide (1.0 g, 2.33 mmol), N-bromosuccinimide (NBS) (457 mg, 2.5675) in THF (10 mL) and H2O (1 mL) was stirred at room temperature for 1 hour. The mixture was diluted with water (20 mL), extracted with EA (20 mL * 2), washed with brine (20 mL). The organic layer was concentrated. The residue was purified by chromatography on silica gel (PE / EtOAc = 3 / 1) to afford N-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzamide (1.0 g, 81% yield) as off-white solid. LC-MS (ES) m / z = 481.4 (M+H)+.1H NMR (400 MHz, DMSO-d6) 59.20 (d, J = 9.2 Hz, 1H), 8.90 (d, J = 3.2 Hz, 1H), 8.74 (d, J = 3.6 Hz, 1H), 7.73-7.72 (m, 1H), 7.62 (s, 1H), 7.60-7.10 (m, 2H), 5.84-5.78 (m, 1H), 5.11-5.10 (m, 2H), 1.86-1.82 (m, 2H) , 1.68-1.63 (m, 2H), 1.58 (d, J = 9.6 Hz, 3H).250083

[0598] 69

[0599] Step 5 : A solution of N-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzamide (205 mg, 0.43 mmol), tert-butyl 2-methylcarbazate (187 mg, 1.28 mmol) in HOAc (1 mL) was stirred at room temperature for 15 hours. The mixture was diluted with water (5 mL), extracted with EA (5 mL * 2), washed with brine (10 mL). The organic layer was concentrated. The residue was purified by prep-HPLC (5-95 % ACN in water with 0.1 % NH4HCO3) to afford 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-(1-(3-(3-methyl-2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)benzamide (135 mg, 66% yield) as a white solid. LC-MS (ES) m / z = 471.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 69.16 (d, J = 6.8 Hz, 1H), 8.69 (d, J = 2.0 Hz, 1H), 8.62 (d, J = 2.4 Hz, 1H), 7.68 (s, 1H), 7.59 (s, 1H), 7.50-7.13 (m, 2H), 5.90-5.86 (m, 1H), 5.51-5.36 (m, 2H), 3.41 (s, 3H), 1.83-1.80 (m, 2H), 1.64-1.61 (m, 2H), 1.58 (d, J = 6.8 Hz, 3H).

[0600] Example 5 : Synthesis of N-(1-(3-(2-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-5) :

[0601] Step 1 : To a solution of diphenyl carbonate (5.0 g, 23.34 mmol) in DCM (50 mL) was added methylhydrazine (5.38 g, 46.68 mmol) was added at -60 °C. The mixture was warmed to 0 °C and stirred at 0 °C for 3 hours. The reaction mixture was concentrated. The residue was purified by chromatography on silica gel (PE / EtOAc = 5 / 1) to afford phenyl N-amino-N-methyl-carbamate (3.4 g, 88% yield) as colorless oil.1H NMR (400 MHz, DMSO-d6) 67.41-7.37 (m, 2H), 7.23-7.19 (m, 1H), 7.12-7.10 (m, 2H), 4.88 (s, 2H), 3.09 (s, 3H).

[0602] Step 2 : A mixture of N-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (2.00 g, 0.004 mol), hexamethylenetetramine (0.57 g, 0.004 mol), Nal (0.61 g, 0.0004 mmol) in EtOH (20 mL) was stirred at room temperature for 2 hours. The mixture was concentrated. The residue was purified by reverse flash (C-18) (5-95% ACN in water with 0.1% HCI) to afford N-(1-(3-glycylpyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (0.86 g, 50% yield) as a brown solid. LC-MS (ES) m / z = 421.4 (M+H)+.

[0603] Step 3 : To a solution of N-(1-(3-glycylpyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-5) (100 mg, 0.21 mmol) and phenyl 1-methylhydrazine-1-carboxylate (79 mg, 0.43 mmol) in EtOH (3 mL). The reaction mixture was stirred at 80 °C for 16 hours. Then K2CO3(59 mg, 0.43 mmol) was added. The reaction mixture was stirred at room temperature for 10 minutes. The mixture was filtered. The filtrate was concentrated. The residue was purified by prep-HPLC (5-95% ACN in water with 0.1% NH4HCO3) to afford N-(1-(3-(2-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (49 mg, 48% yield) as a white solid. LC-MS (ES) m / z = 475.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 59.52 (d, J = 6.8 Hz, 1H), 8.62 (d, J = 2.4 Hz, 1H), 8.58 (d, J = 2.4 Hz, 1H), 8.54 (s, 2H), 8.30 (s, 1H), 7.53 (s, 1H), 5.99-5.92 (m, 1H), 4.52-4.30 (m, 2H), 3.34 (s, 3H), 1.60 (d, J = 6.8 Hz, 3H).

[0604] Example 6 : Synthesis of 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-(1-(3-(2-oxo-3,6-dihydro-2H-1 ,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)benzamide (I-6) :

[0605] A solution of N-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzamide (100 mg, 0.21 mmol), O-methyl hydrazinecarbothioate (27 mg, 0.25 mmol) was stirred at room temperature for 4 hours. The mixture was diluted with water (5 mL), extracted with EA (5 mL * 2), washed with brine (5 mL). The organic layer was concentrated. The residue was purified by prep-HPLC (5-95 % ACN in water with 0.1 % NH4HCO3) to afford 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-(1-(3-(2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-250083

[0606] 70

[0607] yl)pyrazin-2-yl)ethyl)benzamide (I-6) (40 mg, 38% yield) as a white solid. LC-MS (ES) m / z = 473.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 6 11.90 (s, 1H), 9.16 (d, J = 6.8 Hz, 1H), 8.67 (d, J = 2.4 Hz, 1H), 8.63 (d, J = 2.4 Hz, 1H), 7.68 (d, J = 1.2 Hz, 1H), 7.59 (s, 1H), 7.50-7.13 (m, 2H), 5.82-5.80 (m, 1H), 4.43-4.26 (m, 2H), 1.82-1.79 (m, 2H) , 1.63-1.60 (m, 2H), 1.56 (d, J = 6.8 Hz, 3H).

[0608] Example 7 : Synthesis of 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-(1-(3-(3-methyl-2-oxo-3,6-dihydro-2H-1 ,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)benzamide (I-7) :

[0609] A solution of 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-(1-(3-(2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)benzamide (I-6) (300 mg, 0.64 mmol), K2CO3(263 mg, 1.91 mmol) and Mel (180 mg, 1.27 mmol) in DMF (5 mL) was stirred at room temperature for 15 hours. The organic layer was concentrated. The residue was purified by prep-HPLC (5-95 % ACN in water with 0.1 % NH4HCO3) to afford 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-(1-(3-(3-methyl-2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)benzamide (I-7) (150 mg, 49% yield) as a white solid. LC-MS (ES) m / z = 487.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 6 9.16 (d, J = 6.8 Hz, 1H), 8.70 (d, J = 2.0 Hz, 1H), 8.65 (d, J = 2.4 Hz, 1H), 7.67 (s, 1H), 7.59 (s, 1H), 7.50-7.13 (m, 2H), 5.83-5.79 (m, 1H), 4.46-4.30 (m, 2H), 3.45 (s, 3H), 1.83-1.80 (m, 2H) , 1.64-1.58 (m, 5H).

[0610] Example 8 : Synthesis of N-(1-(3-(2,4-dimethyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-8) :

[0611] To a solution of of N-(1-(3-(2-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-5) (100 mg, 0.211 mmol) in DMF (2 mL) was added NaH (60% in mineral oil, 21 mg, 0.527 mmol) at 0 °C under N2atmosphere. The reaction mixture was stirred at 0 °C for 15 minutes. Then lodomethane (33 mg, 0.232 mmol) was added to the mixture. The reaction mixture was stirred at room temperature for 2 hours. The mixture was poured into water (5 mL) and extracted with EtOAc (5 mL). The organic layer was washed with brine (5 mL * 2), dried over Na2SO4and concentrated. The residue was purified by prep-HPLC (5-95% ACN in water with 0.1% NH4HCO3) to afford the desired compound N-(1-(3-(2,4-dimethyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-8) (55 mg, 53% yield) as a white solid. LC-MS (ES) m / z = 489.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 59.51 (d, J = 6.8 Hz, 1H), 8.63 (d, J = 2.0 Hz, 1H), 8.59 (d, J = 2.0 Hz, 1H), 8.54 (s, 2H), 8.31 (s, 1 H), 6.00-5.93 (m, 1 H), 4.62-4.40 (m, 2H), 3.34 (s, 3H), 2.90 (s, 3H), 1.59 (d, J = 6.8 Hz, 3H).

[0612] Example 9 : Synthesis of N-(1-(3-(2-(4-methoxybenzyl)-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-9) :

[0613] Step 1 : To a solution of diphenyl carbonate (352 mg, 1.643 mmol) in DCM (5 mL) was added (4-methoxyphenyl)methylhydrazine (500 mg, 3.285 mmol) at -60 °C under N2atmosphere. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated. The residue was purified by chromatography column on silica gel (PE / EtOAc = 3 / 1) to afford the desired compound phenyl 1-(4-methoxybenzyl)hydrazine-1-carboxylate (400 mg, 45% yield) as colorless oil. LC-MS (ES) m / z = 273.0 (M+H)+.

[0614] Step 2 : A solution of / V-[1-[3-(2-aminoacetyl)pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (100 mg, 0.238 mmol) and phenyl 1-(4-methoxybenzyl)hydrazine-1 -carboxylate (194 mg, 0.357 mmol) in EtOH (2 mL) was stirred at 80 °C for 16 hours. The mixture250083

[0615] 71

[0616] was concentrated. The residue was purified by prep-HPLC (5-95% ACN in water with 0.1% NH4HCO3) to afford the desired compound N-(1-(3-(2-(4-methoxybenzyl)-3-oxo-2, 3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (53.3 mg, 39% yield) as a gray solid. LC-MS (ES) m / z = 581.1 (M+H)+.1H NMR (400 MHz, DMSO-d6) 59.42 (d, J = 6.8 Hz, 1H), 8.59-8.52 (m, 4H), 8.30 (s, 1H), 7.59 (s, 1H), 7.27 (d, J = 8.0 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 5.82-5.76 (m, 1H), 4.84 (s, 2H), 4.56-4.34 (m, 2H) 3.66 (s, 3H), 1.41 (d, J = 6.8 Hz, 3H).

[0617] Example 10 : Synthesis of N-(1-(3-(3-(4-methoxybenzyl)-2-oxo-3,6-dihydro-2H-1 ,3, 4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-10) :

[0618] Step 1 : To a solution of tert- butyl N-(1,3-dioxoisoindolin-2-yl)carbamate (5 g, 0.019 mol), 4-methoxyphenyl)methanol (5.28 g, 0.038 mol) and PPh3(7.51 g, 0.029 mol) in THF (50 mL) was added DIAD (5.79 g, 0.029 mol) dropwise at 0 °C under nitrogen. The reaction mixture was stirred at rt for 16 hours. The mixture was concentrated. The residue was purified by column chromatography on silica gel (PE / EtOAc = 5 / 1) to afford tert-butyl (1,3-dioxoisoindolin-2-yl)(4-methoxybenzyl)carbamate (6 g, 66% yield) as colorless oil. LC-MS (ES) m / z = 405.4 (M+Na)+. Step 2 : A solution of tert- butyl (1 ,3-dioxoisoindolin-2-yl)(4-methoxybenzyl)carbamate (1.0 g, 2.62 mmol), hydrazinium hydroxide solution (251 mg, 7.85 mmol) in EtOH (12 mL) was stirred at rt for 4 hours. The mixture was concentrated and the residue was purified by reverse chromatography (5-95 % ACN in water) to afford tert-butyl 1-(4-methoxybenzyl)hydrazine-1-carboxylate (400 mg, 57% yield) as colorless oil. LC-MS (ES) m / z = 275.4 (M+Na)+.1H NMR (400 MHz, DMSO-d6) 6 7.17 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 4.47 (s, 2H), 4.35 (s, 2H), 3.73 (s, 3H), 1.40 (s, 9H)

[0619] Step 3 : A solution of tert-butyl 1-(4-methoxybenzyl)hydrazine-1 -carboxylate (234 mg, 0.93 mmol), N-[1-[3-(2-bromoacetyl)pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (300 mg, 0.62 mmol) in AcOH (3 mL) was stirred at rt for 3 hours. The mixture was extracted with EtOAc (5 mL * 2). The organic layer was washed with brine (5 mL), dried with Na2SO4and concentrated. The residue was purified with prep-HPLC (5-95 % ACN in water) to afford N-(1-(3-(3-(4-methoxybenzyl)-2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-10) (60 mg, 16% yield) as a white solid. LC-MS (ES) m / z = 582.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 5 9.45 (d, J = 6.4 Hz, 1H), 8.67 (d, J = 2.4 Hz, 1H), 8.61 (d, J = 2.4 Hz, 1H), 8.51 (s, 2H), 8.30 (s, 1H), 7.31 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 5.80-5.77 (m, 1H), 5.56-5.41 (m, 2H), 4.91-4.90 (m, 2H), 3.67 (s, 3H), 1.44 (d, J = 6.8 Hz, 3H).

[0620] Example 11 : Synthesis of N-(1-(3-(4-(cyanomethyl)-2-methyl-3-oxo-2, 3,4, 5-tetrahydro- 1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-11) :

[0621] To a solution of N-(1-(3-(2-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-5) (150 mg, 0.316 mmol) in THF (2 mL) was added LiHMDS (1.0 M in THF, 0.9 mL, 0.949 mmol) at -60 °C under N2atmosphere. Then 2-iodoacetonitrile (528 mg, 3.162 mmol) was added. The reaction mixture was stirred at rt for 2 hours. The mixture was concentrated. The residue was purified by prep-HPLC (5-95% ACN in water with 0.1% NH4HCO3) to afford the desired compound N-(1-(3-(4-(cyanomethyl)-2-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-11) (100 mg, 62% yield) as a white solid. LC-MS (ES) m / z = 514.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 59.52 (d, J =250083

[0622] 72

[0623] 6.8 Hz, 1H), 8.67 (d, J = 2.4 Hz, 1H), 8.62 d, J = 2.4 Hz, 1H), 8.54 (s, 2H), 8.30 (s, 1H), 5.99-5.93 (m, 1H), 4.75-4.48 (m, 4H), 3.38 (s, 3H), 1.60 (d, J = 6.8 Hz, 3H).

[0624] Example 12 : Synthesis of N-(1-(3-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-12) :

[0625] A solution of N-(1-(3-(3-(4-methoxybenzyl)-2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-10) (100 mg, 0.17 mmol) in TFA (0.8 mL) and TfOH (0.2 mL) was stirred at rt for 3 hours. The mixture was concentrated. The residue was purified by prep-HPLC (5-95 % ACN in water with 0.1% NH4HCO3) to afford N-(1-(3-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-12) (60 mg, 71% yield) as a white solid. LC-MS (ES) m / z = 461.9 (M+H)+.1H NMR (400 MHz, DMSO-d6) 5 11.48 (s, 1H), 9.55 (d, J = 6.4 Hz, 1H), 8.69 (s, 1H), 8.63 (s, 1H), 8.54 (s, 2H), 8.31 (s, 1H), 6.02-5.98 (m, 1H), 5.53-5.37 (m, 2H), 1.57 (d, J = 6.8 Hz, 3H).

[0626] Example 13 : Synthesis of / V-[1-[3-(2-methyl-3,5-dioxo-1 ,2,4-triazin-6-yl)pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (1-13) :

[0627] To a solution of N-(1-(3-(2-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-5) (50 mg, 0.105 mmol) in DMF (0.5 mL) was added NaH (60% in mineral oil, 5 mg, 0.211 mmol) at 0 °C under N2atmosphere. The reaction mixture was stirred at 0 °C for 15 minutes. Then 2-(4-nitrophenyl)acetyl chloride (25 mg, 0.126 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. The mixture was filtered. The filtrate was purified by prep-HPLC (5-95% ACN in water with 0.1% NH4HCO3) to afford the desired compound / V-[1-[3-(2-methyl-3,5-dioxo-1 ,2,4-triazin-6-yl)pyrazin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (1-13) (15 mg, 29% yield) as a white solid. LC-MS (ES) m / z = 489.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 5 12.52-12.07 (m, 1H), 9.40 (d, J = 7.6 Hz, 1H), 8.74 (d, J = 1.6 Hz, 1H), 8.67 (d, J = 1.6 Hz, 1H), 8.44 (s, 2H), 8.31 (s, 1H), 5.49-5.42 (m, 1H), 3.33 (s, 3H), 1.57 (d, J = 6.8 Hz, 3H).

[0628] Example 14 : Synthesis of N-(1-(3-(3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-14) :

[0629] A solution of N-(1-(3-(2-(4-methoxybenzyl)-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-9) (100 mg, 0.172 mmol) in TFA (1 mL) and TfOH (0.2 mL) was stirred at room temperature for 2 hours. The mixture was concentrated. The residue was purified by prep-HPLC (5-95% ACN in water with 0.1% NH4HCO3) to afford the desired compound N-(1-(3-(3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-14) (42.2 mg, 53% yield) as a gray solid. LC-MS (ES) m / z = 461.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 510.35 (s, 1H), 9.57-9.47 (m, 1H), 8.66-8.49 (m, 4H), 8.30 (s, 1H), 7.41 (s, 1H), 6.05-5.92 (m, 1H), 4.52-4.29 (m, 2H), 1.64-1.50 (m, 3H).

[0630] Example 15 : Synthesis of N-(1-(3-(4-Methyl-3-oxo-2, 3,4, 5-tetrahydro-1, 2, 4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-15) :

[0631] Step 1 : To a solution of N-(1-(3-(2-(4-methoxybenzyl)-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-9) (250 mg, 0.431 mmol) in DMF (3 mL) was added NaH (60% in mineral oil, 35 mg, 0.861 mmol) at 0 °C under N2atmosphere. The reaction mixture was stirred at 0 °C for 10 minutes. Then CH3I (67 mg, 0.473 mmol) was added to250083

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[0633] the mixture. The reaction mixture was stirred at room temperature for 3 hours. The mixture was poured into sat. NH4CI solution (5 ml_), extracted with EtOAc (5 mL * 2). The combined organic phase was washed with brine (10 mL), dried over Na2SO4and concentrated. The residue was purified by chromatography on silica gel (PE / EtOAc = 1 / 1) to afford the desired compound N-(1-(3-(2-(4-methoxybenzyl)-4-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (160 mg, 62% yield) as a gray solid. LC-MS (ES) m / z = 595.4 (M+H)+.

[0634] Step 2 : A solution of N-(1-(3-(2-(4-methoxybenzyl)-4-methyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (150 mg, 0.252 mmol) in TFA / TfOH (5 / 1 , 2 mL) was stirred at room temperature for 3 hours. The mixture was concentrated. The residue was purified by prep-HPLC (5-95% ACN in water with 0.1% NH4HCO3) to afford the desired compound N-(1-(3-(4-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-15) (37.6 mg, 31% yield) as a gray solid. LC-MS (ES) m / z = 475.0 (M+H)+.1H NMR (400 MHz, DMSO-d6) 5 10.50 (s, 1H), 9.58-9.44 (m, 1H), 8.69-8.55 (m, 4H), 8.31 (s, 1H), 6.07-5.93 (m, 1H), 4.61-4.37 (m, 2H) 2.90 (s, 3H), 1.66-1.47 (m, 3H).

[0635] Example 16 : Synthesis of / V-Methyl- / V-(1-(3-(2-oxo-3,6-dihydro-2H-1,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-16) :

[0636] A mixture of / V-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)- / V-methyl-3,5-bis(trifluoromethyl)benzamide (406 mg, 0.81 mmol) and O-methyl hydrazinecarbothioate (103 mg, 0.97 mmol) in ACN (5 mL) was stirred at 30 °C for 8 hrs. The mixture was concentrated and the residue was purified by column chromatography (PE / EtOAc = 1 / 1) to afford 200 mg crude. The crude was purified by reverse phase column (ACN / H2O = 3 / 1) to afford / V-Methyl- / V-(1-(3-(2-oxo-3,6-dihydro-2 / - / -1,3,4-thiadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (165 mg, 41% yield) as a white solid. LC-MS (ES) m / z = 492.0 (M+H)+.1H NMR (400 MHz, DMSO-cfe) 611.87 - 11.60 (m, 1 H), 8.77 - 8.70 (m, 2H), 8.20 - 7.56 (m, 3H), 6.30 - 5.57 (m, 1 H), 4.40 -3.79 (m, 2H), 3.31 - 2.93 (m, 3H), 1.64 - 1.62 (m, 3H).

[0637] Example 17: Synthesis of / V-Methyl- / V-(1-(3-(2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-17):

[0638] Step 1 : To a mixture of 1-(3-chloropyrazin-2-yl)- / V-methyl-ethanamine (8.80 g, 51.30 mmol) and TEA (10.38 g, 10.26 mmol) in THF (80 mL) was added 3,5-bis(trifluoromethyl)benzoyl chloride (14.29 g,51.30 mmol) at 0 °C. The mixture was stirred at 0 °C for 2 hrs. The mixture was quenched with H2O (100 mL) and extracted with EtOAc (200 mL*3). The organic layer was washed with brine (100 mL*3) and concentrated. The residue was purified by column chromatography (PE / EtOAc = 1 / 1) to afford / V-(1-(3-chloropyrazin-2-yl)ethyl)- / V-methyl-3,5-bis(trifluoromethyl)benzamide (13.60 g, 64% yield) as a yellow solid. LC-MS (ES) m / z = 412.0 (M+H)+.

[0639] Step 2: A mixture of / V-(1-(3-chloropyrazin-2-yl)ethyl)- / V-methyl-3,5-bis(trifluoromethyl)benzamide (2.00 g, 4.80 mmol), tributyl(1-ethoxyvinyl)stannane (2.60 g, 7.20 mmol) and Pd(dppf)CI2(0.34 g, 0.05 mmol) in toluene (20 mL) was stirred at 110 °C for 8 hrs under N2. The mixture was concentrated and the residue was purified by column chromatography (PE / EtOAc = 3 / 1) to afford / V-(1-(3-(1-ethoxyvinyl)pyrazin-2-yl)ethyl)- / V-methyl-3,5-bis(trifluoromethyl)benzamide (2.10 g, 98% yield) as yellow oil. LC-MS (ES) m / z = 448.0 (M+H)+.250083

[0640] 74

[0641] Step 3: To a mixture of / V-(1-(3-(1-ethoxyvinyl)pyrazin-2-yl)ethyl)- / V-methyl-3,5-bis(trifluoromethyl)benzamide (2.10 g, 4.70 mmol) in THF (20 mL) and H2O (2 mL) was added NBS (920 mg, 5.17 mmol) at 25 °C. The mixture was stirred at 25 °C for 2 hrs. The mixture was diluted with H2O (30 mL) and extracted with EtOAc (30 mL*3). The organic layer was concentrated and the residue was purified by column chromatography (PE / EtOAc = 4 / 1) to afford / V-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)- / V-methyl-3,5-bis(trifluoromethyl)benzamide (2.36 g, 100% yield) as a yellow solid. LC-MS (ES) m / z = 499.9 (M+H)+.

[0642] Step 4: A mixture of / V-(1-(3-(2-bromoacetyl)pyrazin-2-yl)ethyl)- / V-methyl-3,5-bis(trifluoromethyl)benzamide (400 mg, 0.80 mmol) and tert-butyl 1-(4-methoxybenzyl)hydrazine- 1 -carboxylate (608 mg, 2.40 mmol) in HOAc (6 mL) was stirred at 50 °C for 16 hrs. The mixture was concentrated to afford / V-(1-(3-(3-(4-methoxybenzyl)-2-oxo-3,6-dihydro-2H-1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)- / V-methyl-3,5-bis(trifluoromethyl)benzamide (400 mg, 84% yield) as a yellow solid. LC-MS (ES) m / z = 596.0 (M+H)+.

[0643] Step 5: To a mixture of / V-(1-(3-(3-(4-methoxybenzyl)-2-oxo-3,6-dihydro-2H-1 ,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)- / V-methyl-3,5-bis(trifluoromethyl)benzamide (400 mg, 0.67 mmol) in TFA (8 mL) was added TfOH (2 mL) at 0 °C. The mixture was stirred at 25 °C for 2 hrs. The mixture was concentrated and the residue was diluted with EtOAc (30 mL). The mixture was adjusted to PH = 9-10 with sat.Na2CO3. The mixture was extracted with EtOAc (30 mL*3) and the organic layer was concentrated. The residue was purified by column chromatography (DCM / EtOAc = 3 / 1) to afford 190 mg crude. The crude was triturated with MeOH (2 mL) to afford / V-Methyl- / V-(1-(3-(2-oxo-3,6-dihydro-2 / - / -1,3,4-oxadiazin-5-yl)pyrazin-2-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (110 mg, 34% yield) as a white solid. LC-MS (ES) m / z = 476.0 (M+H)+.1H NMR (400 MHz, DMSO-cfe) 611.43 - 11.16 (m, 1H), 8.76 - 8.68 (m, 2H), 8.21 - 7.62 (m, 3H), 6.31 - 5.60 (m, 1H), 5.48 -4.82 (m, 2H), 3.33 - 2.96 (m, 3H), 1.62 - 1.56 (m, 3H).

[0644] Synthesis of (1Z)-3-chloro- / V-methoxy-5-[1-[3-(2-oxo-3,6-dihydro-1 ,3,4-oxadiazin-5-yl)pyrazin- 2-yl]ethylcarbamoyl]benzimidoyl cyanide (I-27):

[0645] Step 1: To a solution of 3-chloro-5-methylbenzoic acid (25.0 g,14.65 mmol) in MeOH (250 mL) was added H2SO4(2 mL) dropwise. The reaction mixture was stirred at 80 °C for 16 hours. LCMS show the reaction was completed. The reaction mixture was cooled and concentrated under pressure. The residue was purified by silica gel column chromatography (PE / EtOAc=20:1) to afford methyl 3-chloro-5-methylbenzoate (24.0 g, yield: 84.30%, purity: 95%) as yellow oil. LC-MS: m / z = 185.0 (M+H)+.

[0646] Step 2: To a solution of methyl 3-chloro-5-methylbenzoate (24.0 g, 13.0 mmol) and N-Bromosuccinimide (23.14 g,13.0 mmol) in CCI4(300 mL) was added AIBN (2.13 g, 1.30 mmol) under nitrogen. The reaction mixture was stirred at 80 °C for 16 hours. LCMS showed the reaction was completed. The reaction mixture was cooled and purified by silica gel column chromatography (PE / EtOAc=20:1) to afford methyl 3-(bromomethyl)-5-chlorobenzoate (35.0 g, yield: 81.77%, purity: 80%) as yellow oil.

[0647] LC-MS: m / z = 263.0 (M+H)+.

[0648] Step 3: To a solution of methyl 3-(bromomethyl)-5-chlorobenzoate (35.0 g,132.8 mmol) in ACN (350 mL) was added TBAF (1 M in THF) (199 mL, 199.2 mmol) and TMSCN (19.76 g,199.2mmol) dropwise under nitrogen at 0 °C. The reaction mixture was stirred at room temperature for 16 hours. LCMS show the reaction was completed. The reaction mixture was diluted with water and250083

[0649] 75

[0650] extracted with EA (3x200 ml_). The combined organic layer was washed with brine (100 mL) and concentrated on vacuum. The residue was purified by silica gel column chromatography (PE / EtOAc=6:1) to afford methyl 3-chloro-5-(cyanomethyl)benzoate (7.5 g, yield: 24.32%, purity: 90%) as yellow oil.

[0651] LC-MS: m / z = 210.0 (M+H)+.

[0652] Step 4: To a solution of methyl 3-chloro-5-(cyanomethyl)benzoate (5.0 g,23.92 mmol) in DMF (50 mL) was added t-BuOK (17.9 mL,28.70 mmol) under nitrogen at 0 °C. The reaction mixture was stirred at 0°C for 10 minutes, then tert-Butyl nitrite (4.93 g,47.84 mmol) was added to the mixture. The reaction mixture was stirred at room temperature for 3 hours. LCMS showed the reaction was completed. The reaction mixture was added HCI (1N) (30 mL) until the red disappears and extracted with EA (3 x 200 mL). The combined organic layer ws washed with brine (100 mL) and concentrated on vacuum. The residue was purified by silica gel column chromatography (PE / EtOAc=5:1) to afford methyl (Z)-3-chloro-5-(cyano(hydroxyimino)methyl)benzoate (4.1 g, yield: 68.42%, purity: 95%) as a yellow solid. LC-MS: m / z = 239.0 (M+H)+.

[0653] Step 5: To a solution of methyl (Z)-3-chloro-5-(cyano(hydroxyimino)methyl)benzoate (4.1 g, 17.22 mmol) and dimethyl sulfate (3.26 g,25.83 mmol) in MeOH (50 mL) was added CH3ONa (30%, 3.09 g, 17.22 mmol) in batches at 0 °C. The reaction mixture was stirred at room temperature for 2 hours. LCMS showed the reaction was completed. The reaction mixture was added saturated aqueous NH4CI (100 mL) and extracted with EA (3 x 200 mL). The combined organic layer was washed with brine (100 mL) and concentrated on vacuum. The residue was purified by silica gel column chromatography (PE / EtOAc=6:1) to afford methyl (Z)-3-chloro-5-(cyano(methoxyimino)methyl)benzoate (2.4 g, yield: 52.54%, purity: 95%) as a yellow solid. LC-MS: m / z = 253.2 (M+H)+.

[0654] Step 6: To a solution of methyl (Z)-3-chloro-5-(cyano(methoxyimino)methyl)benzoate (2.4 g, 9.5 mmol) in DCE (30 mL) was added (Me)3SnOH (3.44 g, 19.0 mmol). The reaction mixture was stirred at 90 °C for 4 hours. LCMS showed the reaction was completed. The reaction mixture was cooled, adjusted pH = 2 with HCI (1 N) and extracted with DCM (3 x 30 mL). The combined organic layer was washed with brine (100 mL) and concentrated on vacuum. The residue was purified by silica gel column chromatography (PE / EtOAc=2:1) to afford the crude. The crude was purified by Prep-HPLC(H2C / CAN=0-80%) to obtain (Z)-3-chloro-5-(cyano(methoxyimino)methyl)benzoic acid (1.0 g, yield: 44.05%) as a white solid.

[0655] LC-MS: m / z = 237.0 (M-H)+

[0656] 1H NMR (DMSO-cfe, 400 MHz): 68.28 (t, J = 1.4 Hz, 1H), 8.09 (t, J = 1.8 Hz, 1H), 7.97 (t, J = 1.8 Hz, 1H), 4.26 (s, 3H).

[0657] The Amine intermediate compounds can generally be applied in a subsequent amide coupling reaction with the respective carboxylic acid counter parts as exemplified in step 7 below.

[0658] Step 7: To a solution of 5-[3-(1-aminoethyl)pyrazin-2-yl]-3,6-dihydro-1 ,3,4-oxadiazin-2-one; bis(2,2,2-trifluoroacetate) (lnt-1a) (100 mg, 0.22 mmol, 1 eq.), 3-chloro-5-[(Z)-C-cyano-N-methoxy-carbonimidoyl]benzoic acid (53.1 mg, 0.22 mmol, 1 eq) and [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylene]-dimethyl-ammonium;hexafluorophosphate (110 mg, 0.29 mmol, 1.3 eq), N-ethyl-N-isopropyl-propan-2-amine (0.76 mL, 144 mg, 1.11 mmol, 5 eq) was added in DMF (2mL). The reaction mixture was stirred at 25°C for 20 h. The solvent was removed under reduced250083

[0659] 76

[0660] pressure, the crude product was redissolved in dichloromethane (50 ml_), washed with water (25 mL) and saturated ammonium chloride solution (25 ml_). Afterwards the two phases were separated and the organic phase was dried over MgSO4, filtered and the solvent was removed under reduced pressure. The resulting crude product was purified via column chromatography to obtain the final product (1Z)-3-chloro-N-methoxy-5-[1-[3-(2-oxo-3,6-dihydro-1,3,4-oxadiazin-5-yl)pyrazin-2-yl]ethylcarbamoyl]benzimidoyl cyanide (53 mg, 0.11 mmol, 49%) as a brown solid. LC-MS: m / z = 442.0 (M-H)+

[0661] 1H NMR (DMSO-cfe, 400 MHz): 6 = 11.47 (s, 1 H), 9.34 (d, J = 6.8 Hz, 1 H), 8.67 (d, J = 2.4 Hz, 1H), 8.61 (d, J = 2.4 Hz, 1H), 8.19, (t, J= 1.7 Hz, 1H), 8.07 (t, J= 1.5 Hz, 1H), 7.84 (t, J= 1.8 Hz, 1H), 5.93 (p, J = 6.8 Hz, 1H), 5.50 (d, J = 15.4 Hz, 1H), 5.38 (d, J = 15.4 Hz, 1H), 4.23 (s, 3H), 1.54 (d, J= 6.9 Hz, 3H).

[0662] The carboxylic acid counterpart for compound I-28 can be synthesized in the following way:

[0663] Step 1: To a solution of 1-bromo-3-chloro-5-methyl-benzene (9 g, 44.118 mmol) in CCI4(50 mL) was added NBS (8.24 g, 46.324 mmol) and AIBN (217 mg, 1.323 mmol). The mixture was stirred at 80°C for 12h . TLC (PE:EtOAc=1 :0) showed a major new spot was formed. The mixture was quenched with H2O (50 mL), extracted with DCM (30 mL x 3), dried over Na2SO4, filtered and concentrated. The crude was purified by column (PE:EtOAc = 1:0) to give 1-bromo-3-(bromomethyl)-5-chloro-benzene (11.47 g, yield: crude) as a yellow oil.1H NMR: (400 MHz, CHLOROFORM-d); 5 = 7.45 (td, J = 1.7, 7.8 Hz, 2H), 7.33 (t, J = 1.6 Hz, 1H), 4.38 (s, 2H) Step 2: To a solution of 1-bromo-3-(bromomethyl)-5-chloro-benzene (11.47 g, ~40.53 mmol) in MeCN (115 mL) was added TMSCN (8.02 g, 81.06 mmol) and TBAF (60.8 mL, 1M, 60.795 mmol). The mixture was stirred at 20°C for 16 h. TLC (PE:EtOAc=10:1) showed the reaction was completed. The mixture was quenched with H2O (100 mL), extracted with EtOAc (50 mL x 3), dried over Na2SO4, filtered and concentrated. The crude was purified by column (PE:EtOAc = 100%:0%~80%:20%) to give 2-(3-bromo-5-chloro-phenyl)acetonitrile (5.4 g, yield: 58.2%) as a yellow oil.1H NMR: APR-40358-51-2 (400 MHz, CHLOROFORM-d); 5 = 7.51 (t, J = 1.7 Hz, 1H), 7.40 (s, 1H), 7.32 - 7.28 (m, 1H), 3.73 (s, 2H)

[0664] Step 3: To a solution of 2-(3-bromo-5-chloro-phenyl)acetonitrile (5.4 g, 23.581 mmol) in DMF (50 mL) was added NaH (2.26 g, 94.324 mmol) at 0°C under N2 and stirred at 0°C under N2 for 30 min. Then 1,2-dibromoethane (8.87 g, 47.162 mmol) was added and stirred at 0°C under N2 for 2h. TLC (PE:EtOAc=10:1) showed the reaction was completed. The reaction mixture was quenched with H2O (50 mL), extracted with EtOAc (30 mL x 3), dried over Na2SO4, filtered and concentrated. The crude was purified by column (PE:EtOAc = 100:0% ~ 80%:20%) to give 1-(3-bromo-5-chloro-phenyl)cyclopropanecarbonitrile (5.65 g, yield: 94%) as a yellow solid.

[0665] 1H NMR: (400 MHz, DMSO-d6); 5 = 7.69 (t, J = 1.7 Hz, 1H), 7.50 (t, J = 1.7 Hz, 1H), 7.40 (t, J = 1.7 Hz, 1 H), 1.82 - 1.75 (m, 2H), 1.67 - 1.61 (m, 2H)

[0666] Step 4: To a mixture of H2SO4(14 mL), AcOH (14 mL), and H2O (14 mL) was added 1-(3-bromo-5-chloro-phenyl)cyclopropanecarbonitrile (2.8 g, 10.92 mmol, 1 eq) at 20°C. The mixture was stirred at 120°C under N2 for 16hr. LC-MS showed ES5047P-3-5 was consumed completely and one main peak with desired mass was detected. The reaction mixture was quenched with H2O (30 mL), extracted with EtOAc (20 mL x 3). The combined organic layer was dried over Na2SO4, filtered and concentrated to give 1-(3-bromo-5-chloro-phenyl)cyclopropanecarboxylic acid (3 g, yield: crude) as a yellow solid which used directly for the next step without further250083

[0667] 77

[0668] purification.1H NMR: (400 MHz, DMSO-d6); 0 = 7.60 (t, J = 1.8 Hz, 1H), 7.51 (t, J = 1.5 Hz, 1H), 7.43 (t, J = 1.6 Hz, 1 H), 1.48 - 1.42 (m, 2H), 1.25 - 1.20 (m, 2H).

[0669] Step 5: To a solution of 1-(3-bromo-5-chloro-phenyl)cyclopropanecarboxylic acid (2 g, 7.26 mmol, 1 eq) in DMF (20 mL) was added DIPEA (2.35 g, 18.15 mmol, 3.16 ml_, 2.5 eq) and HATU (3.31 g, 8.71 mmol, 1.2 eq) at 20 °C under N2. The mixture was stirred at 20 °C under N2 for 0.5 hr. Then pyrrolidine (619.50 mg, 8.71 mmol, 727.12 pL, 1.2 eq) was added at 20 °C under N2. The mixture was stirred at 20 °C for 2 hr under N2. LC-MS showed 1-(3-bromo-5-chloro-phenyl)cyclopropanecarboxylic acid was consumed completely and one main peak with desired mass was detected. The reaction mixture was quenched with H2O (20 mL), extracted with EtOAc (10 mL*3). The combined organic layer was dried over Na2SO4, filtered and concentrated. The crude was purified by column (PE:EtOAc = 100:0% ~ 25%:75%) to give [1-(3-bromo-5-chloro-phenyl)cyclopropyl]-pyrrolidin-1-yl-methanone (2.3 g, 96.42%) as yellow oil.1H NMR: (400 MHz, CHLOROFORM-d); 5 = 7.37 (t, J = 1.8 Hz, 1H), 7.23 (t, J = 1.6 Hz, 1H), 7.13 (t, J = 1.7 Hz, 1H), 3.50 (brt, J = 6.4 Hz, 2H), 3.29 - 3.13 (m, 2H), 1.88 - 1.77 (m, 4H), 1.51 - 1.42 (m, 2H), 1.18 -1.11 (m, 2H)

[0670] Step 6: To a solution of [1-(3-bromo-5-chloro-phenyl)cyclopropyl]-pyrrolidin-1-yl-methanone (2.3 g, 7.00 mmol, 1 eq) in t-BuOH (88 mL) and H2O (22 mL) was added Pd(dppf)CI2(512.10 mg, 699.87 pmol, 0.1 eq) and Na2CO3(2.23 g, 21.00 mmol, 3 eq) and stirred at 80 °C under CO (50 Psi) for 12 h. TLC (PE:EtOAc=3:1) indicated [1-(3-bromo-5-chloro-phenyl)cyclopropyl]-pyrrolidin-1-yl-methanone was consumed completely and one new spot formed. The reaction was clean according to TLC. The reaction mixture was quenched with H2O (100 mL), the pH was adjusted to 12-13 via NaOH, then extracted with EtOAc (30 mL x 2) and the organic phase was discard. The aqueous solution phase was adjusted pH to 3-4 via 2 M HCI, and extracted with EtOAc (30 x 4), the combined organic layer was dried over Na2SO4, filtered and concentrated. The crude was purified by column (100%:0%~50%:50%) to give the 3-chloro-5-[1 -(pyrrolidine- 1-carbonyl)cyclopropyl]benzoic acid (1.46 g, yield: 71.02%) as a yellow solid.1H NMR: (400 MHz, DMSO-d6); 5 = 13.73 - 13.06 (m, 1H), 7.77 - 7.71 (m, 1H), 7.66 (t, J = 1.6 Hz, 1H), 7.43 (t, J = 1.9 Hz, 1H), 3.33 (br s, 2H), 3.12 (br s, 2H), 1.81 - 1.63 (m, 4H), 1.41 - 1.28 (m, 2H), 1.27 - 1.17 (m, 2H).

[0671] Synthesis of (S)- / V-(1-(1-(4-Methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-18):

[0672] Step 1: To a mixture of diphenyl carbonate (20.0 g, 93.4 mmol) in DCM (200 mL) was added (4-methoxyphenyl)methylhydrazine (32.6 g, 186.8 mmol) and TEA (18.9 g, 186.8 mmol) at -60 °C under N2. The mixture was stirred at 25 °C for 3 hours. LCMS showed the reaction was completed. The mixture was filtered and the filtrate was concentrated. The residue was purified by column chromatography(PE / EA=1 / 1) to afford phenyl 1-(4-methoxybenzyl)hydrazine-1 -carboxylate (17.0 g, 67% yield) as yellow oil. LC-MS (ES) m / z = 273.0 (M+H)+

[0673] Step 2: To a solution of phenyl 1-(4-methoxybenzyl)hydrazine-1 -carboxylate (5.0 g, 18.4 mmol) in 2-chloro-1, 1,1 -trimethoxyethane (70 mL) was added AcOH (3.3 g, 55.2 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated. The residue was purified by EtOAc / PE (1 / 5) to afford the compound phenyl (E)-2-(2-chloro-1-methoxyethylidene)-1-(4-methoxybenzyl)hydrazine-1 -carboxylate (2.4 g, 36% yield) as colorless oil. LC-MS (ES) m / z = 363.2 (M+H)+250083

[0674] 78

[0675] Step 3: To a solution of phenyl (E)-2-(2-chloro-1-methoxyethylidene)-1-(4-methoxybenzyl)hydrazine-1 -carboxylate (2400 mg, 6.6 mmol) in MeOH (25 mL) was added methylamine (1370 mg, 13.2 mmol). The reaction mixture was stirred at 60 °C for 4 hours. The reaction mixture was concentrated. The residue was purified by EtOAc / PE (1 / 3) to afford the compound 6-methoxy-2-(4-methoxybenzyl)-4-methyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (1100 mg, 63% yield) as a white solid.1H NMR (400 MHz, DMSO-cfe) <57.21 (d, J = 8.4 Hz, 2H), 6.86 (d, J= 8.4 Hz, 2H), 4.57 (s, 2H), 3.97 (s, 2H), 3.72 (s, 3H), 3.62 (s, 3H), 2.78 (s, 3H).

[0676] Step 4 : A solution of 6-methoxy-2-(4-methoxybenzyl)-4-methyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (1100 mg, 4.2 mmol) in hydrazine hydrate (10 mL) and MeOH (5 mL) was stirred at 120 °C for 16 hours. The reaction mixture was concentrated. The residue was purified by DCM / MeOH (20 / 1) to afford the compound 6-hydrazineyl-2-(4-methoxybenzyl)-4-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (690 mg, 63% yield) as yellow oil. LC-MS (ES) m / z = 264.3 (M+H)+

[0677] Step 5: A solution of 6-hydrazineyl-2-(4-methoxybenzyl)-4-methyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (300 mg, 1.1 mmol) and / V-[(1S)-2-[(Z)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]-3,5-bis(trifluoromethyl)benzamide (524 mg, 1.4 mmol) in AcOH (3 mL) was stirred at 50 °C for 16 hours. The reaction mixture was concentrated. The residue was purified by EtOAc / PE (1 / 3) to afford the compound (S)- / V-(1-(1-(2-(4-methoxybenzyl)-4-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (290 mg, 44% yield) as yellow oil. LC-MS (ES) m / z = 584.2 (M+H)+

[0678] Step 6 : To a solution of (S)- / V-(1-(1-(2-(4-methoxybenzyl)-4-methyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-1 H-1 ,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (350 mg, 0.6 mmol) in DCM (4 mL) was added TfOH (2 mL). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated. The residue was dissolved with EA (5 mL). The mixture was added dropwise into saturated sodium bicarbonate solution (20 mL) and extrtacted with EA (10 mL *2). The combined organic phase was washed with brine (20 mL), dried over Na2SO4and concentrated. The crude was purified by prep-HPLC (5-95% ACN in water with 0.1% NH4HCO3) to afford (S)- / V-(1-(1-(4-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1H-1 ,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (60 mg, 21% yield, 99% purity) as a white solid. LC-MS (ES) m / z = 464.2 (M+H)+;1H NMR (400 MHz, DMSO-cfe) 610.18 (s, 1H), 9.58 (d, J= 7.2 Hz, 1H), 8.54 (s, 2H), 8.34 (s, 1H), 8.12 (s, 1H), 5.79-5.68 (m, 1H), 4.60-4.40 (m, 2H), 2.83 (s, 3H), 1.59 (d, J = 6.8 Hz, 3H).

[0679] Synthesis of (S)- / V-(1-(1-(2,4-Dimethyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-20):

[0680] To a solution of (S)- / V-(1-(1-(4-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (350 mg, 0.76 mmol) in DMF (4 mL) was added K2CO3(626 mg, 4.53 mmol) and Mel (536 mg, 3.78 mmol). The reaction mixture was stirred at 80 °C for 16 hours. The mixture was filtered. The filtrate was purified by Prep-HPLC (5-95% ACN in water with 0.1% NH4HCO3) to afford the desired compound (S)- / V-(1-(1-(2,4-Dimethyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (40 mg, 11% yield) as a white solid. LC-MS (ES) m / z = 478.2 (M+H)+.1H NMR (400 MHz, DMSO-cfe) 69.56 (d, J = 6.8 Hz, 1 H), 8.53 (s, 2H), 8.33 (s, 1 H), 8.21 (s, 1H), 5.79-5.72 (m, 1H), 4.61-4.43 (m, 2H), 3.15 (s, 3H), 2.82 (s, 3H), 1.62 (d, J = 6.8 Hz, 3H).250083

[0681] 79

[0682] The introduction of the R4group can, in general, be conducted in the last step of the synthetic route and can also be applied to introduce the propargyl group in e.g. I-24, I-25 and I-26 with 3-bromoprop-1-yne.

[0683] Synthesis of (S)- / V-(1-(1-(2-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (1-21) :

[0684] Step 1 : To a solution of diphenyl carbonate (30.00 g, 0.14 mol) in DCM (300 mL) was added methylhydrazine (32.25 g, 0.28 mol) at -60 °C. The mixture was warmed to 0 °C and stirred at 0 °C for 3 hours. The reaction mixture was concentrated to give a residue. The residue was purified by chromatography on silica gel (PE / EA = 5 / 1) to afford the phenyl 1-methylhydrazine-1-carboxylate (20.00 g, 86% yield) as yellow oil. LC-MS (ES) m / z = 167.2 (M+H)+.

[0685] Step 2: To a solution of phenyl 1-methylhydrazine-1 -carboxylate (27.00 g, 0.16 mol) in 2-chloro-1 ,1 ,1 -trimethoxyethane (300 mL) was added AcOH (29.27 g, 0.49 mol). The reaction mixture was stirred at 25 °C for 16 hrs. The mixture was concentrated to give a residue. The residue was purified by chromatography column on silica gel (PE / EA = 10 / 1) to give the phenyl (E)-2-(2-chloro-1-methoxyethylidene)-1-methylhydrazine-1 -carboxylate (13.50 g, 32% yield) as colorless oil. LC-MS (ES) m / z = 257.0 (M+H)+.

[0686] Step 3: To a solution of phenyl (E)-2-(2-chloro-1-methoxyethylidene)-1-methylhydrazine-1-carboxylate (2.00 g, 7.79 mmol) in MeOH (20 mL) was added (2,4-dimethoxyphenyl)methanamine (6.51 g, 38.95 mmol). The mixture was stirred at 60 °C for 12 hrs. The reaction mixture was concentrated to give a residue. The residue was purified by chromatography column on silica gel (PE / EA = 10 / 1) to give the 4-(2,4-dimethoxybenzyl)-6-methoxy-2-methyl-4,5-dihydro-1,2,4-triazin-3(2 / - / )-one (2.00 g, 88% yield) as a white solid. LC-MS (ES) m / z = 294.2 (M+H)+.

[0687] Step 4: To a solution of 4-(2,4-dimethoxybenzyl)-6-methoxy-2-methyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (1.00 g, 3.41 mmol) in MeOH (5 mL) was added N2H4.H2O (10 mL). The mixture was stirred at 120 °C for 5 hrs. The reaction mixture was concentrated to give a residue which was purified by Prep-HPLC to give the 4-(2,4-dimethoxybenzyl)-6-hydrazinyl-2-methyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (140 mg, 14% yield) as a yellow solid. LC-MS (ES) m / z = 294.2 (M+H)+. Step 5: To solution of / V-[(1S)-2-[(Z)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]-3,5-bis(trifluoromethyl)benzamide (184 mg, 0.48 mmol) in AcOH (2 mL) was added 4-(2,4-Adimethoxybenzyl)-6-hydrazinyl-2-methyl-4,5-dihydro-1,2,4-triazin-3(2 / - / )-one (140 mg, 0.48 mmol). The mixture was stirred at 25 °C for 4 hrs. The mixture was diluted with EtOAc (20 mL), washed with H2O (20 mL), saturated sodium bicarbonate aqueous solution (20 mL) and brine (10 mL). The organic layer was separated, dried over anhydrous Na2SO4(s), concentrated to give a residue which was purified by silica gel chromatography (PE / EtOAc = 5 / 1) to give the (S)- / V-(1-(1-(4-(2,4-dimethoxybenzyl)-2-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (66 mg, 22% yield) as a white solid. LC-MS (ES) m / z = 615.2 (M+H)+.

[0688] Step 6 : To a solution of (S)- / V-(1-(1-(4-(2,4-dimethoxybenzyl)-2-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (66 mg, 0.11 mmol) in DCM (2 mL) was added TFA (122 mg, 1.07 mmol). The mixture was stirred at 25 °C for 2 hrs. The reaction mixture was basified by saturated sodium bicarbonate aqueous250083

[0689] 80

[0690] solution (20 ml_), extracted with EtOAc (20 mL *2). The organic layer was washed with brine (20 ml_), dried over anhydrous Na2SO4(s), concentrated to give a residue. The residue was purified by Prep-HPLC to give the (S)- / V-(1-(1-(2-Methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1H-1 ,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (27 mg, 54% yield) as a white solid. LC-MS (ES) m / z = 464.2 (M+H)+.1H NMR (400 MHz, DMSO-cfe) <59.55 (d, J = 7.2 Hz, 1H), 8.52 (s, 2H), 8.34 (s, 1H), 8.14 (s, 1H), 7.51 (s, 1H), 5.79-5.72 (m, 1H), 4.51-4.34 (m, 2H), 3.12 (s, 3H), 1.61 (d, J= 6.8 Hz, 3H).

[0691] Synthesis of (S)- / V-(1-(1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (I-30) :

[0692] Step 1 : To a solution of (4-methoxyphenyl)methylhydrazine (10 g, 0.05 mol) in DCM (100 mL) was added TEA (8.04 g, 0.08 mol). The reaction mixture was stirred at room temperature for 20 minutes. Then phenyl carbonochloridate (8.3 g, 0.05 mol) was added at 0 °C under N2. The reaction mixture was stirred at room temperature for 3 hours. The mixture was concentrated in vacuo and purified by chromatography column on silica gel (PE / EA=3 / 1) to give product phenyl 1-(4-methoxybenzyl)hydrazine-1-carboxylate (2.7 g, 18.68% yield) as colorless oil. LC-MS (ES) m / z = 273.2 (M+H)+.

[0693] Step 2: To a solution of phenyl 1-(4-methoxybenzyl)hydrazine-1-carboxylate (2.1 g, 7.70 mmol) in 2-chloro-1, 1,1 -trimethoxyethane (20 mL) was added AcOH (1.39 g, 23.10 mol). The reaction mixture was stirred at room temperature for 16 hours. The mixture was concentrated in vacuo. The residue was purified by chromatography column on silica gel (PE / EA=5 / 1) to give product phenyl (E)-2-(2-chloro-1-methoxyethylidene)-1-(4-methoxybenzyl)hydrazine-1 -carboxylate (2.4 g, 85.71% yield) as colorless oil. LC-MS (ES) m / z = 363.2 (M+H)+.

[0694] Step 3: To a solution of phenyl (E)-2-(2-chloro-1-methoxyethylidene)-1-(4-methoxybenzyl)hydrazine-1-carboxylate (1.40 g, 3.86 mmol) in MeOH (14 mL) was added cyclopropanamine (1101 mg, 19.29 mmol). The reaction mixture was stirred at 60 °C for 12 hrs. The reaction mixture was cooled, concentrated in vacuo and purified by silica gel column chromatography (PE / EtOAc=3:1) afford product 4-cyclopropyl-6-methoxy-2-(4-methoxybenzyl)-4,5-dihydro-1,2,4-triazin-3(2H)-one (800 mg, 71.65% yield) as colorless oil. LC-MS (ES) m / z = 290.1 (M+H)+.

[0695] Step 4: To a solution of 4-cyclopropyl-6-methoxy-2-(4-methoxybenzyl)-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (800 mg, 2.76 mmol) in Hydrazine hydrate (6 mL) was added MeOH (6 mL). The reaction mixture was stirred at 140 °C for 16 hours. The reaction mixture was cooled, concentrated in vacuo, diluted with water (30 mL) and extracted with ethyl acetate (30 mL*3). The combined organic extracts were washed with brine (200 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford product 4-cyclopropyl-6-hydrazinyl-2-(4-methoxybenzyl)-4,5-dihydro-1,2,4-triazin-3(2H)-one (500 mg, 62.50% yield) as yellow oil. LC-MS (ES) m / z = 290.1 (M+H)+.

[0696] Step 5: To a solution of 4-cyclopropyl-6-hydrazinyl-2-(4-methoxybenzyl)-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (500 mg, 1.73 mmol) in acetic acid (3 mL) was added a solution / V-[(1S)-2-[(Z)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]-3,5-bis(trifluoromethyl)benzamide (794 mg, 2.07 mmol) in DCM (3 mL) at rt. Then the mixture was stirred at rt for 16h . The reaction mixture was concentrated in vacuo, diluted with water (10 mL) and extracted with DCM (10 mL*3). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4,250083

[0697] 81

[0698] filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (PE / EtOAc=1 :1) afford product (S)- / V-(1-(1-(4-cyclopropyl-2-(4-methoxybenzyl)-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-1 / - / -1 ,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (270 mg, 25.64% yield) as yellow oil. LC-MS (ES) m / z = 610.2 (M+H)+.

[0699] Step 6: To a solution of (S)- / V-(1-(1-(4-cyclopropyl-2-(4-methoxybenzyl)-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-1 / - / -1 ,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (200 mg, 0.33 mol) in TFA (2 mL) was added TfOH (1 ml_). The reaction mixture was stirred at rt for 2 hours. The reaction mixture was concentrated in vacuo, diluted with water (20 mL) and extracted with DCM (20 mL*3). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM / MeOH=30:1) and purified by Prep-HPLC ACN-H2O (0.1%NH4HCO3) to afford product (S)- / V-(1-(1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)- 1 H-1 ,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethyl)benzamide (64 mg, 39.87% yield) as a white solid. LC-MS (ES) m / z = 490.1 (M+H)+.1H NMR (400 MHz, DMSO-cfe) 6 10.21 (s, 1H), 9.55 (d, J = 7.2 Hz, 1H), 8.53 (s, 2H), 8.34 (s, 1H), 8.13 (s, 1H), 5.73-5.70 (m, 1H), 4.51 (d, J = 16 Hz, 1H), 4.33 (d, J = 16 Hz, 1H), 2.57-5.54 (m, 1H), 1.58 (d, J = 6.8 Hz, 3H), 0.72-0.67 (m, 2H), 0.59-0.51 (m, 2H).

[0700] Synthesis of 6-(3-(4-(3,5-Bis(trifluoromethyl)phenyl)-3-methyl-4-oxobutan-2-yl)pyrazin-2-yl)-4-methyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (1-19):

[0701] Step 1 : A mixture of / V-[1-[3-(2-bromoacetyl)pyrazin-2-yl]ethyl]- / V-methyl-3,5-bis(trifluoromethyl)benzamide (1000 mg, 2.0 mmol), phenoxyformohydrazide (365 mg, 2.4 mmol) and cone. HCI (4 mg, 0.1 mmol) in MeOH (10 mL) was stirred at 25 °C for 16 hours. The resulting mixture was concentrated under pressure. The residue was purified by column chromatography on silica gel (PE / EtOAc = 100 / 0 to 4 / 1) to afford the compound phenyl (Z)-2-(2-bromo-1-(3-(1-( / V-methyl-3,5-bis(trifluoromethyl)benzamido)ethyl)pyrazin-2-yl)ethylidene)hydrazine-1 -carboxylate (300 mg, 24% yield) as a yellow solid. LC-MS (ES) m / z = 632.0 (M+H)+.

[0702] Step 2: A mixture of phenyl (Z)-2-(2-bromo-1-(3-(1-( / V-methyl-3,5-bis(trifluoromethyl)benzamido)ethyl)pyrazin-2-yl)ethylidene)hydrazine-1 -carboxylate (300 mg, 0.5 mmol) in CH3NH2in MeOH (33%) (16 mL) was stirred at 25°C for 2 hours. The resulting mixture was concentrated under pressure. The residue was purified by prep-TLC (DCM / MeOH = 20 / 1) to afford the compound 6-(3-(4-(3,5-bis(trifluoromethyl)phenyl)-3-methyl-4-oxobutan-2-yl)pyrazin-2-yl)-4-methyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (17 mg, 7% yield) as a white solid. LC-MS (ES) m / z = 489.2 (M+H)+.1HNMR (400 MHz, DMSO-cfe) 6 10.45-10.16 (m, 1H), 8.68-8.62 (m, 2H), 8.20-7.53 (m, 3H), 6.26-5.62 (m, 1H), 4.57-4.29 (m, 2H), 2.99-2.77 (m, 6H), 1.61-1.57 (m, 3H). Synthesis of (S)-3-(1-cyanocyclopropyl)- / V-(1-(3-cyclopropyl-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-1 / - / -1 ,2,4-triazol-5-yl)ethyl)-5-(trifluoromethoxy)benzamide (1-31): Step 1 : To a solution of cyclopropanamine (8000 mg, 140 mmol), 2-bromoacetonitrile (15.12 g, 126 mmol) and DIEA (36.21 g, 280 mmol) in ACN (100 mL) was stirred at 60 °C for 2 hours. 4-nitrophenyl chloroformate (33.89g, 168 mmol) and K2CO3(23.24 g, 168 mmol) was added to the mixture at R.T., then stirred at R.T. for 2h. The reaction mixture was filtrated, then concentrated in vacuo, purified by silica gel column chromatography (PE / EtOAc=5:1) afford product 4-250083

[0703] 82

[0704] nitrophenyl (cyanomethyl)(cyclopropyl)carbamate (36 g, 98% yield) as yellow oil.LC-MS (ES) m / z = 262.1 (M+H)+.

[0705] Step 2 : To a solution of 4-nitrophenyl (cyanomethyl)(cyclopropyl)carbamate (15 g, 57.4 mmol) in Hydrazine hydrate (150 ml_). The reaction mixture was stirred at 100 °C for 5 hours. The reaction mixture was concentrated in vacuo to afford crude 4-cyclopropyl-6-hydrazinyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (16 g, 100% yield) as orange oil. LC-MS (ES) m / z = 170.2 (M+H)+.

[0706] Step 3: A mixture of 4-cyclopropyl-6-hydrazinyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one (12 g, 70.9 mmol) and (Boc)20 (46.42 g, 212.7 mmol) in EtOH (120 mL) was stirred at 90 °C for 3 hrs. The reaction mixture was concentrated in vacuo, purified by flash chromatography on silica gel (DCM / MeOH=50:1) to afford tert-butyl 2-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)hydrazine-1 -carboxylate (10 g, 52% yield) as yellow solid. LC-MS (ES) m / z = 270.2 (M+H)+.

[0707] Step 4 : A mixture of tert-butyl 2-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)hydrazine-1 -carboxylate (10 g, 37 mmol) in 1 ,4-dioxane / HCI (50 mL) was stirred at R.T. for 2 hrs. The reaction mixture was filtered, filter residue was washed with MTBE (50 mL), concentrated in vacuo to afford 4-cyclopropyl-6-hydrazinyl-4,5-dihydro-1,2,4-triazin-3(2H)-one hydrochloride (6.2 g, 99% yield) as yellow solid. LC-MS (ES) m / z = 170.2 (M+H)+.

[0708] Step 5 : To a solution of (tert-butoxycarbonyl)-L-alanine (560 mg, 2.96 mmol), ethyl cyclopropanecarboximidate hydrochloride (443 mg, 2.96 mmol) and DIEA (1148 mg, 8.88 mmol) in DCM (5 mL) was added HATU (443 mg, 2.96 mmol) at 0 °C, then the mixture was stirred at 0 °C for 2 h. 4-Cyclopropyl-6-hydrazinyl-4,5-dihydro-1,2,4-triazin-3(2H)-one hydrochloride (500 mg, 2.96 mmol) in DCM (2 mL) was added to the mixture. The mixture was stirred at R.T. for 16 h. The reaction mixture was concentrated in vacuo, purified by silica gel column chromatography (PE / EtOAc=2:1) afford yellow solid, then purified by Prep-HPLC ACN-H2O (0.1%FA) to afford product tert-butyl (S)-(1-(3-cyclopropyl-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (180 mg, 15% yield) white solid. LC-MS (ES) m / z = 390.3 (M+H)+.

[0709] Step 6 : A mixture of tert-butyl (S)-(1-(3-cyclopropyl-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)carbamate (180 mg, 0.46 mmol) in in DCM (3 mL) was added TFA (0.5 mL), then the mixture was stirred at R.T. for 2 hrs. The reaction mixture was concentrated in vacuo to afford crude product (S)-6-(5-(1-aminoethyl)-3-cyclopropyl-1H-1,2,4-triazol-1-yl)-4-cyclopropyl-4,5-dihydro-1,2,4-triazin-3(2 / - / )-one (150 mg, 100% yield) as yellow solid. LC-MS (ES) m / z = 290.2 (M+H)+.

[0710] Step 7 : To a solution of 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)benzoic acid (140 mg, 0.52 mmol) in SOCI2(2 mL) was stirred at 70 °C for 2 h. The reaction mixture was concentrated in vacuo, then diluted with DCM (2 mL) to afford solution A. (S)-6-(5-(1-aminoethyl)-3-cyclopropyl-1H-1,2,4-triazol-1-yl)-4-cyclopropyl-4,5-dihydro-1,2,4-triazin-3(2 / - / )-one (150 mg, 0.52 mmol) and TEA (524 mg, 5.18 mmol) in DCM (2 mL) was added solution A. The mixture was stirred at R.T. for 2 h. The mixture was diluted with H2O (20 mL), then extracted with DCM (20 mL*3). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, concentrated in vacuo, purified by silica gel column chromatography (DCM / MeOH=30:1) to afford yellow solid, then purified by Prep-HPLC ACN-H2O (0.1%NH4HCO3) to afford product (S)-3-(1-cyanocyclopropyl)- / V-(1-(3-cyclopropyl-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-5-(trifluoromethoxy)benzamide (113 mg, 40% yield) white solid. LC-MS (ES) m / z = 543.2 (M+H)+.1H NMR (400 MHz, DMSO-cfe) <510.12 (s, 1H), 9.25 (d, J= 7.2Hz, 1H), 7.82 (t, J= 1.4 Hz, 1H), 7.75 (s, 1H), 7.49 (s, 1H), 5.61-5.58 (m, 1H), 4.46 (d, J= 16 Hz, 1H), 4.26 (d, J = 16 Hz, 1H), 2.56-2.52 (m, 1H), 2.01-1.96 (m, 1H), 1.86-1.83 (m, 2H), 1.68-1.64 (m, 2H), 1.52 (d, J= 6.8 Hz, 3H), 0.95-0.91 (m, 2H), 0.84-0.77 (m, 2H), 0.72-0.66 (m, 2H), 0.60-0.52 (m, 2H).

[0711] Synthesis of (S)- / V-(1-(3-Amino-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)benzamide (I-35)

[0712] Step 1 : To a mixture of (2S)-2-{[(tert-butoxy)carbonyl]amino}propanoic acid (2.19 g, 11.55 mmol), tert-butyl / V-[(1Z)-amino(methylsulfanyl)methylidene]carbamate (2.00 g, 10.50 mmol) and DIPEA (4.07 g, 31.50 mmol) in DCM (40 mL) was added HATU (5.99 g, 15.75 mmol)at 0 °C. The reaction mixture was stirred at 0 °C for 2 hours. The reaction mixture was filtered. The tert-butyl (S,Z)-(1-((((tert-butoxycarbonyl)imino)(methylthio)methyl)amino)-1-oxopropan-2-yl)carbamate (3.70 g, calculated) in filtrate was used in the next step without further purification. LC-MS (ES) m / z = 362.2 (M+H)+.

[0713] Step 2: The 4-cyclopropyl-6-hydrazinyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one hydrochloride (1.90 g, 6.80 mmol) was added into the solution of tert-butyl (S,Z)-(1-((((tert-butoxycarbonyl)imino)(methylthio)methyl)amino)-1-oxopropan-2-yl)carbamate (3.69 g, 10.20 mmol) and DIPEA (3.52 g, 27.20 mmol) in DCM (40 mL). The mixture was stirred at 50 °C for 16 hours. The reaction mixture was concentrated. The residue was purified by column chromatography on silica gel (DCM / MeOH = 50 / 1) to afford tert-butyl (S)-(1-(3-((tert-butoxycarbonyl)amino)-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (1.30 g, 41% yield) as a white solid.1H NMR (400 MHz, DMSO-cfe) 5 10.10 (s, 1H), 9.90 (s, 1H), 7.47-7.16 (m, 1H), 5.17-5.10 (m, 1H), 4.46-4.23 (m, 2H), 2.59-2.54 (m, 1H), 1.43 (s, 9H), 1.33-1.18 (m, 12H), 0.78-0.62 (m, 4H).

[0714] Step 3 : A mixture of tert-butyl (S)-(1-(3-((tert-butoxycarbonyl)amino)-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)carbamate (400 mg, 0.86 mmol) in HCI / 1,4-dioxane (10 mL, 4 M) was stirred at 25 °C for 2 hours. The reaction mixture was concentrated to afford (S)-6-(3-amino-5-(1-aminoethyl)-1H-1 ,2,4-triazol-1-yl)-4-cyclopropyl-4,5-dihydro-1,2,4-triazin-3(2H)-one dihydrochloride (290 mg, 100% yield) as a white solid. LC-MS (ES) m / z = 265.2 (M+H)+.

[0715] Step 4: A mixture of 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)benzoic acid (350 mg, 1.29 mmol) in SOCI2(6 mL) was stirred at 80 °C for 1 hour. The reaction mixture was concentrated. To a mixture of (S)-6-(3-amino-5-(1-aminoethyl)-1 / - / -1,2,4-triazol-1-yl)-4-cyclopropyl-4,5-dihydro-1 ,2,4-triazin-3(2H)-one dihydrochloride (290 mg, 0.86 mmol) and TEA (435 mg, 4.30 mmol) in DCM (8 mL) was added dropwise a solution of the residue in DCM (2 mL) at 0 °C. The reaction was stirred at 0 °C for 10 minutes. The reaction mixture was diluted with ice-water (20 mL) and extracted DCM (20 mL*2). The combined organic phase was concentrated. The residue was purified by column chromatography on silica gel (DCM / MeOH = 50 / 1) to afford (S)- / V-(1-(3-amino-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)benzamide (350 mg, 79% yield) as a white solid. LC-MS (ES) m / z = 518.2 (M+H)+.1H NMR (400 MHz, DMSO-cfe) <59.96 (s, 1H), 9.19 (d, J= 6.8 Hz, 1H), 7.86 (d, J = 1.6 Hz, 1 H), 7.79 (s, 1 H), 7.49 (s, 1 H), 5.72 (s, 2H), 5.58-5.51 (m, 1 H), 4.40-4.20 (m, 2H), 2.55-2.52 (m, 1 H), 1.85-1.64 (m, 4H), 1.50 (d, J = 6.8 Hz, 3H), 0.74-0.48 (m, 4H).Synthesis of (S)- / V-(1-(3-bromo-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)benzamide (I-34):

[0716] To a mixture of (S)- / V-(1-(3-amino-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)benzamide (300 mg, 0.58 mmol) and CuBr2(155 mg, 0.70 mmol) in HBr (6 ml_, 48% in water) was added a solution of NaNO2(60 mg, 0.87 mmol) in H2O (6 mL) at 0 °C. The resulting mixture was stirred at 0 °C for 1 hour. The reaction mixture was filtered and the filter cake was collected to give a residue, which was purified by Prep-HPLC (5-95% ACN in water) to afford (S)- / V-(1-(3-Bromo-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)benzamide (150 mg, 45% yield) as a white solid. LC-MS (ES) m / z = 581.1 (M+H)+.1H NMR (400 MHz, DMSO-cfe) 610.27 (s, 1H), 9.33 (d, J = 6.8 Hz, 1H), 7.85 (s, 1H), 7.77 (s, 1H), 7.50 (s, 1H), 5.66-5.59 (m, 1H), 4.48-4.26 (m, 2H), 2.57-2.53 (m, 1H), 1.86-1.64 (m, 4H), 1.56 (d, J= 6.8 Hz, 3H), 0.73-0.51 (m, 4H).

[0717] Synthesis of (S)-3-(1-cyanocyclopropyl)- / V-(1-(1-(4-cyclopropyl-3-oxo-2, 3,4, 5-tetrahydro- 1,2,4-triazin-6-yl)-3-methoxy-1H-1 ,2,4-triazol-5-yl)ethyl)-5-(trifluoromethoxy)benzamide (I-33) :

[0718] Step 1 : To a solution of 4-cyclopropyl-6-hydrazinyl-4,5-dihydro-1,2,4-triazin-3(2H)-one hydrochloride (500 mg, 2.95 mmol) and O-methyl / V-[(2S)-2-(1,3-dioxoisoindolin-2-yl)propanoyl]carbamothioate (864 mg, 2.95 mmol) in EtOH (12 mL) was stirred at 90°C for 16h. The reaction mixture was concentrated in vacuo, purified by silica gel column chromatography (DCM / MeOH=30:1) afford product (S)-2-(1-(1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-3-methoxy-1H-1, 2, 4-triazol-5-yl)ethyl)isoindoline-1, 3-dione (790 mg, 65% yield) yellow solid. LC-MS (ES) m / z = 410.2 (M+H)+.

[0719] Step 2 : To a solution of (S)-2-(1-(1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-3-methoxy-1H-1, 2, 4-triazol-5-yl)ethyl)isoindoline-1, 3-dione (300 mg, 0.73 mmol) in EtOH (15 mL) was added N2H4.H2O (147 mg, 3.66 mmol) then stirred at 40°C for 16 h. The mixture was diluted with H2O (20 mL), then extracted with DCM (20 mL*3). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, concentrated in vacuo to afford crude product (S)-6-(5-(1-aminoethyl)-3-methoxy-1 / - / -1,2,4-triazol-1-yl)-4-cyclopropyl-4,5-dihydro-1,2,4-triazin-3(2 / - / )-one (230 mg, 100% yield) white solid. LC-MS (ES) m / z = 280.2 (M+H)+.

[0720] Step 3 : To a solution of 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)benzoic acid (223 mg, 0.82 mmol) in SOCI2(2 mL) was stirred at 70°C for 2 h. The reaction mixture was concentrated in vacuo, then diluted with DCM (2 mL) to afford solution A. (S)-6-(5-(1-aminoethyl)-3-methoxy-1H-1,2,4-triazol-1-yl)-4-cyclopropyl-4,5-dihydro-1,2,4-triazin-3(2 / - / )-one (230 mg, 0.82 mmol) and TEA (833 mg, 8.23 mmol) in DCM (2 mL) was added solution A. The mixture was stirred at R.T. for 2 h. The mixture was diluted with H2O (20 mL), then extracted with DCM (20 mL*3). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, concentrated in vacuo, purified by silica gel column chromatography (DCM / MeOH = 30:1) to afford yellow solid, then purified by Prep-HPLC ACN-H2O (0.1% FA), then purified by Prep-HPLC ACN-H2O (0.1%NH4HCO3) to afford product (S)-3-(1-cyanocyclopropyl)- / V-(1-(1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-3-methoxy-1 H-1 ,2,4-triazol-5-yl)ethyl)-5-(trifluoromethoxy)benzamide (155 mg, 35% yield) white solid. LC-MS (ES) m / z = 533.2 (M+H)+.85

[0721] 1H NMR (400 MHz, DMSO-cfe) 610.13 (s, 1H), 9.28 (d, J= 6.8 Hz, 1H), 7.85 (t, J= 1.6 Hz, 1H), 7.77 (s, 1H), 7.50 (s, 1H), 5.59-5.52 (m, 1H), 4.44 (d, J= 16 Hz, 1H), 4.25 (d, J= 16 Hz, 1H), 3.89 (s, 3H), 2.56-2.52 (m, 1H), 1.86-1.83 (m, 2H), 1.68-1.64 (m, 2H), 1.53 (d, J = 6.8 Hz, 3H), 0.74-0.67 (m, 2H), 0.61-0.53 (m, 2H).

[0722] Synthesis of (S)- / V-(1-(3-Amino-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-1H-1 ,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethoxy)benzamide (I-36) :

[0723] A mixture of 3,5-bis(trifluoromethoxy)benzoic acid (372 mg, 1.28 mmol) in SOCI2(6 mL) was stirred at 80 °C for 1 hour. The reaction mixture was concentrated. To a mixture of 4-cyclopropyl-6-hydrazinyl-4,5-dihydro-1,2,4-triazin-3(2H)-one hydrochloride (360 mg, 1.07 mmol) and TEA (540 mg, 5.34 mmol) in DCM (8 mL) was added dropwise a solution of the residue in DCM (2 mL) at 0 °C. The reaction was stirred at 0 °C for 10 minutes. The reaction mixture was diluted with icewater (20 mL) and extracted DCM (20 mL*2). The combined organic phase was concentrated. The residue was purified by column chromatography on silica gel (DCM / MeOH = 50 / 1) to afford (S)- / V-(1-(3-amino-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethoxy)benzamide (400 mg, 70% yield) as a white solid. LC-MS (ES) m / z = 537.2 (M+H)+.1H NMR (400 MHz, DMSO-cfe) 69.96 (s, 1H), 9.29 (d, J= 6.8 Hz, 1H), 7.95 (d, J= 1.6 Hz, 2H), 7.76 (s, 1 H), 5.73 (s, 2H), 5.58-5.51 (m, 1H), 4.40-4.21 (m, 2H), 2.56-2.52 (m, 1H), 1.50 (d, J= 6.8 Hz, 3H), 0.74-0.50 (m, 4H).

[0724] Synthesis of (S)- / V-(1-(1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-3-(dimethylamino)-1H-1 ,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethoxy)benzamide (I-32) :

[0725] A mixture of (S)- / V-(1-(3-amino-1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1 ,2,4-triazin-6-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethoxy)benzamide (280 mg, 0.52 mmol), HCHO (261 mg, 2.61 mmol, 30% in water) and NaBH3CN (131 mg, 2.09 mmol) in MeOH (5 mL) and AcOH (1 mL) was stirred at 25 °C for 2 hours. The reaction mixture was concentrated. The residue was purified by column chromatography on silica gel (DCM / MeOH = 50 / 1) to afford the crude product. The crude product was purified by prep-HPLC to afford (S)- / V-(1-(1-(4-cyclopropyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-3-(dimethylamino)-1 / - / -1,2,4-triazol-5-yl)ethyl)-3,5-bis(trifluoromethoxy)benzamide (150 mg, 51% yield) as a white solid. LC-MS (ES) m / z = 565.2 (M+H)+.1H NMR (400 MHz, DMSO-cfe) 610.01 (s, 1H), 9.33 (d, J = 6.8 Hz, 1H), 7.91 (s, 2H), 7.75 (s, 1H), 5.57-5.51 (m, 1H), 4.44-4.20 (m, 2H), 2.89 (s, 6H), 2.55-2.53 (m, 1H), 1.52 (d, J = 6.8 Hz, 3H), 0.73-0.55 (m, 4H).

[0726] With appropriate modification of the starting materials, the procedures given in the synthesis descriptions were used to obtain further compounds I, in particular further compounds I.A.N.1, I.A.N.Ia, I.A.N.2, or I.A.N.2a. The compounds obtained in this manner are listed in the tables that follow (Table I and Table II), together with physical data.

[0727]

[0728] > > >

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[0731]

[0732] 250083

[0733] 88

[0734]

[0735] wherein R5cis H.

[0736] Table II

[0737]

[0738] 250083

[0739] 89

[0740]

[0741] wherein Y is N-cPr.

[0742] B Biological examples

[0743] If not otherwise specified, the test solutions are prepared as follow:[0744...

Claims

25008394Claims1) Compounds of formulawhereinR1is H, OR10a, NR12R13, Ci-C6-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci- C6-alkyl-C3-C6-cycloalkyl, Ci-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkyl-Ci- C6-alkoxy, Ci-C6-alkoxy-C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C6-alkoxy, C2-C6- alkenyl-C3-C6-cycloalkyl, C2-C6-alkynyl-C3-C6-cycloalkyl, C3-C6-cycloalkyl-C2-C6- alkenyl, C3-C6-cycloalkyl-C2-C6-alkynyl, wherein the alkyl, alkoxy, alkenyl, alkynyl, and cycloalkyl moieties are unsubstituted or substituted with one or more R11; or C(O)R11a; R2is H, Ci-C3-alkyl, C2-C3-alkenyl, C3-C6-cycloalkyl, or C2-C3-alkynyl, wherein the alkyl, alkenyl, alkynyl and cycloalkyl moieties are unsubstituted or substituted with one or more halogen;R3is independently halogen, CN, NO2, SF5, Ci-C6-alkyl, Ci-C6-alkoxy, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6- cycloalkyl, 3- to 6-membered heterocyclyl, wherein the alkyl, alkenyl, alkynyl, alkoxy, heterocyclyl and cycloalkyl moieties are unsubstituted or substituted with one or more R11; OR10a, NR12R13, C(O)NR12R13, C(O)OR10, C(O)R14, OS(O)2-R14, S(O)m-R14, - N=S(O)R12aR13a; ortwo R3bound to two adjacent C-atoms can form a 4-, 5-, or 6-membered ring, which may contain one or two heteroatoms selected from N, O, and S as ring members, wherein the ring is unsubstituted or substituted with one or more halogen, CN, Ci-C3- alkyl, and / or Ci-C3-haloalkyl;R4H, Ci-C3-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C3-C6-cycloalkyl-Ci-C2-alkyl, Ci-C2-alkyl- C3-C6-cycloalkyl, C3-C6-cycloalkyl, wherein the alkyl, alkenyl, alkynyl or cycloalkyl moieties are unsubstituted or substituted with one or more halogen, OH, Ci-C3-alkoxy, CN, or C(O)NH2; phenyl or 5- or 6-membered hetaryl, wherein the phenyl or hetaryl moiety are unsubstituted or substituted with one or more halogen, CN, C(O)NH2, Ci- C3-alkyl, Ci-C3-haloalkyl or Ci-C3-alkoxy, or Ci-C3-haloalkoxy;HET is a groupwherein # is the bond to the CH(R2)amide spacer, and % is the bond to the diazinone ring;25008395R5a, R5bare independently from each other H, halogen, CN, Ci-C3-alkyl, Ci-C3-haloalkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C3-alkyl, Ci-C3-alkyl-C3-C6-cycloalkyl, Ci-C3- alkoxy, Ci-C3-haloalkoxy, C2-C3-alkenyl, or C2-C3-alkynyl;R5cis H, halogen, CN, OR10a, NR12R13, C(O)NR12R13, C(O)OR10a, C(O)R14, S(O)m-R14, Ci- C3-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C3-alkyl, Ci-C3-alkyl-C3-C6-cycloalkyl, Ci-C3-alkoxy, C2-C3-alkenyl, C2-C3-alkynyl, -C(=NOCi-C4-alkyl)H, or -C(=NOCI-C4- alkyl)-Ci-C4-alkyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl and alkoxy are unsubstituted or substituted with one or more halogen and / or CN;R6, R7are independently from each other H, halogen, CN, C(O)NH2, Ci-C3-alkyl, Ci-C3- haloalkyl, or C3-C6-cycloalkyl; orR6and R7together with the carbon atom to which they are bound, form a 3-, 4-, 5-, or 6-membered saturated or partially, unsaturated carbocycle, wherein the carbocycle is unsubstituted or substituted with one or more halogen, cyano, Ci-C3-alkyl, or Ci-C3- haloalkyl; or form a 3-, 4-, 5-, or 6-membered saturated or partially unsaturated heterocycle, which may contain 1 or 2 heteroatoms or heteroatom-containing groups selected from N, O, S(O)m, and optionally one or two C(O) groups as ring members, wherein the heterocycle is unsubstituted or substituted with one or more halogen, cyano, Ci-C3-alkyl, or Ci-C3-haloalkyl; orR6and R7together with the carbon atom to which they are bound form a C(O) group; R10is H, Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C4- cycloalkyl-Ci-C2-alkyl, C3-C4-halocycloalkyl-Ci-C2-alkyl, C(O)-Ci-C4-alkyl, C(O)-Ci- C4-haloalkyl, C(C)-C3-C4-cycloalkyl, C(C)-C3-C4-halocycloalkyl, SOm-Ci-C4-alkyl, SOm-Ci-C4-haloalkyl, SOm-C3-C6-cycloalkyl, or phenyl which is unsubstituted or substituted one or more with Ra;R10ais H, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C4-cycloalkyl-Ci-C2-alkyl, C3-C4- halocycloalkyl-Ci-C2-alkyl, C(O)-Ci-C4-alkyl, C(C)-Ci-C4-haloalkyl, C(O)-C3-C4- cycloalkyl, C(C)-C3-C4-halocycloalkyl, SOm-Ci-C4-alkyl, SOm-Ci-C4-haloalkyl, SOm- C3-C6-cycloalkyl, or phenyl which is unsubstituted or substituted one or more with Ra; R11is halogen, CN, NO2, NR12R13, C(O)NH2, C(S)NH2, C(O)OH, OR10; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the heterocyclyl, hetaryl and phenyl moieties are unsubstituted or substituted with one or more halogen, Ci- C3-haloalkyl, and / or CN;R11ais NR12R13, Ci-C6-alkyl, Ci-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C4-cycloalkyl- Ci-C2-alkyl, wherein the alkyl, alkoxy, alkenyl, alkynyl or cycloalkyl moiety is unsubstituted or substituted with one or more halogen; or 3- to 6-membered heterocyclyl, wherein the heterocyclyl moiety is unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN;R12, R13are independently from each other H, Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-halo- alkoxy, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C(O)-Ci-C4-alkyl, C(C)-Ci-C4-haloalkyl, C(C)-C3-C4-cycloalkyl, C(C)-C3-C4-halocycloalkyl, C(O)NH-Ci-C4-alkyl, C(O)NH-Ci- C4-haloalkyl, C(O)N(Ci-C4-alkyl)-Ci-C4-alkyl, C(0)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(C)N(Ci-C4-haloalkyl)-Ci-C4-haloalkyl, C(C)NH-Ci-C4-alkoxy, C(C)NH-Ci-C4-halo- alkoxy, C(C)NH-Ci-C4-alkoxy-Ci-C4-alkyl, C(C)NH-Ci-C4-alkoxy-Ci-C4-haloalkyl; C(O)NH-phenyl, C(O)NH-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, C(O)NH-Ci-C4-alkyl-phenyl, C(O)NH-Ci-C4-alkyl-3-6-membered heterocyclyl or 5- or250083966-membered hetaryl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN; S(0)m-Ci-C4-haloalkyl, S(0)m-C3-C4-cycloalkyl, S(0)m-C3-C4-halocycloalkyl; 3- to 6- membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN; orR12and R13together with the atom / atoms to which they are bound, form a 3-, 4-, 5-, 6-, or 7-membered saturated, partially or fully unsaturated heterocycle, which heterocycle may additionally contain 1 or 2 heteroatoms or heteroatom-containing groups selected from N, O, S(O)m, and optionally one or two groups C(O) as ring members, and wherein the heterocycle moiety is unsubstituted or substituted with one or more Ra;R-i2a, Ri3a areindependently from each other Ci-C4-alkyl or C3-C6-cycloalkyl, which are unsubstituted or substituted with one or more halogen and / or CN; or R12aand R13atogether with the atom to which they are bound, form a 3-, 4-, 5-, 6-, or 7-membered saturated, partially or fully unsaturated heterocycle, wherein the heterocycle moiety may additionally contain 1 or 2 heteroatoms or heteroatom-containing groups selected from N, O, S(O)m, and optionally one or two groups C(O) as ring members, and wherein the heterocycle moiety is unsubstituted or substituted with one or more Ra; R14is H, Ci-C6-alkyl, C3-C6-cycloalkyl, wherein the alkyl and cycloalkyl moieties are unsubstituted or substituted with one or more R11; or 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more Ra;Rais halogen, CN, NO2, OH, Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-haloalkyl, Ci-C4-alkoxy-Ci- C4-alkyl, Ci-C4-haloalkoxy, C3-C4-cycloalkyl, C3-C4-halocycloalkyl, S(O)m-Ci-C4-alkyl, S(0)m-Ci-C4-haloalkyl, S(0)m-C3-C4-cycloalkyl, or S(0)m-C3-C4-halocycloalkyl; m is 0, 1, or 2;n is 0, 1, 2, or 3;X is N, CH, orCR3;Y is O, S, or N-RN;RNis as defined for R4;and the N-oxides, stereoisomers, tautomers, and agriculturally or veterinarily acceptable salts thereof.2) Compounds of formula I according to claim 1 , whereinR5cis selected from H, halogen, CN, Ci-C3-alkyl, C3-C6-cycloalkyl, NH2, NHC(O)-CI-C3- alkyl, NH(Ci-C3-alkyl), Ci-C4-haloalkyl, Ci-C3-alkoxy, or S-Ci-C3-alkyl;R5ais selected from H, halogen, CN, Ci-C3-alkyl, Ci-C3-alkoxy, Ci-C3-haloalkyl, Ci-C3- haloalkoxy or C3-C6-cycloalkyl;R5bis selected from H, halogen, CN, Ci-C3-alkyl, Ci-C3-alkoxy, Ci-C3-haloalkyl, Ci-C3- haloalkoxy or C3-C6-cycloalkyl.3) Compounds of formula I according to any one of the preceding claims, wherein n is 2 and R3is in positions 3 and 5.250083974) Compounds of formula I according to any one of the preceding claims, wherein R2is CH3.5) Compounds of formula I according to any one of the preceding claims, wherein R1is H, Ci- C6-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-Ci-C4-alkyl, Ci-C4-alkyl-C3-C6-cycloalkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkyl-Ci-C6-alkoxy, wherein the alkyl, alkoxy, alkenyl, alkynyl and cycloalkyl moieties are unsubstituted or substituted with one or more halogen, preferably wherein R1is H or CH3.6) Compounds of formula I according to any one of the preceding claims, wherein at least one R3group in (R3)nis selected from R3dif HET is HB, whereineach R3dis independently C4-C6-alkyl, C4-C6-alkoxy, C3-C6-cycloalkyl, C2-C6-alkenyl, C2- C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, 3- to 6-membered heterocyclyl, wherein the alkyl, alkenyl, alkynyl, alkoxy, heterocyclyl and cycloalkyl moieties are unsubstituted or substituted with one or more R11; Ci-C3alkyl, Ci-C3alkoxy, Ci-C3- alkylthio, wherein alkyl and alkoxy are substituted with one or more R11b; OR10a, NR12R13, C(O)NR12bR13b, C(S)NR12bR13b, C(O)OR10b, C(O)R14, OS(O)2-R14, S(O)I.2-R14, - N=S(O)R12aR13a;R10bis Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C4- cycloalkyl-Ci-C2-alkyl, C3-C4-halocycloalkyl-Ci-C2-alkyl, C(O)-Ci-C4-alkyl, C(O)-Ci-C4- haloalkyl, C(0)-C3-C4-cycloalkyl, C(0)-C3-C4-halocycloalkyl, SOm-Ci-C4-alkyl, SOm-Ci-C4- haloalkyl, SOm-C3-C6-cycloalkyl, or phenyl which is unsubstituted or substituted with one or more Ra;R11bis CN, NO2, NR12R13, C(O)NH2, C(S)NH2, C(O)OH, OR10, Si(CH3)3; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the heterocyclyl, hetaryl and phenyl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN;R12b, R13bare independently from each other Ci-C4-alkyl, Ci-C4-alkoxy, Ci-C4-haloalkoxy, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C(O)-Ci-C4-alkyl, C(0)-Ci-C4-haloalkyl, C(O)-C3-C4- cycloalkyl, C(0)-C3-C4-halocycloalkyl, C(O)NH-Ci-C4-alkyl, C(0)NH-Ci-C4-haloalkyl, C(O)N(Ci-C4-alkyl)-Ci-C4-alkyl, C(0)N(Ci-C4-haloalkyl)-Ci-C4-alkyl, C(O)N(CI-C4- haloalkyl)-Ci-C4-haloalkyl, C(0)NH-Ci-C4-alkoxy, C(0)NH-Ci-C4-haloalkoxy, C(O)NH-Ci- C4-alkoxy-Ci-C4-alkyl, C(0)NH-Ci-C4-alkoxy-Ci-C4-haloalkyl; C(O)NH-phenyl, C(O)NH-3- 6-membered heterocyclyl or 5- or 6-membered hetaryl, C(O)NH-Ci-C4-alkyl-phenyl, C(O)NH-Ci-C4-alkyl-3-6-membered heterocyclyl or 5- or 6-membered hetaryl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN; S(0)m-Ci-C4-haloalkyl, S(0)m-C3-C4-cycloalkyl, S(O)m- C3-C4-halocycloalkyl; 3- to 6-membered heterocyclyl, 5- or 6-membered hetaryl, or phenyl, wherein the phenyl, heterocyclyl and hetaryl moieties are unsubstituted or substituted with one or more halogen, Ci-C3-haloalkyl, and / or CN; or R12band R13btogether with the atom(s) to which they are bound, form a 3-, 4-, 5-, 6-, or 7-membered saturated, partially or fully unsaturated heterocycle, which heterocycle may additionally contain 1 or 2 heteroatoms or heteroatom-containing groups selected from N, O, S(O)m, and optionally one or two groups C(O) as ring members, and wherein the heterocycle moiety is unsubstituted or substituted with one or more Ra.250083987) The compound of claim 6, wherein each R3dis independently C3-C6-cycloalkyl, C2-C6- alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, wherein alkyl, alkenyl, alkynyl, and cycloalkyl are unsubstituted or substituted independently with one or more halogen, CN, NO2, or OH; Ci-C6-alkyl substituted with one or more CN, NO2, or OH; NR12R13, C(O)NR12bR13b, C(O)OR10b, C(O)R14, OS(O)2-R14and S(O)m-R14wherein m is 1 or 2.8) The compound of claim 6 or 7, wherein each R3dis independently NH2, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-Ci-C6-alkyl, Ci-C6-alkyl-C3-C6-cycloalkyl, wherein alkyl, alkenyl, alkynyl, and cycloalkyl are unsubstituted or substituted with one or more halogen or CN; Ci-C6-alkyl substituted with one or more CN; OS(O)2-Ci-C4-alkyl, OS(0)2-Ci-C4-haloalkyl; S(O)m-Ci-C4-alkyl, S(0)m-Ci-C4-haloalkyl, wherein m is 1 or 2. 9) Compounds of formula I according to any one of the preceding claims, wherein R6and R7are independently from each other H, halogen, CN, C(O)NH2, CH3, CH2CH3, CH(CH3)2or CH2CH2CH3; or R6and R7together with the carbon atom to which they are bound, form a cyclopropyl ring.10) Compounds of formula I according to any one of the preceding claims, which consist mainly of the isomer I.S.11) Compounds according to any one of the preceding claims, wherein the compounds are of formulaand the N-oxides, stereoisomers, and agriculturally or veterinarily acceptable salts thereof.12) The compound of any one of the preceding claims, wherein the compound is selected from the group consisting of:25008399250083100wherein R5cis H;or wherein the compound is selected from the group consisting of:250083101wherein Y is N-cPr;and the N-oxides, stereoisomers, and agriculturally or veterinarily acceptable salts thereof.13) An agricultural or veterinary composition comprising at least one compound according toany one of claims 1 to 12 and / or at least one agriculturally or veterinarily acceptable salt thereof, and at least one inert liquid and / or solid agriculturally or veterinarily acceptable carrier.14) An agricultural composition for combating animal pests comprising at least one compound as defined in any of claims 1 to 12 and at least one inert liquid and / or solid acceptable carrier and, if desired, at least one surfactant.15) A method for combating or controlling invertebrate pests, which method comprises contacting said pest or its food supply, habitat or breeding grounds with a pesticidally effective amount of at least one compound as defined in any one of claims 1 to 12.16) A method for protecting growing plants from attack or infestation by invertebrate pests, which method comprises contacting a plant, or soil or water in which the plant is growing, with a pesticidally effective amount of at least one compound as defined in any of claims 1 to 12.17) Seed comprising a compound as defined in any of claims 1 to 12, or the enantiomers, diastereomers or salts thereof, in an amount of from 0.1 g to 10 kg per 100 kg of seed.18) A method for treating or protecting an animal from infestation or infection by invertebrate pests which comprises bringing the animal in contact with a pesticidally effective amount of at least one compound of the formula I as defined in any of claims 1 to 12, a stereoisomer thereof and / or at least one veterinarily acceptable salt thereof.

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