Fused heterocyclic compound containing sulfur-containing substituent, preparation method, insecticide composition, and use

Abstract

The present invention relates to the field of insecticides, and in particular to a fused heterocyclic compound represented by general formula I and containing a sulfur-containing substituent, a stereoisomer thereof, an agriculturally acceptable salt thereof, a preparation method therefor, an insecticide composition, and a use of the compound in the field of pest control. R1, R2, R3, R4, R5, R6, W, and Q are as defined in the present text.

Description

Fused heterocyclic compounds with sulfur substituents, preparation methods, insecticide compositions and uses Technical Field

[0001] This invention relates to the field of insecticides, and more specifically to a fused heterocyclic compound containing a sulfur substituent as shown in formula (I), its stereoisomers, its agriculturally acceptable salts, its preparation method, insecticidal compositions, and their use in the control of pests. Background Technology

[0002] Currently, the pesticide market is showing a trend towards diversification and greening. On the one hand, with the continuous development of agricultural production, the demand for pesticides is constantly increasing, leading to increasingly fierce market competition. On the other hand, with the improvement of environmental awareness and consumers' focus on food safety, green, environmentally friendly, and highly effective pesticides have become the new favorites in the market. Therefore, developing highly effective, low-toxicity, and environmentally friendly pesticides has become an important direction.

[0003] Patents WO2016 / 129684A1, WO2017 / 125340A1, JP2018 / 177759A, JP2020 / 111539A, WO2019 / 124548A1, JP2020 / 105188A, JP2020 / 79324A, and WO2019 / 038195A1 disclose certain fused bicyclic heterocyclic derivatives with insecticidal properties. For example, Nissan Chemical Industries, Ltd. specifically discloses the following compound CK1 in WO2016129684A1 (compound 2-1-002a in the patent specification); Bayer Crop Science specifically discloses the following compound CK2 in WO2017125340A1 (compounds 1-5 in the patent specification).

[0004] However, currently known sulfur-substituent fused heterocyclic compounds are still not ideal in terms of insecticidal activity, toxicity, and management of resistant pests. Therefore, there is an urgent market need for novel insecticides that not only possess good insecticidal activity and safety but also effectively control resistant pests. The prior art does not cover novel sulfur-substituent fused heterocyclic compounds as shown in this invention, their stereoisomers, their agriculturally acceptable salts, their preparation methods, insecticidal compositions, or their uses in the field of pest control. Summary of the Invention

[0005] This invention provides a fused heterocyclic compound with sulfur substituents as shown in general formula (I), its stereoisomers, and its agriculturally acceptable salts:

[0006] In the formula, W is selected from O or NH;

[0007] In the formula, R1-R5 are each independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, mercapto, pentafluorothio, cyano, amino, or nitro.

[0008] In the formula, R6 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl or C3-C6 halocycloalkyl;

[0009] In the formula, Q represents Q1-Q 32 Group shown:

[0010] In the formula R 10 It is selected from C1-C4 haloalkyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl or C1-C4 haloalkoxy.

[0011] Preferred,

[0012] In the formula, W is selected from O or NH;

[0013] In the formula, R1-R5 are each independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl or cyano;

[0014] In the formula, R6 is a C1-C4 alkyl group;

[0015] In the formula, Q represents expressions Q1-Q7 and Q 10 -Q 13 and Q 15 Group shown:

[0016] In the formula R 10 It is selected from C1-C4 haloalkyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl or C1-C4 haloalkylsulfonyl.

[0017] More preferably,

[0018] In the formula, W is selected from O or NH;

[0019] In the formula, R1-R5 are each independently selected from hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, or cyano;

[0020] In the formula, R6 is methyl or ethyl;

[0021] In the formula, Q represents expressions Q1-Q7 and Q 15 Group shown:

[0022] In the formula R 10 It is selected from trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl.

[0023] Preferably, a fused heterocyclic compound with sulfur substituents as shown in general formula (I), its stereoisomers, and its agriculturally acceptable salts:

[0024] In the formula, W is selected from O or NH;

[0025] In the formula, R1-R5 are each independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, mercapto, pentafluorothio, cyano, amino, or nitro.

[0026] In the formula, R6 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl or C3-C6 halocycloalkyl;

[0027] In the formula, Q represents the expression Q 33 The shown groups;

[0028] In the formula R 10 It is selected from C1-C4 haloalkyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl or C1-C4 haloalkoxy.

[0029] Preferably, the compound of formula (I), its stereoisomers, and its agriculturally acceptable salts are:

[0030] In the formula, W is selected from O or NH;

[0031] In the formula, R1-R5 are each independently selected from hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, or cyano;

[0032] In the formula, R6 is methyl or ethyl;

[0033] In the formula R 10 It is selected from trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl.

[0034] Preferably, a composition comprises at least one of the compound of formula (I), its stereoisomers or salts thereof, wherein the compound of formula (I) is the active component, and the composition contains the active component in a weight percentage of 0.1-99.9%.

[0035] Preferably, a method for controlling pests involves applying the compound of formula (I), its stereoisomers, agriculturally acceptable salts thereof, or the composition thereof to the pest or its growth environment.

[0036] Preferably, the use of the compound of formula (I), its stereoisomers, agriculturally acceptable salts thereof, or the composition thereof in the control of pests.

[0037] The compounds of formula (I) of the present invention can be described by the specific compounds listed in Table 1, but the present invention is not limited to these compounds.

[0038] Table 1

[0039] This article also provides a method for preparing a fused heterocyclic compound (I) containing a sulfur substituent, its stereoisomers, and its agriculturally acceptable salts, the method comprising the following steps:

[0040] Option 1: When Q in the formula is selected from Q1-Q5 or Q 15 When the compound is defined by the general formula (I-a1) or (I-a2), its preparation method includes the following steps:

[0041] (1) The compound of general formula (Va) undergoes a condensation reaction with an aromatic amine to generate the compound of general formula (IV-a);

[0042] (2) The compound of general formula (IV-a) undergoes a cyclization reaction to generate the compound of general formula (III-a);

[0043] (3) The compound of general formula (III-a) reacts with alkyl thiols or alkyl thiols to produce the compound of general formula (II-a);

[0044] (4) The compound of general formula (II-a) is converted into the compound of general formula (I-a1) by oxidation reaction; or into the compound of general formula (I-a2) by oxidation and amination reaction.

[0045] In the formula, X1 is chlorine, bromine or iodine, and M is selected from hydrogen, potassium or sodium.

[0046] Option 2: When Q is selected from Q6-Q7 in the formula, the compound can be defined as general formula (I-b1) or (I-b2), and its preparation method includes the following steps:

[0047] (1) The compound of general formula (Va) undergoes the Curtius rearrangement reaction to produce the compound of general formula (Vb);

[0048] (2) The compound of general formula (Vb) undergoes a substitution reaction with different substituted aromatic benzyl halides and loses the Boc protecting group to generate the compound of general formula (IV-b);

[0049] (3) The compound of general formula (IV-b) undergoes hydrolysis and cyclization to generate the compound of general formula (III-b);

[0050] (4) The compound of general formula (III-b) reacts with alkyl thiols or alkyl thiols to produce the compound of general formula (II-b);

[0051] (5) The compound of general formula (II-b) is converted into the compound of general formula (I-b1) by oxidation reaction; or into the compound of general formula (I-b2) by oxidation and amination reaction.

[0052] In the formula, X1 and X2 are chlorine, bromine, or iodine, M is selected from hydrogen, potassium, or sodium, and R 11 Selected from C1-C4 alkyl groups.

[0053] Option 3: When formula W is selected from O or NH, the compound can be defined as general formula (I-c1) or (I-c2), and its preparation method includes the following steps:

[0054] (1) The compound of general formula (Va) undergoes a condensation reaction with an aromatic amine to produce the compound of general formula (IV-c);

[0055] (2) The compound represented by general formula (IV-c) undergoes a cyclization reaction to generate the compound represented by general formula (III-c);

[0056] (3) The compound of general formula (III-c) reacts with alkyl thiols or alkyl thiols to produce the compound of general formula (II-c);

[0057] (4) The compound shown in general formula (II-c) is converted into the compound shown in general formula (I-c1) by oxidation reaction; or into the compound shown in general formula (I-c2) by oxidation and amination reaction.

[0058] In the formula, X1 is chlorine, bromine or iodine, and M is selected from hydrogen, potassium or sodium.

[0059] In the definitions of compounds of formula (I) given above, the terms used in the compilation are generally defined as follows:

[0060] Alkyl groups refer to saturated straight-chain or branched hydrocarbon groups having a specified number of carbon atoms in each case, such as C1-C6-alkyl groups, including methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, etc. 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.

[0061] Halogen-substituted alkyl groups (halogenated alkyl groups) refer to the following straight-chain or branched alkyl groups in which some or all of the hydrogen atoms can be replaced by halogen atoms, such as C1-C2 haloalkyl groups, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, and 1,1,1-trifluoropropyl-2-yl.

[0062] Alkoxy refers to a saturated straight-chain or branched alkoxy group having a specified number of carbon atoms in each case, such as C1-C6-alkoxy groups, including methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1,1-dimethylpropoxy, and 1,2-dimethylpropoxy. The compounds are: 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy, and 1-ethyl-2-methylpropoxy. Halogen-substituted alkoxy groups refer to the following straight-chain or branched alkoxy groups having a specified number of carbon atoms in each case: wherein in these groups, some or all of the hydrogen atoms may be replaced by halogen atoms as described above, such as C1-C2 haloalkoxy groups, such as chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy, and 1,1,1-trifluoroprop-2-oxy.

[0063] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. If the term is used with a group, then "halogen" or "halogen atom" refers to a fluorine, chlorine, bromine, or iodine atom.

[0064] The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, wherein the cycloalkyl ring contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, more preferably 3 to 8 carbon atoms, and most preferably 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cyclohepttrienyl, cyclooctyl, etc.; polycyclic cycloalkyl groups include spirocyclic, fused-ring, and bridged-ring cycloalkyl groups, preferably cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, and cycloheptyl.

[0065] The present invention also provides a composition, characterized in that it comprises at least one of the compound of formula (I) described above, its stereoisomer or salt thereof, wherein the compound of formula (I) is used as the active component, and the weight percentage of the active component in the composition is 0.1-99.9%.

[0066] Compositional forms include, for example, liquid irrigation, drip irrigation, and spraying. Optionally, the application form contains other pesticides and / or adjuvants that enhance action, such as penetrants, like vegetable oils (e.g., rapeseed oil, sunflower oil), mineral oils (e.g., paraffin oil), alkyl esters of vegetable fatty acids (e.g., rapeseed oil methyl ester or soybean oil methyl ester), or alkanol alkoxylates; and / or spreaders, such as alkylsiloxanes and / or salts (e.g., organic or inorganic ammonium salts or phosphonium salts, such as ammonium sulfate or diammonium hydrogen phosphate); and / or retention promoters, such as dioctyl sulfosuccinate or hydroxypropyl guar gum polymers; and / or wetting agents, such as glycerin; and / or fertilizers, such as ammonium-, potassium-, or phosphorus-containing fertilizers.

[0067] Conventional formulations include: water-soluble liquid formulations (SL), emulsion concentrates (EC), emulsions (EW), suspension concentrates (SC, SE, FS, OD), water-dispersible granules (WG), granules (GR), and capsule concentrates (CS); these formulations and other possible formulation types are documented by Crop Life International and described in the following documents: Pesticide Standards, FAO / WHO Manual on the Development and Use of Pesticide Standards, and FAO Document on Plant Production and Protection-173 (prepared by the FAO / WHO Joint Conference on Pesticide Standards, 2004, ISBN: 9251048576). In addition to one or more compounds of formula (I), the formulations may optionally contain other agrochemically active compounds.

[0068] Preferred formulations or application forms include at least one adjuvant, such as a extender, solvent, spontaneous growth promoter, carrier, emulsifier, dispersant, antifreeze, biocide, thickener; and / or other adjuvants, such as adjuvants. In the context of this invention, an adjuvant is a component that enhances the biological efficacy of the formulation, while the component itself does not possess any biological efficacy. Examples of adjuvants are agents that promote retention, spreading, adhesion to leaf surfaces, or penetration.

[0069] These formulations are prepared in a known manner, for example by mixing a compound of formula (I) with an adjuvant such as a extender, a solvent, and / or a solid carrier and / or other adjuvants such as a surfactant. The formulation is prepared in a suitable facility or before or during application.

[0070] The adjuvants used may be substances suitable for imparting specific properties (e.g., certain physical, technical, and / or biological characteristics) to formulations of compounds of formula (I) or application forms prepared from such formulations (e.g., ready-to-use pesticides, such as spray liquids or seed dressing products). Furthermore, compounds of formula (I) may be mixed with other active compounds or chemical pheromones such as attractants and / or bird repellents and / or plant activators and / or growth regulators and / or fertilizers. Similarly, compounds of formula (I) can be used to improve plant performance, such as the growth, yield, and quality of harvested crops.

[0071] The present invention also provides a method for controlling pests, characterized in that the compound of formula (I) described above, its stereoisomers and agriculturally acceptable salts thereof, or the composition described above are applied to the pest or its growth environment.

[0072] Harmful organisms include agricultural or non-agricultural invertebrate pests, such as:

[0073] Eggs, larvae, and adults of lepidopteran pests, such as armyworms, caterpillars, inchworms, and bollworms (e.g., corn borer (Sesamia inferens Walker), corn borer (Sesamia nonagrioides Lefebvre), southern gray-winged armyworm (Spodoptera eridania Cramer), fall armyworm (Spodoptera frugiperda JESmith), beet armyworm (Spodoptera exigua Hübner), cotton leafworm (Spodoptera littoralis Boisduval), yellow-banded armyworm (Spodoptera ornithogalli Guenée), cutworm (Agrotis ipsilon Hufnagel), velvet bean hairy caterpillar (Anticarsia gemmatalis Hübner), green-fruit winter armyworm (Lithophane antennata Walker), cabbage armyworm (Barathra brassicae Linnaeus), soybean armyworm (Pseudoplusia includens)). Walker), cabbage silver-striped noctuid moth (Trichoplusiani Hübner), tobacco aphid (Heliothis virescens Fabricius);Pyralidae (Moth Borers) include borers, sheath moths, web-forming caterpillars, pine cone shoot borers, cabbage caterpillars, and leaf-carving insects (such as the European corn borer (Ostrinia nubilalis Hübner), the navel orange borer (Amyelois transitella Walker), the corn root web-forming caterpillar (Crambus caliginosellus Clemens), and meadow moths (Pyralidae: Pyralinae subfamily) such as the rice leaf cutter borer (Herpetogramma licarsisalis Walker), the sugarcane two-spotted borer (Chilo infuscatellus Snellen), the tomato borer (Neoleucinodes elegantalis Guenée), the rice leaf roller (Cnaphalocrocis medinalis), the grape leaf roller (Desmiafuneralis Hübner), the melon borer (Diaphania nitidalis Stoll), and the cabbage core grub (Hellualahydralis). Guenée, Scirpophaga incertulas Walker, Scirpophaga infuscatellus Snellen, Scirpophaga innotata Walker, Scirpophaga nivella Fabricius, Chilo polychrysus Meyrick, Chilo suppressalis Walker, Crocidolomia binotalis English;Leafrollers, bud borers, seed borers, and fruit borers (e.g., apple leafroller (Cydia pomonella Linnaeus), grape berry moth (Endopiza viteana Clemens), pear fruit moth (Grapholita molesta Busck), apple heterocarpa (Cryptophlebia leucotreta Meyrick), citrus longhorn beetle (Ecdytolopha aurantiana Lima), red-banded leafroller (Argyrotaenia velutinana Walker), rose-banded leafroller (Choristoneura rosaceana Harris), apple light brown leafroller (Epiphyas postvittana Walker), privet leafroller (Eupoecilia ambiguella Hübner), apple terminal bud leafroller (Pandemis pyrusana Kearfott), omnivorous leafroller (Platynota stultana Walsingham), grape brown leafroller (Pandemis cerasana)) Hübner, apple leafroller (Pandemis heparana Denis & Schiffermüller); and many other economically important lepidopteran insects (such as diamondback moth (Plutella xylostella Linnaeus), bollworm (Pectinophora gossypiella Saunders), gypsy moth (Lymantria dispar Linnaeus), peach fruit moth (Carposina niponensis Walsingham), peach striped wheat moth (Anarsia lineatella Zeller), potato tuber moth (Phthorimaea operculella Zeller), striped leaf miner (Lithocolletis blancardella Fabricius), apple golden leafminer (Lithocolletis ringoniella Matsumura), rice leaf roller (Lerodea eufala Edwards), and spiral leafminer (Leucoptera scitella Zeller)).The eggs, pupae, and adults of cockroaches, including cockroaches of the families Blattodea and Blattidae (such as the Oriental cockroach (Blatta orientalis Linnaeus), the Asian cockroach (Blatella asahinai Mizukubo), the German cockroach (Blattella germanica Linnaeus), the brown-banded cockroach (Supella longipalpa Fabricius), the American cockroach (Periplaneta americana Linnaeus), the brown cockroach (Periplaneta brunnea Burmeister), the Madeira cockroach (Leucophaea maderae Fabricius), the black-breasted cockroach (Periplaneta fuliginosa Service), the Australian cockroach (Periplaneta australasiae Fabr.), the lobster cockroach (Nauphoeta cinerea Olivier), and the pale-tailed cockroach (Symploce pallens). Stephens); Coleoptera pests, including their eggs, larvae, and adults that feed on leaves, fruits, roots, seeds, and vesicle tissue, such as weevils of the families Anthonomus, Fabaceae, and Cestidae (e.g., cottonseed weevil (Anthonomus grandis Boheman), rice water weevil (Lissorhoptrus oryzophilus Kuschel), grain weevil (Sitophilus granarius Linnaeus), rice weevil (Sitophilus oryzae Linnaeus)), Kentucky bluegrass weevil (Listronotus maculicollis Dietz), forage weevil (Sphenophorus parvulus Gyllenhal), hunter weevil (Sphenophorus venatus vestitus), and Denver weevil (Sphenophorus cicatristriatus). Fahraeus; Leaf beetles, including flea beetles, melon beetles, root worms, leaf beetles, potato beetles, and leaf miners (e.g., Colorado potato beetle (Leptinotarsa ​​decemlineata Say) and western corn root worm (Diabrotica virgifera LeConte));Scarab beetles and other beetles (e.g., Japanese scarab beetle (Popillia japonica Newman), Oriental scarab beetle (Anomala orientalis waterhouse, Exomala orientalis (waterhouse) Baraud), Northern round-headed rhinoceros beetle (Cyclocephala borealis Arrow), Southern round-headed rhinoceros beetle (Cyclocephala immaculata Olivier or C. lurida Bland), dung beetles and grubs (genus *Cyclocephala*), black turf beetle (Ataenius spretulus Haldeman), green scarab beetle (Cotinis nitida Linnaeus), chestnut velvet scarab beetle (Maladera castanea Arrow), June-gill scarab (genus *Phyllophaga*), and European scarab beetle (Rhizotrogus majalis Razoumowsky)); dermatophytes (family Dermestidae); nematodes (family Click beetles); bark beetles (family Bark beetles); and face weevils (family Tenebrionidae).

[0074] In addition, agricultural and non-agricultural pests include: eggs, adults, and larvae of Dermaptera pests, including earwigs (e.g., the European ball earwig (Forficula auricularia Linnaeus) and the black earwig (Chelisoches morioFabricius)); eggs, larvae, adults, and pupae of Hemiptera and Homoptera pests, such as mirid bugs (Miridae), cicadas (Cicadae), leafhoppers (e.g., Empoasca), and bedbugs (e.g., Cimex lectularius). Linnaeus, planthoppers of the families Cicadaidae and Cnidiidae, treehoppers of the family Cicadaidae, psyllids of the family Psyllididae, whiteflies of the family Aphididae, aphids of the family Aphididae, root aphids of the family Aphididae, mealybugs of the family Mealybugidae, scale insects of the families Scale Insecta, scale insects of the families Scale Insecta and Scale Insecta, lace bugs of the family Lacebugidae, stink bugs of the family Stink Bugidae, long bugs of the family Long bugidae (e.g., hairy long bug (Blissus leucopterus hirtus Montandon) and southern wheat bug (Blissus insularis Barber)) and other long bugs of the family Long bugidae, grasshoppers of the family Flea-like bugs, cucurbit grasshoppers of the family Marginaceae, and red bugs and cotton bollworms of the family Red bugidae.

[0075] Agricultural and non-agricultural pests also include the eggs, larvae, pupae, and adults of mites, such as spider mites and red spider mites (e.g., apple red spider mite (Panonychus ulmi Koch), two-spotted spider mite (Tetranychus urticae Koch), and McDaniel spider mite (Tetranychus mcdanieli McGregor)); grape mites (e.g., citrus red spider mite (Brevipalpus lewisi McGregor)); rust ticks and bud ticks (Gallidae) and other leaf-feeding mites, dust mites (Gallidae), demodicid mites (Demodex mites), and grain mites (Gallidae); and hard ticks (Ixodes scapularis Say, Ixodes holocyclus Neumann, Dermacentor variabilis Say, and Amblyomma americanum). Linnaeus and ticks commonly known as soft ticks (e.g., relapsing thermos tick (Ornithodoros turicata), common chicken tick (Argasradiatus)); itch mites and scabies mites of the families Ophiopogonidae, Pyratidae, and Sarcoptera; eggs, adults, and larvae of orthoptera pests, including grasshoppers, locusts, and crickets (e.g., migratory grasshoppers (e.g. Melanoplus sanguinipes Fabricius, M. differentialis Thomas)), American grasshoppers (e.g., Schistocerca americana Drury), desert locusts (Schistocerca gregaria Forskal), migratory locusts (Locusta migratoria Linnaeus), shrub locusts (Zonocerus), house crickets (Acheta domesticus Linnaeus), mole crickets (e.g., yellowish mole cricket (Scapteriscus vicinus Scudder) and southern mole crickets (Scapteriscus borellii)). Giglio-Tos));Eggs, adults, and larvae of Diptera pests include leaf miners (e.g., *Liriomyza*, such as the vegetable leafminer *Liriomyzasativae* Blanchard), midges, fruit flies (*Tephritidae*), eye flies (e.g., *Oscinella frit* Linnaeus), maggots, houseflies (e.g., *Musca domestica* Linnaeus), summer toilet flies (e.g., *Fannia canicularis* Linnaeus, *F. femoralis* Stein), stable flies (e.g., *Stomoxys calcitrans* Linnaeus), autumn houseflies, hornflies, blowflies (e.g., *Chrysomya*, *Phormia*) and other housefly pests, horseflies (e.g., *Tabanus*), skin flies (e.g., *Gastrophilus*, *Oestrus*), cow flies (e.g., *Hypoderma*), deer flies (e.g., *Chrysops*), and sheep ticks (e.g., *Melophagus ovinus*). Linnaeus and other short-horned insects, mosquitoes (e.g., Aedes, Anopheles, Culex), black flies (e.g., Prosimulium, Simulium), midges, sandflies, fungus gnats, and other long-horned insects; eggs, adults, and larvae of Thysanura pests, including onion thrips (Thrips tabaci Lindeman), flower thrips (Frankliniella), and other leaf-feeding thrips; Hymenoptera insect pests, including formic ants, including Florida carpenter ants (Camponotus floridanus Buckley), red carpenter ants (Camponotus ferrugineus Fabricius), black carpenter ants (Camponotus pennsylvanicus De Geer), white-legged ants (Technomyrmex albipes fr. Smith), big-headed ants (Pheidole), and black-headed sour ants (Tapinoma melanocephalum Fabricius);Pharaoh ants (Monomorium pharaonis Linnaeus), small fire ants (Wasmannia auropunctata Roger), fire ants (Solenopsis geminata Fabricius), invasive red fire ants (Solenopsis invicta Buren), Argentine ants (Iridomyrmex humilis Mayr), crazy ants (Paratrechina longicornis Latreille), pavement ants (Tetramorium caespitum Linnaeus), corn hairy ants (Lasius alienus Forster), and stink ants (Tapinoma sessile Say). Other hymenopteran pests include bees (including carpenter bees), giant hornets, wasps, and sawflies (genus *Neodiprion*; *Cephus*); isoptera insect pests include termites of the families Macrotermes (e.g., *Macrotermes*, *Odontotermes obesus* Rambur), wood termites (e.g., *Cryptotermes*), and rhinoceros termites (e.g., *Reticulitermes*, *Coptotermes*, *Heterotermes tenuis* Hagen), North American subterranean termites (*Reticulitermes flavipes* Kollar), western subterranean termites (*Reticulitermes hesperus* Banks), yellow subterranean termites (*Coptotermes formosanus* Shiraki), western Indian drywood termites (*Incisitermes immigrans* Snyder), sand termites (*Cryptotermes brevis* Walker), drywood termites (*Incisitermes snyderi* Light), and southern subterranean termites (*Reticulitermes virginicus*). Banks, western drywood termites (Incisitermes minor Hagen), tree termites such as the Elephant genus, and other economically important termites;Thysanura insect pests, such as silver beetles (Lepisma saccharina Linnaeus) and domestic silverfish (Thermobia domestica Packard). Other arthropod pests involved include: spiders such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and centipedes such as the house centipede (Scutigera coleoptrata Linnaeus).

[0076] Examples of invertebrate pests that infest stored grains include the large grain beetle (Prostephanus truncatus), the grain beetle (Rhyzopertha dominica), the rice weevil (Stiophilus oryzae), the maize weevil (Stiophilus zeamais), the four-striped bean weevil (Callosobruchus maculatus), the red flour beetle (Tribolium castaneum), the grain weevil (Stiophilus granarius), the Indian flour borer (Plodia interpunctella), the Mediterranean flour borer (Ephestia kuhniella), and the rusty red flat flour beetle (Cryptolestis ferrugineus).

[0077] Examples of Lepidoptera pests include *Alabama argillacea* Hübner (clothes moth), *Archips argyrospila* Walker (fruit tree leafroller), *A. rosana* Linnaeus (European leafroller), and other species of the genus *Chilo suppressalis* Walker (rice stem borer), *Cnaphalocrosis medinalis* Guenée (rice leafroller), *Crambus caliginosellus* Clemens (corn root webbing caterpillar), *Crambus teterrellus* Zincken (bluegrass leaf borer), *Cydia pomonella* Linnaeus (apple leafroller), *Earias insulana* Boisduval (diamond borer), *Earias vittella* Fabricius (green bollworm), *Helicoverpa armigera* Hübner (American bollworm), *Helicoverpa zea* Boddie (cotton bollworm), *Heliothis virescens* Fabricius (tobacco aphid), and *Herpetogramma licarsisalis*. Walker (grass moth), Lobesia botrana Denis & Schiffermüller (grape berry moth), Pectinophora gossypiella Saunders (cotton bollworm), Phyllocnistis citrella Stainton (citrus leafminer), Pieris brassicae Linnaeus (cabbage white butterfly), Pieris rapae Linnaeus (cabbage white moth), Plutellaxylostella Linnaeus (diamond moth), Spodoptera exigua Hübner (beet armyworm), Spodoptera litura Fabricius (beet armyworm, tea silkworm), Spodoptera frugiperda JESmith (fall armyworm), Trichoplusia ni Hübner (cabbage silver-striped armyworm), and Tuta absoluta Meyrick (tomato leafminer).

[0078] Examples of Hemiptera pests include: *Acyrthosiphon pisum Harris* (bean aphid), *Aphis craccivora Koch* (black bean aphid), *Aphis fabae Scopoli* (broad bean aphid), *Aphis gossypii Glover* (cotton aphid, melon aphid), *Aphis pomi De Geer* (apple aphid), *Aphis spiraecola Patch* (leaf-rolling aphid), *Aulacorthum solani Kaltenbach* (eggplant aphid), *Chaetosiphon fragaefolii Cockerell* (strawberry aphid), *Diuraphis noxia Kurdjumov / Mordvilko* (Russian wheat aphid), *Dysaphis plantaginea Paaserini* (rose aphid), *Eriosoma lanigerum Hausmann* (apple aphid), *Hyalopterus pruni Geoffroy* (peach aphid), *Lipaphis erysimi Kaltenbach* (radish aphid), *Metopolophium dirrhodum Walker* (wheat aphid), and *Macrosiphum*. *Euphorbiae Thomas* (potato aphid), *Myzus persicae Sulzer* (peach aphid), *Nasonovia ribisnigri* Mosley (lettuce aphid), *Pemphigus* (root aphid and gall aphid), *Rhopalosiphum maidis Fitch* (corn leaf aphid), *Rhopalosiphumpadi Linnaeus* (grain tube aphid), *Schizaphis graminum Rondani* (wheat two-forked aphid), *Sitobionavenae Fabricius* (wheat long-tube aphid), *Therioaphis maculata Buckton* (alfalfa spotted aphid), *Toxoptera aurantii Boyer de Fonscolombe* (orange two-forked aphid), and *Toxoptera citricida Kirkaldy* (brown orange aphid); *Adelges* (ball aphid); *Phylloxera devastatrix Pergande* (American pecan root phylloxera);Bemisiatabaci Gennadius (sweet potato whitefly), Bemisia argentifolii Bellows & Perring (silver leaf whitefly), Dialeurodes citri Ashmead (citrus whitefly), and Trialeurodes vaporariorum Westwood (greenhouse whitefly); Empoasca fabae Harris (potato leafhopper), Laodelphax striatellus Fallen (gray leafhopper), Macroleses quadrilineatus Forbes (two-spotted leafhopper), Nephotettix cinticeps Uhler (green leafhopper), Nephotettix nigropictus Stal (black-tailed leafhopper), Nilaparvatalugens Stal (brown leafhopper), Peregrinus maidis Ashmead (corn planthopper), Sogatella furcifera Horvath (white-backed leafhopper), Sogatodes orizicola Muir (rice planthopper), Typhlocyba pomaria McAtee (apple leafhopper), *Erythroneoura* (grape leafhopper); *Magicidada septendecim* Linnaeus (periodic leafhopper); *Icerya purchasi* Maskell (cotyledonous scale insect), *Quadraspidiotus perniciosus* Comstock (Saint Joseph's leafhopper); *Planococcus citri Risso* (citrus mealybug); *Pseudococcus* (other mealybug complex); *Cacopsylla pyricola* Foerster (pear psyllid), *Trioza diospyri* Ashmead (persimmon psyllid).

[0079] Members of the order Hemiptera are active and include: *Acrosternum hilare* Say (rice green bug), *Anasa tristis* De Geer (pumpkin bug), *Blissus leucopterus* Say (sorghum long bug), *Cimex lectularius* Linnaeus (bed bug), *Corythuca gossypii* Fabricius (cotton web bug), *Cyrtopeltis modesta* Distant (tomato bug), *Dysdercus suturellus* Herrich-Schaffer (cotton weevil), *Euchistus servus* Say (tea-winged bug), *Euchistus variolarius* Palisot de Beauvois (single-spotted bug), *Graptosthetus* (long bug complex), *Halymorpha halys* Stal (tea-winged bug), *Leptoglossus corculus* Say (pine nut bug of the family Lygus lineolaris), and *Lygus lineolaris* Palisot de Beauvois (pasture mirid bug), Nezara viridula Linnaeus (southern rice green bug), Oebalus pugnax Fabricius (rice brown bug), Oncopeltus fasciatus Dallas (large milkweed bug), Pseudatomoscelis seriatus Reuter (cotton mirid bug). Other insect orders that can be controlled by the compounds of this invention include Thysanura (e.g., Frankliniella occidentalis Pergande (western flower thrips), Scirthothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips), and Thrips tabaci Lindeman (onion thrips); and Coleoptera (e.g., Leptinotarsa ​​decemlineata Say (Colorado potato beetle), Epilacachna varivestis Mulsant (Mexican bean ladybug), and nematodes of the genera *Clickworm*, *Clickworm*, or *Clickworm*).

[0080] In some classification systems, Hemiptera is classified as a suborder within Hemiptera.

[0081] The growth environment of pests includes plants and plant parts, all of which can be treated according to the methods provided in this invention. In this document, "plant" should be understood to mean all plants and plant populations, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants), such as cereals (wheat, rice, rye, barley, rye, oats), corn, soybeans, potatoes, sugar beets, sugarcane, tomatoes, bell peppers, cucumbers, melons, carrots, watermelons, onions, lettuce, spinach, leeks, legumes, cabbage (such as head cabbage) and other vegetable varieties, cotton, tobacco, rapeseed, and fruit plants (fruits include apples, pears, citrus fruits, and grapes). Crop plants can be plants that can be obtained through conventional breeding and optimization methods or through biotechnological methods and genetic engineering methods or a combination of these methods, including transgenic plants and plant cultivars that may or may not be protected by plant breeders' rights. "Plant" should be understood to mean all developmental stages, such as seeds, seedlings, and early (immature) plants up to and including mature plants. Plant parts should be understood to refer to all above-ground and underground parts and organs of a plant, such as buds, leaves, flowers, and roots. Examples given include leaves, needles, stems, branches, flowers, fruiting bodies, fruits, and seeds, as well as roots, tubers, and rhizomes. Plant parts also include harvested plants or harvested plant parts, as well as materials for asexual and sexual reproduction, such as cuttings, tubers, rhizomes, slips, and seeds.

[0082] The present invention also provides the use of a compound of formula (I) as described above, its stereoisomers, and agriculturally acceptable salts thereof, or the composition described above, in the control of pests.

[0083] Conventional treatment methods utilize the compound of formula (I) to directly treat plants and plant parts, or to treat them by acting on their environment, habitat, or storage space. These conventional treatment methods include, for example, soaking, spraying, atomizing, irrigating, evaporating, dusting, misting, sowing, foaming, smearing, spreading, injection, watering (soaking), drip irrigation, and, in the case of propagation material, especially seeds, dry seed treatment as powder, wet seed treatment as solution, slurry treatment as water-soluble powder, treatment by crusting, or coating with one or more layers. The compound of formula (I) can also be applied using ultra-low volume methods or injected into the soil in its application form or the compound of formula (I) itself.

[0084] The present invention also relates to the use of the compound of formula (I) for treating seeds to protect the seeds and the resulting plants from animal pests.

[0085] Furthermore, the use of the compound of formula (I) to treat seeds can promote the germination and emergence of the treated seeds.

[0086] Furthermore, compounds of formula (I) can also be used specifically for transgenic seeds.

[0087] Furthermore, the compound of formula (I) can be used in combination with signal technology compositions or compounds to enable better colonization and / or optimization of nitrogen fixation through symbionts (e.g., rhizobia, mycorrhizae, and / or endophytic bacteria or fungi).

[0088] Compound (I) is suitable for protecting the seeds of any plant variety used in agriculture, greenhouses, forestry, or horticulture. Specifically, it is suitable for the protection of the seeds of the following plants: cereals (e.g., wheat, barley, rye, millet, and oats), corn, cotton, soybeans, rice, potatoes, sunflowers, coffee, tobacco, canola, rapeseed, sugar beets (e.g., sugar beets and forage beets), peanuts, vegetables (e.g., tomatoes, cucumbers, beans, cruciferous vegetables, onions, and lettuce), fruiting plants, turfgrass, and ornamental plants. Of particular importance are the treatment of the seeds of cereals (wheat, barley, rye, oats), corn, soybeans, cotton, canola, rapeseed, vegetables, and rice.

[0089] The compound of formula (I) provided by this invention can also be applied to the field of animal health.

[0090] In the field of animal health, specifically veterinary medicine, compounds of formula (I) are active against animal parasites, particularly ectoparasites or endoparasites. The term "endoparasites" specifically includes worms and protozoa, such as coccidia. Ectoparasites are generally and preferably arthropods, especially insects or mites.

[0091] In the field of veterinary medicine, compounds of formula (I) with favorable warm-blooded animal toxicity are suitable for the prevention and control of parasites in animal breeding and reproduction of livestock, breeding animals, zoo animals, laboratory animals, experimental animals, and domestic animals. They are active against all or specific developmental stages of parasites.

[0092] Agricultural livestock include, for example, mammals such as sheep, goats, horses, donkeys, camels, buffalo, rabbits, reindeer, deer, and especially cattle and pigs; or poultry such as turkeys, ducks, geese, and especially chickens; or fish or crustaceans in aquaculture; or, depending on the circumstances, insects such as bees.

[0093] Domestic animals include mammals such as hamsters, guinea pigs, rats, mice, chinchillas, ferrets, especially dogs, cats, caged birds; reptiles, amphibians, or ornamental fish.

[0094] According to one specific embodiment, the compound of formula (I) is applied to a mammal.

[0095] According to another specific embodiment, the compound of formula (I) is applied to poultry, i.e., caged birds or, in particular, domestic poultry.

[0096] By using compounds of formula (I) to control animal parasites, the aim is to reduce or prevent disease, mortality, and performance decline (in the case of meat, milk, wool, hides, eggs, honey, etc.), thereby making animal husbandry more economical and simpler, and achieving better animal health.

[0097] In the field of animal health, the term "control" or "controlling" as used herein refers to compound (I) effectively reducing the incidence of various parasites in animals infected with parasites to a harmless level. More specifically, "control" as used herein refers to compound (I) effectively killing various parasites, inhibiting their growth, or suppressing their proliferation.

[0098] Therefore, one embodiment of the present invention relates to a compound of formula (I) used as a medicament.

[0099] Another aspect involves compounds of formula (I) used as endoparasitic agents for antibodies.

[0100] Another specific aspect involves compounds of formula (I) used as an anti-worm agent, and more particularly as a nematicide, flatworm agent, acanthocephalan agent or lingulate agent.

[0101] Another specific aspect involves compounds of formula (I) used as antigenic agents for animals.

[0102] On the other hand, it relates to compounds of formula (I) used as antiparasitic agents, especially arthropod scavengers, and even more particularly insecticides or acaricides.

[0103] Other aspects of the invention are veterinary formulations comprising an effective amount of at least one compound of formula (I) and at least one of the following substances: pharmaceutically acceptable excipients (e.g., solid or liquid diluents), pharmaceutically acceptable adjuvants (e.g., surfactants), particularly pharmaceutically acceptable excipients and / or pharmaceutically acceptable adjuvants commonly used in veterinary formulations.

[0104] A related aspect of the present invention is a method for preparing a veterinary formulation as described herein, comprising the steps of: mixing at least one compound of formula (I) with a pharmaceutically acceptable excipient and / or adjuvant, particularly with a pharmaceutically acceptable excipient and / or adjuvant commonly used in veterinary formulations.

[0105] Another specific aspect of the present invention is a veterinary preparation and its preparation method, wherein the veterinary preparation is selected from preparations that kill ectoparasites and preparations that kill endoparasites, and more particularly from the above-mentioned anthelmintic, antiprotozoan, and arthropod preparations, and even more particularly from preparations that kill nematodes, flatworms, acanthocephalans, lingula, insects, and mites.

[0106] On the other hand, it relates to a method for treating parasitic infections, particularly those caused by parasites selected from the ectoparasites and endoparasites mentioned herein, by administering an effective amount of a compound of formula (I) to animals requiring treatment, especially non-human animals.

[0107] On the other hand, it relates to a method of treating parasitic infections, particularly those caused by parasites selected from ectoparasites and endoparasites mentioned herein, by administering veterinary preparations as defined herein to animals in need of treatment, especially non-human animals.

[0108] On the other hand, the use of compounds of formula (I) in the treatment of parasitic infections in animals, especially non-human animals, particularly infections caused by parasites selected from the ectoparasites and endoparasites mentioned herein.

[0109] In the context of the animal health or veterinary field of this invention, the term "treatment" includes preventative, remedial, or therapeutic treatment.

[0110] In one specific embodiment, at least one compound of formula (I) for use in the veterinary field is provided in combination with other active ingredients, particularly with mixtures of endoparasite-killing agents and ectoparasite-killing agents.

[0111] In the field of animal health, a "mixture" refers not only to a product containing two (or more) different active ingredients formulated as a combined preparation and administered together, but also to a product containing individual formulations of each active compound. Therefore, when administering two or more active compounds, all active compounds may be formulated as a combined preparation or as individual formulations; alternatively, they may be in a mixture form, where some active compounds are formulated together and others are formulated individually. Individual formulations may be administered individually or sequentially with respect to the active compounds.

[0112] The compound of formula (I) provided by this invention can also be applied to the field of vector control.

[0113] The vectors are arthropods, especially insects or arachnids, which can transmit pathogens such as viruses, worms, single-celled organisms, and bacteria from a host (plant, animal, human, etc.) to a host. Pathogens can be transmitted to the host mechanically (e.g., trachoma transmitted by non-stinging flies) or by injection (e.g., malaria parasites transmitted by mosquitoes).

[0114] The compound of formula (I) provided by this invention can also be used in the field of hygiene for the prevention and control of animal pests.

[0115] Compounds of Formula (I) are suitable for controlling animal pests in the sanitation field. In particular, the present invention can be used for the protection of indoor, sanitation, and stored products, especially for controlling insects, arachnids, ticks, and mites encountered in enclosed spaces such as dwellings, factory lobbies, offices, vehicle cabins, and livestock farms. For controlling animal pests, compounds of Formula (I) can be used alone or in combination with other active compounds and / or adjuvants. They are preferably used in indoor insecticide products. Compounds of Formula (I) are effective against susceptible and resistant species, as well as their entire developmental stages.

[0116] These pests include, for example, the following: Arachnida, Scorpiones, Araneae, and Opiliones; Chilopoda and Diplopoda; Insecta, Blattodea, Coleoptera, Dermaptera, Diptera, Heteroptera, Hymenoptera, Isoptera, Lepidoptera, Psittacoidea, Saltatoria, Orthoptera, Siphonaptera, and Silverfish; Malacostraca, Isopoda.

[0117] They are used in, for example, aerosols, unpressurized spray products such as pump-operated sprays and atomized sprays, automatic atomization systems, sprays, foams, gels, evaporation products with evaporating tablets made of cellulose or plastic, liquid evaporators, gel and film evaporators, propeller-driven evaporators, energy-free or passive evaporation systems, moth traps, moth traps and moth traps, as granules or powders, for use in spread baits or bait stations.

[0118] Based on the properties of the substituents defined above, compounds of formula (I) are acidic and can form salts, and, if suitable, can form internal salts, or form adducts with inorganic or organic bases or with metal ions. If compounds of formula (I) contain a hydroxyl group, a carboxyl group, or other groups that cause acidity, these compounds can react with bases to form salts. Suitable bases are, for example, hydroxides, carbonates, and bicarbonates of alkali metals and alkaline earth metals, particularly sodium, potassium, magnesium, and calcium; and ammonia; primary, secondary, and tertiary amines having C1-C4-alkyl groups; monoalkylolamines, dialkylolamines, and trialkylolamines of C1-C4-alkanols; choline and choline chloride; and organic amines such as trialkylamines, morpholine, piperidine, or pyridine. These salts are compounds in which the acidic hydrogen is replaced by an agriculturally suitable cation, for example, metal salts, especially alkali metal salts or alkaline earth metal salts, particularly sodium and potassium salts; or ammonium salts, organic amine salts, or quaternary ammonium salts, such as salts of cations having the formula [NRR′R″R″′]+ (where R to R″′ each independently represents an organic group, particularly alkyl, aryl, aralkyl, or alkylaryl). Also suitable are alkyl sulfonium salts and alkyl oxide sulfonium salts, such as C1-C4-trialkyl sulfonium salts and C1-C4-trialkyl oxide sulfonium salts.

[0119] Compounds of formula (I) can form salts by adding a suitable inorganic or organic acid to a basic group; the inorganic acid being, for example, HCl, HBr, H₂SO₄, H₃PO₄, or HNO₃, the organic acid being, for example, a carboxylic acid (e.g., formic acid, acetic acid, propionic acid, oxalic acid, lactic acid, or salicylic acid) or a sulfonic acid (e.g., p-toluenesulfonic acid), and the basic group being, for example, an amino, alkylamino, dialkylamino, piperidinyl, morpholinyl, or pyridinyl group. In this case, the salts contain the conjugate base of the acid as an anion.

[0120] Suitable substituents (e.g., sulfonic acids or carboxylic acids) in deprotonated form can form internal salts with groups that are themselves protonable (e.g., amino groups).

[0121] In this invention, if there is a conflict between the naming of compounds and their structural formulas, the structural formula shall prevail, unless the structural formula is obviously incorrect. Detailed Implementation

[0122] The following examples are for illustrative purposes only and should not be construed as limiting the invention in any way. The scope of protection of this invention is defined by the claims. Simple substitutions or modifications made to this invention by those skilled in the art are all within the scope of the technical solutions protected by this invention.

[0123] Several methods for preparing the compounds of the present invention are described in detail in the following schemes and examples. The raw materials can be commercially available or prepared by methods known in the literature or as detailed in the description. Those skilled in the art will understand that other synthetic routes can also be used to synthesize the compounds of the present invention. Although specific raw materials and conditions in the synthetic routes have been described below, they can be easily replaced with other similar raw materials and conditions. Such variations or modifications to the preparation methods of the present invention, such as various isomers of the compounds, are all included within the scope of the present invention. Furthermore, the preparation methods described below can be further modified according to the disclosure of the present invention using conventional chemical methods well known to those skilled in the art. For example, protecting appropriate groups during the reaction process, etc.

[0124] The following method examples are provided to further illustrate the preparation methods of the present invention. The specific substances, types, and conditions used are intended to further explain the invention and are not intended to limit its reasonable scope. The reagents used in the synthetic compounds described below are either commercially available or can be easily prepared by those skilled in the art.

[0125] The analytical instruments described in the examples are as follows:

[0126] I. High Performance Liquid Chromatography (hereinafter referred to as HPLC): Using an Agilent Technologies 1260 Infinity II instrument.

[0127] Column: Agilent Eclipse Plus C 18 3.5μm, 4.6*100mm

[0128] Mobile phase: A: water + 0.1% phosphoric acid; B: acetonitrile; Temperature: 30℃

[0129] Gradient: 10%B to 95%B over 15 min; 95%B over 3 min

[0130] Flow rate: 1 mL / min

[0131] II. Ultra-high performance liquid chromatography-tandem mass spectrometry (hereinafter referred to as LC-MS): Using a Waters, ACQUITY H-Class UPLC-SQ Detector 2 instrument.

[0132] Column: ACQUITY BEH C 18 1.7μm, 2.1*50mm Column

[0133] Mobile phase: A: Water + 0.2% formic acid; B: Acetonitrile; Temperature: 30℃

[0134] Gradient: 10%B to 95%B over 5 minutes; 95%B over 1 minute

[0135] Flow rate: 0.5 mL / min

[0136] MS method: ESI positive, negative, quality range (m / z): 100-800

[0137] III. Gas Chromatography-Tandem Mass Spectrometry (hereinafter referred to as GC-MS): Using Agilent Technologies, 7890B GC System-5977A MSD equipment.

[0138] Column: Agilent Technologies, HP-5MS UI 0.25μm, 30m*0.250mm

[0139] Injector temperature: 250℃

[0140] Column flow rate: Helium 1 mL / min

[0141] Method: Hold at 40℃ for 2 min, increase temperature to 280℃ at 20℃ / min, hold at 280℃ for 5 min, total time 19 min.

[0142] MSD transmission line temperature: 280℃

[0143] EI ion source temperature: 230℃, MS quadrupole temperature: 150℃, scan range: 30.00-400.00

[0144] In addition, the proton nuclear magnetic resonance spectra described below (hereinafter referred to as...) 1 The chemical shift values ​​of H-NMR were measured at 400 MHz (Bruker, AVANCE III HD 400M) in deuterated chloroform (CDCl3) using Me4Si (tetramethylsilane) as the reference material. When measured in deuterated dimethyl sulfoxide, the chemical shift values ​​are shown as "(DMSO-d6)" in the data. It should be noted that... 1 The symbols in the chemical shift values ​​of H-NMR have the following meanings:

[0145] s: singlet, d: doublet, dd: doublett, dt: doublettuplet, td: triplettuplet, ddd: doublettuplet, t: triplet, q: quartet, sep: septet, m: multiplet, brs: broad singlet. Furthermore, in cases where two or more stereoisomers are present, the chemical shift values ​​for the resolvable signal are marked with "and".

[0146] Examples of representative compounds are given below. The synthesis methods of other compounds are similar and will not be described in detail here.

[0147] Example 1-1: Preparation of 2-cyclopropyl-5-(ethylsulfonyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (compound 1-1)

[0148] Step 1: Preparation of ethyl 2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylate

[0149] At room temperature, 1.0 g (7.08 mmol) of 2-amino-5-cyclopropyl-1,3,4-thiadiazole and 10 mL of N,N-dimethylformamide were added to a 100 mL single-necked flask, followed by 2.76 g (14.16 mol) of 3-bromo-2-oxopropionate. The mixture was heated to 90 °C and stirred for 1 hour. After the reaction was complete, the reaction solution was poured into water (50 mL), and then extracted with ethyl acetate (20 mL × 3). The solution was washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain crude ethyl 2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylic acid (brown oil, 1.0 g). This was used directly in the next step.

[0150] Step 2: Preparation of ethyl 5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylate

[0151] At room temperature, 1.0 g (4.22 mmol) of 2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylic acid ethyl ester and 10 mL of N,N-dimethylformamide were added to a 100 mL single-necked flask. N-bromosuccinimide (0.75 g, 4.22 mmol) was added in portions. The mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was poured into water (50 mL), extracted three times with ethyl acetate (20 mL × 3), the organic phases were combined, washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, and purified by silica gel column chromatography to obtain 0.80 g (white solid).

[0152] 1H NMR (400MHz, CDCl3) δ4.43(q,J=7.1Hz,2H),2.35–2.26(m,1H),1.43(t,J=7.1Hz,3H),1.36–1.29(m,2H),1.27–1.19(m,2H).

[0153] Step 3: Preparation of 5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylic acid

[0154] At room temperature, ethyl 5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylic acid (0.80 g, 2.53 mmol), tetrahydrofuran (6 mL), and water (2 mL) were added to a 50 mL single-necked flask. Lithium hydroxide monohydrate (160 mg, 3.80 mmol) was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, tetrahydrofuran was removed under reduced pressure, and water (10 mL) was added to the residue. The pH was then adjusted to 1 with 36% hydrochloric acid, and a white solid precipitated. The solid was filtered and dried to obtain 5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylic acid (white solid, 0.65 g).

[0155] 1 H NMR (400MHz, DMSO-d6) δ2.59–2.53(m,1H),1.32–1.25(m,2H),1.16–1.10(m,2H).

[0156] Step 4: Preparation of 5-bromo-2-cyclopropyl-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-6-carboxamide

[0157] At room temperature, 5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylic acid (200 mg, 0.69 mmol), tetrahydrofuran (5 mL), 2-chloro-1-methylpyridine iodide (176.2 mg, 0.69 mmol), and triethylamine (96.8 μL, 0.69 mmol) were added to a 50 mL single-necked flask. N2 was added in portions at room temperature. 25-Methyl-5-(trifluoromethyl)pyridine-2,3-diamine (131.1 mg, 0.69 mmol) was heated to 50 °C and stirred for 3 h. After the reaction was completed, the reaction solution was poured into water (50 mL) and extracted with ethyl acetate (20 mL × 3). The organic phases were combined and washed successively with water and saturated brine. The mixture was dried over anhydrous sodium sulfate and the solvent was removed by vacuum evaporation to obtain crude 5-bromo-2-cyclopropyl-N-(2-(methylamino)-5-(trifluoromethyl)pyridine-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-6-carboxamide (brown oil, 350 mg).

[0158] Step 5: Preparation of 5-bromo-2-cyclopropyl-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole

[0159] At room temperature, 350 mg (0.76 mmol) of 5-bromo-2-cyclopropyl-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-6-carboxamide and acetic acid (5 mL) were added to a 50 mL single-necked flask and heated to 110 °C under reflux with stirring overnight. After the reaction was completed, the reaction solution was poured into water (50 mL) and extracted with ethyl acetate (20 mL × 3). The organic phase was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation. The solution was purified by silica gel column chromatography to obtain 5-bromo-2-cyclopropyl-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (white solid, 218 mg).

[0160] 1 H NMR (400MHz, CDCl3) δ8.67(s,1H),8.35(s,1H),4.26(s,3H),2.40–2.30(m,1H),1.39–1.28(m,4H).

[0161] Step Six: Preparation of 2-cyclopropyl-5-(ethio)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole

[0162] At room temperature, 5-bromo-2-cyclopropyl-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (218 mg, 0.49 mmol), sodium ethanethiol (64 mg, 0.74 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene (56 mg, 0.098 mmol), tris(dibenzylacetone)dipalladium(0) (45 mg, 0.049 mmol) and anhydrous 1 4-Dioxane (4 mL) was added to a 15 mL pressure-resistant bottle. After purging with nitrogen for 15 minutes, diisopropylethylamine (126.6 mg, 0.98 mmol) was added, and the bottle was immediately sealed. The mixture was heated to 110 °C and stirred overnight. After the reaction was complete, the insoluble matter was filtered off, and the solvent was removed by vacuum distillation to obtain 2-cyclopropyl-5-(ethylthio)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (brown oil, 280 mg).

[0163] 1 H NMR (400MHz, CDCl3) δ8.67(s,1H),8.35(s,1H),4.20(s,3H),3.12(q,J=7.4Hz,2H),2.42–2.29(m,1H),1.36–1.31(m,2H),1.27–1.22(m,5H).

[0164] Step 7: Preparation of 2-cyclopropyl-5-(ethylsulfonyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (Compound 1-1)

[0165] 2-Cyclopropyl-5-(ethylthio)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (187 mg, 0.49 mmol) and dichloromethane (5 mL) were added to a 100 mL single-necked flask. 75% m-chloroperoxybenzoic acid (225.5 mg, 0.98 mmol) was added in portions. The mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was evaporated under reduced pressure. The product was purified by reverse phase to obtain 2-cyclopropyl-5-(ethylsulfonyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (white solid, 150 mg).

[0166] 1H NMR (400MHz, CDCl3) δ8.73(s,1H),8.34(s,1H),4.05(s,3H),3.79(q,J=14.5,7.1Hz,2H),2.54–2.40(m,1H),1.57–1.36(m,5H),1.26(s,2H).

[0167] Examples 1-7: Preparation of 5-(ethylsulfonyl)-2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (compounds 1-7)

[0168] Step 1: Preparation of 5-((1R,2S)-2-fluorocyclopropyl)-1,3,4-thiadiazole-2-amine

[0169] At room temperature, (1S,2S)-2-fluorocyclopropane-1-carboxylic acid (300 mg, 2.88 mmol), aminothiourea (262 mg, 2.88 mmol), and phosphorus oxychloride (2 mL) were added to a 50 mL single-necked flask, heated to 75 °C, and stirred for 1 h. After the reaction was complete, the reaction mixture was slowly added dropwise to a saturated sodium bicarbonate aqueous solution to adjust the pH to 8. The mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum to obtain crude 5-((1R,2S)-2-fluorocyclopropyl)-1,3,4-thiadiazole-2-amine (260 mg). The crude product was used directly in the next step.

[0170] Step 2: Preparation of 3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine

[0171] At room temperature, N 2 20 g of methyl-5-(trifluoromethyl)pyridine-2,3-diamine (0.105 mmol) and 60 mL of 88% formic acid were added to a 250 mL single-bottle container. The reaction mixture was heated to 120 °C and stirred overnight. After the reaction was completed, the solvent was removed by vacuum distillation, and the solution was purified by silica gel column chromatography to obtain 18 g of 3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0172] Step 3: Preparation of 1-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)ethyl-1-one

[0173] To a 500 mL three-necked flask, 3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5- b]pyridine (18 g, 0.09 mol) and tetrahydrofuran (100 mL) were added at room temperature. After the reaction vessel was replaced with nitrogen, it was cooled to -78 °C and stirred. To this, lithium diisopropylamide (45 mL, 2.0 M tetrahydrofuran solution) was added dropwise, and stirring was continued at -78 °C for 30 min. Subsequently, N-methoxy-N-methylacetamide (10.3 g, 0.1 mol) was added dropwise, and stirring was continued at -78 °C for 1 h, and then the temperature was raised to room temperature. After the completion of the reaction, the reaction solution was poured into saturated aqueous ammonium chloride solution, and extracted with ethyl acetate (3 x 100 mL). The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to give 1-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)ethan-1-one (18 g).

[0174] Step Four: Preparation of 2-bromo-1-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2- yl)ethan-1-one

[0175] To a 500 mL three-necked flask, 3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5- b]pyridine (18 g, 0.09 mol) and tetrahydrofuran (100 mL) were added at room temperature. After the reaction vessel was replaced with nitrogen, it was cooled to -78 °C and stirred. To this, lithium diisopropylamide (45 mL, 2.0 M tetrahydrofuran solution) was added dropwise, and stirring was continued at -78 °C for 30 min. Subsequently, N-methoxy-N-methylacetamide (10.3 g, 0.1 mol) was addeddropwise, and stirring was continued at -78 °C for 1 h, and then thetemperature was raised to room temperature. After the completion of the reaction, the reaction solution was poured into a saturated aqueous ammonium chloride solution, and extracted with dichloromethane. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulphate. The organic phase was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to obtain 2-bromo-1-(3-methyl-6-(trifluoromethyl)-

[0176] Step Five: Preparation of 2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole

[0177] At room temperature, 2-bromo-1-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)ethyl-1-one (250 mg, 0.78 mmol), 5-((1R,2S)-2-fluorocyclopropyl)-1,3,4-thiadiazole-2-amine (185 mg, 1.17 mmol), p-toluenesulfonic acid monohydrate (15 mg, 0.078 mmol), and toluene (10 mL) were added to a 50 mL single-necked flask, and the reaction mixture was heated to 110 °C and stirred overnight. After the reaction was completed, the reaction mixture was concentrated to obtain crude 2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole, which was directly used in the next step.

[0178] Step Six: Preparation of 5-bromo-2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole

[0179] At room temperature, 300 mg of 2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole and 4 mL of N,N-dimethylformamide were added to a 50 mL single-necked flask, followed by 166 mg (0.94 mmol) of N-bromosuccinimide. The mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was poured into water, and the mixture was extracted with ethyl acetate (3 × 50 mL). The resulting organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The residue obtained by vacuum concentration of the filtrate was purified by silica gel column chromatography to obtain 5-bromo-2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (200 mg).

[0180] Step 7: Preparation of 5-(eththio)-2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole

[0181] The following solutions were prepared: 5-bromo-2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (200 mg, 0.44 mmol), sodium ethanethiol (55 mg, 0.65 mmol), 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (51 mg, 0.088 mmol), tris(dibenzylacetone)dipalladium(0) (40 mg, 0.044 mmol), and anhydrous 1,4-dioxane (4 mL). Add to a 15 mL pressure-resistant bottle, purge with nitrogen for 15 minutes, add diisopropylethylamine (84 mg, 0.65 mmol), seal immediately, heat to 110 °C and stir overnight. After the reaction is complete, add ethyl acetate (10 mL) to the reaction solution and filter out the insoluble matter. Concentrate the filtrate under reduced pressure and purify by reverse-phase column chromatography to obtain 5-(ethylthio)-2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (white solid, 150 mg).

[0182] Step 8: Preparation of 5-(ethylsulfonyl)-2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (compounds 1-7)

[0183] At room temperature, 150 mg (0.34 mmol) of 5-(ethylthio)-2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole and 5 mL of dichloromethane were added to a 25 mL single-necked flask, followed by the addition of 75% m-chloroperoxybenzoic acid (16... 5 mg (0.71 mmol), stirred at room temperature for 2 hours. After the reaction was completed, the mixture was directly evaporated under reduced pressure and purified by reversed-phase column chromatography to obtain 5-(ethylsulfonyl)-2-((1R,2S)-2-fluorocyclopropyl)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (white solid, 137 mg).

[0184] 1H NMR (400MHz, CDCl3) δ8.73(s,1H),8.34(s,1H),5.16(td,J=5.8,3.5Hz,0.5H),5.00(td,J=5.7,3.8Hz, 0.5H), 4.07 (s, 3H), 3.83 (q, J = 7.4Hz, 2H), 2.77–2.66 (m, 1H), 1.81–1.64 (m, 2H), 1.48 (t, J = 7.4Hz, 3H).

[0185] Examples 1-45: Preparation of 2-(2-cyclopropyl-5-(ethylsulfonyl)imidazol[2,1-b][1,3,4]thiadiazol-6-yl)-5-((trifluoromethyl)sulfinyl)benzo[d]oxazole (compounds 1-45)

[0186] Step 1: Preparation of 5-bromo-2-cyclopropyl-N-(2-hydroxy-5-(trifluoromethyl)sulfinyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazole-6-carboxamide

[0187] At room temperature, 5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylic acid (287 mg, 1.00 mmol), dichloromethane (3 mL), and N,N-dimethylformamide (7.3 mg, 0.1 mmol), along with oxalyl chloride (382 mg, 3.00 mmol), were added dropwise. The mixture was stirred at room temperature for 1 hour. After the reaction was completed, the crude acyl chloride (brown oily substance, 320 mg) was obtained by direct evaporation under reduced pressure.

[0188] At room temperature, 2-amino-4-((trifluoromethyl)sulfinyl)phenol (337 mg, 1.50 mmol), dichloromethane (3 mL), and triethylamine (304 mg, 3.00 mmol) were added to a 100 mL single-necked flask, and a dichloromethane solution of the above acyl chloride was added dropwise. The mixture was stirred at room temperature for 1 hour. After the reaction was completed, the mixture was directly evaporated to dryness under reduced pressure and purified by reversed-phase column chromatography to obtain 5-bromo-2-cyclopropyl-N-(2-hydroxy-5-(trifluoromethyl)sulfinyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazole-6-carboxamide (white solid, 307 mg).

[0189] Step 2: Preparation of 2-(5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-5-((trifluoromethyl)sulfinyl)benzo[d]oxazole

[0190] At room temperature, 5-bromo-2-cyclopropyl-N-(2-hydroxy-5-(trifluoromethyl)sulfinyl)phenyl)imidazo[2,1-b][1,3,4]thiadiazole-6-carboxamide (307 mg, 0.62 mmol), anhydrous 1,4-dioxane (3 mL), and triphenylphosphine (328 mg, 1.25 mmol) were added to a 100 mL single-necked flask. Under nitrogen protection, bis-2-methoxyethyl An anhydrous 1,4-dioxane (2 mL) solution of azodicarboxylic acid ester (293 mg, 1.25 mmol) was heated to 110 °C and stirred for 1 hour. After the reaction was completed, the solution was directly evaporated under reduced pressure and purified by reversed-phase column chromatography to obtain 2-(5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-5-((trifluoromethyl)sulfinyl)benzo[d]oxazole (white solid, 216 mg).

[0191] Step Six: Preparation of 2-(2-cyclopropyl-5-(ethylsulfonyl)imidazol[2,1-b][1,3,4]thiadiazol-6-yl)-5-((trifluoromethyl)sulfinyl)benzo[d]oxazole (compounds 1-45)

[0192] At room temperature, 2-(5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-5-((trifluoromethyl)sulfinyl)benzo[d]oxazole (200 mg, 0.42 mmol), cuprous iodide (8.0 mg, 0.042 mmol), sodium ethanesulfinate (487 mg, 4.2 mmol), and N,N-dimethylformamide (5 mL) were added to a 100 mL single-necked flask, and the reaction system was heated to 75 °C and reacted overnight. After the reaction was completed, the reaction was cooled to room temperature, and water and ethyl acetate were added for extraction (20 mL × 3). The concentrated organic phase was purified by silica gel column chromatography to obtain 5-cyclopropyl-2-(2-cyclopropyl-5-(ethylsulfonyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-methyl-6-(trifluoromethyl)-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one.

[0193] 1 H NMR (400MHz, CDCl3) δ8.31 (s, 1H), 7.88 (d, J = 2.1Hz, 2H), 3.84 (q, J = 7.4Hz, 2H), 2.53–2.41(m,1H),1.50(t,J=7.4Hz,3H),1.45–1.38(m,2H),1.29–1.25(m,2H).

[0194] Examples 1-78: Preparation of 6-(2-cyclopropyl-5-(ethylsulfonyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (compound 1-78)

[0195] Step 1: (5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl) tert-butyl carbamate

[0196] At room temperature, 5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylic acid (460 mg, 1.60 mmol), triethylamine (259 mg, 2.56 mmol), and tert-butanol (5 mL) were added to a 50 mL single-necked flask. Diphenyl azide phosphate (704 mg, 2.56 mmol) was slowly added dropwise with stirring at 90 °C. After the addition was complete, the reaction mixture was kept at 90 °C for 1 hour. After the reaction was complete, the reaction solution was poured into water, extracted three times with ethyl acetate, and the organic phases were combined. The mixture was washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation. The purified product was obtained by silica gel column chromatography to yield tert-butyl 5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-yl)carbamate.

[0197] Step 2: Preparation of ethyl 2-(((5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)(tert-butoxycarbonyl)amino)methyl)-5-(trifluoromethyl)nicotinic acid

[0198] At room temperature, tert-butyl (5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)carbamate (400 mg, 1.12 mmol), cesium carbonate (478 mg, 1.46 mmol), and acetonitrile (10 mL) were added to a 50 mL single-necked flask, followed by ethyl 2-(bromomethyl)-5-(trifluoromethyl)nicotinate (350 mg, 1.12 mmol). The mixture was heated to 50 °C and stirred for 1 hour. After the reaction was complete, the reaction solution was poured into water and extracted three times with ethyl acetate. The organic phases were combined, washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain ethyl 2-(((5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)(tert-butyloxycarbonyl)amino)methyl)-5-(trifluoromethyl)nicotinate, which was used directly in the next step.

[0199] Step 3: Preparation of ethyl 2-(((5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)amino)methyl)-5-(trifluoromethyl)nicotinic acid

[0200] At room temperature, ethyl 2-(((5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)(tert-butoxycarbonyl)amino)methyl)-5-(trifluoromethyl)nicotinic acid (660 mg, 1.12 mmol) and trifluorotoluene (16 mL) were added to a 100 mL single-necked flask, and trifluoroacetic acid (5 mL) was added dropwise. The mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was poured into water, and the mixture was adjusted to neutral with saturated sodium bicarbonate solution. Then, it was extracted three times with ethyl acetate. The organic phases were combined, washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum evaporation to obtain ethyl 2-(((5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)amino)methyl)-5-(trifluoromethyl)nicotinic acid, which was used directly in the next step.

[0201] Step 4: Preparation of 2-(((5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)amino)methyl)-5-(trifluoromethyl)nicotinic acid

[0202] At room temperature, ethyl 2-(((5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)amino)methyl)-5-(trifluoromethyl)nicotinic acid (547 mg, 1.12 mmol), tetrahydrofuran (4 mL), and water (2 mL) were added to a 50 mL single-necked flask, along with lithium hydroxide monohydrate (120 mg, 2.82 mmol). The mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction solution was poured into water, adjusted to acidity with 1 M hydrochloric acid, extracted three times with ethyl acetate, and the organic phases were combined. The mixture was washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation to obtain crude 2-(((5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)amino)methyl)-5-(trifluoromethyl)nicotinic acid, which was used directly in the next step.

[0203] Step 5: Preparation of 6-(5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

[0204] At room temperature, 2-(((2-cyclopropyl-5-(ethylsulfonyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)amino)methyl)-5-(trifluoromethyl)nicotinic acid (516 mg, 1.12 mmol) and pyridine (3 mL) were added to a 50 mL single-necked flask. The mixture was cooled to 0 °C and phosphorus oxychloride (344 mg, 2.24 mmol) was added dropwise. The reaction was maintained at 0 °C for 30 minutes. After the reaction was completed, the reaction solution was poured into water and extracted three times with ethyl acetate. The organic phases were combined, washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was removed by vacuum distillation. The solution was purified by silica gel column chromatography to obtain 6-(5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one.

[0205] Step Six: Preparation of 6-(2-cyclopropyl-5-(ethio)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

[0206] The following ingredients were added: 6-(5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (250 mg, 0.56 mmol), sodium ethanethiol (71 mg, 0.85 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene (65 mg, 0.112 mmol), tris(dibenzylideneacetone)dipalladium(0) (51 mg, 0.056 mmol), and anhydrous 1,4-dioxane. Add (4 mL) to a 15 mL pressure-resistant bottle, purge with nitrogen for 15 minutes, add diisopropylethylamine (106 mg, 0.82 mmol), seal immediately, heat to 110 °C and stir overnight. After the reaction is complete, add ethyl acetate (10 mL) to the reaction solution and filter out the insoluble matter. Concentrate the filtrate under reduced pressure and purify by reverse-phase column chromatography to obtain: 6-(2-cyclopropyl-5-(ethylthio)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one.

[0207] Step 7: Preparation of 6-(2-cyclopropyl-5-(ethylsulfonyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (compound 1-78)

[0208] At room temperature, 144 mg (0.34 mmol) of 6-(2-cyclopropyl-5-(ethylthio)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one and 5 mL of dichloromethane were added to a 25 mL single-necked flask, followed by the addition of 75% m-chloroperoxybenzoic acid (165 mg, 0.71 mmol). The mixture was stirred at room temperature for 2 hours. After the reaction was completed, the mixture was directly evaporated to dryness under reduced pressure and purified by reversed-phase column chromatography to obtain 6-(2-cyclopropyl-5-(ethylsulfonyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one.

[0209] 1 H NMR (400MHz, CDCl3) δ9.09 (s, 1H), 8.46 (s, 1H), 5.11 (s, 2H), 3.66 (q, J = 7.4Hz, 2H ),2.47–2.34(m,1H),1.50(t,J=7.5Hz,3H),1.41–1.32(m,2H),1.24–1.15(m,2H).

[0210] Example 1-111: Preparation of 5-cyclopropyl-2-(2-cyclopropyl-5-(ethylsulfonyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-methyl-6-(trifluoromethyl)-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (compound 1-111)

[0211] Step 1: Preparation of 5-bromo-2-cyclopropyl-N-(1-cyclopropyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-4-yl)imidazo[2,1-b][1,3,4]thiadiazole-6-carboxamide

[0212] At room temperature, 4-amino-1-cyclopropyl-3-(methylamino)-6-(trifluoromethyl)pyridin-2(1H)-one (200 mg, 0.8 mmol) (synthetic method according to patent WO 2017133994A1), 5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-carboxylic acid (193 mg, 0.67 mmol), 2-chloro-1-methylpyridine iodide (204 mg, 0.8 mmol), triethylamine (68 mg, 0.67 mmol) and tetrahydrofuran (5 mL) were added to a 100 mL single-necked flask, and the reaction system was heated to 50 °C and reacted for 1 hour. After the reaction was completed, the reaction was cooled to room temperature, and the solvent was removed by vacuum evaporation to obtain crude 5-bromo-2-cyclopropyl-N-(1-cyclopropyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-4-yl)imidazo[2,1-b][1,3,4]thiadiazole-6-carboxamide.

[0213] Step 2: Preparation of 2-(5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one

[0214] At room temperature, crude 5-bromo-2-cyclopropyl-N-(1-cyclopropyl-3-(methylamino)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-4-yl)imidazo[2,1-b][1,3,4]thiadiazole-6-carboxamide was added to acetic acid (3 mL), and the mixture was heated to 110 °C and reacted overnight. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was purified by silica gel column chromatography to obtain 150 mg of 2-(5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole-6-yl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one.

[0215] Step 3: Preparation of 5-cyclopropyl-2-(2-cyclopropyl-5-(ethylsulfonyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-methyl-6-(trifluoromethyl)-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (compound 1-111)

[0216] At room temperature, 2-(5-bromo-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-5-cyclopropyl-3-methyl-6-(trifluoromethyl)-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (150 mg, 0.3 mmol), cuprous iodide (6 mg, 0.03 mmol), sodium ethanesulfinate (348 mg, 3 mmol), and N,N-dimethylformamide (5 mL) were added to a 100 mL single-necked flask, and the reaction system was heated to 75 °C and reacted overnight. After the reaction was completed, the reaction was cooled to room temperature, and water and ethyl acetate were added for extraction (20 mL × 3). The concentrated organic phase was purified by silica gel column chromatography to give 5-cyclopropyl-2-(2-cyclopropyl-5-(ethylsulfonyl)imidazo[2,1-b][1,3,4]thiadiazol-6-yl)-3-methyl-6-(trifluoromethyl)-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (white solid, 62 mg).

[0217] 1 H NMR(400MHz, CDCl3)δ7.22(s,1H),4.17(s,3H),3.66(q,J=7.4Hz,2H),3.16–3.0 4(m,1H),2.53–2.38(m,1H),1.46–1.36(m,5H),1.31–1.20(m,4H),1.04(s,2H).

[0218] Example 2-1: (2-Cyclopropyl-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)(ethyl)(imino)-λ 6 Preparation of sulfamethoxazole (compound 2-1)

[0219] At room temperature, 2-cyclopropyl-5-(ethylthio)-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole (200 mg, 0.47 mmol) and methanol (5 mL) were added to a 50 mL single-necked flask. Ammonium carbamate (74 mg, 0.94 mmol) and iodophenyl diacetic acid (378 mg, 1.17 mmol) were then added, and the mixture was reacted at room temperature for 2 hours. After the reaction was complete, the reaction solution was concentrated, and the mixture was purified by reverse-phase column chromatography to obtain (2-cyclopropyl-6-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-yl)(ethyl)(imino)-λ 6- Sulfamethoxazole (compound 2-1) (white solid, 160 mg).

[0220] 1 H NMR (400MHz, DMSO-d6) δ8.84(s,1H),8.63(s,1H),5.11(s,1H),3.92(s,3H),3.64–3.45(m,2H),2.65(s,1H),1.49–1.29(m,2H),1.28–1.12(m,5H).

[0221] Compounds 1-1 to 2-121 were prepared in a manner similar to the preparation examples given above.

[0222] The analytical data for the compounds in the examples, CK1 and CK2 are shown in Table 2 below.

[0223] Table 2 shows the analytical data of compound (I) and CK1-CK2.

[0224] The compound of formula (I) of this invention was tested for its control activity against various agricultural pests, including cotton aphids, peach aphids, diamondback moths, rice stem borers, rice leaf rollers, beet armyworms, fall armyworms, cotton bollworms, whiteflies, thrips, brown planthoppers, gray planthoppers, flea beetles, and root-knot nematodes. The tested compound of formula (I) showed superior control efficacy, achieving unexpected technical results compared to existing technologies. Furthermore, the compound of formula (I) of this invention was tested for toxicity against environmental organisms such as bees, large daphnia, zebrafish, earthworms, and algae. The tested compound of formula (I) showed low toxicity.

[0225] Biological Example 1

[0226] Cotton aphid (Aphis gossypii (Glover))

[0227] The activity of cotton aphids was tested using the immersion method. The test unit consisted of a 9cm plastic petri dish containing cucumber leaves that had grown for one month, and was kept moist with absorbent cotton. Healthy adult aphids were inoculated onto the cucumber leaves, and after 24 hours, the adult aphids were removed, and the total number of nymphs on each plate was recorded.

[0228] Prepare the test compound, add an appropriate amount of organic solvent (solvent content not exceeding 2%), and then dilute it to different concentrations with 0.1% Tween-80 aqueous solution. Soak cucumber leaves with 2-day-old aphid nymphs in the solution for 5 seconds, and allow the residual solution to dry completely. Perform three parallel treatments. Place all test units at 25±1℃ and a photoperiod of 16h:8h (L:D) for rearing and observation. Record the number of dead insects 72 hours after treatment and calculate the mortality rate.

[0229] The compounds of formula (I) of the present invention, such as 1-1, 1-2, 1-3, 1-4, 1-5, 1-7, 1-12, 1-23, 1-34, 1-45, 1-56, 1-67, 1-78, 1-89, 1-100, 1-111, and 2-1, at a concentration of 50 ppm, exhibit a mortality rate of ≥90% against cotton aphids 3 days after application.

[0230] Biological Example 2

[0231] Diamondback moth (Plutella xylostella (Linnaeus))

[0232] The activity of diamondback moth was tested by leaf immersion feeding. The test unit consisted of a 9cm plastic petri dish containing three fresh cabbage leaves of equal area.

[0233] Prepare the test compound by adding an appropriate amount of organic solvent (solvent content not exceeding 2%), then dilute it to different concentrations with 0.5% Triton X-100 aqueous solution. Soak fresh cabbage leaves in the solution for 10 seconds, and after the residual solution is fully dried, place them in petri dishes. Then, pick out third-instar larvae of diamondback moths and place them in the petri dishes. Perform three parallel treatments. Place all test units at 25±1℃ and a photoperiod of 16h:8h (L:D) for rearing and observation. Record the number of dead insects 3-5 days after treatment and calculate the mortality rate.

[0234] The compounds of formula (I) of this invention, such as 1-1, 1-2, 1-3, 1-4, 1-5, 1-7, 1-12, 1-23, 1-34, 1-45, 1-56, 1-67, 1-78, 1-89, 1-100, and 2-1, at a concentration of 50 ppm, exhibit a mortality rate of ≥90% against diamondback moth 5 days after application.

[0235] Biological Example 3

[0236] Rice stem borer (Chilo suppressalis (Walker))

[0237] The activity test of rice stem borer was conducted by leaf-immersion feeding method. The test unit was a 9cm plastic petri dish containing 15 6cm long 1-month-old rice stems.

[0238] Prepare the test compound by adding an appropriate amount of organic solvent (solvent content not exceeding 2%), and then dilute it to different concentrations with 0.5% Triton X-100 aqueous solution. Cut rice plants that have grown for one month at the root, clean them, and let them dry. Soak them in the drug solution for 10 seconds, and let the residual drug solution dry completely. Place them in a petri dish, and place filter paper in the petri dish to keep them moist. Then pick out the late second instar larvae of the rice stem borer and put them into the petri dish. Cover them with two layers of black cloth, and then put the petri dish lid on. Place all test units in a 28±1℃ environment with a photoperiod of 16h:8h (L:D) for rearing and observation. Record the number of dead insects 5 days after the drug treatment and calculate the mortality rate.

[0239] The compounds of formula (I) of the present invention, such as 1-1, 1-2, 1-3, 1-4, 1-5, 1-7, 1-12, 1-23, 1-34, 1-45, 1-56, 1-78, 1-89, and 1-111, at a concentration of 50 ppm, exhibit a mortality rate of ≥90% against rice stem borer 5 days after application.

[0240] Biological Example 4

[0241] Rice leaf roller (Cnaphalocrocis medinalis Guenee)

[0242] The activity test of rice leaf roller was carried out by the leaf immersion method. The test unit consisted of a 7cm glass petri dish containing 10 wheat leaves about 5cm in length. Qualitative filter paper was placed at the bottom of the glass petri dish and moistened with water.

[0243] Prepare the test compound by adding an appropriate amount of organic solvent (solvent content not exceeding 2%), then dilute it to different concentrations with 0.1% Tween-80 aqueous solution. Cut wheat leaves to a length of about 5 cm and set aside. Immerse the wheat leaves in the prepared solutions of different concentrations for 20 seconds, then remove them and allow them to dry thoroughly on tissue paper. Transfer the wheat leaves to corresponding petri dishes, and inoculate each petri dish with rice leaf roller larvae. Perform three parallel treatments. Place all test units in an incubator at 28±1℃ with a photoperiod of 16h:8h (L:D) for observation. Record the number of dead insects 48 hours after treatment and calculate the mortality rate.

[0244] The compound of formula (I) of this invention has excellent control efficacy against rice leaf roller.

[0245] Biological Example 5

[0246] Brown planthopper *Nilaparvata lugens* (Stal)

[0247] The activity test of brown planthopper was conducted using the rice seedling immersion method. The test unit consisted of a flat-bottomed glass test tube with a diameter of 3 cm and a height of 20 cm. Five rice seedlings with a height of 15 cm and a growth period of 15 days were placed inside the test tube, and 10 ml of water agar was poured into the bottom of the test tube to keep the roots of the rice seedlings moist.

[0248] Prepare the test compound by adding an appropriate amount of organic solvent (solvent content not exceeding 2%), then dilute it to different concentrations with 0.1% Triton X-100 aqueous solution. Clean and dry 15-day-old rice seedlings, immerse them in the drug for 10 seconds, and allow the residual drug solution to dry thoroughly on tissue paper. Pour agar into a glass flat-bottomed test tube, place the rice seedlings inside, and after the agar solidifies, use a suction device to inoculate brown planthopper nymphs, plugging the tube opening with cotton to prevent nymph escape. Perform three parallel treatments, placing all test units in an incubator at 28±1℃ with a photoperiod of 16h:8h (L:D) for observation. Record the number of dead insects 96 hours after drug application and calculate the mortality rate.

[0249] The compounds of formula (I) of the present invention, such as 1-1, 1-2, 1-3, 1-4, 1-5, 1-7, 1-12, 1-23, 1-34, 1-45, 1-56, 1-67, 1-78, 1-89, 1-111, and 2-1, have a mortality rate of ≥90% against brown planthoppers at a concentration of 50 ppm.

[0250] The insecticidal activity data of the compounds in the examples and CK1-CK2 are shown in Table 3 below.

[0251] Table 3 shows the insecticidal activity data of compound (I) and CK1-CK2.

[0252] NT indicates that no test was performed.

[0253] Biological Example 6

[0254] Zebrafish (Barchydanio rerio)

[0255] Use healthy, disease-free zebrafish of uniform size. Before the experiment, they should be pre-reared under the same environmental conditions as the experimental one for 7-14 days. During the pre-rearing period, feed them 1-2 times a day, provide 12-16 hours of light per day, and clean up feces and food scraps promptly. Stop feeding 24 hours before the experiment.

[0256] The test unit was a 3L beaker, and a static test method was used. Test compounds were prepared by using organic solvents (DMSO, DMF, etc.) to create stock solutions, with a solvent content not exceeding 2%. Five to seven concentration gradients were prepared using tap water aerated for at least 24 hours. Zebrafish were placed in each test unit, with a carrying capacity of at least 500mL. The poisoning symptoms and mortality rate of the fish were observed and recorded continuously for the first 6 hours of the experiment. Subsequently, the poisoning symptoms and mortality rate were observed and recorded at 24h, 48h, 72h, and 96h. The mortality rate was calculated and determined according to LC-125. 50 To determine toxicity level, the ratio of (96h) / (mg ai / L) is used. The toxicity classification standard is as follows: Extremely toxic: LC 50 ≤0.1; Highly toxic: 0.1 < LC 50 ≤1; Poisoning: 1 < LC 50 ≤10; Low toxicity: LC 50 >10.

[0257] The compound of formula (I) of the present invention exhibits low toxicity to fish.

[0258] Biological Example 7

[0259] Large Daphnia magna

[0260] Non-primate daphnia were cultured for at least three generations under laboratory conditions in a parthenogenetic state. The daphnia used in the experiment were healthy daphnia from the same maternal lineage, i.e., those that did not show any signs of stress (such as high mortality, presence of male daphnia and hibernating eggs, delayed primiparity, abnormal body color, etc.).

[0261] The test unit was a 50mL plastic cup. Test compounds were prepared using organic solvents (DMSO, DMF, etc.) to create a stock solution, with a solvent concentration not exceeding 0.1g / L. Five to seven concentration groups were set up. Young Daphnia were introduced into each test unit. All test units were cultured under conditions of a water temperature of 18℃~22℃ and a photoperiod of 16h:8h (L:D). After 48 hours, the mortality rate of large Daphnia was observed and statistically analyzed according to EC... 50 To determine toxicity level, the ratio of (48h) / (mg ai / L) is as follows: Extremely toxic: EC 50 ≤0.1; Highly toxic: 0.1 < EC 50 ≤1; Poisoning: 1 < EC 50 ≤10; Low toxicity: EC 50 >10.

[0262] The compound of formula (I) of the present invention exhibits low toxicity to daphnia.

[0263] Biological Example 8

[0264] Italian worker bee (Apis mellifera L.)

[0265] Using adult Italian worker bees (Apis mellifera L.), test bees should be collected in the early morning; avoid conducting bee tests in early spring and late autumn; bees should not be used for testing within four weeks of receiving antibiotics or anti-mite drugs. Test bees should be healthy individuals of uniform size. Bees used for acute oral toxicity tests should be starved for 2 hours before the test.

[0266] 1. Acute oral toxicity

[0267] Prepare the test compound by using an organic solvent (acetone, etc.) to create a stock solution. Prepare 5-7 gradient concentrations of 50% sucrose solution, and introduce each concentration into the bees. Then, add 200 μL of 50% sucrose aqueous solution containing different concentrations of the compound to the feeder. Set up a blank control group and a solvent control group. Measure the consumption of the drug solution. After the drug solution is consumed, feed the bees with the sucrose solution without the compound. Observe and record the poisoning symptoms and number of deaths in the bees after 48 hours, calculate the mortality rate, and determine the 48-hour LD50. 50 Value and 95% confidence limit.

[0268] 2. Acute contact toxicity of honeybees

[0269] Prepare the test compound by using an organic solvent (acetone, etc.) to prepare a stock solution. Prepare 5-7 concentration gradients using a 50% sucrose solution, and include a blank control group and a solvent control group. After anesthetizing the bees, apply 2 μL of the test solution at different concentrations to the mesothorax of the bees. After the solvent evaporates, transfer the bees to test cages and feed them with cotton wool soaked in an appropriate amount of sucrose water. Observe and record the poisoning symptoms and the number of deaths of the bees after 48 hours, calculate the mortality rate, and determine the LD50 after 48 hours. 50 Value and 95% confidence limit.

[0270] According to LD 50 The toxicity level is determined by (48h) / (μg ai / bee). The toxicity levels are classified as follows: Extremely Toxic: LD 50 ≤0.001; Highly toxic: 0.001 < LD50 50 ≤2; Poisoning: 2 < LD 50 ≤11; Low toxicity: LD 50 >11.

[0271] Biological Example 9

[0272] A child loves earthworms (Eisenia foetida)

[0273] Adult Eisenia foetida earthworms, weighing between 0.3 and 0.6 g, were used in the experiment. The experimental temperature was 20℃ ± 2℃, the relative humidity was 70%–90%, and the light intensity was 400 lx–800 lx.

[0274] Prepare the test compound by using an organic solvent (acetone, etc.) to create a stock solution. Set up 5-7 concentration gradients, with the amount of organic solvent generally not exceeding 0.1 mL / L. Include a blank control group and a solvent control group. Weigh 500 g of artificial soil into a specimen bottle and add the different concentrations of the drug solution, mixing thoroughly. Place earthworms in each treatment, seal the bottle opening with gauze, and incubate for two weeks. Observe and record the poisoning symptoms and mortality of earthworms on days 7 and 14, and calculate the median lethal concentration (LC50) of the drug solution for earthworms. 50 Value and 95% confidence limit.

[0275] According to LC 50 To determine toxicity level using (14d) / (mg ai / kg dry soil), the toxicity levels are classified as follows: Extremely toxic: LD50 50 ≤0.1; Highly toxic: 0.1 < LC 50 ≤1; Poisoning: 1 < LC 50 ≤10; Low toxicity: LC 50 >10.

[0276] Biological Example 10

[0277] Chlorella vulgaris

[0278] The experiment used common Chlorella vulgaris, which was cultured under sterile conditions to achieve synchronous growth. The experimental environment temperature was 21℃~24℃ (the temperature of a single experiment was controlled within ±2℃); continuous and uniform light was provided, with the light intensity difference maintained within ±15%, and the light intensity was 4440lx~8880lx.

[0279] Prepare the test compound by using an organic solvent (acetone, etc.) to create a stock solution. Set up 5-7 concentration gradients, with the organic solvent volume generally not exceeding 0.1 mL / L. Include a blank control group and a solvent control group. Add different concentrations of the drug solution to the Chlorella solution. The experimental observation period is 72 hours, with samples taken every 24 hours. Measure the absorbance of the algae directly using a spectrophotometer. Calculate the algal growth inhibition rate according to EC. 50 To determine toxicity level using (72h) / (mg ai / L), the toxicity levels are classified as follows: Highly toxic: EC 50 ≤0.3; Poisoning: 0.3<EC 50 ≤3; Low toxicity: EC 50 >3.

[0280] Biological Example 11

[0281] North American quail (Colinus virginianus)

[0282] The test species is the North American quail (Colinus virginianus). The test birds should be in good health and without obvious deformities. A mortality rate of less than 5% within the first 7 days after introduction into the laboratory, and growth patterns consistent with the species' growth characteristics, are considered to indicate good health. The test birds should pass animal quarantine to ensure they are free of disease. The test birds should come from the same maternal parent and hatch on the same day.

[0283] 1. Acute oral toxicity

[0284] Prepare the test compound by using an organic solvent (acetone, etc.) to form a stock solution. Set up 5-7 concentration gradients, with half male and half female birds used for each concentration. Include a blank control group and a solvent control group. Administer different doses of the test compound (I) orally at a single dose of 1 mL / 100g body weight. Observe the poisoning and mortality of the test birds for 7 consecutive days, and determine the 7-day LD50. 50 Values ​​and 95% confidence limits. Based on LD... 50 To determine toxicity level using / (mg(ai) / kg body weight), the toxicity levels are classified as follows: Extremely Toxic: LD50 50 ≤10; Highly toxic: 10 < LD50 50 ≤50; Poisoning: 50<LD 50 ≤500; Low toxicity: LD 50 >500.

[0285] 2. Acute feeding toxicity

[0286] Prepare the test compound by using an organic solvent (acetone, etc.) to create a stock solution. Set up 5-7 concentration gradients, with half male and half female birds used for each concentration. Include a blank control group and a solvent control group. Use a sprayer to spray the different concentrations of the solution onto the food, stirring constantly until evenly mixed. Feed the test birds with feed containing different concentrations of the test compound (I) for 5 days. Starting from day 6, feed them with feed without the test compound for 3 days. Record the poisoning and mortality of the birds daily and calculate the LC50 over 8 days. 50 Values ​​and 95% confidence limits. According to LC... 50 To determine toxicity level using / (mg(ai) / kg feed), the toxicity levels are classified as follows: Extremely toxic: LC 50 ≤50; Highly toxic: 50 < LC 50 ≤500; Poisoning: 500 < LC 50 ≤1000; Low toxicity: LC 50 >1000.

[0287] As shown in the results above, the compounds of the present invention generally exhibit good insecticidal effects, producing excellent insecticidal efficacy even at low application doses. Furthermore, they demonstrate relatively good safety for environmental organisms.

[0288] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several changes and improvements without departing from the inventive concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A fused heterocyclic compound with sulfur substituents as shown in general formula (I), its stereoisomers, and its agriculturally acceptable salts: In the formula, W is selected from O or NH; In the formula, R1-R5 are each independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, mercapto, pentafluorothio, cyano, amino, or nitro. In the formula, R6 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl or C3-C6 halocycloalkyl; In the formula, Q represents Q1-Q 32 Group shown: In the formula R 10 It is selected from C1-C4 haloalkyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl or C1-C4 haloalkoxy.

2. The compound of formula (I) according to claim 1, its stereoisomers, and its agriculturally acceptable salts: In the formula, W is selected from O or NH; In the formula, R1-R5 are each independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl or cyano; In the formula, R6 is a C1-C4 alkyl group; In the formula, Q represents expressions Q1-Q7 and Q 10 -Q 13 and Q 15 Group shown: In the formula R 10 It is selected from C1-C4 haloalkyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl or C1-C4 haloalkylsulfonyl.

3. The compound of formula (I) according to claim 2, its stereoisomers, and its agriculturally acceptable salts: In the formula, W is selected from O or NH; In the formula, R1-R5 are each independently selected from hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, or cyano; In the formula, R6 is methyl or ethyl; In the formula, Q represents expressions Q1-Q7 and Q 15 Group shown: In the formula R 10 It is selected from trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl.

4. A fused heterocyclic compound with a sulfur-containing substituent as shown in general formula (I), its stereoisomers, and its agriculturally acceptable salts: In the formula, W is selected from O or NH; In the formula, R1-R5 are each independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 haloalkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, mercapto, pentafluorothio, cyano, amino, or nitro. In the formula, R6 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl or C3-C6 halocycloalkyl; In the formula, Q represents the expression Q 33 The shown groups; In the formula R 10 It is selected from C1-C4 haloalkyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl or C1-C4 haloalkoxy.

5. The compound of formula (I) according to claim 4, its stereoisomers, and its agriculturally acceptable salts: In the formula, W is selected from O or NH; In the formula, R1-R5 are each independently selected from hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, or cyano; In the formula, R6 is methyl or ethyl; In the formula R 10 It is selected from trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl.

6. A composition, characterized in that, It includes at least one of the compounds of formula (I) as described in any one of claims 1-5, their stereoisomers or salts thereof, wherein the active component is a compound of formula (I), and the composition contains an active component in a weight percentage of 0.1-99.9%.

7. A method for controlling pests, characterized in that, The compound of formula (I) as described in any one of claims 1-5, its stereoisomers and agriculturally acceptable salts thereof, or the composition of claim 6, is applied to the pest or its growth environment.

8. The use of a compound of formula (I) as claimed in any one of claims 1-5, its stereoisomers, agriculturally acceptable salts thereof, or the composition of claim 6 in the control of pests.

9. A method for preparing the sulfur-containing fused heterocyclic compound (I) of claim 3, its stereoisomers, and agriculturally acceptable salts thereof, the method comprising the following schemes: Option 1: When Q in the formula is selected from Q1-Q5 or Q 15 When W is selected from O or NH, the compound can be defined as general formula (I-a1) or (I-a2), and its preparation method includes the following steps: (1) The compound of general formula (Va) undergoes a condensation reaction with an aromatic amine to generate the compound of general formula (IV-a); (2) The compound represented by general formula (IV-a) undergoes a cyclization reaction to generate the compound represented by general formula (III-a); (3) The compound of general formula (III-a) reacts with alkyl thiols or alkyl thiols to produce the compound of general formula (II-a); (4) The compound of general formula (II-a) is converted into the compound of general formula (I-a1) by oxidation reaction; or into the compound of general formula (I-a2) by oxidation and amination reaction. In the formula, X1 is chlorine, bromine or iodine, and M is selected from hydrogen, potassium or sodium; Option 2: When Q is selected from Q6-Q7 and W is selected from O or NH, the compound can be defined as general formula (I-b1) or (I-b2), and its preparation method includes the following steps: (1) The compound of general formula (Va) undergoes the Curtius rearrangement reaction to produce the compound of general formula (Vb); (2) The compound of general formula (Vb) undergoes a substitution reaction with different substituted aromatic benzyl halides and loses the Boc protecting group to generate the compound of general formula (IV-b); (3) The compound of general formula (IV-b) undergoes ester hydrolysis and cyclization to generate the compound of general formula (III-b); (4) The compound of general formula (III-b) reacts with alkyl thiols or alkyl thiols to produce the compound of general formula (II-b); (5) The compound of general formula (II-b) is converted into the compound of general formula (I-b1) by oxidation reaction; or into the compound of general formula (I-b2) by oxidation and amination reaction. In the formula, X1 and X2 are chlorine, bromine, or iodine, M is selected from hydrogen, potassium, or sodium, and R 11 Selected from C1-C4 alkyl groups.

10. A method for preparing the sulfur-containing fused heterocyclic compound (I) of claim 5, its stereoisomers, and its agriculturally acceptable salts, wherein when formula W is selected from O or NH, the compound can be defined as general formula (I-c1) or (I-c2), and the preparation method comprises the following steps: (1) The compound of general formula (Va) undergoes a condensation reaction with an aromatic amine to produce the compound of general formula (IV-c); (2) The compound represented by general formula (IV-c) undergoes a cyclization reaction to generate the compound represented by general formula (III-c); (3) The compound of general formula (III-c) reacts with alkyl thiols or alkyl thiols to produce the compound of general formula (II-c); (4) The compound shown in general formula (II-c) is converted into the compound shown in general formula (I-c1) by oxidation reaction; or into the compound shown in general formula (I-c2) by oxidation and amination reaction. In the formula, X1 is chlorine, bromine or iodine, and M is selected from hydrogen, potassium or sodium.

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