An imidazo[1,2-a]pyridine compound or a pesticidally acceptable salt thereof, and a preparation method and application thereof

Abstract

The present application relates to the field of hygiene and agricultural insecticide, and in particular to an imidazo[1,2-a]pyridine compound or a salt thereof, and a preparation method and application thereof. The imidazo[1,2-a]pyridine compound or the salt thereof has high insecticidal activity, excellent control effect on piercing-sucking pests, good safety to main crops, and is not prone to phytotoxicity at an effective dose, has good environmental compatibility, and has good application prospect.

Description

Technical Field

[0001] This invention relates to the technical field of sanitary and agricultural pesticides, specifically to an imidazo[1,2-a]pyridine compound or a pesticide-acceptable salt thereof, its preparation method, and its application. Background Technology

[0002] With global population growth and increasing demand for food, the use of chemical pesticides in agricultural production continues to play a crucial role in ensuring crop yields. However, the long-term and large-scale use of traditional pesticides has led to a series of problems, including increasingly serious pest resistance, potential threats to non-target organisms, and environmental pollution. Therefore, the continuous development of novel insecticides with novel chemical structures, unique mechanisms of action, high efficiency, low toxicity, and environmental friendliness has become an important issue that urgently needs to be addressed in the global pesticide innovation field.

[0003] Imidazolo[1,2-a]pyridine, as an important nitrogen-containing fused heterocyclic skeleton, has been extensively studied in medicinal chemistry and materials science due to its rigid planar structure and unique electronic properties. Studies have shown that this type of skeleton is a preferred skeleton for constructing bioactive molecules, and many derivatives containing this skeleton exhibit diverse biological activities.

[0004] Existing technologies disclose various compounds containing an imidazo[1,2-a]pyridine skeleton. For example, patent JP2015003906A discloses a fused heterocyclic compound that can be used as an agricultural and horticultural insecticide, and is also effective against pests parasitizing pets such as dogs and cats, or livestock such as cattle and sheep. Although these disclosed imidazo[1,2-a]pyridine skeleton compounds have insecticidal activity, their efficacy remains relatively poor. Therefore, developing imidazo[1,2-a]pyridine compounds with high insecticidal activity to meet the needs of the health, agriculture, forestry, and horticulture sectors has become an urgent technical problem to be solved. Summary of the Invention

[0005] To address the aforementioned problems in the existing technology, the primary objective of this invention is to provide an imidazo[1,2-a]pyridine compound. The imidazo[1,2-a]pyridine compound provided by this invention exhibits high insecticidal activity and excellent control effect against pests.

[0006] A second objective of this invention is to provide an imidazo[1,2-] a Preparation methods of pyridine compounds.

[0007] A third objective of this invention is to provide an agricultural composition.

[0008] The fourth object of the present invention is to provide an imidazo[1,2-] aThe use of pyridine compounds or their pesticide-acceptable salts or the agricultural compositions thereof in the preparation of pesticides for controlling pests or in the preparation of insecticides.

[0009] To achieve the above objectives, the present invention is implemented through the following technical solution: This invention claims protection for an imidazo[1,2-] a ] Pyridine compounds or agriculturally acceptable salts thereof, wherein the structure of the imidazo[1,2-a]pyridine compound is shown in formula (I):

[0010] R1 is selected from 5-6 aryl and 5-6 heteroaryl groups; the 5-6 aryl and 5-6 heteroaryl groups are unsubstituted or derived from one or more C groups. 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Substitution of alkyl, nitro, and cyano groups; R2, R3, R4, and R5 are each independently selected from hydrogen, halogen, cyano, nitro, and C. 1~6 Acyl group, C 1~6 Ester group, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy or C 1~6 Alkylthio; R6 is selected from hydrogen, cyano, C… 1~6 Acyl group, C 1~6 Ester group, C 1~6 Alkyl, C 1~6 Halogenated alkyl, cyano C 1~6 Alkyl, C 1~6 Alkoxy or C 1~6 Halogenated alkoxy groups; R7 is selected from hydrogen, cyano, and C. 1~6 Ester group, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkylthio, C 1~6 Alkyl thioc 1~6 Alkyl, C 3~6 cycloalkyl, C 3~6 cycloalkyl C 1~6 Alkyl, Halogenated C 3~6 cycloalkyl, cyano C 3~6 cycloalkyl, C 3~6 Heterocyclic group, C 3~6 Heterocyclic C 1~6 Alkyl, Halogenated C 3~6Heterocyclic group, cyano group C 3~6 Heterocyclic group, C 1~6 Alkyl C 3~6 Heterocyclic, 5-6 aryl, 5-6 heteroaryl; wherein, C 1~6 Alkyl, C 3~6 cycloalkyl C 1~6 In alkyl groups, C 1~6 Alkyl groups are unsubstituted or derived from one or more C16 groups. 1~6 amide group, C 1~6 Haloamide group, C 1~6 The sulfonyl group is substituted; wherein the 5-6 aryl group or the 5-6 heteroaryl group is unsubstituted or substituted by one or more groups selected from C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Substitution of alkyl, nitro, and cyano groups; Or R6 and R7, together with the nitrogen atoms they are attached to, form C 3~6 Heterocyclic group, carbonyl group C 3~6 Heterocyclic group.

[0011] Preferably, R1 is selected from phenyl or pyridyl; the phenyl or pyridyl group is unsubstituted or via one or more C1 groups. 1~4 Alkyl, C 1~4 Alkoxy, halogen, C 1~4 Substitution of alkyl, nitro, and cyano groups; R2 and R3 are each independently selected from hydrogen; R4 is selected from hydrogen, fluorine, chlorine, bromine, cyano, and C. 1~4 Alkyl, C 1~4 Haloalkyl, C 1~4 Alkoxy; R5 is selected from hydrogen; R6 is selected from hydrogen, C 1~4 alkyl; R7 is selected from hydrogen, C 1~4 Ester group, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~4 Alkoxy, C 1~4 Alkoxy C 1~4 Alkyl, C 1~4 Alkylthio, C 1~4 Alkyl thioc 1~4 Alkyl, C 3~6 cycloalkyl, C 3~6 cycloalkyl C 1~4 Alkyl, Halogenated C 3~6 cycloalkyl, cyano C 3~6 cycloalkyl, C 3~6 Heterocyclic group, C 3~6 Heterocyclic C 1~4Alkyl, Halogenated C 3~6 Heterocyclic group, cyano group C 3~6 Heterocyclic group, C 1~4 Alkyl C 3~6 Heterocyclic, 5-6 aryl, 5-6 heteroaryl; wherein, C 1~4 Alkyl, C 3~6 cycloalkyl C 1~4 In alkyl groups, C 1~4 Alkyl groups are unsubstituted or derived from one or more C16 groups. 1~4 amide group, C 1~4 Haloamide group, C 1~4 The sulfonyl group is substituted; wherein the 5-6 aryl group or the 5-6 heteroaryl group is unsubstituted or substituted by one or more groups selected from C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Substitution of alkyl, nitro, and cyano groups; Or R6 and R7, together with the nitrogen atoms they are attached to, form C 3~5 Heterocyclic group, carbonyl group C 3~5 Heterocyclic group.

[0012] Preferably, R1 is selected from phenyl or pyridyl; the phenyl group is unsubstituted or substituted with one or more substituents selected from methyl, methoxy, fluorine, chlorine, trifluoromethyl, nitro, or cyano. R2 and R3 are each independently selected from hydrogen; R4 is selected from hydrogen or methyl; R5 is selected from hydrogen; R6 is selected from hydrogen or methyl; R7 is selected from -CH(CH3)2, -C(CH3)3, -CHCH3CH2CH3, -CH2CH2Cl, -CH2CH2F, -CH2CH2OCH3, -CH2CH2SCH3, -CH2CONHCH2CF3, -CH2CH2SO2CH3, cyclopropyl, -CH2-cyclopropyl, cyclobutyl, -CH2-cyclobutyl, -cyanocyclopropyl, -CH2-methylcyclopropyl, -CH2-methylcyclobutyl, - Difluorocyclobutyl, -difluorocyclopropyl, -oxetyl, -methyl-oxetyl, -thiocyclobutyl, -methylcyclopropyl, -CH2CF3, phenyl, pyridyl, pyrimidinyl, thiopheneyl, furanyl, thiazolyl, oxazolyl; wherein the phenyl, pyridyl, pyrimidinyl, thiopheneyl, furanyl, thiazolyl, oxazolyl are unsubstituted or substituted with methyl, methoxy, fluorine, chlorine, bromine, iodine, cyano, nitro, trifluoromethyl, or hydroxyl groups.

[0013] Preferably, the imidazo[1,2-a]pyridine compound is selected from any of the structures shown:

[0014]

[0015]

[0016]

[0017]

[0018]

[0019]

[0020]

[0021]

[0022]

[0023]

[0024]

[0025]

[0026]

[0027]

[0028]

[0029]

[0030]

[0031]

[0032]

[0033]

[0034]

[0035]

[0036]

[0037]

[0038]

[0039]

[0040]

[0041] .

[0042] Preferably, the imidazo[1,2-a]pyridine compound is selected from any of the structures shown:

[0043]

[0044]

[0045]

[0046]

[0047]

[0048]

[0049]

[0050]

[0051]

[0052]

[0053]

[0054]

[0055]

[0056]

[0057]

[0058]

[0059]

[0060]

[0061]

[0062]

[0063] .

[0064] Under the above-mentioned preferred compound structure, when the compound is used at a dose of up to 100 mg / L, it maintains a 100% high lethality rate against rice planthoppers or aphids.

[0065] Preferably, the imidazo[1,2-a]pyridine compound is selected from any of the structures shown:

[0066]

[0067]

[0068]

[0069]

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077]

[0078]

[0079] .

[0080] Under the above-mentioned preferred compound structure, when the compound is used at a dose of up to 50 mg / L, it maintains a 100% high lethality rate against rice planthoppers or aphids.

[0081] Furthermore, the present invention claims protection for an imidazo[1,2- a The preparation method of pyridine compounds includes the following steps: (1) The 6-bromo-2-aminopyridine derivative intermediate shown in formula (II) and the α-haloketone derivative shown in formula (III) were subjected to a cyclization condensation reaction in an organic solvent to obtain the intermediate shown in formula (IV);

[0082] (2) The intermediate shown in formula (IV) is subjected to a substitution reaction with CuCN in an organic solvent to obtain the intermediate shown in formula (V);

[0083] (3) Hydrolyze the product shown in formula (V) under alkaline conditions to obtain the carboxylic acid intermediate shown in formula (VI);

[0084] (4) The carboxylic acid shown in formula (VI) is subjected to acyl chlorination or condensation with different amines or amine hydrochlorides to obtain the compound shown in formula (Ia); .

[0085] Preferably, the organic solvent in step (1) is selected from ethanol, xylene, isopropanol, acetonitrile, dichloromethane, pyridine, tetrahydrofuran, dimethyl sulfoxide, 1,4-dioxane, or... N,N - At least one of dimethylformamide; and / or the organic solvent in step (2) is selected from acetonitrile, dimethyl sulfoxide ，N 1,4-dioxane or methylpyrrolidone N,N - At least one of dimethylformamide; and / or the organic solvent in step (3) is selected from acetonitrile, ethanol, isopropanol, methanol, acetone, or N,N - At least one of dimethylformamide; and / or the organic solvent in step (4) is selected from acetonitrile, dichloromethane, pyridine, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide or N,N At least one of dimethylformamide.

[0086] Preferably, in step (1), the cyclization condensation reaction is carried out under alkaline conditions. These alkaline conditions can be formed by adding a base conventionally used in the art; more specifically, the base includes, but is not limited to, any one or a combination of at least two of sodium bicarbonate, potassium carbonate, cesium carbonate, trimethylamine, triethylamine, N,N-diisopropylethylamine, tri-n-butylamine, pyridine, piperidine, 3-methylpyridine, 2,6-dimethylpyridine, N-methylmorpholine, 3-methylimidazolium, and 4-N,N-dimethylaminopyridine.

[0087] Preferably, in step (1), the reaction temperature of the cyclization condensation reaction is 25-35℃.

[0088] Preferably, in step (2), the reaction temperature of the substitution reaction is 130-170℃.

[0089] Preferably, in step (3), the hydrolysis reaction temperature is 80-120℃.

[0090] Preferably, in step (3), the hydrolysis reaction temperature is 80-120°C. The alkali added to the hydrolysis reaction can be any alkali conventionally used in the art; more specifically, the alkali includes, but is not limited to, any one or a combination of at least two of sodium bicarbonate, potassium carbonate, cesium carbonate, trimethylamine, triethylamine, N,N-diisopropylethylamine, tri-n-butylamine, pyridine, piperidine, 3-methylpyridine, 2,6-dimethylpyridine, N-methylmorpholine, 3-methylimidazolium, and 4-N,N-dimethylaminopyridine.

[0091] Preferably, in step (4), the condensing agent can be a condensing agent commonly used in the art; more specifically, the condensing agent includes, but is not limited to, 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethylurea hexafluorophosphate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, 1-hydroxybenzotriazole, 4-dimethylaminopyridine, etc.

[0092] Preferably, in step (4), the base added during the reaction includes, but is not limited to, any one or a combination of at least two of the following: sodium bicarbonate, potassium carbonate, cesium carbonate, trimethylamine, triethylamine, N,N-diisopropylethylamine, tri-n-butylamine, pyridine, piperidine, 3-methylpyridine, 2,6-dimethylpyridine, N-methylmorpholine, 3-methylimidazolium, and 4-N,N-dimethylaminopyridine.

[0093] Furthermore, the present invention claims protection for an agricultural composition comprising: (a) 0.001-99.99% by weight of the imidazo[1,2- a Pyridine compounds or their pesticide-acceptable salts, or combinations thereof; and (b) Acceptable carriers and / or excipients for pesticides.

[0094] Preferably, in this invention, the agricultural composition can be formulated into dosage forms such as bait, wettable powder, suspension concentrate, water-in-oil emulsion, or emulsifiable concentrate.

[0095] Furthermore, the present invention claims protection for the imidazo[1,2-] a The use of pyridine compounds or their pesticide-acceptable salts or the agricultural compositions thereof in the preparation of pesticides for controlling pests or in the preparation of insecticides.

[0096] Preferably, the drug or insecticide is applied directly to the pest or the place where it comes into contact with it.

[0097] Preferably, the areas or places for pest control include, but are not limited to, public health areas, agriculture, forestry, horticulture, or plants.

[0098] Preferably, the pests include agricultural and forestry pests, sanitary pests, or pests that endanger animal health.

[0099] More preferably, the pests include one or more of the following: Lepidoptera, Coleoptera, Hemiptera, Thysanoptera, Diptera, Orthoptera, Homoptera, Isoptera, Hymenoptera, and Blattodea.

[0100] Preferably, the pest is one or more of the piercing-sucking insects. Specifically, the pests include, but are not limited to: peach aphid, cotton aphid, alfalfa aphid, apple yellow aphid, wheat aphid, gray planthopper, brown planthopper, white-backed planthopper, carmine spider mite, citrus red spider mite, etc.

[0101] Furthermore, the plants mainly include the following categories: vegetables, such as cucumber, loofah, watermelon, cantaloupe, pumpkin, gourd, spinach, celery, cabbage, Chinese cabbage, gourd, chili pepper, eggplant, tomato, scallion, ginger, garlic, leek, lettuce, green bean, cowpea, broad bean, radish, carrot, potato, or yam; cereals, such as wheat, barley, corn, rice, or sorghum; fruit trees, such as apple, pear, banana, citrus, grape, lychee, or mango; flowers, such as peony, rose, or flamingo flower; oil crops, such as peanut, soybean, rapeseed, sunflower, or sesame; sugar crops, such as sugar beet or sugarcane; and other crops, such as strawberry, potato, sweet potato, tobacco, or tea.

[0102] Compared with the prior art, the present invention has the following beneficial effects: This invention provides an imidazo[1,2-a]pyridine compound or a pharmaceutically acceptable salt thereof, which retains high insecticidal activity even at low concentrations and exhibits excellent control effects against piercing-sucking pests. The imidazo[1,2-a]pyridine compound provided by this invention demonstrates good safety for major crops, is unlikely to cause phytotoxicity at effective doses, has good environmental compatibility, and shows promising application prospects. Detailed Implementation

[0103] The present invention will be further described below with reference to the specification and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0104] The term "halogen" refers to fluorine, chlorine, bromine, and iodine. The term "halogen" preceding the group name indicates that the group is partially or completely halogenated, that is, replaced by F, Cl, Br, or I in any combination.

[0105] The term "alkyl" refers to a saturated straight-chain or branched hydrocarbon group. The alkyl group is preferably C10. 1~6 Alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, or similar groups.

[0106] The term "cycloalkyl" refers to a saturated or partially unsaturated cycloalkyl group, including monocyclic or polycyclic groups. Unless otherwise specified, cycloalkyl groups have 3 to 6 carbon atoms. For example, a cycloalkyl group can be a monocyclic group having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-3-enyl, cyclohexene, 1-cyclohex-1-enyl, cyclohexadiene, cycloheptene, cyclooctene, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, or similar groups. The cycloalkyl group may be saturated or have at least one double bond, but is not fully conjugated and is not aromatic.

[0107] The term "alkoxy group" refers to a saturated straight-chain or branched group connected to the rest of the molecule by an oxygen atom, usually denoted by RO-, where R is an alkyl group. Unless otherwise stated, the alkoxy group is an alkoxy group having 1 to 6 carbon atoms, examples of which include, but are not limited to, methoxy groups.

[0108] The term "ester group" refers to the group -COOR, where R is an alkyl group. Unless otherwise stated, the alkyl group in the ester group has 1 to 6 carbon atoms.

[0109] The term "5-6 aryl" refers to a 5-6 nucleotide aromatic ring, wherein at least one ring in the bicyclic system is an aromatic ring. 5-6 nucleotides include, but are not limited to, phenyl and furan rings. The term "5-6 heteroaryl" refers to a 5-7 nucleotide aromatic monocyclic ring containing heteroatoms; it contains 1, 2, 3, or 4 heteroatoms selected from N, O, and S, with the remaining ring atoms being carbon. 5-6 heteroaryl groups include, but are not limited to, pyridyl groups.

[0110] In this invention, unless otherwise specified in the context, the words, phrases, and symbols used below shall have the following meanings. The following abbreviations and terms shall have the same meaning throughout the document: DIPEA is N,N-diisopropylethylamine; PE is petroleum ether; EA is ethyl acetate; TLC is thin-layer chromatography; Oxone is potassium persulfate; HATU is a common polypeptide condensation reagent, systematically named 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate; DMF is N,N-dimethylformamide; KF is potassium fluoride; THF is tetrahydrofuran; NBS is N-bromosuccinimide; RT refers to room temperature; TBAB is tetrabutylammonium bromide.

[0111] Example 1 In this embodiment, N-cyclopropyl-2-phenylimidazo[1,2-a]pyridine-8-carboxamide (compound Ia-10 in Table 1 below) is used as an example, and its specific synthesis process is as follows: (1) Preparation of 8-bromo-2-phenylimidazo[1,2-a]pyridine:

[0112] In a 100 mL sealed tube, 1.73 g of 3-bromopyridine-2-amine (10 mmol of compound (II-1)), 2.19 g of 2-bromo-1-phenylethyl ketone (11 mmol, 1.1 eq of compound (III-1)), 1 g of sodium bicarbonate (12 mol, 1.2 eq), and 40 mL of ethanol were added sequentially. The mixture was reacted at 30 °C for 4–5 h, monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, and the ethanol was removed by vacuum concentration. The mixture was then extracted with ethyl acetate (30 mL × 3). The organic phase was washed with saturated brine (30 mL × 3), dried over anhydrous sodium sulfate, filtered through a Buchner funnel to remove the anhydrous sodium sulfate, and concentrated under vacuum. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 10 / 1; v / v) to give a bluish-green solid (compound (IV-1)), which was used directly in the next step. The 1H NMR data of compound (IV-1) are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.07 (d, J =6.7 Hz, 1H), 7.99 – 7.94 (m, 2H), 7.89 (s, 1H), 7.40 (q, J = 7.7 Hz, 3H), 7.32(t, J = 7.4 Hz, 1H), 6.61 (t, J = 7.0 Hz, 1H).

[0113] (2) Preparation of 2-phenylimidazo[1,2-a]pyridine-8-carboxynitrile

[0114] Under nitrogen protection, 1.7 g (6.2 mmol) of 8-bromo-2-phenylimidazo[1,2-a]pyridine (Formula (IV-1)) obtained in step (1) was added to 40 mL of dry DMF, followed by 1.67 g (18.6 mmol, 3 eq) of CuCN. The reaction mixture was stirred at 150 °C for 5 h. The reaction was monitored by TLC until completion. After cooling to room temperature, the solid was filtered, the filter cake was washed with EA, the filtrate was diluted with water, extracted with EA, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered through a Buchner funnel to remove anhydrous sodium sulfate, concentrated under vacuum, and the crude product was purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1; v / v) to obtain a pale yellow solid (Formula (V-1), 2-phenylimidazo[1,2-a]pyridine-8-carboxynitrile), which was directly used in the next step. The 1H NMR data of Formula (V-1) are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 8.32 (d, J = 6.8 Hz, 1H), 7.99 (d, J = 7.7 Hz, 2H), 7.94 (s, 1H), 7.58 (d, J = 7.1 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.4 Hz, 1H), 6.85 (t, J = 7.0 Hz, 1H).

[0115] (3) Preparation of 2-phenylimidazo[1,2-a]pyridine-8-carboxylic acid

[0116] The compound 2-phenylimidazo[1,2-a]pyridine-8-carboxylonitrile (0.7 g, 3.2 mmol) of formula (V-1) obtained in step (2) was dissolved in 20 ml of ethanol. 3.58 g of KOH (64 mmol, 20 eq) was dissolved in 10 mol of water at 0 °C to obtain an aqueous solution of KOH. This solution was slowly added dropwise to the ethanol mixture of 2-phenylimidazo[1,2-a]pyridine-8-carboxylonitrile. The reaction was carried out at 100 °C for 4-5 h, and the reaction was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature and concentrated under vacuum to remove some of the ethanol. The reaction solution was then placed at 0 °C, and the pH was adjusted to 3-4 with concentrated hydrochloric acid. The reaction solution was concentrated, diluted with EA, and the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under vacuum, and dried to obtain 0.3 g of compound (VI-1), a pale pink solid, which was directly used in the next reaction. The 1H NMR data of compound (VI-1) are as follows: 1 H NMR (600 MHz, Chloroform- d ) δ 10.21 (s, 1H), 8.25 (d, J = 6.6 Hz, 1H), 8.19 (d, J = 7.2 Hz, 1H), 7.96 – 7.93 (m, 2H), 7.92(s, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.37 (t, J = 7.4 Hz, 1H), 6.94 (t, J = 6.9Hz, 1H), 6.22 (s, 1H).

[0117] (4) Preparation of N-cyclopropyl-2-phenylimidazo[1,2-a]pyridine-8-carboxamide (Ia-16)

[0118] The compound 2-phenylimidazo[1,2-a]pyridine-8-carboxylic acid (0.3 g, 1 mmol) of formula (VI-1) obtained in step (3) was dissolved in 5 mL of dry DMF (N,N-dimethylformamide). 0.38 mL of DIPEA (2.2 equivalents) and 0.456 g of HATU (1.2 mmol, 1.2 eq) were added at room temperature. After stirring until homogeneous, 0.07 g of cyclopropylamine (1.5 mmol, 1.5 eq) was added dropwise. After the addition was complete, the mixture was stirred at room temperature for 3 h. The reaction was monitored by TLC until complete. The mixture was filtered, diluted with EA, washed with saturated brine, dried over anhydrous sodium sulfate, filtered through a Buchner funnel to remove anhydrous sodium sulfate, concentrated under vacuum, and purified by column chromatography (petroleum ether / ethyl acetate = 2 / 1; v / v). The crude product was concentrated under vacuum and dried to obtain 0.249 g of DIPEA. g of white solid, namely N-cyclopropyl-2-phenylimidazo[1,2-a]pyridine-8-carboxamide (Ia-16), in 90% yield. The 1H and 1C spectral data for compound Ia-16 are as follows: 1 H NMR (600MHz, Chloroform- d ) δ 10.50 (s, 1H), 8.20 (ddd, J = 10.5, 6.9, 1.3 Hz, 2H),7.92 (s, 1H), 7.90 (d, J = 4.3 Hz, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.37 (t, J =7.4 Hz, 1H), 6.93 (t, J = 6.9 Hz, 1H), 3.09 (dq, J = 7.3, 3.7 Hz, 1H), 0.96 –0.93 (m, 2H), 0.77 (d, J = 2.4 Hz, 2H). 13 C NMR (151 MHz, Chloroform- d ) δ164.86, 145.16, 143.70, 132.94, 128.99, 128.62, 128.12, 127.92, 126.14,121.06, 112.52, 108.49, 23.05, 6.90.

[0119] Example 2 Imidazolo[1,2-a]pyridine compounds of the present invention, numbered Ia-1 to Ia-105 as shown in the following formula (Ia), were synthesized according to Example 1 above. In formula (Ia), R1 is selected from phenyl; R2, R3, R4, and R5 are selected from H; and the substituents of R6 and R7 are selected as shown in Table 1 below.

[0120]

[0121] Table 1

[0122] The imidazo[1,2-a]pyridine compounds of the present invention, numbered Ib-1 to Ib-44, as shown in the following formula (Ib), were synthesized according to the preparation method of Example 1 above. In formula (Ib), R2, R3, R5, and R6 are selected from H, R7 is selected from 1-methyl-cyclopropyl, and the substituents of R1 and R4 are selected as shown in Table 2 below.

[0123]

[0124] Table 2

[0125] The imidazo[1,2-a]pyridine compounds of the present invention, numbered Ib-45 to Ib-59, as shown in the following formula (Ib), were synthesized according to the preparation method of Example 1 above. In formula (Ib), R2, R3, R5, and R6 are selected from H, and the substituents of R1, R4, and R7 are selected as shown in Table 3 below.

[0126]

[0127] Table 3

[0128] Example 3 Insecticidal Activity Determination (1) For rice planthoppers ( Nilaparvata Lugens Indoor bioactivity assay The rice seedling immersion method was used to conduct bioassays on rice planthopper nymphs. In this experiment, a breathable plastic cup with a diameter of 90 cm was used as the test container. 14-day-old rice plants with uniform growth that were planted indoors were dug up with their roots, the roots were washed, and the roots were trimmed into rice stems about 10 cm long with roots. The stems were then dried for later use.

[0129] The test compound prepared in the examples was dissolved in DMSO to prepare a 10,000 mg / L stock solution. An appropriate amount of the stock solution was diluted with water containing 0.1% Tween-80 dechlorination to create solutions of different concentration gradients. Prepared rice stems were immersed in the prepared solutions for 60 seconds, removed, dried, and placed in plastic cups separated by a sponge. Yoshida rice nutrient solution (Shanghai Xinyu Biotechnology Co., Ltd.) was poured into the bottom of the cups, and insects were introduced into the top. Twenty second-instar nymphs were introduced into each container using a suction device, with three replicates per group. The containers were placed in a constant-temperature insect rearing room, and the mortality rate of the nymphs was observed and recorded 72 hours after application.

[0130] (2) For aphids ( Aphis craccivora Indoor bioactivity assay The insecticidal activity of the imidazopyridine derivatives prepared in the examples against aphids was tested using the leaf immersion method. The test compounds prepared in the examples were dissolved in DMSO to prepare a 10000 mg / L stock solution, which was then diluted with dechlorinated water containing 0.1% Tween 80 to create solutions of different concentration gradients. Fresh broad bean leaves were then prepared into uniformly sized leaf dishes using a leaf dish apparatus, immersed in the solution for 10 seconds, removed, and allowed to air dry naturally before being placed in a petri dish containing 30 second-instar aphids. The petri dish was lined with moistened filter paper, and the dried leaves were wrapped with moistened absorbent cotton. The aphids were pre-starved for 3 hours. Each treatment was repeated three times. Dechlorinated water containing 0.1% Tween 80 was used as a positive control, and thiamethoxam technical grade was used as a control agent. The plants were incubated at 26°C, 85% relative humidity, and 16 hours of light (8 hours of darkness). The treatment results were examined and mortality rates were calculated after 24 and 48 hours.

[0131] The insecticidal activity experiments in (1) and (2) above were conducted in parallel using commercially available pesticides for controlling rice planthoppers and aphids, flonicamid and pymetrozine, as positive controls. The results are shown in Table 4 below. In the patent with publication number JP2015003906A, compound I-25 was used as the control compound of this invention, and its structural formula is shown below:

[0132] Table 4

[0133] As can be seen from the data in Table 4, most of the imidazo[1,2-a]pyridine compounds synthesized in this invention exhibited excellent insecticidal activity of 100% at a high concentration of 500 mg / L. At lower concentrations of 50 mg / L and 100 mg / L, their insecticidal effects were also superior to existing control compounds.

[0134] Among them, some of the preferred compounds maintained a 100% lethality rate even when the dose was reduced to 100 mg / L, demonstrating excellent activity comparable to commercially available control agents (flupyridine and pymetrozine). For rice planthoppers: compounds Ia-2, Ia-3, Ia-4, Ia-6 to Ia-14, Ia-16 to Ia-18, Ia-21 to Ia-40, Ia-42 to Ia-44, Ia-48 to Ia-49, Ia-52 to Ia-54, Ia-58 to Ia-59, Ia-62 to Ia-64, Ia-66 to Ia-88, Ia-91 to Ia-105, Ib-1 to Ib-4, Ib-6 to Ib-8, Ib-10 to Ib-13, Ib-23 to Ib-27, Ib-29 to Ib-40, and Ib-42 to Ib-57 all achieved 100% mortality at a concentration of 100 mg / L, which was significantly better than the control compounds. For aphids: Compounds Ia-3, Ia-6 to Ia-11, Ia-16 to Ia-18, Ia-21 to Ia-23, Ia-26, Ia-27, Ia-30 to Ia-35, Ia-38 , Ia-39, Ia-42, Ia-44, Ia-48, Ia-49, Ia-52, Ia-54, Ia-58, Ia-66, Ia-67, Ia-82, Ia-83, Ia-85 Ia-92, Ia-93, Ia-96, Ia-97, Ia-99, Ia-101 to Ia-103, Ib-1, Ib-3, Ib-4, Ib-6, Ib-8, Ib-11 to Ib-13, Ib-23, Ib-25, Ib-27, Ib-29, Ib-30, Ib-32 to Ib-34, Ib-36 to Ib-40, Ib-42, Ib-44 to Ib-57 achieved 100% mortality at a concentration of 100 mg / L, which was significantly better than the control compound.

[0135] Among them, some of the preferred compounds maintained a 100% lethality rate even when the dosage was reduced to 50 mg / L, demonstrating excellent activity comparable to commercially available control agents (flupyridine and pymetrozine). For rice planthoppers: Compounds Ia-3, Ia-6 to Ia-11, Ia-16 to Ia-18, Ia-21 to Ia-23, Ia-26, Ia-27, Ia-30 to Ia-35, Ia-38, Ia-39, Ia-42, Ia-44, Ia-48, Ia-49, Ia-52, Ia-54, Ia-58, Ia-66, Ia-67, Ia-82, Ia-83, Ia-8 5. Ia-92, Ia-93, Ia-96 to Ia-97, Ia-99, Ia-101 to Ia-103, Ib-1, Ib-3, Ib-4, Ib-6, Ib-8, Ib-11 to Ib-13, Ib-23, Ib-25 to Ib-27, Ib-29, Ib-30, Ib-32 to Ib-34, Ib-36 to Ib-40, Ib-42, and Ib-44 to Ib-57 all achieved 100% mortality at a concentration of 50 mg / L, which was significantly better than the control compound. For aphids: compounds Ia-6 to Ia-8, Ia-11, Ia-18, Ia-32, Ia-35, Ia-39, Ia-48, Ia-49, Ia-58, Ia-82, Ia-83, Ia-96, Ia-97, Ib-3, Ib-8, Ib-11 to Ib-13, Ib-30, Ib-34, Ib-44 to Ib-48, and Ib-54 to Ib-57 achieved 100% mortality at a concentration of 50 mg / L, which was significantly better than the control compounds.

[0136] Among them, compounds Ia-6, Ia-7, Ia-8, Ia-11, Ia-18, Ia-32, Ia-35, Ia-39, Ia-49, Ia-58, Ia-82, Ia-83, Ia-96, Ia-97, Ib-3, Ib-11 to Ib-13, Ib-30, Ib-34, Ib-44 to Ib-48, and Ib-54 to Ib-57 all showed extremely high activity against both pests, exhibiting broad-spectrum and high-efficiency characteristics, and were significantly superior to the control compounds.

[0137] The foregoing examples are merely illustrative, used to explain some features of the method described in this invention. The appended claims are intended to claim the broadest possible scope, and the embodiments presented herein are demonstrated by the applicant's actual experimental results. Therefore, the applicant intends that the appended claims are not limited by the selection of examples illustrating the features of the invention. Some numerical ranges used in the claims also include sub-ranges within them, and variations within these ranges should also be interpreted as being covered by the appended claims where possible.

Claims

1. An imidazo[1,2- a ]Pyridine compounds or their agriculturally acceptable salts, characterized in that, The structure of the imidazo[1,2-a]pyridine compound is shown in formula (I): R1 is selected from 5-6 aryl and 5-6 heteroaryl groups; the 5-6 aryl and 5-6 heteroaryl groups are unsubstituted or derived from one or more C groups. 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Substitution of alkyl, nitro, and cyano groups; R2, R3, R4, and R5 are each independently selected from hydrogen, halogen, cyano, nitro, and C. 1~6 Acyl group, C 1~6 Ester group, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy or C 1~6 Alkylthio; R6 is selected from hydrogen, cyano, C… 1~6 Acyl group, C 1~6 Ester group, C 1~6 Alkyl, C 1~6 Halogenated alkyl, cyano C 1~6 Alkyl, C 1~6 Alkoxy or C 1~6 Halogenated alkoxy groups; R7 is selected from hydrogen, cyano, and C. 1~6 Ester group, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Alkoxy C 1~6 Alkyl, C 1~6 Alkylthio, C 1~6 Alkyl thio group C 1~6 Alkyl, C 3~6 cycloalkyl, C 3~6 cycloalkyl C 1~6 Alkyl, Halogenated C 3~6 cycloalkyl, cyano C 3~6 cycloalkyl, C 3~6 Heterocyclic group, C 3~6 Heterocyclic C 1~6 Alkyl, Halogenated C 3~6 Heterocyclic group, cyano group C 3~6 Heterocyclic group, C 1~6 Alkyl C 3~6 Heterocyclic, 5-6 aryl, 5-6 heteroaryl; wherein, C 1~6 Alkyl, C 3~6 cycloalkyl C 1~6 In alkyl groups, C 1~6 Alkyl groups are unsubstituted or derived from one or more C16 groups. 1~6 amide group, C 1~6 Haloamide group, C 1~6 The sulfonyl group is substituted; wherein the 5-6 aryl group or the 5-6 heteroaryl group is unsubstituted or substituted by one or more groups selected from C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Substitution of alkyl, nitro, and cyano groups; Or R6 and R7, together with the nitrogen atoms they are attached to, form C 3~6 Heterocyclic group, carbonyl group C 3~6 Heterocyclic group.

2. The imidazo[1,2-] according to claim 1 a Pyridine compounds, characterized in that, R1 is selected from phenyl or pyridyl; phenyl or pyridyl is unsubstituted or via one or more C1 groups. 1~4 Alkyl, C 1~4 Alkoxy, halogen, C 1~4 Substitution of alkyl, nitro, and cyano groups; R2 and R3 are each independently selected from hydrogen; R4 is selected from hydrogen, fluorine, chlorine, bromine, cyano, and C. 1~4 Alkyl, C 1~4 Haloalkyl, C 1~4 Alkoxy; R5 is selected from hydrogen; R6 is selected from hydrogen, C 1~4 alkyl; R7 is selected from hydrogen, C 1~4 Ester group, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~4 Alkoxy, C 1~4 Alkoxy C 1~4 Alkyl, C 1~4 Alkylthio, C 1~4 Alkyl thio group C 1~4 Alkyl, C 3~6 cycloalkyl, C 3~6 cycloalkyl C 1~4 Alkyl, Halogenated C 3~6 cycloalkyl, cyano C 3~6 cycloalkyl, C 3~6 Heterocyclic group, C 3~6 Heterocyclic C 1~4 Alkyl, Halogenated C 3~6 Heterocyclic group, cyano group C 3~6 Heterocyclic group, C 1~4 Alkyl C 3~6 Heterocyclic, 5-6 aryl, 5-6 heteroaryl; wherein, C 1~4 Alkyl, C 3~6 cycloalkyl C 1~4 In alkyl groups, C 1~4 Alkyl groups are unsubstituted or derived from one or more C16 groups. 1~4 amide group, C 1~4 Haloamide group, C 1~4 The sulfonyl group is substituted; wherein the 5-6 aryl group or the 5-6 heteroaryl group is unsubstituted or substituted by one or more groups selected from C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Substitution of alkyl, nitro, and cyano groups; Or R6 and R7, together with the nitrogen atoms they are attached to, form C 3~5 Heterocyclic group, carbonyl group C 3~5 Heterocyclic group.

3. The imidazo[1,2-] according to claim 2 a Pyridine compounds, characterized in that, R1 is selected from phenyl or pyridyl; the phenyl group is unsubstituted or substituted with one or more substituents selected from methyl, methoxy, fluorine, chlorine, trifluoromethyl, nitro, or cyano. R2 and R3 are each independently selected from hydrogen; R4 is selected from hydrogen or methyl; R5 is selected from hydrogen; R6 is selected from hydrogen or methyl; R7 is selected from -CH(CH3)2, -C(CH3)3, -CHCH3CH2CH3, -CH2CH2Cl, -CH2CH2F, -CH2CH2OCH3, -CH2CH2SCH3, -CH2CONHCH2CF3, -CH2CH2SO2CH3, cyclopropyl, -CH2-cyclopropyl, cyclobutyl, -CH2-cyclobutyl, -cyanocyclopropyl, -CH2-methylcyclopropyl, -CH2-methylcyclobutyl, - Difluorocyclobutyl, -difluorocyclopropyl, -oxetyl, -methyl-oxetyl, -thiocyclobutyl, -methylcyclopropyl, -CH2CF3, phenyl, pyridyl, pyrimidinyl, thiopheneyl, furanyl, thiazolyl, oxazolyl; wherein the phenyl, pyridyl, pyrimidinyl, thiopheneyl, furanyl, thiazolyl, oxazolyl are unsubstituted or substituted with methyl, methoxy, fluorine, chlorine, bromine, iodine, cyano, nitro, trifluoromethyl, or hydroxyl groups.

4. The imidazo[1,2-] according to claim 3 a Pyridine compounds, characterized in that, Imidazolo[1,2-a]pyridine compounds are selected from any of the structures shown: 。 5. The imidazo[1,2-] according to claim 4 a Pyridine compounds, characterized in that, Imidazolo[1,2-a]pyridine compounds are selected from any of the structures shown: 。 6. The imidazo[1,2-] according to claim 4 a Pyridine compounds, characterized in that, Imidazolo[1,2-a]pyridine compounds are selected from any of the structures shown: 。 7. The imidazo[1,2-] according to any one of claims 1-6 a A method for preparing pyridine compounds, characterized in that, Includes the following steps: (1) The 6-bromo-2-aminopyridine derivative intermediate shown in formula (II) and the α-haloketone derivative shown in formula (III) were subjected to a cyclization condensation reaction in an organic solvent to obtain the intermediate shown in formula (IV); (2) The intermediate shown in formula (IV) is subjected to a substitution reaction with CuCN in an organic solvent to obtain the intermediate shown in formula (V); (3) Hydrolyze the product shown in formula (V) under alkaline conditions to obtain the carboxylic acid intermediate shown in formula (VI); (4) The carboxylic acid shown in formula (VI) is subjected to acyl chlorination or condensation with different amines or amine hydrochlorides to obtain the compound shown in formula (Ia); 。 8. An agricultural composition, characterized in that, Include: (a) 0.001-99.99% by weight of the imidazo[1,2-] according to any one of claims 1-6 a Pyridine compounds or their pesticide-acceptable salts, or combinations thereof; and (b) Acceptable carriers and / or excipients for pesticides.

9. The imidazo[1,2-] according to any one of claims 1-6 a The use of pyridine compounds or their pesticide-acceptable salts or the agricultural composition of claim 8 in the preparation of a pesticide for controlling pests or in the preparation of an insecticide.

10. The application according to claim 9, characterized in that, The pests include one or more of the following: Lepidoptera, Coleoptera, Hemiptera, Thysanoptera, Diptera, Orthoptera, Homoptera, Isoptera, Hymenoptera, and Blattodea.

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