Imidazopyrimidone-containing derivative as well as preparation method and application thereof

Abstract

The invention discloses an imidazo pyrimidone-containing derivative and a preparation method and application thereof, and a series of imidazo pyrimidone-containing skeleton derivatives are synthesized by taking an imidazo pyrimidone-containing skeleton as a pilot structure and grafting different pharmacophores on the basis of the pilot structure. In-vitro tests of the compounds show that the compounds have effects on plant pathogenic bacteria such as Xanthomonas oryzae pv. Oryzae, Xanthomonas citri, Xanthomonas oryzae pv. Oryzae and Xanthomonas syringae pv. Actinidia; the compound has an excellent inhibition effect on plant pathogenic fungi such as rhizoctonia solani, colletotrichum chinense, alternaria solani and the like. Especially, the EC50 of most of the halogen-containing compounds to Xanthomonas oryzae pv. Oryzae and Xanthomonas citri pv. Citri is within 10 [mu] g / mL, especially the EC50 of the compound 14 to Xanthomonas oryzae pv. Oryzae is 3.86 [mu] g / mL, the EC50 of the compound 14 to Xanthomonas citri pv. Citri is 4.04 [mu] g / mL, and the halogen-containing compounds have good antibacterial activity.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical chemistry, and specifically relates to a class of imidazo[1,2 - a]pyrimidin - 4(3H)-one derivatives, their preparation methods and applications. Background Art

[0002] Plant fungal and bacterial diseases are high - frequency diseases in agricultural production, causing great losses to grain yields every year and leading to a decline in the quality of agricultural products. Plant bacterial diseases are very difficult to control due to their characteristics of explosiveness, epidemicity and destructiveness. Once a plant is infected, the planting area may become a lifelong epidemic area. Bacterial diseases can occur in vegetables, fruit trees or other cash crops, and a single plant can be affected by multiple diseases. Common pathogenic bacteria causing bacterial diseases include Xanthomonas oryzae pv. oryzae, Xanthomonas citri subsp. citri, and Pseudomonas syringae pv. actinidiae. It is reported that the diseased fruit rate of citrus canker in Hunan region reaches 15%; after kiwifruit is infected with canker, local ulcers rot, resulting in weak tree vigor and the diseased plant rate as high as 20%.

[0003] Agricultural fungicides have become the most important means for controlling plant bacterial diseases due to their characteristics of high efficiency and quick - acting. However, due to limited varieties, long - term non - standard use and abuse, drug resistance of strains has emerged, and serious problems such as excessive pesticide residues and environmental pollution have been caused. In the context of the national agricultural green development era, it is necessary to closely follow the policies and place the creation of new pesticides with high efficiency, low toxicity and low residues in an important position to provide strong support for the green development of agricultural production.

[0004] Imidazo[1,2 - a]pyrimidin - 4(3H)-one - skeleton - containing compounds such as small molecules like ONC212 and ONC201 have anti - tumor and anti - leukemia cell effects in the medical field. Among them, ONC201 has been put into clinical research. In addition, in the field of pesticides, it has been found that the in vitro antibacterial activity of ONC212 against Xanthomonas oryzae pv. oryzae reaches 10.9 μg / mL, and it has a significant protective effect on the Xanthomonas oryzae pv. oryzae model in the greenhouse, which also opens up a broad space for the research of pesticide formulations. How to use the imidazo[1,2 - a]pyrimidin - 4(3H)-one skeleton as a lead structure to find highly antibacterial active compounds is an urgent problem to be solved. Summary of the Invention

[0005] In view of the deficiencies in the above - mentioned problems, the present invention provides a compound containing an imidazo[1,2 - a]pyrimidin - 4(3H)-one skeleton, or its stereoisomer, or its salt, or its solvate. The compound has a structure shown in the general formula (I):

[0006]

[0007] Wherein, Y is any one of CH 2 , C = O, S(=O) 2 among them.

[0008] R1 is selected from one or more of: hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted amino or heterocyclic amino, and optionally substituted or unsubstituted heteroaryl.

[0009] R2 is selected from one or more of hydrogen, deuterium, halogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted amino or heterocyclic amino, and optionally substituted or unsubstituted heteroaryl.

[0010] Preferably, the substitution is by one or more of halogen, methyl, methoxy, cyclopropyl, cyclohexyl, tert-butyl, nitro, trifluoromethyl, and trifluoromethoxy.

[0011] The present invention also provides a method for preparing a compound containing an imidazopyrimidinone skeleton as described above, comprising the following steps:

[0012] (1) Ethylene thiourea and methyl iodide are mixed in methanol, heated and stirred until the reaction is complete, and after removing the solvent, the intermediate 1 is obtained by purification through column chromatography.

[0013] (2) Dichloromethane is added to the intermediate 1 obtained in step (1), and after adding triethylamine, methyl chloroformate is added dropwise thereto, and the reaction is carried out with stirring at 0 °C. After the reaction is complete, it is extracted multiple times with saturated brine, dried, and the solvent is removed to obtain intermediate 2.

[0014] (3) The intermediate 2 obtained in step (2) is dissolved in a methanol solution containing acetic acid, and a substituted benzylamine is added for reaction. After the reaction is completed, the pH is adjusted to 9-10 with an aqueous sodium hydroxide solution, extracted with ethyl acetate, dried, and the solvent is removed to obtain intermediate 3.

[0015] (4) The intermediate 3 obtained in step (3) and ethyl 1-Boc-5-oxoazepane-4-carboxylate are dissolved in methanol, and the reaction is carried out with stirring under heating conditions using sodium methoxide as a catalyst. After the reaction is complete, the solvent is removed to obtain intermediate 4.

[0016] (5) The intermediate 4 obtained in step (4) is added to a 5:1 mixture of dichloromethane and trifluoroacetic acid. After the reaction is completed, the pH is adjusted to 9-10 with an aqueous sodium hydroxide solution, extracted with ethyl acetate, dried, and the solvent is removed to obtain intermediate 5.

[0017] (6) The intermediate 5 obtained in step (5) is dissolved in dichloromethane or N,N-dimethylformamide containing triethylamine, and after adding the substituted halide, the reaction is carried out at 0 °C or room temperature to obtain the target compound 6.

[0018] The specific synthetic chemical equation is as follows:

[0019]

[0020] Correspondingly, the composition contains an imidazopyrimidinone skeleton compound or its stereoisomer, or its salt or its solvate.

[0021] Preferably, the dosage form of the required composition is selected from: emulsifiable concentrate, powder, wettable powder, granule, aqueous solution, suspension, ultra-low volume spray, soluble powder, microcapsule, smoke agent, emulsion in water or water dispersible granule.

[0022] Correspondingly, the application of the compound shown in the above formula (I) or its stereoisomer or its salt or its solvate or the above composition in controlling agricultural pests and diseases.

[0023] Preferably, the agricultural pests and diseases are plant bacterial or fungal diseases.

[0024] Preferably, the bacterial disease is any one of Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri, Pseudomonas syringae pv. actinidiae, Ralstonia solanacearum.

[0025] Preferably, the fungal disease is any one of Botryosphaeria dothidea, Fusarium oxysporum, Colletotrichum coccodes, Colletotrichum gloeosporioides, Colletotrichum camelliae, Colletotrichum graminicola, Alternaria alternata, Verticillium dahliae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. nicotianae, Fusarium solani, Alternaria solani, Rhizoctonia solani.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] Using the imidazopyrimidinone skeleton as a lead structure and incorporating different pharmacophores thereon, a series of derivatives containing the imidazopyrimidinone skeleton were synthesized. This class of compounds showed excellent inhibitory effects against phytopathogenic bacteria such as Xanthomonas oryzae pv. oryzae and Xanthomonas citri subsp. citri. In vitro test data indicated that the target compounds exhibited good inhibitory activities against phytopathogenic bacteria (such as Xanthomonas oryzae pv. oryzae, Xanthomonas citri subsp. citri, and Pseudomonas syringae pv. actinidiae). Among them, the EC50 values of most compounds containing halogens in their structures against Xanthomonas oryzae pv. oryzae and Xanthomonas citri subsp. citri were within 10 μg / mL. In particular, the EC50 value of compound 14 against Xanthomonas oryzae pv. oryzae was 3.86 μg / mL, and the EC50 value against Xanthomonas citri subsp. citri was 4.04 μg / mL. In the in vitro experiment, compound 14 showed good antibacterial activities against Colletotrichum graminicola and Alternaria solani, and the inhibition rates were 69.55% and 61.10% respectively when the concentration was 25 μg / mL. Compound 16 had the best antibacterial activity against Rhizoctonia solani, and its inhibition rate was 41.37%, better than the commercial drug carbendazim. Thus, it can be seen that this series of compounds has excellent antibacterial activities. Detailed implementation manners

[0028] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention. If not specifically specified, the technical means used in the implementation examples are conventional means well-known to those skilled in the art.

[0029] Example 1

[0030] Intermediate 1: Preparation of 2-(methylthio)-4,5-dihydro-1H-imidazole hydroiodide.

[0031] The preparation route is as follows:

[0032]

[0033] The preparation process is as follows:

[0034] In a 150 mL round-bottom flask, add ethylene thiourea (10.00 g, 0.098 mol) and 75 mL of anhydrous methanol and stir. Then add methyl iodide (9.14 mL, 0.15 mol) thereto, heat and stir for 6 h until the reaction is complete, and monitor the completion of the reaction by TLC. After the reaction is complete, evaporate the solvent by rotary evaporation, and purify and separate by column chromatography to obtain 2-(methylthio)-4,5-dihydro-1H-imidazole hydroiodide.

[0035] Example 2

[0036] Intermediate 2: Preparation of 2-(methylthio)-4,5-dihydro-1H-imidazole-1-carboxylate.

[0037]

[0038] The preparation process is as follows:

[0039] In a 500 mL round-bottom flask, add 2-(methylthio)-4,5-dihydro-1H-imidazole hydroiodide (20.00 g, 0.082 mol), then add 200 mL of dichloromethane as a solvent. After adding triethylamine (34.07 mL, 0.25 mol), dropwise add methyl chloroformate (7.62 mL, 0.098 mol) into it, and stir the reaction at 0 °C. Monitor the completion of the reaction by TLC. After the reaction is completed, extract it multiple times with saturated brine, dry it with anhydrous sodium sulfate, and remove the solvent by rotary evaporation to obtain the compound 2-(methylthio)-4,5-dihydro-1H-imidazole-1-carboxylate, and then directly proceed to the next experiment.

[0040] Example 3

[0041] Intermediate 3: Preparation of 2-(((4-(trifluoromethyl)phenyl)methyl)amino)-4,5-dihydro-3H-imidazole.

[0042]

[0043] The preparation process is as follows:

[0044] In a 250 mL round-bottom flask, add 2-(methylthio)-4,5-dihydro-1H-imidazole-1-carboxylate (10.00 g, 0.057 mol) and 100 mL of anhydrous methanol solution as a solvent, add 32.83 mL of glacial acetic acid, and finally add 4-(trifluoromethyl)benzylamine (10.56 g, 0.060 mol) to carry out the reaction. Monitor the completion of the reaction by TLC. After the reaction is completed, add redistilled water, adjust the pH to 9 - 10 with sodium hydroxide solution, extract it with ethyl acetate and then dry it, and remove the solvent by rotary evaporation to obtain 2-(((4-(trifluoromethyl)phenyl)methyl)amino)-4,5-dihydro-3H-imidazole.

[0045] Example 4

[0046] Intermediate 4: Preparation of 5-oxo-4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepine-8-carboxylic acid 2-methylpropan-2-yl ester.

[0047]

[0048] The preparation process is as follows:

[0049] Add 2-(((4-(trifluoromethyl)phenyl)methyl)amino)-4,5-dihydro-3H-imidazole (6.39 g, 0.026 mol) dissolved in 60 mL of methanol into a 150 mL round-bottom flask. Use sodium methoxide (1.89 g, 0.035 mol) as a catalyst, add ethyl 1-Boc-5-oxoazepane-4-carboxylate (5.00 g, 0.018 mol), stir and react under reflux conditions, and monitor the completion of the reaction by TLC. After the reaction is completed, remove the solvent and purify by column chromatography to obtain the intermediate 5-oxo-4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepane-8-carboxylic acid 2-methylpropyl ester.

[0050] Example 5

[0051] Preparation of Intermediate 5: 4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepan-5-one.

[0052]

[0053] The preparation process is as follows:

[0054] Add 5-oxo-4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepane-8-carboxylic acid 2-methylpropyl ester into a 150 mL round-bottom flask, then add dichloromethane (60 mL) and trifluoroacetic acid (12 mL) in a ratio of 5:1. After the reaction is completed, add redistilled water, adjust the pH to 9-10 with sodium hydroxide solution, extract with ethyl acetate, dry with anhydrous sodium sulfate, and rotary evaporate to remove the solvent to obtain the intermediate 4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepan-5-one.

[0055] Example 6

[0056] Preparation of Target Compound 6: 8-benzyl-4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepan-5-one.

[0057]

[0058] The preparation process is as follows:

[0059] Add the intermediate 4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepin-5-one (0.25 g, 0.686 μmol) into a 15 mL pressure-resistant tube. After dissolving it with N,N-dimethylformamide, add triethylamine (0.19 mL, 1.39 mmol), and finally add benzyl bromide (0.097 mL, 0.823 mmol). Stir the reaction at room temperature, and monitor the completion of the reaction by TLC. After the reaction is completed, remove the solvent and purify it by column chromatography to obtain the target compound 8-benzyl-4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepin-5-one.

[0060] Example 7

[0061] Preparation of the target compound 6: 8-[(4-methylphenyl)carbonyl]-4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepin-5-one.

[0062]

[0063] Add the intermediate 4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepin-5-one (0.25 g, 0.686 μmol) into a 100 mL round-bottom flask. After dissolving it with dichloromethane, add triethylamine (0.19 mL, 1.39 mmol), and finally add 4-methylbenzoyl chloride (0.109 mL, 0.823 mmol). Stir the reaction at 0 °C, and monitor the completion of the reaction by TLC. After the reaction is completed, remove the solvent and purify it by column chromatography to obtain the target compound 8-[(4-methylphenyl)carbonyl]-4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepin-5-one.

[0064] Example 8

[0065] Preparation of Target Compound 6: 8-[(4-Methylphenyl)dioxido-λ6-sulfanyl]-4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepin-5-one

[0066]

[0067] Add intermediate 4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepin-5-one (0.25 g, 0.686 μmol) into a 100 mL round-bottom flask. After dissolving it with dichloromethane, add triethylamine (0.19 mL, 1.39 mmol), and finally add 4-methylbenzenesulfonyl chloride (0.157 g, 0.823 μmol). Stir the reaction at 0 °C, and monitor the completion of the reaction by TLC. After the reaction is completed, remove the solvent and purify by column chromatography to obtain the target compound 8-[(4-methylphenyl)dioxido-λ6-sulfanyl]-4-{[4-(trifluoromethyl)phenyl]methyl}-2,4,5,6,7,8,9,10-octahydro-1H-imidazo[1',2':1,2]pyrimido[6,5-d]azepin-5-one

[0068] The structures, 1H NMR and 13C NMR data of other synthesized imidazopyrimidinone skeleton compounds are shown in Table 1, and their physical and chemical properties are shown in Table 2

[0069] Table 1: 1H NMR, 13C NMR and HRMS Data of Compounds

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077]

[0078]

[0079] Table 2: Physicochemical properties of the target compounds

[0080]

[0081]

[0082] Example 9

[0083] Applications of the target compounds.

[0084] EC of the compound against phytopathogenic bacteria 50 value.

[0085] The effective median concentration EC50 of the target compound against phytopathogenic bacteria was tested by the turbidimetry method. The test objects were Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas citri subsp. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa). DMSO was dissolved in the culture medium as a blank control.

[0086] The specific operations are as follows: 1) Transfer the monoclonal strains of Xoo, Xac, and Psa (originally cultured on NA solid medium) to NB medium and shake-culture them in a constant-temperature shaker at 28°C and 180 rpm until the logarithmic growth phase for standby; 2) Add 5 mL of toxic NB liquid medium with different concentrations (e.g., 100, 50, 25, 12.5, and 6.25 μg / mL) of the agent / compound to test tubes, and measure the OD595 value of the corresponding concentration of toxic sterile NB liquid medium (recorded as the OD value of the sterile medium); 3) Add 40 μL of the bacterial solution cultured to the logarithmic growth phase to all the treated test tubes, shake-culture them in a constant-temperature shaker at 28°C and 180 rpm until the OD595 value of the CK group is 0.6 - 0.8, and then measure the OD595 value of the bacterial solution at each concentration on a spectrophotometer (recorded as the OD value of the bacteria-containing medium); 4) Calculate the inhibition rate (%) using the following formula: Corrected OD value = OD value of the bacteria-containing medium - OD value of the sterile medium; Inhibition rate % = [(OD value of the bacterial solution in the control medium after correction - OD value of the toxic medium after correction) / OD value of the bacterial solution in the control medium after correction] × 100; According to the above method, the experimental results of the target compounds in Table 1 above are shown in Table 3. It can be seen from Table 3 that in the in vitro test, the target compounds showed good inhibitory activity against phytopathogenic bacteria (such as Xanthomonas oryzae pv. oryzae, Xanthomonas citri subsp. citri, and Pseudomonas syringae pv. actinidiae). Among them, most of the compounds containing halogens in the structure had EC50 values against Xanthomonas oryzae pv. oryzae and Xanthomonas citri subsp. citri within 10 μg / mL. In particular, the EC50 of compound 14 against Xanthomonas oryzae pv. oryzae was 3.86 μg / mL, and the EC50 against Xanthomonas citri subsp. citri was 4.04 μg / mL.

[0087] Table 3: EC50 values of the compounds against phytopathogenic bacteria

[0088]

[0089]

[0090]

[0091] Example 10

[0092] Application of the target compound

[0093] The mycelial growth rate method, also known as the toxic medium method, is one of the conventional methods for determining the toxicity of fungicides. The main principle is to mix the test agent with the culture medium, and measure the toxicity of the agent by the growth rate of the colony on the toxic culture medium. In this example, Rhizoctonia solani, Colletotrichum graminicola, and Alternaria solani were used as test objects, and DMSO was used as the blank control. The specific operations are as follows: 1) Weigh an appropriate amount of the drug according to the test concentration, dissolve it with DMSO (the dosage does not exceed 1% of the final toxic culture medium), then add a 0.1% Tween 20 solution to make up to 10 mL, pour it into 90 mL of melted PDA culture medium, mix well and pour it into 9 petri dishes for standby; 2) Sterilize the puncher (inner diameter 5 mm) by burning. After it cools down, punch the mycelium at the edge of the pre-activated strain, and use an inoculation needle to attach its mycelial surface to the center of the toxic culture medium. After the treatment is completed, place them in an incubator at 25 °C for cultivation; 3) After the colony diameter of the control group grows to 5.5 - 6.6 cm, use the cross method to measure the colony diameters of the control group and each agent treatment group; 4) Use the following formula to calculate the inhibition rate (%): Inhibition rate % = (C - T) / (C - 0.5) × 100; where C is the colony diameter of the control group, T is the colony diameter of the agent treatment group, and 0.5 is the diameter of the inoculated fungal cake. According to the above method, the experimental results of the target compounds in Table 1 above are shown in Table 4. It can be seen from Table 4 that in the in vitro experiment, compound 14 has good antibacterial activity against Colletotrichum graminicola and Alternaria solani, and the inhibition rates are 69.55% and 61.10% respectively when the concentration is 25 μg / mL. Compound 16 has the best antibacterial activity against Rhizoctonia solani, and its inhibition rate is 41.37%, which is better than the commercial drug carbendazim. Thus, it can be known that this series of compounds can be used to prepare pesticides against plant pathogenic fungi.

[0094] Table 4: Inhibitory activity of compounds against plant pathogenic fungi (25 μg / mL)

[0095]

[0096] The embodiments described above are only descriptions of the preferred embodiments of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

[0097] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not limitations. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the purpose and scope of the technical solutions of the present invention, and they should all be covered by the scope of the claims of the present invention. The protection scope of this application should be subject to the protection scope of the claims.

Claims

1. A class of imidazopyrimidone derivatives, characterized in that : The compound has a structure as shown in the general formula (I): Wherein, Y is any one of CH2, C=O, S(=O)2; R1 is selected from the group consisting of: hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted amine or heterocyclic amine, optionally substituted or unsubstituted heteroaryl; R2 is selected from one or more of hydrogen, deuterium, halogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted amine or heterocyclic amine, and optionally substituted or unsubstituted heteroaryl.

2. The imidazopyrimidone derivative according to claim 1, characterized in that: The substitution refers to one or more of hydrogen, deuterium, amino, hydroxyl, halogen, methyl, methoxy, cyclopropane, cyclohexane, tert-butyl, nitro, trifluoromethyl, and trifluoromethoxy.

3. A method for preparing a class of imidazopyrimidone derivatives according to any one of claims 1-2, characterized in that: The preparation method comprises the following steps: (1) Ethylene thiourea and methyl iodide are mixed in methanol, heated and stirred to complete the reaction, and then the solvent is removed and purified by column chromatography to obtain intermediate 1; (2) adding dichloromethane to the intermediate 1 obtained in step (1), and then adding triethylamine and dropwise adding methyl chloroformate thereto, stirring at 0° C. to react, and after the reaction is completed, extracting with saturated brine for multiple times, drying and removing the solvent to obtain the intermediate 2; (3) The intermediate 2 obtained in step (2) is dissolved in a methanol solution containing acetic acid, and a substituted benzylamine is added to react. After the reaction is completed, the pH is adjusted to 9-10 with an aqueous sodium hydroxide solution, extracted with ethyl acetate and dried, and the solvent is removed to obtain an intermediate 3; (4) dissolving the intermediate 3 obtained in step (3) and ethyl 1-Boc-5-oxoazepane-4-carboxylate in methanol, using sodium methoxide as a catalyst and stirring to react under heating conditions, and after the reaction is completed, removing the solvent to obtain intermediate 4; (5) adding dichloromethane and trifluoroacetic acid in a ratio of 5:1 to the intermediate 4 obtained in step (4), adjusting the pH to 9-10 with an aqueous sodium hydroxide solution after the reaction is completed, extracting with ethyl acetate and drying, and removing the solvent to obtain the intermediate 5; (6) Dissolving the intermediate 5 obtained in step (5) in dichloromethane or triethylamine After adding the substituted halide to N,N-dimethylformamide, the reaction is carried out at 0°C or room temperature to obtain the target compound 6.

4. A composition, characterized in that The composition contains the imidazopyrimidone derivative or its stereoisomer, or its salt or solvate according to any one of claims 1 to 3.

5. The dosage form of the composition as claimed in claim 4 is selected from: emulsifiable concentrate, dust, wettable powder, granule, aqueous solution, suspension, ultra-low volume spray, soluble powder, microcapsule, smoke agent, aqueous emulsion or water-dispersible granule.

6. Use of the compound represented by formula (I) according to claim 1 or 2, or its stereoisomer, or its salt, or its solvate, or the composition according to claim 4 or 5 in controlling agricultural pests and diseases.

7. The use according to claim 6, characterized in that: The agricultural pests and diseases are plant bacterial or fungal diseases.

8. The use according to claim 7, characterized in that: The bacterial disease is any one of rice bacterial blight pathogen, citrus canker pathogen, kiwi fruit canker pathogen and tobacco bacterial wilt pathogen.

9. The use according to claim 7, characterized in that: The fungal disease is any one of Botrytis cinerea, Fusarium oxysporum, Colletotrichum solani, Colletotrichum gloeosporioides, Colletotrichum kaoliang, Colletotrichum kaoliang, Alternaria alternata, Verticillium wilt of eggplant, Fusarium wilt of pepper, Fusarium wilt of tobacco, Fusarium wilt of tobacco, Alternaria alternata, and Sheath blight of rice.

Images