Pyridino [1, 2-a] pyrimidine mesoion derivative containing five-membered heterocyclic structure as well as preparation and application of pyridino [1, 2-a] pyrimidine mesoion derivative

Abstract

The invention relates to a pyrido [1, 2-a] pyrimidine mesoion derivative containing a five-membered heterocyclic structure as well as a preparation method and application of the pyrido [1, 2-a] pyrimidine mesoion derivative. The compound is shown as a general formula (I), and in the general formula (I), R1 represents cyanoalkyl, aryl or heterocyclic radical; e, G, M and Q independently represent O, S, N or CR3 respectively; r2 and R3 represent hydrogen, alkyl, nitryl, cyano, halogen and the like. The compound has excellent insecticidal activity on pea myzus persicae, spodoptera frugiperda, ostrinia nubilalis, beet armyworm, brown planthopper, chilo suppressalis, alfalfa aphid and the like. (I).

Description

Technical Field

[0001] This invention relates to the fields of chemical engineering and pesticides, and more specifically to pyrido[1,2-]pyrido[ ... a Pyrimidine mesonotropic derivatives and their preparation methods, and pyrido[1,2-]pyrido[1,2-]pyridyl[2,2-]pyridyl[3 ... a Application of pyrimidine derivatives in pesticides for controlling pests such as pea aphid, fall armyworm, corn borer, beet armyworm, brown planthopper, rice stem borer and alfalfa aphid. Background Technology

[0002] To address the challenges of a growing global population and decreasing arable land due to urbanization, it is essential to continuously increase food production. Pests are a major threat to food security. Insecticides play a crucial role in protecting crops from pests and ensuring food security. However, due to the long-term, excessive, and unregulated use of traditional insecticides, pests have developed significant resistance. For example, according to the Arthropod Pesticide Resistance Database (APRD), the brown planthopper (… Nilaparvata is mourning. The beet armyworm (Spodoptera litura) has developed varying degrees of resistance to 36 effective insecticides, with resistance to imidacloprid generally exceeding 1000 times. This was observed in beet armyworms collected from Zhejiang Province in 2019. Spodoptera small The population exhibited a resistance fold of over 2000 times to chlorantraniliprole. In 2024, the rice stem borer (Chilodonella esculenta)... Kilo suppressed The populations all exhibited high levels of resistance to chlorantraniliprole, with resistance multiples ranging from 160 to 1698 times. Therefore, there is an urgent need to develop new, highly effective insecticides to alleviate the increasingly serious resistance problem.

[0003] Corteva (formerly DuPont) has developed two novel mesoionic insecticides, trifluoropyrimidine and dicloromezotiaz, which possess novel structures, unique mechanisms of action, and no cross-resistance with existing insecticides. Therefore, research into novel mesoionic insecticides, spearheaded by trifluoropyrimidine and dicloromezotiaz, has become a hot topic in pesticide development research both domestically and internationally.

[0004] WO2011017342A2, WO2012106495A1, WO2016171053A1 and WO2021151034A1 disclose a large number of pyridyl[1,2-] ... a [Methanogenic compounds derived from the 1- and 3-positions of the pyrimidine ring. Our research team has also confirmed the presence of five-membered heterocycles in pyrido[1,2-]pyrimidine rings in patents CN113651811B and CN117720535B.] a Substitution at the 3-position of the pyrimidine ring exhibits excellent insecticidal activity.

[0005] Therefore, in pyrido[1, 2- a The pyrimidine ring retains the active group commonly found in neonicotinoid insecticides at the 1-position, and incorporates the broadly bioactive structures of thiazole, thiophene, furan, and oxazole into the pyridine ring [1, 2-]. a The 3-position of the pyrimidine ring holds promise for creating highly efficient and broad-spectrum insecticidal compounds.

[0006] invention content.

[0007] One objective of this invention is to provide a class of pyrido[1,2-]pyridines containing a five-membered heterocyclic structure. a Pyrimidine mesonotropic derivatives and their preparation methods.

[0008] Another object of the present invention is to provide a composition containing the above-mentioned compound or its salt.

[0009] Another object of the present invention is to provide the use of the above-mentioned compound or its salt, or the composition thereof.

[0010] Another object of the present invention is to provide a method for controlling agricultural pests using the above-mentioned compound or its salt, or the composition thereof.

[0011] The present invention relates to a pyrido[1,2-] ... a The general structural formula (I) of pyrimidine mesonotropic derivatives is as follows: To achieve the above objectives, the present invention adopts the following technical solution: (I) R 1 Independently selected from cyanoalkyl, aryl, or heterocyclic groups; more preferably, R 1 Selected from cyano C1-C8 alkyl, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; E, G, M, and Q independently represent O, S, N, or CR, respectively. 3 ; R 2 R 3 Independently representing hydrogen, nitro, cyano, halogen, hydroxyl, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, formyl, alkylcarbonyl, alkyl sulfoxide, alkylsulfonyl, alkyl-substituted amino, cycloalkyl, aryl, or heterocyclic group; preferably, R 2 R 3 Independently representing hydrogen, nitro, cyano, halogen, hydroxyl, mercapto, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, C1-C8 alkoxy, C1-C8 alkylthio, halo-C1-C8 alkoxy, halo-C1-C8 alkylthio, formyl, C1-C8 alkyl carbonyl, C1-C8 alkyl sulfoxide, C1-C8 alkyl sulfonyl, amino group substituted with C1-C8 alkyl, C3-C8 cycloalkyl, aryl or heterocyclic group; more preferably, R 2 R 3 Each of these groups independently represents hydrogen, nitro, cyano, halogen, hydroxyl, mercapto, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkylthio, halo-C1-C6 alkoxy, halo-C1-C6 alkylthio, formyl, C1-C6 alkyl carbonyl, C1-C6 alkyl sulfoxide, C1-C6 alkyl sulfonyl, amino group substituted with C1-C6 alkyl, C3-C6 cycloalkyl, aryl or heterocyclic group; The aforementioned "cycloalkyl" is optionally replaced by at least one group selected from halogen, cyano, nitro, alkyl, alkenyl, ynyl, cycloalkyl, haloalkyl, haloalkenyl, haloynyl, halocycloalkyl, alkyl-substituted cycloalkyl, or cycloalkylalkyl; preferably, it is replaced by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, haloC1-C8 alkyl, haloC2-C8 alkenyl, haloC2-C8 ynyl, haloC3-C8 cycloalkyl, alkyl-substituted cycloalkyl, or cycloalkylalkyl. The alkyl-substituted C3-C8 cycloalkyl or C3-C8 cycloalkyl-C1-C8 alkyl group is substituted; more preferably, it is substituted by at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 ynyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted with C1-C6 alkyl or C3-C6 cycloalkyl-C1-C6 alkyl. The aforementioned "heterocyclic group" or "aryl group" is optionally selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, alkyl-substituted cycloalkyl, cycloalkylalkyl, unsubstituted or substituted by at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy. Preferably, the aryl or heterocyclic group is selected from oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, halo-C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted with C1-C8 alkyl, C3-C8 cycloalkyl C1-C8 alkyl, unsubstituted or substituted with at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halo-C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halo-C1-C8 alkoxy. More preferably, the aryl or heterocyclic group is selected from at least one group selected from oxo, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted with C1-C6 alkyl, C3-C6 cycloalkyl C1-C6 alkyl, unsubstituted or substituted with at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halo-C1-C6 alkoxy.

[0012] Preferably, yes , , , , , , , , , , .

[0013] Preferred compounds include compounds S1-S19 as described below.

[0014] The method for preparing the compound includes: Preferably, it further includes: Wherein, X is selected from iodine, bromine or chlorine, and the catalyst is [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride or bis(triphenylphosphino)palladium dichloride.

[0015] The present invention also provides a composition comprising the compound or a salt thereof, and an agriculturally available adjuvant or fungicide, insecticide or herbicide; preferably, the formulation of the composition is selected from emulsifiable concentrates (EC), powders (DP), wettable powders (WP), granules (GR), aqueous solutions (AS), suspensions (SC), ultra-low volume sprays (ULV), soluble powders (SP), microcapsules (MC), fumigants (FU), emulsions (EW), water-dispersible granules (WG), and microemulsions (ME).

[0016] The compound or its salt, or composition, can be used to prepare pesticides for controlling agricultural pests and diseases, wherein the agricultural pests and diseases are hemiptera and lepidopteran pests; preferably, the agricultural pests are pea aphids, fall armyworms, corn borers, beet armyworms, brown planthoppers, rice stem borers, and alfalfa aphids.

[0017] This invention provides a method for controlling agricultural pests and diseases, by applying the compound or its salt, or the composition, to a pest or its habitat; preferably, the pest is a hemiptera or lepidopteran insect; more preferably, the agricultural pest is a pea aphid, fall armyworm, corn borer, beet armyworm, brown planthopper, rice stem borer, and alfalfa aphid.

[0018] As used herein, the term "alkyl" includes branched and straight-chain saturated hydrocarbon groups having a specific number of carbon atoms. For example, "C1-C6 alkyl" refers to an alkyl group having 1 to 6 carbon atoms, and "C1-C8 alkyl" refers to an alkyl group having 1 to 8 carbon atoms. Alkyl groups can be unsubstituted or substituted, such that one or more of their hydrogen atoms are replaced by other chemical groups. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl (such as n-propyl and isopropyl), butyl (such as n-butyl, isobutyl, and tert-butyl), pentyl (such as n-pentyl, isopentyl, and neopentyl), and the like.

[0019] "Alkenyl" refers to hydrocarbons that can be straight-chain or branched and have one or more carbon-carbon double bonds that appear at any stable point in the chain. For example, "C2-C6 alkenyl" (or alkenylidene) aims to include C2, C3, C4, C5, and C6 alkenyl groups. Examples of alkenyl groups include, but are not limited to, vinyl, 1-propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl, and their analogues.

[0020] The term "cycloalkyl" refers to cycloalkyl groups, including mono-, di-, or polycyclic systems. The C3-C6 cycloalkyl group aims to include C3, C4, C5, and C6 cycloalkyl groups. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and their analogues. As used herein, "carbocyclic" or "carbocyclic remnant" refers to any stable 3, 4, 5, 6, or 7-membered monocyclic or bicyclic, or 7, 8, 9, 10, 11, 12, or 13-membered dicyclic or tricyclic, which may be saturated, partially unsaturated, unsaturated, or aromatic. Examples of these carbocyclic rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, pentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadiene, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane, [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, anthracene, and tetrahydronaphthyl (naphthyl). As mentioned above, bridged rings are also included in the definition of carbocyclic rings (such as [2.2.2]bicyclooctane). Unless otherwise specified, preferred carbocyclic rings are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. When the term "carbocyclic ring" is used, it is intended to include "aryl". A bridged ring occurs when one or more carbon atoms are connected to two non-adjacent carbon atoms. Preferred bridges are one or two carbon atoms. It is noted that a bridge always transforms a monocyclic ring into a bicyclic ring. When the rings are bridged, the substituents of the rings are also present on the bridges.

[0021] The term "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group having 5 to 12 carbon atoms in the ring moiety, including but not limited to phenyl, naphthyl, and others. , Each one can be replaced.

[0022] The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine, and iodine.

[0023] The term "heterocyclic group" refers to, but is not limited to, non-aromatic cyclic groups, whether saturated or unsaturated. , , , , , , , , , , , , , , , , , , , , The range also includes substituted and unsubstituted aromatic 5- or 6-membered monocyclic groups, 9- or 10-membered bicyclic groups, and 11- to 14-membered tricyclic groups, having at least one heteroatom (O, S, or N) in at least one ring, wherein the heteroatom-containing ring preferably has 1, 2, or 3 heteroatoms selected from O, S, and N. Each ring of the heteroatom-containing heteroaryl group may contain one or two oxygen or sulfur atoms and / or 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less, and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. Nitrogen and sulfur atoms may optionally be oxidized and nitrogen atoms may optionally be quaternized. Bicyclic or tricyclic heteroaryl groups must include at least one fully aromatic ring, but the other fused rings may be aromatic or non-aromatic. The heteroaryl group may be attached to any available nitrogen or carbon atom in any ring. Where valence permits, if the other ring is a cycloalkyl or heterocyclic ring, it may optionally be substituted with =O (oxygen), for example... , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , . Attached Figure Description

[0024] Figure 1 The compound used in the examples was in 10 μ g / mL and 1 μ The insecticidal activity against the pea aphid was measured at a concentration of g / mL, with CK serving as the blank control.

[0025] Figure 2 The compound used in the examples was in 10 μ g / mL and 1 μ Insecticidal activity against fall armyworm at a concentration of g / mL, where CK was the blank control.

[0026] Figure 3 The compound used in the examples was in 10 μ g / mL and 1 μ Insecticidal activity against corn borer at a concentration of g / mL, where CK was the blank control. Detailed Implementation

[0027] The present invention will be further illustrated below through examples. It should be understood that the methods described in the examples are merely illustrative and not intended to limit the invention. Simple modifications to the preparation methods of the present invention within the framework of the present invention's concept are all within the scope of protection claimed by the present invention. All raw materials and solvents used in the examples are commercially available reagents of the corresponding purity.

[0028] Example 1: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(2-chlorothiazol-5-yl)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S1): (1) Preparation of 2-(3-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaboranecyclopentane: 20.0 g (80.70 mmol, 1.0 eq) of 3-iodophenylboronic acid was added to a 250 mL Schlenk flask. The air in the system was replaced with nitrogen, and then 100 mL of an ethyl acetate solution of pinacol (11.4 g, 96.8 mmol, 1.2 eq) was added to the system under a nitrogen atmosphere. After the addition was complete, the system was reacted at room temperature for 6 h, and then purified by silica gel column chromatography to give 24.8 g of white solid, with a yield of 93.1%. (2) Preparation of diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate: 2-(3-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentane (24.8 g, 75.2 mmol, 1.0 eq), 2-pyridinecarboxylic acid (1.9 g, 15.0 mmol, 0.2 eq), cuprous iodide (1.4 g, 7.5 mmol, 0.1 eq), and cesium carbonate (61.2 g, 187.9 mmol, 2.5 eq) were added to a 500 mL Schlenk flask. Diethyl malonate (24.1 g, 150.3 mmol) was added to the system under a nitrogen atmosphere, along with 200 mL of anhydrous 1,4-dioxane as a solvent. After the addition was complete, the system was heated to 60 °C and reacted for 5–6 h. After the reaction was complete, the system temperature was lowered to room temperature, and the reaction was quenched by adding 500 mL of saturated ammonium chloride aqueous solution. Ethyl acetate (250 mL) was added to the system. Extracted by 3 mL of the sample, the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 18.2 g of colorless oil, with a yield of 66.85%.

[0029] (3) Preparation of diethyl 2-(3-(2-chlorothiazol-5-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 2-chloro-5-bromothiazole (730.5 mg, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :Vwather =2:1) ​​30 mL, after the addition of the materials, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried with anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 0.7 g of colorless oil, with a yield of 53.8%.

[0030] (4) Preparation of 2-(3-(2-chlorothiazol-5-yl)phenyl)malonic acid: Diethyl 2-(3-(2-chlorothiazol-5-yl)phenyl)malonate (0.7 g, 2.0 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (0.2 g, 5.0 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 450.0 mg of a colorless oil, with a yield of 76.4%.

[0031] (5) Preparation of 2-(3-(2-chlorothiazol-5-yl)phenyl)malonyl chloride: Add 2-(3-(2-chlorothiazol-5-yl)phenyl)malonic acid (450.0 mg, 1.5 mmol), 20 mL of dichloromethane, and 1 drop N , N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0032] (6) N Preparation of 3-((2-chlorothiazol-5-yl)methyl)-3-methylpyridine-2-amine: 2-Amino-3-methylpyridine (10.0 g, 92.5 mmol), 2-chloro-5-chloromethylthiazole (15.5 g, 92.5 mmol), N , NDiisopropylethylamine (14.3 g, 111.0 mmol), potassium iodide (1.5 g, 9.3 mmol), and 150 mL of xylene were mixed in a 500 mL three-necked flask and reacted at 78 °C for 6–10 h. After the reaction was complete, the reaction mixture was desolvated under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 10.8 g of a pale yellow solid, with a yield of 48.72%.

[0033] (7) 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(2-chlorothiazol-5-yl)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S1): Will N A solution of 10 mL of 2-(3-(2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (362.0 mg, 1.5 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(2-chlorothiazol-5-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the mixture was reacted at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 189.0 mg of a yellow solid, with a yield of 25.0%.

[0034] Example 2: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(2-bromothiazol-5-yl)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S2): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(2-bromothiazol-5-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 2-bromo-5-iodothiazole (1.1 g, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather=2:1) ​​30 mL, after the addition of the material, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried with anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 0.9 g of colorless oil, with a yield of 61.4%.

[0035] (4) Preparation of 2-(3-(2-bromothiazol-5-yl)phenyl)malonic acid: Diethyl 2-(3-(2-bromothiazol-5-yl)phenyl)malonate (0.9 g, 2.3 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (226.0 mg, 5.7 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 620.0 mg of a colorless oil, with a yield of 80.2%.

[0036] (5) Preparation of 2-(3-(2-bromothiazol-5-yl)phenyl)malonyl chloride: Add 2-(3-(2-bromothiazol-5-yl)phenyl)malonic acid (620.0 mg, 1.8 mmol), 20 mL of dichloromethane, and 1 drop N , N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0037] Step (6) is the same as step (6) in Example 1. (7) 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(2-bromothiazol-5-yl)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S2): Will NA solution of 10 mL of 2-(3-(2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (434.4 mg, 1.8 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(2-bromothiazol-5-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the mixture was reacted at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 245.0 mg of a yellow solid, with a yield of 24.8%.

[0038] Example 3: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-4-oxo-3-(3-(thiazol-5-yl)phenyl)-4 H -pyrido[1,2- a Pyrimidine inner salt (S3): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(thiazol-5-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 5-bromothiazole (0.6 g, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather =2:1) ​​30 mL, after the addition of the materials, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried with anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 733.0 mg of colorless oil, with a yield of 62.4%.

[0039] (4) Preparation of 2-(3-(thiazol-5-yl)phenyl)malonic acid: Diethyl 2-(3-(thiazol-5-yl)phenyl)malonate (733.0 mg, 2.3 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (229.5 mg, 5.7 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 532.0 mg of a colorless oil, with a yield of 88.1%.

[0040] (5) Preparation of 2-(3-(thiazol-5-yl)phenyl)malonyl chloride: Add 2-(3-(thiazol-5-yl)phenyl)malonic acid (532.0 mg, 2.0 mmol), 20 mL of dichloromethane, and 1 drop N , N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0041] Step (6) is the same as step (6) in Example 1. (7) 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-4-oxo-3-(3-(thiazol-5-yl)phenyl)-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S3): Will N A solution of 10 mL of 2-(3-(2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (484.4 mg, 2.0 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(thiazol-5-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 168.0 mg of yellow solid, with a yield of 17.8%.

[0042] Example 4: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(furan-3-yl)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2-a Pyrimidine inner salt (S4): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(furan-3-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 3-bromofuran (541.0 mg, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather =2:1) ​​30 mL, after the addition of the materials, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried with anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 764.0 mg of colorless oil, with a yield of 68.7%.

[0043] (4) Preparation of 2-(3-(furan-3-yl)phenyl)malonic acid: Diethyl 2-(3-(furan-3-yl)phenyl)malonate (764.0 mg, 2.5 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (252.7 mg, 6.3 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 572.0 mg of a colorless oil, with a yield of 91.9%.

[0044] (5) Preparation of 2-(3-(furan-3-yl)phenyl)malonyl chloride: Add 2-(3-(furan-3-yl)phenyl)malonic acid (572.0 mg, 2.3 mmol), 20 mL of dichloromethane, and 1 drop N ,N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0045] Step (6) is the same as step (6) in Example 1. (7) 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(furan-3-yl)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S4): Will N A solution of 10 mL of 2-((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (556.9 mg, 2.3 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(furan-3-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 301.0 mg of yellow solid, with a yield of 28.8%.

[0046] Example 5: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(furan-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S5): Steps (1) to (5) are the same as steps (1) to (5) in Example 4. (6) N Preparation of -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine: 2-Aminopyridine (10.0 g, 106.3 mmol), 2-chloro-5-chloromethylthiazole (17.9 g, 106.3 mmol), N , N Diisopropylethylamine (16.5 g, 127.5 mmol), potassium iodide (1.8 g, 10.6 mmol), and 150 mL of xylene were mixed in a 500 mL three-necked flask and reacted at 78 °C for 6–10 h. After the reaction was complete, the reaction mixture was desolvated under reduced pressure, stirred with silica gel, and separated by column chromatography to obtain 13.6 g of a pale yellow solid, with a yield of 56.7%.

[0047] (7) 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(furan-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S5): Will N A solution of 10 mL of 2-((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (360.7 mg, 1.6 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(furan-3-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 167.0 mg of yellow solid, with a yield of 24.0%.

[0048] Example 6: 1-((2-chlorothiazol-5-yl)methyl)-4-oxo-3-(3-(thiophen-3-yl)phenyl)-4 H -pyrido[1,2- a Pyrimidine inner salt (S6): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(thiophen-3-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 3-iodothiophene (0.8 g, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather =2:1) ​​30 mL, after the addition of the material, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried with anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 0.8 g of colorless oil, with a yield of 68.3%.

[0049] (4) Preparation of 2-(3-(thiophen-3-yl)phenyl)malonic acid: Diethyl 2-(3-(thiophen-3-yl)phenyl)malonate (800.0 mg, 2.5 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (251.2 mg, 6.3 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 564.0 mg of a colorless oil, with a yield of 85.6%.

[0050] (5) Preparation of 2-(3-(thiophen-3-yl)phenyl)malonyl chloride: Add 2-(3-(thiophen-3-yl)phenyl)malonic acid (564.0 mg, 2.2 mmol), 20 mL of dichloromethane, and 1 drop N , N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0051] Step (6) is the same as step (6) in Example 5. (7) 1-((2-chlorothiazol-5-yl)methyl)-4-oxo-3-(3-(thiophen-3-yl)phenyl)-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S6): Will N A solution of 10 mL of 2-((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (485.3 mg, 2.2 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(thiophen-3-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 182.0 mg of yellow solid, with a yield of 18.7%.

[0052] Example 7: 1-((6-chloropyridin-3-yl)methyl)-4-oxo-3-(3-(thiophen-3-yl)phenyl)-4 H -pyrido[1,2- aPyrimidine inner salt (S7): Steps (1) to (5) are the same as steps (1) to (5) in Example 6. (6) N Preparation of -((6-chloropyridin-3-yl)methyl)pyridin-2-amine: 10.0 g (106.3 mmol) of 2-aminopyridine, 13.4 g (159.4 mmol) of sodium bicarbonate, and 100 mL of water were mixed in a 250 mL three-necked flask and stirred at 90 °C for half an hour. Then, 50 mL of an ethanol solution of 2-chloro-5-chloromethylpyridine (17.2 g, 106.3 mmol) was added. After the addition was complete, the temperature was raised to 100 °C and the reaction proceeded for 4–6 h. After the reaction was complete, the reaction mixture was cooled to room temperature, 100 mL of water was added, and the mixture was extracted with ethyl acetate (100 mL × 2). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed with silica gel, and separated by column chromatography to obtain 13.4 g of a yellowish-brown oily substance, with a yield of 57.4%.

[0053] (7) 1-((6-chloropyridin-3-yl)methyl)-4-oxo-3-(3-(thiophen-3-yl)phenyl)-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S7): Will N A solution of 10 mL of 1-((6-chloropyridin-3-yl)methyl)pyridin-2-amine (325.7 mg, 1.5 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(thiophen-3-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel, and the sample was separated by column chromatography to obtain 89.0 mg of yellow solid, with a yield of 13.5%.

[0054] Example 8: 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(2-chlorothiaphen-3-yl)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S8): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(2-chlorothiophen-3-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 3-bromo-2-chlorothiophene (726.9 mg, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather =2:1) ​​30 mL, after the addition of the materials, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 829.0 mg of colorless oil, with a yield of 63.8%.

[0055] (4) Preparation of 2-(3-(2-chlorothiophene-3-yl)phenyl)malonic acid: Diethyl 2-(3-(2-chlorothiophen-3-yl)phenyl)malonate (829.0 mg, 2.4 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (234.9 mg, 5.9 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 566.0 mg of a colorless oil, with a yield of 91.9%.

[0056] (5) Preparation of 2-(3-(2-chlorothiophene-3-yl)phenyl)malonyl chloride: Add 2-(3-(2-chlorothiophene-3-yl)phenyl)malonic acid (566.0 mg, 1.9 mmol), 20 mL of dichloromethane, and 1 drop N , N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0057] Step (6) is the same as step (6) in Example 1. (7) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(2-chlorothiaphen-3-yl)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S8): Will N A solution of 10 mL of 2-(3-(2-chlorothiazo-5-yl)methyl)-3-methylpyridin-2-amine (457.3 mg, 1.9 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(2-chlorothiaphen-3-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 247.0 mg of yellow solid, with a yield of 25.9%.

[0058] Example 9: 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(2-chlorothiaphen-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S9): Steps (1) to (5) are the same as steps (1) to (5) in Example 8. Step (6) is the same as step (6) in Example 5. (7) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(2-chlorothiaphen-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S9): Will N A solution of 10 mL of 2-((2-chlorothiazo-5-yl)methyl)pyridine-2-amine (245.8 mg, 1.1 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(2-chlorothiaphen-3-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel, and the sample was separated by column chromatography to obtain 78.0 mg of yellow solid, with a yield of 14.7%.

[0059] Example 10: 1-((6-chloropyridin-3-yl)methyl)-3-(3-(2-chlorothiophen-3-yl)phenyl)-4-oxo-4H -pyrido[1,2- a Pyrimidine inner salt (S10): Steps (1) to (5) are the same as steps (1) to (5) in Example 8. Step (6) is the same as step (6) in Example 7. (7) 1-((6-chloropyridin-3-yl)methyl)-3-(3-(2-chlorothiophen-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S10): Will N A solution of 10 mL of 1-((6-chloropyridin-3-yl)methyl)pyridin-2-amine (293.9 mg, 1.3 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(2-chlorothiophen-3-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel, and the sample was separated by column chromatography to obtain 65.0 mg of yellow solid, with a yield of 10.1%.

[0060] Example 11: 1-((2-chlorothiazo-5-yl)methyl)-9-methyl-3-(3-(5-methylthiophen-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S11): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(5-methylthiophen-3-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborphane-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 4-bromo-2-methylthiophene (651.7 mg, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather=2:1) ​​30 mL, after the addition of the material, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried with anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 925.0 mg of colorless oil, with a yield of 75.6%.

[0061] (4) Preparation of 2-(3-(5-methylthiophen-3-yl)phenyl)malonic acid: Diethyl 2-(3-(5-methylthiophen-3-yl)phenyl)malonate (925.0 mg, 2.8 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (278.2 mg, 7.0 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 698.0 mg of a colorless oil, with a yield of 90.8%.

[0062] (5) Preparation of 2-(3-(5-methylthiophen-3-yl)phenyl)malonyl chloride: Add 2-(3-(5-methylthiophene-3-yl)phenyl)malonic acid (698.0 mg, 2.5 mmol), 20 mL of dichloromethane, and 1 drop N , N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0063] Step (6) is the same as step (6) in Example 1. (7) 1-((2-chlorothiazo-5-yl)methyl)-9-methyl-3-(3-(5-methylthiophen-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S11): Will NA solution of 10 mL of 2-(3-(2-chlorothiazo-5-yl)methyl)-3-methylpyridin-2-amine (605.6 mg, 2.5 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(2-chlorothiaphen-3-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 368.0 mg of yellow solid, with a yield of 30.4%.

[0064] Example 12: 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(5-methylthiophen-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S12): Steps (1) to (5) are the same as steps (1) to (5) in Example 11. Step (6) is the same as step (6) in Example 5. (7) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(5-methylthiophen-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S12): Will N 10 mL of a solution of 2-(3-(5-methylthiophene-3-yl)phenyl)pyridine-2-amine (337.25 mg, 1.5 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(5-methylthiophene-3-yl)phenyl)malonyl chloride in dichloromethane. 3 drops of triethylamine were added, and the mixture was reacted at room temperature for 20 min. After the reaction was complete, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel, and the sample was separated by column chromatography to obtain 208.0 mg of a yellow solid, with a yield of 29.9%.

[0065] Example 13: 1-((6-chloropyridin-3-yl)methyl)-3-(3-(5-methylthiophen-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S13): Steps (1) to (5) are the same as steps (1) to (5) in Example 11. Step (6) is the same as step (6) in Example 7. (7) 1-((6-chloropyridin-3-yl)methyl)-3-(3-(5-methylthiophen-3-yl)phenyl)-4-oxo-4 H -pyrido[1,2-a Preparation of pyrimidine inner salt (S13): Will N A solution of 10 mL of 1-((6-chloropyridin-3-yl)methyl)pyridin-2-amine (267.9 mg, 1.2 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(5-methylthiophen-3-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 126.0 mg of yellow solid, with a yield of 22.5%.

[0066] Example 14: 1-((2-chlorothiazo-5-yl)methyl)-9-methyl-4-oxo-3-(3-(thiophen-2-yl)phenyl)-4H-pyrido[1,2-a]pyrimidine onium inner salt (S14): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(thiophen-2-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 2-iodothiophene (773.1 mg, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather =2:1) ​​30 mL, after the addition of the material, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried with anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 886.0 mg of colorless oil, with a yield of 75.6%.

[0067] (4) Preparation of 2-(3-(thiophen-2-yl)phenyl)malonic acid: Diethyl 2-(3-(thiophen-2-yl)phenyl)malonate (886.0 mg, 2.8 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (278.3 mg, 7.0 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 692.0 mg of a colorless oil, with a yield of 94.8%.

[0068] (5) Preparation of 2-(3-(thiophen-2-yl)phenyl)malonyl chloride: Add 2-(3-(thiophen-2-yl)phenyl)malonic acid (692.0 mg, 2.6 mmol), 20 mL of dichloromethane, and 1 drop N , N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0069] Step (6) is the same as step (6) in Example 1. (7) 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-4-oxo-3-(3-(thiophen-2-yl)phenyl)-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S14): Will N A solution of 10 mL of 2-(3-(2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (605.6 mg, 2.5 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(thiophen-2-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 271.0 mg of yellow solid, with a yield of 22.0%.

[0070] Example 15: 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(5-chlorothiaphen-2-yl)phenyl)-9-methyl-4-oxo-4 H-pyrido[1,2- a Pyrimidine inner salt (S15): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(5-chlorothiophen-2-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 2-bromo-5-chlorothiophene (726.9 mg, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather =2:1) ​​30 mL, after the addition of the materials, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 826.0 mg of colorless oil, with a yield of 63.6%.

[0071] (4) Preparation of 2-(3-(5-chlorothiophen-2-yl)phenyl)malonic acid: Diethyl 2-(3-(5-chlorothiophene-2-yl)phenyl)malonate (826.0 mg, 2.3 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (234.1 mg, 5.9 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 601.0 mg of a colorless oil, with a yield of 86.5%.

[0072] (5) Preparation of 2-(3-(5-chlorothiophen-2-yl)phenyl)malonyl chloride: Mix 2-(3-(5-chlorothiophene-2-yl)phenyl)malonic acid (601.0 mg, 2.0 mmol), 20 mL of dichloromethane, and 1 drop of... N , N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0073] Step (6) is the same as step (6) in Example 1. (7) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(5-chlorothiaphen-2-yl)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S15): Will N A solution of 10 mL of 2-(3-(5-chlorothiazo-5-yl)methyl)-3-methylpyridin-2-amine (485.6 mg, 2.0 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(5-chlorothiaphen-2-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the mixture was reacted at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 147.0 mg of yellow solid, with a yield of 14.5%.

[0074] Example 16: 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(5-chlorothiaphen-2-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S16): Steps (1) to (5) are the same as steps (1) to (5) in Example 15. Step (6) is the same as step (6) in Example 5. (7) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(5-chlorothiaphen-2-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S16): Will NA solution of 10 mL of 2-(3-(5-chlorothiazo-5-yl)methyl)pyridine-2-amine (324.7 mg, 1.4 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(5-chlorothiaphen-2-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 146.0 mg of yellow solid, with a yield of 20.9%.

[0075] Example 17: 1-((6-chloropyridin-3-yl)methyl)-3-(3-(5-chlorothiophen-2-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S17): Steps (1) to (5) are the same as steps (1) to (5) in Example 15. Step (6) is the same as step (6) in Example 7. (7) 1-((6-chloropyridin-3-yl)methyl)-3-(3-(5-chlorothiophen-2-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S17): Will N A solution of 10 mL of 1-((6-chloropyridin-3-yl)methyl)pyridin-2-amine (316.1 mg, 1.4 mmol) in dichloromethane was added to a solution of 2-(3-(5-chlorothiophen-2-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the mixture was reacted at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 115.0 mg of a yellow solid, with a yield of 16.6%.

[0076] Example 18: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S18): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 2-bromo-5-methyl-1,3,4-oxadiazole (599.9 mg, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather =2:1) ​​30 mL, after the addition of the materials, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 736.0 mg of colorless oil, with a yield of 62.8%.

[0077] (4) Preparation of 2-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)malonic acid: Diethyl 2-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)malonate (736.0 mg, 2.3 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (231.2 mg, 5.8 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 509.0 mg of a colorless oil, with a yield of 84.0%.

[0078] (5) Preparation of 2-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)malonyl chloride: Mix 2-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)malonic acid (509.0 mg, 1.9 mmol), 20 mL of dichloromethane, and 1 drop N , NDimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0079] Step (6) is the same as step (6) in Example 1. (7) 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine inner salt (S18): Will N A solution of 10 mL of 2-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)malonyl chloride in dichloromethane was added to a solution of 2-(3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the mixture was reacted at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 95.0 mg of a yellow solid, with a yield of 10.5%.

[0080] Example 19: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(oxazol-5-yl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine inner salt (S19): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) Preparation of diethyl 2-(3-(oxazol-5-yl)phenyl)malonate: Diethyl 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)phenyl)malonate (2.0 g, 5.5 mmol, 1.5 eq), 5-bromooxazole (544.6 mg, 3.7 mmol, 1.0 eq), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (538.7 mg, 0.7 mmol, 0.2 eq), and potassium carbonate (2.0 g, 14.7 mmol, 4.0 eq) were added to a 100 mL Schlenk flask, and a mixture of tetrahydrofuran and water (V) was added to the system under a nitrogen atmosphere. THF :V wather=2:1) ​​30 mL, after the addition of the materials, the system was placed under reflux for 4-8 h. After the reaction was completed, the system temperature was lowered to room temperature, 100 mL of water was added to the system, and ethyl acetate (50 mL × 3) was used for extraction. The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 784.0 mg of colorless oil, with a yield of 70.2%.

[0081] (4) Preparation of 2-(3-(oxazol-5-yl)phenyl)malonic acid: Diethyl 2-(3-(oxazol-5-yl)phenyl)malonate (784.0 mg, 2.6 mmol, 1.0 eq), 50 mL of anhydrous ethanol, and 50 mL of sodium hydroxide aqueous solution (258.5 mg, 6.5 mmol, 2.5 eq) were added to a 250 mL round-bottom flask and stirred at room temperature. After complete hydrolysis, the system was concentrated to remove the ethanol. 50 mL of water was added to the residue, and the mixture was extracted once with ethyl acetate (50 mL) to remove impurities. The aqueous phase was collected, and the pH was adjusted to acidic with 6 N hydrochloric acid. The mixture was extracted with ethyl acetate (50 mL × 3 times). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 578.0 mg of a colorless oil, with a yield of 90.5%.

[0082] (5) Preparation of 2-(3-(oxazol-5-yl)phenyl)malonyl chloride: Add 2-(3-(oxazol-5-yl)phenyl)malonic acid (578.0 mg, 2.3 mmol), 20 mL of dichloromethane, and 1 drop N , N Dimethylformamide was added to a 50 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (1 mL) was added dropwise while stirring at room temperature. The reaction was carried out at room temperature for 2–3 hours. After the reaction was completed, the solvent was removed under reduced pressure. No purification was required. 20 mL of dichloromethane was added for later use.

[0083] Step (6) is the same as step (6) in Example 5. (7) Preparation of 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(oxazol-5-yl)phenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt (S19): Will NA solution of 10 mL of 2-((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (527.7 mg, 2.3 mmol, 1.0 eq) in dichloromethane was added to a solution of 2-(3-(oxazol-5-yl)phenyl)malonyl chloride in dichloromethane. Three drops of triethylamine were added, and the reaction was carried out at room temperature for 20 min. After the reaction was completed, 2 mL of anhydrous methanol was added to quench the reaction. The mixture was stirred with silica gel and separated by column chromatography to obtain 108.0 mg of yellow solid, with a yield of 10.6%.

[0084] The compound's nuclear magnetic resonance hydrogen spectrum ( 1 H NMR, carbon spectrum 13 The 12C NMR and high-resolution mass spectrometry (HRMS) data are shown in Table 1. Table 1. Spectral data of compounds in Examples S1-S19

[0085] Example 1: Determination of the bioactivity of the target compound in controlling the pea aphid in the room.

[0086] The target compound was dissolved in DMSO solution and diluted with TW-80 to obtain a stock solution with a concentration of 1 g / L. Subsequent dilutions with TW-80 yielded concentrations of 100.0, 10.0, and 1.0 g / L. μ Test solutions of g / mL and other concentrations.

[0087] 20-30 pea aphids (3rd instar) were used to infect broad bean seedlings in flowerpots, and 2 mL of test solution was sprayed on top. A TW-80 solution containing DMSO was used as a blank control. Each group was repeated in triplicate. The treated pea aphids were placed in an artificial climate chamber (temperature 26±2 ℃, humidity 85±5%, light / dark ratio = 14 / 10 h) and reared. The number of dead aphids was recorded after 48 h. The mortality rate and corrected mortality rate were calculated as follows, and the activity data are shown in Table 2. Mortality rate = (Number of dead insects) / (Total number of insects treated) × 100 Corrected lethality = (treatment lethality - blank lethality) / (1 - blank lethality) × 100 Table 2. Mortality rates of the compounds in the examples against the pea bud aphid

[0088] Note: The control compound A is the compound disclosed in WO2011017342 A2: Insecticidal activity results showed that the compounds exhibited good insecticidal activity against the pea aphid. Compounds S8, S15, and S19 showed good insecticidal activity at 100 μL / min. µ g / mL and 10 µ The mortality rate against the pea aphid was 100% at a concentration of g / mL, and it was also 1 µ Even at a concentration of g / mL, it still showed a mortality rate of over 20% against the pea aphid, which was superior to the control compound A.

[0089] Example 2: Indoor bioactivity assay of target compound for controlling fall armyworm.

[0090] The target compound was dissolved in DMSO solution and diluted with TW-80 to obtain a stock solution with a concentration of 1 g / L. Subsequent dilutions with TW-80 yielded concentrations of 100.0, 10.0, and 1.0 g / L. μ Test solutions of g / mL and other concentrations were added, and 100 g / mL was added to each well of a 24-well culture plate that had been pre-fed. μ For each treatment, 12 wells were added to the drug solution corresponding to concentration L, with three replicates. A TW-80 solution containing DMSO served as a blank control. After the drug solution in the wells evaporated, one third-instar larva of the fall armyworm was placed in each well. The treated fall armyworms were then reared in an artificial climate chamber (temperature 26±2 ℃, humidity 85±5%, light / dark ratio = 14 / 10 h). The number of dead larvae was recorded after 48 h. The mortality rate and corrected mortality rate were calculated as follows, and the activity data are shown in Table 3. Mortality rate = (Number of dead insects) / (Total number of insects treated) × 100 Corrected lethality = (treatment lethality - blank lethality) / (1 - blank lethality) × 100 Table 3. Lethality of the compounds in the examples against fall armyworm

[0091] Insecticidal activity results showed that the compound had good insecticidal activity against fall armyworm, at 100... μ At a concentration of g / mL, the tested compounds all showed a 100% lethality against the fall armyworm, and at 10 g / mL... μ g / mL and 1 μ At a concentration of g / mL, the insecticidal activity of the tested compounds was superior to that of control compound A.

[0092] Example 3: Indoor bioactivity assay of target compound for controlling corn borer.

[0093] The target compound was dissolved in DMSO solution and diluted with TW-80 to obtain a stock solution with a concentration of 1 g / L. Subsequent dilutions with TW-80 yielded concentrations of 100.0, 10.0, and 1.0 g / L. μ Test solutions of g / mL and other concentrations were added, and 100 g / mL was added to each well of a 24-well culture plate that had been pre-fed. μ For each treatment, 12 wells were added to each solution corresponding to concentration L, with three replicates. A TW-80 solution containing DMSO served as a blank control. After the solution in each well had evaporated, one third-instar corn borer larva was placed in each well. The treated corn borers were then reared in an artificial climate chamber (temperature 26±2 ℃, humidity 85±5%, light / darkness = 14 / 10h). The number of dead larvae was recorded after 48 h. The mortality rate and corrected mortality rate were calculated as follows, and the activity data are shown in Table 4. Mortality rate = (Number of dead insects) / (Total number of insects treated) × 100 Corrected lethality = (treatment lethality - blank lethality) / (1 - blank lethality) × 100 Table 4. Lethality of the compounds in the examples against corn borers

[0094] Bioactivity tests showed that the compounds exhibited excellent insecticidal activity against corn borers, especially compounds S1 and S2. μ At a concentration of g / mL, the lethality against corn borers remained at 100%, significantly better than that of control compound A.

[0095] Example 4 of biological test: Screening of the prevention and control spectrum of target compound S1.

[0096] Beet armyworm: According to NYT 1154.14-2008, the experimental guidelines for indoor bioassay of pesticides, the leaf immersion method, is used. Fresh cabbage leaves are immersed in pesticide solutions of different concentrations for 10 seconds each, then removed. The same pesticide is used in order of increasing concentration. The treated leaves are then placed on newspaper to air dry. Disposable petri dishes are lined with filter paper and labeled. Healthy, early third instar larvae of uniform size are placed in each dish, with 10 larvae per dish. Each treatment is repeated three times.

[0097] Rice stem borer: According to NYT 1154.14-2008, "Experimental Guidelines for Indoor Bioassay of Pesticides - Leaf Immersion Method," fresh water bamboo shoots are cut into 2-3 mm thick round slices. Each slice is immersed in a pesticide solution of different concentrations for 10 seconds, then removed. The same pesticide is used in order of increasing concentration. The treated water bamboo slices are then placed on newspaper to air dry. Disposable petri dishes are lined with filter paper and labeled. Healthy, uniform-sized third-instar larvae of the rice stem borer are placed in each dish, with 10 larvae per dish. Each treatment is repeated three times.

[0098] Spodoptera litura: According to NYT 1154.14-2008, "Experimental Guidelines for Indoor Bioassay of Pesticides: Leaf Immersion Method," fresh cabbage leaves were immersed in pesticide solutions of different concentrations for 10 seconds each, then removed. The same pesticide was used in order of increasing concentration. The treated leaves were then placed on newspaper to air dry. Disposable petri dishes were lined with filter paper and labeled. Ten healthy, early third instar larvae of Spodoptera litura of uniform size were placed in each dish, with three replicates per treatment.

[0099] Rice brown planthopper: According to the "NYT 1154.9-2008 Guidelines for Indoor Bioassay of Pesticides - Spraying Method", third-instar rice planthopper nymphs of uniform growth stage were anesthetized with carbon dioxide. The stunned rice planthopper nymphs were gently transferred with a brush to a prepared simple culture dish of rice seedlings. Each culture dish contained no less than 30 test insects, and the process was repeated twice. The dish was placed under a Potter spray tower, and the spray volume was 2.5 mL. After standing for 30 seconds, the dish was removed and covered with a disposable plastic cup.

[0100] Alfalfa aphids: According to the "NYT 1154.9-2008 Guidelines for Indoor Bioassay of Pesticides - Spraying Method", flat broad bean leaves were placed in petri dishes with absorbent cotton and kept moist. Alfalfa aphids were transferred to the broad bean leaves using filter paper. The number of aphids per treatment should not be less than 30, and the treatment was repeated twice. The dishes were placed under a Potter spray tower, and the spray volume was 2.5 mL. After standing for 30 seconds, the dishes were removed.

[0101] Table 5. Lethality (%) of compound S1 against various test insects

[0102] Note: " / " indicates no data.

[0103] The results of insecticidal activity tests on beet armyworm, rice stem borer, cotton bollworm, brown planthopper and alfalfa aphid showed that compound S1 had excellent insecticidal activity against beet armyworm, and still had a 100% lethality rate at a concentration of 6.25 mg / kg. In addition, it also had good insecticidal activity against brown planthopper and rice stem borer.

[0104] The above bioactivity test results indicate that pyrido[1,2-] ... a Pyrimidine metronid derivatives exhibit good insecticidal activity against hemiptera and lepidopteran insects, such as the pea aphid, fall armyworm, corn borer, brown planthopper, beet armyworm, and rice stem borer. Compound S1, in particular, has considerable commercial value.

[0105] 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 pyrido[1,2-] ... a Pyrimidine mesonotropic compounds or their salts, characterized in that, The compound is shown in general formula (I): (I) Among them, R 1 Represents cyanoalkyl, aryl, or heterocyclic groups; E, G, M, and Q independently represent O, S, N, or CR, respectively. 3 ; R 2 R 3 Independently represents hydrogen, nitro, cyano, halogen, hydroxyl, mercapto, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, formyl, alkylcarbonyl, alkyl sulfoxide, alkyl sulfonyl, alkyl-substituted amino, cycloalkyl, aryl or heterocyclic group; The aforementioned "cycloalkyl" may optionally be replaced by at least one group selected from halogen, cyano, nitro, alkyl, alkenyl, ynyl, cycloalkyl, haloalkyl, haloalkenyl, haloynyl, halocycloalkyl, alkyl-substituted cycloalkyl or cycloalkylalkyl. The aforementioned "heterocyclic group" or "aryl group" is optionally selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, alkyl-substituted cycloalkyl, cycloalkylalkyl, unsubstituted or substituted by at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy.

2. The pyrido[1,2-]pyrido[ ... a Pyrimidine mesonotropic compounds or their salts, characterized in that: R 1 Represents cyano C1-C8 alkyl, aryl, or heterocyclic groups; R 2 R 3 Independently represents hydrogen, nitro, cyano, halogen, hydroxyl, mercapto, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, C1-C8 alkoxy, C1-C8 alkylthio, halo-C1-C8 alkoxy, halo-C1-C8 alkylthio, formyl, C1-C8 alkyl carbonyl, C1-C8 alkyl sulfoxide, C1-C8 alkyl sulfonyl, amino group substituted with C1-C8 alkyl, C3-C8 cycloalkyl, aryl or heterocyclic group; The aforementioned "C3-C8 cycloalkyl" is optionally replaced by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 ynyl, C3-C8 cycloalkyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 ynyl, halo-C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted with C1-C8 alkyl, or C3-C8 cycloalkyl-C1-C8 alkyl; The aforementioned "heterocyclic group" or "aryl group" is optionally selected from oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halo-C1-C8 alkyl, halo-C2-C8 alkenyl, halo-C2-C8 alkynyl, halo-C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted with C1-C8 alkyl, C3-C8 cycloalkyl C1-C8 alkyl, unsubstituted or substituted with at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halo-C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halo-C1-C8 alkoxy.

3. The pyrido[1,2-]pyrido[ ... a Pyrimidine mesonotropic compounds or their salts, characterized in that: R 1 Independently selected from cyanoC1-C8 alkyl groups , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; R 2 R 3 Each of these groups independently represents hydrogen, nitro, cyano, halogen, hydroxyl, mercapto, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkylthio, halo-C1-C6 alkoxy, halo-C1-C6 alkylthio, formyl, C1-C6 alkyl carbonyl, C1-C6 alkyl sulfoxide, C1-C6 alkyl sulfonyl, amino group substituted with C1-C6 alkyl, C3-C6 cycloalkyl, aryl or heterocyclic group; The aforementioned "C3-C6 cycloalkyl" is optionally substituted by at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C6 cycloalkyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 ynyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted with C1-C6 alkyl, or C3-C6 cycloalkyl-C1-C6 alkyl; The aforementioned "heterocyclic" or "aryl" may optionally be selected from oxo, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halo-C1-C6 alkyl, halo-C2-C6 alkenyl, halo-C2-C6 alkynyl, halo-C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted with C1-C6 alkyl, C3-C6 cycloalkyl C1-C6 alkyl, unsubstituted or substituted with at least one group selected from halogen, cyano, nitro, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halo-C1-C6 alkoxy; The yes , , , , , , , , , , .

4. The pyrido[1,2-]pyrido[ ... a Pyrimidine mesonotropic compounds or their salts, characterized in that Selected from the following specific compounds: 。 5. The pyrido[1,2-]pyrido[ ... a A method for preparing pyrimidine mesonotropic compounds or their salts includes the following steps: The compound of general formula II is reacted with the compound of general formula III to prepare the compound of general formula I. The reaction equation is as follows: Among them, L 1 L 2 Each can independently represent a halogen or an OH group, with substituent R. 1 R 2 The definitions of E, G, M, and Q are as described in any one of claims 1-4; Also includes: Wherein, X is selected from iodine, bromine or chlorine, and the catalyst is [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride or bis(triphenylphosphino)palladium dichloride.

6. A composition, characterized in that... The composition contains any of the compounds or salts thereof as described in claims 1-4, and agriculturally available adjuvants or fungicides, insecticides or herbicides; preferably, the formulation of the composition is selected from emulsifiable concentrates (EC), powders (DP), wettable powders (WP), granules (GR), aqueous solutions (AS), suspensions (SC), ultra-low volume sprays (ULV), soluble powders (SP), microcapsules (MC), fumigants (FU), emulsions (EW), water-dispersible granules (WG), and microemulsions (ME).

7. Use of the compound or salt thereof of any one of claims 1-4, or the composition of claim 6, in the preparation of a pesticide for controlling agricultural pests and diseases, wherein the agricultural pests and diseases are hemiptera and lepidopteran pests; and wherein the agricultural pests are pea aphids, fall armyworms, and corn borers.

8. A method for preventing and controlling agricultural pests and diseases, characterized in that: The compound or its salt or solvate according to any one of claims 1-4, or the composition according to claim 6, is applied to a pest or its habitat; the pest is a hemiptera or lepidopteran pest; the pest is a pea aphid, a fall armyworm, or a corn borer.

9. Compound S1 Uses in the preparation of pesticides for controlling corn borers, beet armyworms, rice stem borers, brown planthoppers, and alfalfa aphids.

10. An intermediate as described in Formula 5, II or IV.

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