Pyridopyrimidinone mesoion derivative containing dithioacetal unit as well as preparation method and application of pyridopyrimidinone mesoion derivative

Abstract

The invention relates to a dithioacetal unit-containing pyridopyrimidinone mesoion derivative as well as a preparation method and an application of the dithioacetal unit-containing pyridopyrimidinone mesoion derivative. The compound disclosed by the invention has a structure shown as a formula (I) or a formula (II), has excellent insecticidal activity and antiviral activity on broad bean aphids and potato Y viruses, and can be used for preventing and treating broad bean aphids and medicines or medicaments for preventing and treating potato Y viruses at the same time. The structure and the preparation process are simple, and the production cost is low.

Description

Technical Field

[0001] This invention relates to the fields of chemical industry and pesticides, and more specifically to pyridopyrimidine ketone mechanotropic derivatives containing dithioacetal units, methods for their preparation, and the application of these pyridopyrimidine ketone mechanotropic derivatives containing dithioacetal units in the preparation of drugs for controlling broad bean aphids and potato virus Y. Background Technology

[0002] The broad bean aphid (Aphis craccivora) (Hemiptera: Aphididae) is a major agricultural pest that primarily infests leguminous crops, causing severe economic losses to agricultural production. This pest directly damages crop growth by sucking plant sap, resulting in annual yield reductions of 15-30% or more, and in severe cases, complete crop failure. Furthermore, it indirectly harms crops by transmitting highly destructive plant viruses such as Potato Virus Y (PVY). Globally, PVY causes potato yield reductions of 10-100% and tobacco yield reductions of 39-75%, making it one of the "world's ten most damaging plant viruses." Neonicotinic insecticides (such as imidacloprid and thiamethoxam) have rapidly become the main agents for controlling hemiptera pests like the broad bean aphid due to their high efficiency, low toxicity, and low residue. However, long-term excessive use has led to increasing resistance among pest populations, and the significant toxicity of these agents to non-target organisms such as bees and birds significantly limits their application. Therefore, the development of highly effective insecticides with novel mechanisms of action has become an urgent priority.

[0003] On July 29, 2016, trifluoropyrimidine, developed by DuPont (now Corteva), received its first registration in my country. Trifluoropyrimidine is DuPont's first metronidicide with a novel chemical structure and mechanism of action, specifically developed for the Asia-Pacific region. It can be used on crops such as rice, cotton, corn, and soybeans, and exhibits excellent control efficacy against various pests, including Lepidoptera and Homoptera. Based on these characteristics, the development of novel metronidicides, spearheaded by trifluoropyrimidine, is a hot topic in pesticide research both domestically and internationally.

[0004] Inventors Holyoke CW, Tong MT, Coats RA, Zhang WM, McCann SF, and Chan D.M. first disclosed a method for preparing pyridopyrimidinone metronidazole compounds and their application as insecticides in 2009 under patent publication number WO2009099929A1. These compounds exhibit good to excellent insecticidal activity against lepidopteran pests such as corn planthoppers, potato leafhoppers, diamondback moths, fall armyworms, beet armyworms, and cotton bollworms in cornfields. Among them, dicloromezotiaz exhibits excellent and broad-spectrum insecticidal activity against lepidopteran pests, leading DuPont to develop it as a commercial drug.

[0005] Inventors Holyoke CW, Zhang W.M., Patel KM, Lahm GP, and Tong M.T. disclosed in 2011, patent publication number WO2011017347A2, a method for preparing a class of pyridopyrimidine mesoionic compounds and their application as insecticides. These compounds exhibit good insecticidal activity against four hemiptera pests: corn planthopper, potato leafhopper, brown planthopper (imidacloprid-resistant), and rice green leafhopper. Among them, trifluorophenylpyrimidine not only shows excellent insecticidal activity against hemiptera pests but also good insecticidal activity against lepidopteran pests such as diamondback moth and fall armyworm. Therefore, DuPont developed it as a commercial drug.

[0006] Inventors Holyoke CW, Tong MT, and Zhang WM disclosed a class of pyridinidone metronidazole compounds containing diaryl groups in patent publication number WO2012106495A1 in 2012. These compounds exhibit good to excellent insecticidal activity against lepidopteran and hemiptera pests. Some compounds showed 100% lethality against diamondback moth and fall armyworm at a concentration of 2 μg / mL, and over 80% lethality against green peach aphid, corn planthopper, and potato leafhopper at a concentration of 10 μg / mL.

[0007] Inventors Bandur NG, Culbertson DL, Deshmukh P., Dickhaut J., Kaiser F., Koerber K., Langewald J., Narine A., and Veitch G. disclosed in 2012, patent publication number WO2012136724A1, a pyridinidone metronidazole compound containing an amidine structure. This type of compound has moderate insecticidal activity, with a mortality rate of over 75% against cowpea aphids and orchid thrips at a concentration of 300 μg / mL.

[0008] Inventors Narine A., Dickhaut J., Kaiser F., Bandur NG, Koerber K., and Von Deyn W. disclosed in 2014 a pyridopyrimidine metronid compound containing a carbonyl azirthyl ylide structure (patent publication number EP2684879A1) and a pyridopyrimidine metronid compound containing a hydrazine structure (patent publication number WO2014033244A2). The insecticidal activity of these compounds is generally moderate, with a lethality of over 75% against cowpea aphids at a concentration of 300 μg / mL and a lethality of over 75% against brown planthoppers and cowpea aphids at a concentration of 500 μg / mL.

[0009] Inventors Holmes M., Holyoke CW, Kar M., and Lahm GP disclosed in 2021 a pyridopyrimidinone metronidazole compound containing an alkyne structural unit. This class of compounds exhibits good to excellent insecticidal activity against lepidopteran and hemiptera pests. Some compounds showed 100% lethality against fall armyworm and diamondback moth at a concentration of 0.4 μg / mL, and over 80% lethality against cotton aphid, peach aphid, and corn planthopper at a concentration of 50 μg / mL.

[0010] Inventors Song Baoan, Zhang Jian, Hu Deyu, Wu Shang, Cai Di, and Wu Zengxue disclosed in 2021 a pyridopyrimidine ketone compound containing isoxazole. This type of compound has good to excellent insecticidal activity against hemiptera pests, and some of the compounds have a 100% lethality against white-backed planthoppers at a concentration of 2 μg / mL.

[0011] Inventors Song Runjiang, Wu Shang, Song Baoan, Hu Deyu, Zhang Jian, Wang Xiaoyi, Ma Qingqing, Chen Dan, Zhang Xingjie, Jin Fangru, Wu Huan, Li Yan, Wang Ruilan, and Yang Honggui disclosed in 2023, in patent publication number CN117720535A, a pyridinidine mesoionic compound containing a 1,2,4-isooxazole structure. This type of compound exhibits good to excellent insecticidal activity against lepidopteran and hemiptera pests. Some compounds show a 100% lethality against broad bean aphids, diamondback moths, and fall armyworms at a concentration of 10 μg / mL, and a lethality exceeding 90% against armyworms, beet armyworms, rice leaf rollers, rice stem borers, and corn borers at a concentration of 5 μg / mL.

[0012] In recent years, our research team has developed a novel plant immune inducer with dithioacetal as a new skeleton, conducted activity screening of highly efficient lead compounds and candidate drugs, obtained 10 highly active lead compounds against plant viruses, and successively created the plant immune inducers "vanilla thioacetal" and "flubenzuron thioacetal".

[0013] The inventors Song Baoan, Zhang Jian, Hu Deyu, Xue Wei, Wu Zengxue, Zhao Lei, Zhang Guoping, Pan Jianke, and Chen Jin disclosed a vanillin derivative containing dithioacetal in patent publication number CN106467478B in 2018. This type of compound has good to excellent antiviral activity, and some of the compounds show good to excellent antiviral activity against tobacco mosaic virus, cucumber mosaic virus, and potato virus Y. The in vivo therapeutic and protective activities of some of the compounds are superior to those of ningnanmycin.

[0014] Inventors Hu Deyu, Chen Jin, Song Baoan, Shi Jing, and Xie Dandan disclosed in 2018, in patent publication number CN108484457A, a dithioacetal derivative containing methacrylate. This type of compound exhibits good to excellent antiviral activity against potato virus Y, tobacco mosaic virus, and cucumber mosaic virus. Among them, some compounds have better in vivo therapeutic and protective activity than natriuretic acid.

[0015] Inventors Song Baoan, Wei Chunle, Hu Deyu, Gan Xiuhai, and Zhang Jian disclosed in patent publication number CN110343062B in 2023 an indole derivative containing a dithioacetal unit. This type of compound exhibits good to excellent antiviral activity against potato virus Y, tobacco mosaic virus, and cucumber mosaic virus. Among them, some compounds have better in vivo therapeutic and protective activities than ribavirin, ningnanmycin, and vanillin.

[0016] Inventors Song Baoan, Yin Limin, Song Runjiang, Hu Deyu, Wu Huan, Yang Tangbing, Li Jianzhuan, Zhao Chunni, and Liu Ting disclosed in 2025 a benzoxazole derivative containing a dithioacetal unit. This type of compound exhibits good to excellent antiviral activity against cucumber green mottle mosaic virus, and some of the compounds show better in vivo inactivation, therapeutic and protective activities than ningnanmycin.

[0017] In summary, pyridopyrimidine ketone mechanotropic insecticides possess novel chemical structures and excellent insecticidal activity, effectively controlling various agricultural pests such as broad bean aphids and rice planthoppers, making them a current hot topic in insecticide research and development. Dithioacetal antiviral agents exhibit excellent antiviral activity, effectively controlling various plant viruses such as potato virus Y and tobacco mosaic virus. Introducing dithioacetal units into the pyridopyrimidine ketone mechanotropic structure aims to develop novel control agents that combine insecticidal and antiviral activity. Summary of the Invention

[0018] One of the objectives of this invention is to provide a class of pyridopyrimidine ketone mesonotropic derivatives containing dithioacetal units and a method for their preparation.

[0019] Another object of the present invention is to provide a composition containing derivatives.

[0020] Another object of the present invention is to provide the use of the above-described derivatives or compositions.

[0021] Another object of the present invention is to provide a method for preventing and controlling agricultural pests and diseases using the above-mentioned derivatives or the above-mentioned compositions.

[0022] To achieve the above objectives, the present invention adopts the following technical solution:

[0023] The pyridopyrimidinone mesonoionic derivatives of the present invention, comprising a compound having the general formula (I) or a stereoisomer thereof, a salt thereof, or a solvate thereof:

[0024]

[0025] R1 is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; R2 is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted aryl; R3 is independently selected from one or more of hydrogen, deuterium, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted aryl.

[0026] Preferably, R1 is independently selected from hydrogen, deuterium, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkenyl, substituted or unsubstituted C6-C 15 One or more of aryl, substituted or unsubstituted C5-C6 heteroaryl groups; R2 is independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, C1-C6 alkyl, C1-C6 alkenyl, substituted or unsubstituted C6-C 15 One or more of aryl, substituted or unsubstituted C5-C6 heteroaryl groups; R3 is independently selected from hydrogen, deuterium, C1-C6 alkyl, C1-C6 alkenyl, substituted or unsubstituted C6-C 15 One or more of aryl, substituted or unsubstituted C5-C6 heteroaryl groups, wherein the substitution refers to optional substitution by one or more of halogen, nitro, hydroxyl, amino, mercapto, or C1-C6 alkyl.

[0027] More preferably, R1 is independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, pyrazolyl, pyrroleyl, furanyl, thiophene, thiazolyl, benzopyrroleyl, pyridazine, pyrimidine, pyrazine, -CH2CH2CN, -CHCNCH3, -CH2CH2CH2CN, -CH2CHCNCH3, -CHCNCH2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHClCH3, -CH2CH2CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3, -CHBrCH2CH3.

[0028]

[0029] R2 is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, and pyridyl; R3 and R4 are independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, cyclopropyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, -CH2CH2CN, -CHCNCH3, -CH2CH2CH2CN, -CH2CHCNCH3, and -CHC NCH2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHClCH3, -CH2CH2 CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3, -CHBrCH2CH3.

[0030] Specifically, pyridopyrimidine ketone mesonotropic derivatives containing dithioacetal units include the following compounds:

[0031]

[0032]

[0033] Preferred compounds include compounds J1-J36 as described below. The preparation method of these compounds includes:

[0034]

[0035] Preferably, it further includes:

[0036]

[0037] Most preferably, it includes:

[0038]

[0039] The present invention also provides a composition comprising the aforementioned pyridopyrimidine ketone mesonotropic derivative containing a dithioacetal unit, and agriculturally usable 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), and water-dispersible granules (WG).

[0040] The pyridopyrimidine ketone metronidogens or compositions containing dithioacetal units can be used to prepare drugs for the prevention and control of agricultural pests and diseases, wherein the agricultural pests and diseases are hemiptera or plant viral diseases; preferably, the agricultural pests and diseases are broad bean aphids or potato virus Y.

[0041] This invention provides a method for preventing and controlling agricultural pests and diseases, wherein the compound or its stereoisomer, its salt or its solvate, or the composition thereof acts on the harmful substance or its habitat; preferably, the agricultural pest or disease is the broad bean aphid or potato virus Y.

[0042] The term "alkyl" as used here refers to both branched and straight-chain saturated hydrocarbon groups having a specific number of carbon atoms. For example, "C 1-10 Alkyl (or alkylene) refers to C1, C2, C3, C4, C5, C6, C7, C8, C9, and C10 alkyl groups. Additionally, for example, "C 1-6 "Alkyl" means an alkyl group having 1 to 6 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 (Me), ethyl (Et), propyl (such as n-propyl and isopropyl), butyl (such as n-butyl, isobutyl, tert-butyl), pentyl (such as n-pentyl, isopentyl, neopentyl) and the like.

[0043] "Alkenyl" refers to hydrocarbons that include both straight-chain and branched structures and have one or more carbon-carbon double bonds that appear at any stable point in the chain. For example, "C 2-6The term "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.

[0044] The term "cycloalkyl" refers to cycloalkyl groups, including mono-, di-, or polycyclic systems. 3-7 The purpose of cycloalkyl groups is to include C3, C4, C5, C6, and C7 cycloalkyl groups. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, 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 bicyclic 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.

[0045] The term "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group, such as phenyl and naphthyl, having 6 to 12 carbon atoms in the ring moiety, each of which can be substituted.

[0046] The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine, and iodine.

[0047] The term "heteroaryl" refers to 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 a heteroatom-containing heteroaryl 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, and the other fused rings may be aromatic or non-aromatic. Heteroaryl groups 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).

[0048] Beneficial effects:

[0049] This invention introduces a thioacetal unit into a pyridinidinone mesoionic structure, obtaining a class of derivatives with simple and novel structure, simple preparation process, and low production cost. It also exhibits excellent insecticidal and antiviral activity against broad bean aphids and Potato Virus Y (PVY), making it suitable for controlling both broad bean aphids and PVY. In particular, compound J1 maintains a 100% lethality against broad bean aphids at a concentration of 10 μg / mL, demonstrating higher insecticidal activity than the control agent trifluoropyrimidine. At a concentration of 500 mg / L, J1 exhibits 58.6% protective activity against PVY, exceeding the protective activity of the control agents ningnanmycin and vanillin thioacetate (51.5% and 55.4%, respectively).

[0050] The method of this invention is simple and easy to operate, and has a high yield. Except for compound J31, the yield is 57.95%, and the yields of the other compounds are all greater than 60%. Example

[0051] 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.

[0052] Example 1: 3-(3-(bis(methylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J1)

[0053] (1) Preparation of diethyl 2-(3-formylphenyl)malonate:

[0054] 10 g (43.10 mmol) of m-iodobenzaldehyde, 1.06 g (8.26 mmol) of pyridine-2-carboxylic acid, 21.06 g (64.65 mmol) of cesium carbonate, and 0.82 g (4.31 mmol) of cuprous iodide were added to a 200 mL reaction flask, and the system was protected under nitrogen atmosphere. Diethyl malonate (13.81 g, 86.20 mmol) was injected into the system, and finally 1,4-dioxane (60 mL) was added as a solvent. After the addition was complete, the mixture was reacted at 60 °C for 6 hours, washed with 100 mL of water, extracted three times with ethyl acetate (60 mL), and purified by column chromatography to obtain 9.70 g of a pale yellow oily liquid (78.70% yield).

[0055] (2) 2-(3-formylphenyl)malonic acid:

[0056] Diethyl 2-(3-formylphenyl)malonate (9.70 g, 36.70 mmol) was added to a 200 mL reaction flask, followed by 30 mL of ethanol and 30 mL of water as solvents, and sodium hydroxide (3.67 g, 91.76 mmol). The mixture was stirred at room temperature for 30 minutes. The solution was then diluted with 30 mL of ethyl acetate and washed with 60 mL of water. After separation, concentrated hydrochloric acid was added dropwise to the aqueous phase to adjust the pH to 1–2. Ethyl acetate was added and extracted three times (30 mL each time). The organic phase was collected by separation, evaporated, and concentrated to obtain 6.56 g of an oily liquid, with a yield of 85.85%.

[0057] (3) Preparation of 2-(3-formylphenyl)malonyl dichloride:

[0058] 2-(3-formylphenyl)malonic acid (6.56 g, 31.51 mmol), 20 mL of dichloromethane, and 3 drops of N,N-dimethylformamide were added to a 100 mL single-necked round-bottom flask and mixed. Oxaloyl chloride (6.23 g, 63.03 mmol) was added dropwise with stirring at room temperature. The reaction was carried out at room temperature for 2–4 hours. After the reaction was completed, the solvent was removed under reduced pressure, and 20 mL of dichloromethane was added for later use.

[0059] (4) Preparation of N-((2-chlorothiazo-5-yl)methyl)-3-methylpyridine-2-amine:

[0060] 2-Amino-3-methylpyridine (10.0 g, 92.5 mmol), 2-chloro-5-chloromethylthiazole (15.5 g, 92.5 mmol), N,N-diisopropylethylamine (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 4.75 g of a pale yellow solid, with a yield of 35.28%.

[0061] (5) Preparation of 1-((2-chlorothiazo-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0062] A 5 mL solution of N-((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (0.239 g, 1 mmol) in dichloromethane was added to a dichloromethane solution of 2-(3-formylphenyl)malonyl dichloro, followed by 5 drops of triethylamine. The reaction was carried out at room temperature for 1–2 hours. 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 0.281 g of a yellow solid, with a yield of 68.55%.

[0063] (6) Preparation of 3-(3-(bis(methylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0064] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), methanethiol (0.048 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.375 g of a yellow solid, with a yield of 80.48%.

[0065] Example 2: 3-(3-(bis(ethylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J2):

[0066] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0067] (6) Preparation of 3-(3-(bis(methylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0068] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), ethanethiol (0.062 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.349 g of a yellow solid, with a yield of 67.63%.

[0069] Example 3: 3-(3-(bis(propylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J3):

[0070] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0071] (6) Preparation of 3-(3-(bis(propylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0072] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), propanethiol (0.076 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.326 g of a yellow solid, with a yield of 59.68%.

[0073] Example 4: 3-(3-(bis(butyrothio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J4):

[0074] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0075] (6) Preparation of 3-(3-(bis(butyrothio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0076] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), butanethiol (0.09 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.451 g of yellow solid, with a yield of 78.54%.

[0077] Example 5: 3-(3-(bis((2-methylbutyl)thio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J5):

[0078] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0079] (6) Preparation of 3-(3-(bis((2-methylbutyl)thio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0080] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), 2-methylbutanethiol (0.104 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.506 g of a yellow solid, with a yield of 84.01%.

[0081] Example 6: 3-(3-(bis(isobutylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J6):

[0082] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0083] (6) Preparation of 3-(3-(bis(isobutylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium inner salt:

[0084] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), isobutyritin (0.09 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.412 g of yellow solid, with a yield of 71.17%.

[0085] Example 7: 3-(3-(bis(3-methylbutyrothio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J7):

[0086] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0087] (6) Preparation of 3-(3-(bis(3-methylbutyrothio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium inner salt:

[0088] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), 3-methylbutanethiol (0.104 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.442 g of a yellow solid, with a yield of 73.38%.

[0089] Example 8: 3-(3-(bis(cyclohexylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J8):

[0090] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0091] (6) Preparation of 3-(3-(bis(cyclohexylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0092] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onium-2-ol (0.411 g, 1 mmol), cyclohexanethiol (0.116 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.542 g of a yellow solid, with a yield of 86.52%.

[0093] Example 9: 3-(3-(bis(allylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J9):

[0094] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0095] (6) Preparation of 3-(3-(bis(allylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0096] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), allyl mercaptan (0.044 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.421 g of a yellow solid, with a yield of 77.65%.

[0097] Example 10: 3-(3-(bis((furan-2-ylmethyl)thio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J10):

[0098] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0099] (6) Preparation of 3-(3-(bis((furan-2-ylmethyl)thio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0100] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), furan-2-methanethiol (0.114 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.519 g of a yellow solid, with a yield of 83.41%.

[0101] Example 11: 3-(3-(bis(benzylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J11):

[0102] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0103] (6) Preparation of 3-(3-(bis(benzylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0104] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), benzyl thiol (0.124 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.445 g of a yellow solid, with a yield of 69.28%.

[0105] Example 12: 3-(3-(bis(cyclopentylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J12):

[0106] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0107] (6) Preparation of 3-(3-(bis(cyclopentylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0108] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), cyclopentanethiol (0.102 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.456 g of a yellow solid, with a yield of 76.22%.

[0109] Example 13: 3-(3-(bis(sec-butylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J13):

[0110] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0111] (6) Preparation of 3-(3-(bis(sec-butylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0112] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.411 g, 1 mmol), sec-butylthiol (0.09 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.481 g of a yellow solid, with a yield of 83.76%.

[0113] Example 14: 3-(3-(bis(methylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J14)

[0114] Steps (1) to (5) are the same as steps (1) to (3) in Example 1.

[0115] (4) Preparation of N-((2-chlorothiazol-5-yl)methyl)-pyridine-2-amine:

[0116] 2-Aminopyridine (4.7 g, 50 mmol), 2-chloro-5-chloromethylthiazole (8.4 g, 50 mmol), N,N-diisopropylethylamine (12.9 g, 100 mmol), potassium iodide (0.083 g, 0.5 mmol), and xylene (100–150 mL) were mixed in a 250 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 4.93 g of a pale yellow solid, with a yield of 43.82%.

[0117] (5) Preparation of 1-((2-chlorothiazo-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0118] A 20 mL solution of N-((2-chlorothiazol-5-yl)methyl)-pyridine-2-amine (4.75 g, 21 mmol) in dichloromethane was added to a solution of 2-(3-formylphenyl)malonyl dichloromethane. Five drops of triethylamine were added, and the reaction was carried out at room temperature for 1–2 hours. After the reaction was completed, 5 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 5.44 g of a yellow solid, with a yield of 65.14%.

[0119] (6) Preparation of 3-(3-(bis(methylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0120] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), methanethiol (0.048 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.284 g of a yellow solid, with a yield of 63.39%.

[0121] Example 15: 3-(3-(bis(ethylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J15):

[0122] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0123] (6) Preparation of 3-(3-(bis(methylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0124] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), ethanethiol (0.062 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.344 g of a yellow solid, with a yield of 68.24%.

[0125] Example 16: 3-(3-(bis(propylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J16):

[0126] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0127] (6) Preparation of 3-(3-(bis(propylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0128] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), propanethiol (0.076 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.348 g of a yellow solid, with a yield of 65.39%.

[0129] Example 17: 3-(3-(bis(butyrothio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J17):

[0130] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0131] (6) Preparation of 3-(3-(bis(butyrothio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0132] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), butanethiol (0.076 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.411 g of a yellow solid, with a yield of 73.36%.

[0133] Example 18: 3-(3-(bis((2-methylbutyl)thio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J18):

[0134] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0135] (6) Preparation of 3-(3-(bis((2-methylbutyl)thio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0136] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), 2-methylbutanethiol (0.104 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.398 g of a yellow solid, with a yield of 67.65%.

[0137] Example 19: 3-(3-(bis(isobutylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J19):

[0138] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0139] (6) Preparation of 3-(3-(bis(isobutylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0140] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), isobutyritin (0.090 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.374 g of a yellow solid, with a yield of 65.14%.

[0141] Example 20: 3-(3-(bis(3-methylbutyrothio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J20):

[0142] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0143] (6) Preparation of 3-(3-(bis(3-methylbutyrothio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0144] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), 3-methylbutanethiol (0.104 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.471 g of yellow solid, with a yield of 78.20%.

[0145] Example 21: 3-(3-(bis(cyclohexylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J21):

[0146] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0147] (6) Preparation of 3-(3-(bis(cyclohexylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0148] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), cyclohexanethiol (0.116 g, 1 mmol), and NaHSO4·SiO2 (0.662 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.504 g of yellow solid, with a yield of 82.31%.

[0149] Example 22: 3-(3-(bis(allylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J22):

[0150] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0151] (6) Preparation of 3-(3-(bis(allylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0152] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), allyl mercaptan (0.044 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.351 g of a yellow solid, with a yield of 66.46%.

[0153] Example 23: 3-(3-(bis((furan-2-ylmethyl)thio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J23):

[0154] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0155] (6) Preparation of 3-(-(bis((furan-2-ylmethyl)thio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium inner salt:

[0156] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), furan-2-methanethiol (0.114 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.476 g of a yellow solid, with a yield of 78.27%.

[0157] Example 24: 3-(3-(bis(benzylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J24):

[0158] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0159] (6) Preparation of 3-(3-(bis(benzylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0160] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), benzyl thiol (0.124 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.494 g of a yellow solid, with a yield of 78.63%.

[0161] Example 25: 3-(3-(bis(cyclopentylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J25):

[0162] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0163] (6) Preparation of 3-(3-(bis(cyclopentylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0164] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), cyclopentanethiol (0.102 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.429 g of yellow solid, with a yield of 84.12%.

[0165] Example 26: 3-(3-(bis(sec-butylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J26):

[0166] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0167] (6) Preparation of 3-(3-(bis(sec-butylthio)methyl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0168] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onthium-2-ol (0.397 g, 1 mmol), sec-butylthiol (0.090 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.407 g of a yellow solid, with a yield of 72.66%.

[0169] Example 27: 3-(3-(bis(methylthio)methyl)phenyl)-1-(2-cyanoethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J27):

[0170] Steps (1) to (3) are the same as steps (1) to (3) in Example 1.

[0171] (4) Preparation of 3-(pyridin-2-ylamino)propionitrile:

[0172] NaH (1.7 g, 42.4 mmol) and 2-aminopyridine (2 g, 21.3 mmol) were added to a 200 mL dry Shrek flask. The flask was then completely sealed, and the system was evacuated and nitrogen gas was introduced. Subsequently, 30 mL of anhydrous tetrahydrofuran was added to the system, and the reaction was carried out at 70 °C for 30 min. Then, 5.7 g of 3-bromopropionitrile (42.5 mmol) was added, and the reaction was carried out at 70 °C for 5 h. After the reaction was complete, 5 mL of methanol was added to quench the reaction, silica gel was added and stirred, and the solution was separated by column chromatography to obtain 1.91 g of a colorless liquid, with a yield of 61.02%.

[0173] (5) Preparation of 1-(2-cyanoethyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0174] A solution of 0.147 g (1 mmol) of 3-(pyridin-2-ylamino)propionitrile in 5 mL of dichloromethane was added to a solution of 2-(3-formylphenyl)malonyl dichloromethane. Five drops of triethylamine were added, and the mixture was reacted at room temperature for 1–2 hours. 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 0.215 g of a yellow solid, with a yield of 63.37%.

[0175] (6) Preparation of 3-(3-(bis(methylthio)methyl)phenyl)-1-(2-cyanoethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0176] 1-(2-cyanoethyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.319 g, 1 mmol), methanethiol (0.048 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.289 g of a yellow solid, with a yield of 72.77%.

[0177] Example 28: 3-(3-(bis(allylthio)methyl)phenyl)-1-(2-cyanoethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J28)

[0178] Steps (1) to (5) are the same as steps (1) to (5) in Example 27.

[0179] (6) Preparation of 3-(3-(bis(allylthio)methyl)phenyl)-1-(2-cyanoethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0180] 1-(2-cyanoethyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.319 g, 1 mmol), allyl thiol (0.044 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.308 g of a yellow solid, with a yield of 68.57%.

[0181] Example 29: 3-(3-(bis(sec-butylthio)methyl)phenyl)-1-(2-cyanoethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J29)

[0182] Steps (1) to (5) are the same as steps (1) to (5) in Example 27.

[0183] (6) Preparation of 3-(3-(bis(sec-butylthio)methyl)phenyl)-1-(2-cyanoethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0184] 1-(2-cyanoethyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.319 g, 1 mmol), sec-butanethiol (0.090 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.314 g of a yellow solid, with a yield of 65.28%.

[0185] Example 30: 3-(3-(bis(methylthio)methyl)phenyl)1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onthium-2-enol (J30)

[0186] Steps (1) to (3) are the same as steps (1) to (3) in Example 1.

[0187] (4) Preparation of N-((6-chloropyridin-3-yl)methyl)pyridin-2-amine:

[0188] 4.7 g (50 mmol) of 2-aminopyridine, 3.18 g (75 mmol) of NaHCO3, and 100 mL of water were mixed in a 250 mL three-necked flask and reacted at 70 °C for 30 min. Then, 15 mL of an ethanol solution of 8.1 g (50 mmol) of 2-chloro-5-chloromethylpyridine was added, and the reaction was continued at 100 °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 3.82 g of a pale yellow solid, with a yield of 41.82%.

[0189] (5) Preparation of 1-((6-chloropyridin-3-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0190] A 5 mL solution of N-((6-chloropyridin-3-yl)methyl)pyridin-2-amine (0.219 g, 1 mmol) in dichloromethane was added to a dichloromethane solution of 2-(3-formylphenyl)malonyl dichloro, followed by 5 drops of triethylamine. The reaction was carried out at room temperature for 1–2 hours. 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 0.228 g of a yellow solid, with a yield of 58.30%.

[0191] (6) Preparation of 3-(3-(bis(methylthio)methyl)phenyl)1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium inner salt:

[0192] 1-((6-chloropyridin-3-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.391 g, 1 mmol), methanethiol (0.044 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.341 g of a yellow solid, with a yield of 72.69%.

[0193] Example 31: 3-(3-(bis(allylthio)methyl)phenyl)1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J31)

[0194] Steps (1) to (5) are the same as steps (1) to (5) in Example 30.

[0195] (6) Preparation of 3-(3-(bis(methylthio)methyl)phenyl)1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium inner salt:

[0196] 1-((6-chloropyridin-3-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.391 g, 1 mmol), allyl mercaptan (0.048 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.302 g of a yellow solid, with a yield of 57.95%.

[0197] Example 32: 3-(3-(bis(sec-butyl)methyl)phenyl)1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J32)

[0198] Steps (1) to (5) are the same as steps (1) to (5) in Example 30.

[0199] (6) Preparation of 3-(3-(bis(sec-butyl)methyl)phenyl)1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0200] 1-((6-chloropyridin-3-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.391 g, 1 mmol), sec-butanethiol (0.090 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.375 g of a yellow solid, with a yield of 67.79%.

[0201] Example 33: 3-(3-(1,3-dithiopentane-2-yl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J33)

[0202] Steps (1) to (5) are the same as steps (1) to (5) in Example 1.

[0203] (6) Preparation of 3-(3-(1,3-dithiopentane-2-yl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0204] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onthium-2-ol (0.411 g, 1 mmol), 1,2-ethanedithiol (0.093 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.334 g of a yellow solid, with a yield of 68.58%.

[0205] Example 34: 3-(3-(1,3-dithiopentane-2-yl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J34)

[0206] Steps (1) to (5) are the same as steps (1) to (5) in Example 14.

[0207] (6) Preparation of 3-(3-(1,3-dithiopentane-2-yl)phenyl)-1-((2-chloro-1,3-thiazo-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt:

[0208] 1-((2-chlorothiazol-5-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.397 g, 1 mmol), 1,2-ethanedithiol (0.093 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.384 g of a yellow solid, with a yield of 81.18%.

[0209] Example 35: 3-(3-(1,3-dithiopentane-2-yl)phenyl)-1-(2-cyanoethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J35)

[0210] Steps (1) to (5) are the same as steps (1) to (5) in Example 27.

[0211] (6) Preparation of 3-(3-(1,3-dithiopentane-2-yl)phenyl)-1-(2-cyanoethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium salt:

[0212] 1-(2-cyanoethyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.319 g, 1 mmol), 1,2-ethanedithiol (0.093 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.289 g of a yellow solid, with a yield of 73.07%.

[0213] Example 36: 3-(3-(1,3-dithiopentane-2-yl)phenyl)1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium inner salt (J36)

[0214] Steps (1) to (5) are the same as steps (1) to (5) in Example 30.

[0215] (6) Preparation of 3-(3-(bis(methylthio)methyl)phenyl)1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine ononium inner salt:

[0216] 1-((6-chloropyridin-3-yl)methyl)-3-(3-formylphenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine onium salt (0.391 g, 1 mmol), 1,2-ethanedithiol (0.093 g, 1 mmol), and NaHSO4·SiO2 (0.622 g, 2 mmol) were reacted at room temperature for 8–12 hours. After the reaction was complete, silica gel was added to the system and stirred. The mixture was separated by column chromatography to obtain 0.356 g of a yellow solid, with a yield of 76.22%.

[0217] The compound's nuclear magnetic resonance hydrogen spectrum ( 1 HNMR and carbon spectroscopy 13 The C NMR data are shown in Table 1.

[0218] Table 1. Spectral data of compounds J1-J36 in Examples

[0219]

[0220]

[0221]

[0222]

[0223]

[0224]

[0225]

[0226]

[0227]

[0228] Example 1: Determination of the bioactivity of the target compound in controlling broad bean aphids indoors.

[0229] The target compound was dissolved in DMSO solution and diluted with distilled water to obtain a stock solution with a concentration of 1 g / L. Then, it was diluted with Tween 80 (0.1%) to obtain test solutions of 100, 10 μg / mL and other concentrations.

[0230] 20-30 adult broad bean aphids were used to infest broad bean seedlings in flowerpots, and 2 mL of test solution was sprayed on each seedling. A 0.1% Tween 80 solution containing DMSO was used as a blank control. Each group was replicated in triplicate. The treated aphids were reared in a greenhouse (temperature 26±2℃, humidity 85±5%, light / dark ratio = 16 / 8h). The number of dead aphids was recorded after 48 hours. The mortality rate and corrected mortality rate were calculated as follows, and the activity data are shown in Table 2.

[0231] Mortality rate = (Number of dead insects) / (Total number of insects treated) × 100

[0232] Corrected lethality = (treatment lethality - blank lethality) / (1 - blank lethality) × 100

[0233] Table 2. Lethality of compounds prepared in Examples J1-J36 against broad bean aphids

[0234]

[0235] The insecticidal activity results showed that the compounds had good activity against broad bean aphids. Some compounds, J1, J9, J13 and J33, had a lethality of 100% against broad bean aphids at a concentration of 100 μg / mL. Compound J1 also had a lethality of 100% against broad bean aphids at a concentration of 10 μg / mL. The insecticidal activity was higher than that of the control agent trifluoropyrimidine.

[0236] Example 2: Indoor bioactivity assay of target compound against potato virus Y.

[0237] (1) Test method

[0238] A. Test methods and material testing methods:

[0239] Half-leaf necrotic spot method; test concentration: 500 μg / mL; virus: potato virus Y (PVY); test plant: amaranth; control agents: vanilla thiophanate-methyl, ningnanmycin.

[0240] B. Virus purification:

[0241] Upper leaves of *Nicotiana tabacum* L. plants inoculated for more than 3 weeks were selected. The PVY system was used to infect the leaves, homogenized in phosphate buffer, filtered through double-layer gauze, centrifuged at 8000g, treated twice with polyethylene glycol, centrifuged again, and the precipitate was resuspended in phosphate buffer to obtain the purified PVY extract. The entire experiment was conducted at 4℃. The absorbance at 260nm was measured using a UV spectrophotometer, and the virus concentration was calculated according to the formula.

[0242] C. Preparation of compound solutions:

[0243] Accurately weigh 2 mg of the test compound into a 10 mL centrifuge tube using an analytical balance, add 30 μL DMSO to dissolve it completely, and then add 4 mL of double-distilled water containing 1% Tween 20 to prepare a reagent concentration of 500 μg / mL. Weigh 2 mg of vanillin into a 10 mL centrifuge tube, add 30 μL DMSO to dissolve it completely, and then add 4 mL of double-distilled water containing 1% Tween 20 to prepare a reagent concentration of 500 μg / mL. Separately, take 25 μL of 8% ningnanmycin aqueous solution, add 30 μL of DMSO solvent, and prepare the control reagent ningnanmycin concentration according to the above method.

[0244] D. The in vivo protective effect of the agent against PVY infection:

[0245] In vivo protective effect of the agent against PVY infection: Selected 5-6 leafy plants of uniform growth, topped, with 4-5 leaves of uniform growth retained per plant. The agent was lightly applied to the left half of the leaves with a brush, while the right half was treated with a solvent of the corresponding concentration as a control. 24 hours later, emery was evenly sprinkled onto the entire leaf. The entire leaf was then inoculated with a pre-prepared virus extract using a brush. After natural drying, the emery was washed off with water and the plants were dried again. All inoculated plants were then transferred to a greenhouse and cultured at 25±1℃ and 10000 Lux. The average number of necrotic spots on the untreated left half and the number of necrotic spots on the treated right half were both calculated using the average of three replicates. After 3-4 days, obvious necrotic spots appeared on the leaves, and the corresponding number of necrotic spots was recorded. Each compound was tested in triplicate. Vanillin and ningnanmycin were used as controls, and their inhibition rates were calculated using the following formula:

[0246]

[0247] (2) Antiviral activity test results

[0248] Table 3. Protective activity of compounds obtained in Examples J1-J36 against PVY

[0249]

[0250]

[0251] The anti-PVY protective activity of pyridopyrimidine ion derivatives containing dithioacetal units was tested using the half-leaf necrozonal method at a concentration of 500 mg / L, with ningnanmycin and vanillin as control agents. The bioassay results in Table 3 show that the pyridopyrimidine ion derivatives containing dithioacetal units exhibited moderate to good anti-PVY protective activity. Among them, J1 and J18 showed protective activities of 58.6% and 62.7%, respectively, which were higher than those of the control agents ningnanmycin and vanillin (51.5% and 55.4%).

Claims

1. A pyridopyrimidinone mesonic derivative containing a dithioacetal unit, characterized in that, Including compounds having the general formula (I) or (II) or their stereoisomers, salts thereof, or solvates thereof: Where n is 0, 1, 2; R1 is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, alkyl (either substituted or unsubstituted), alkoxy (either substituted or unsubstituted), alkenyl (either substituted or unsubstituted), cycloalkyl (either substituted or unsubstituted), and aryl (either substituted or unsubstituted). R2 is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, alkyl (either substituted or unsubstituted), alkoxy (either substituted or unsubstituted), alkenyl (either substituted or unsubstituted), cycloalkyl (either substituted or unsubstituted), aryl (either substituted or unsubstituted), and heteroaryl (either substituted or unsubstituted). R3 is independently selected from one or more of hydrogen, deuterium, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted benzyl.

2. The pyridopyrimidinone compound containing a dithioacetal unit according to claim 1, or its stereoisomer, salt, or solvate thereof, is characterized in that: R1 is independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkenyl, substituted or unsubstituted C6-C 15 One or more of aryl, substituted or unsubstituted C5-C6 heteroaryl groups; R2 is independently selected from hydrogen, deuterium, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkenyl, substituted or unsubstituted C6-C 15 One or more of aryl, substituted or unsubstituted C5-C6 heteroaryl groups; R3 is independently selected from one or more of hydrogen, deuterium, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. The substitution refers to the option of being substituted with one or more of halogen, nitro, hydroxyl, amino, mercapto, or C1-C6 alkyl groups.

3. The pyridopyrimidinone mesonoionic derivative containing a dithioacetal unit as described in claim 1, characterized in that, R1 is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, and pyridyl; R2 is independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, pyrazolyl, pyrroleyl, furanyl, thiophene, thiazolyl, benzopyrroleyl, pyridazine, pyrimidine, pyrazine, -CH2CH2CN, -CHCNCH3, -CH2CH2CH2CN, and -C. H2CHCNCH3, -CHCNCH2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHClCH3, -CH2CH2CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3, -CHBrCH2CH3, R3 is independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, cyclopropyl, sec-propyl, propenyl, n-butyl, sec-butyl, isobutyl, 2-methylbutyl, 3-methylbutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, furanyl, pyridyl, -CH2CH2CN, -CHCNCH3, -CH2CH2CH2CN, -CH2CHCNCH3, -CHCNCH2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHClCH3, -CH2CH2CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3, -CHBrCH2CH3.

4. A pyridopyrimidine ketone mesonoionic derivative containing a dithioacetal unit as described in any one of claims 1-3, characterized in that, Selected from the following specific compounds:

5. The method for preparing a pyridopyrimidine ketone mesonoionic derivative containing a dithioacetal unit as described in claim 1, characterized in that, include:

6. The method for preparing a pyridopyrimidine ketone mesonoionic derivative containing a dithioacetal unit as described in claim 5, characterized in that, include 7. A composition, characterized in that... The composition contains a pyridopyrimidine ketone metronidogen as described in any one of claims 1-4, and agriculturally applicable adjuvants or fungicides, insecticides or herbicides; 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), and water-dispersible granules (WG).

8. The use of the pyridopyrimidine ketone mesonotropic derivative containing a dithioacetal unit as described in any one of claims 1-4, or the composition of claim 7, in the preparation of a pesticide for controlling agricultural pests and diseases; wherein the agricultural pests and diseases are broad bean aphids and potato virus Y.

9. A method for preventing and controlling agricultural pests and diseases, characterized in that: The pyridopyrimidinone metronidogen derivative containing a dithioacetal unit as described in any one of claims 1-4, or the composition as described in claim 7, is applied to the harmful substance or its living environment; the agricultural pests are broad bean aphids and potato virus Y.

10. A method for protecting plants from agricultural pests and diseases, comprising the method step of contacting the pest with a pyridopyrimidine ketone mesonotropic derivative containing a dithioacetal unit as described in any one of claims 1-4, or the composition as described in claim 7.

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