Pyrido [1, 2-a] pyrimidine mesoion derivative containing amide structure as well as preparation method and application of pyrido [1, 2-a] pyrimidine mesoion derivative

Abstract

The invention relates to a pyrido [1, 2-a] pyrimidine mesoion derivative containing an amide structure as well as a preparation method and application of the pyrido [1, 2-a] pyrimidine mesoion derivative. The compound disclosed by the invention has a structure as shown in a formula (I), has excellent insecticidal activity on peas aphis, sogatella furcifera, plutella xylostella, spodoptera litura and the like, and can be used for preparing drugs for preventing and treating pests such as the peas aphis, the sogatella furcifera, the plutella xylostella, the spodoptera litura and the like; the structure and the preparation process are simple, and the production cost is low. (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 metronid derivatives in pesticides for controlling pests such as aphids, white-backed planthoppers, diamondback moths, and fall armyworms. Background Technology

[0002] Hemiptera and Lepidoptera are two important categories of agricultural pests, characterized by their numerous species, significant impact, and frequent outbreaks that cause widespread damage. Their occurrence and severity often result in substantial losses to my country's national economy, particularly agricultural production, severely impacting crop yield and quality. Therefore, the control of agricultural pests and diseases plays a crucial role in ensuring food security, improving crop quality, and protecting the ecological environment.

[0003] Rice planthoppers belong to the order Hemiptera ( Hemiptera Planthopper family ( Delphicidae The brown planthopper (Brassica napus) is a migratory pest that causes the largest area of ​​occurrence and the most severe damage in rice production in my country and the world. Nilaparvata mourning ), white-backed planthopper ( Sogatella furcifera ) and gray planthoppers ( Laodelphax striatellus There are three categories of rice planthoppers. These pests reproduce rapidly, are highly destructive, and are also major carriers of viruses. They can spread pathogens such as Southern Black-streaked Dwarf Disease virus and Rice Sheath Blight, hindering rice growth and, in severe cases, causing the entire rice plant to wither, lodging, or even resulting in complete crop failure, significantly impacting rice health and yield. During severe outbreaks, the affected area of ​​rice planthoppers nationwide reached 330 million mu (approximately 22 million hectares), causing an average annual actual loss of over 1 million tons of rice yield, with losses potentially reaching 40-60%.

[0004] aphid( Aphid Aphids are a collective term for the superfamily Aphididae in the order Hemiptera. Currently, a total of 4,400 species belonging to 10 families have been discovered, most of which are Aphididae. These pests are among the most prolific and destructive pests of all cultivated crops, directly or indirectly damaging them. Direct damage mainly occurs when adult and nymph aphids suck sap from leaves and young spikes, causing leaf curling and wilting, severely impacting plant growth. Indirect damage refers to aphids acting as vectors for plant viruses, inducing plant viral diseases and causing yield reductions, resulting in huge losses to agricultural production each year, sometimes reaching 40-50%.

[0005] Lepidoptera ( Lepidoptera Pests include agricultural pests such as the fall armyworm and the diamondback moth. The diamondback moth ( Plutella xylostellaIt is one of the most destructive pests of cruciferous crops worldwide, belonging to the Pyrendicidae family (Pyrendicidae). Plutellidae It is characterized by a short occurrence cycle, high reproductive capacity, rapid generational turnover, and long growing season. It is particularly harmful to cruciferous vegetables, causing damage of 70%-90%. In severely affected fields, the yield loss of vegetables can reach 80%-90% or more, resulting in huge economic losses and seriously threatening food security.

[0006] fall armyworm ( Spodoptera frugiperda ), belonging to the family Noctuidae of the order Lepidoptera ( Noctuidae genus *Greywing noctuid* ( Spodoptera The fall armyworm, native to tropical and subtropical regions of the Americas, is a polyphagous pest with over 350 host plant species. It has a high potential for reproduction and spread, particularly favoring gramineous plants such as corn, sorghum, and sugarcane. Statistics show that in areas severely affected by the fall armyworm, over 90% of corn plants can be damaged. Due to the strong migratory ability of adult fall armyworms, it has spread rapidly globally. Since invading Yunnan Province in January 2019, it has been found in multiple provinces in China. Within a short period after its invasion, millions of hectares of crops have been affected. In September 2020, the fall armyworm was listed as the top pest in the "List of Class A Crop Diseases and Pests" by the Ministry of Agriculture and Rural Affairs, and its control was explicitly required to be strengthened in the Central Government's No. 1 Document for three consecutive years from 2020 to 2022.

[0007] The rational use of pesticides is crucial for ensuring agricultural production. However, many pesticides currently used to control agricultural pests such as hemipterans and lepidopterans are experiencing increasing resistance due to long-term, large-scale, and irrational use. This severely impacts pest control effectiveness and significantly increases costs. Furthermore, the toxicity of many pesticides to non-target organisms and their environmental pollution are receiving growing attention, leading to the banning or restriction of some existing pesticides due to these issues. Therefore, developing novel, highly efficient, low-risk pesticides with unique mechanisms of action has become an urgent issue for green agricultural development and food security.

[0008] In 2016, Corteva (formerly DuPont) developed a new class of insecticides that attracted worldwide attention due to their unique chemical structure, high insecticidal activity, and novel mode of action. These insecticides are metronid compounds, hence the name metronid insecticides. The first two commercially available metronid insecticides were triflumezopyrim and didicloromezotiazine, which can be used to control hemiptera and lepidopteran pests, respectively. These two insecticides do not exhibit cross-resistance with existing insecticides and can be used to control resistant pests. These characteristics of metronid insecticides have made them a new hot topic in global research and development, opening the prelude to the synthesis of metronid compounds. However, they still carry the risk of high toxicity to bees and high levels of resistance (acute exposure and acute oral LD50 of triflumezopyrim after 72 hours). 50 They are 0.39 and 0.51 respectively. μ (g / animal, all highly toxic). Therefore, it is of great significance to develop novel, highly efficient, and low-risk metronidazole insecticides based on trifluorophenylpyrimidine.

[0009] In 2009, Holyoke CW et al. first disclosed a pyrido[1,2-]pyrido[1,2-]pyrido[1,2- a This paper discusses the preparation methods and applications of pyrimidine metronidazole compounds as insecticides. These compounds exhibit good to excellent insecticidal activity against pests such as diamondback moth, fall armyworm, green peach aphid, cotton aphid, rice brown planthopper, and corn leafhopper. In recent years, researchers have focused on structural optimization of pyridopyrimidine ketone insecticides, primarily at the 1, 3, and 9 positions. DuPont has conducted extensive research on the 1-position substitution, publishing seven patents between 2009 and 2015. Structure-activity relationship results indicate that when pyrido[1,2-...]... a Pyrimidinone mesoionic skeletons containing 2-chlorothiazol-5-ylmethyl, pyrimidin-5-ylmethyl, and 6-chloropyridin-3-ylmethyl at the 1-position exhibit good to excellent insecticidal activity. In 2016, Hasegawa S. et al. of Nippon Kayaku Co., Ltd. disclosed a series of pyrido[1,2-]pyrimidinone compounds in patent publication number WO2016171053A1. a Among pyrimidine metronid compounds, compounds containing a cyanoethyl group at the 1-position were found to exhibit good to excellent insecticidal activity against cotton aphids and brown planthoppers, with some compounds showing activity at 0.1%... μ g·mL -1 At the specified concentrations, the lethality against aphids was 100%, and some compounds showed even better insecticidal activity against cotton aphids than trifluorophenylpyrimidine and dichlorothiapyrimidine. The results indicate that, for compounds containing the 1-position moiety, cyanoethyl can serve as an excellent substitution group for 2-chlorothiazol-5-ylmethyl, pyrimidin-5-ylmethyl, and 6-chloropyridin-3-ylmethyl.

[0010] p-pyrido[1,2- a Analysis of patents for pyrimidine ketone metronidazole compounds revealed that researchers achieved the most and most successful substitution at the 3-position of the parent structure. In 2012, Holyoke CW et al. disclosed a class of pyridopyrimidine metronidazole compounds containing diaryl groups in patent WO2012106495A1. These compounds exhibited excellent insecticidal activity against Lepidoptera, Homoptera, and Thysanoptera pests such as the diamondback moth and fall armyworm. Some compounds showed activity at 2... μ g·mL -1 At the specified concentrations, it showed 100% lethality against diamondback moth and fall armyworm. From 2012 to 2014, BASF disclosed phenyl compounds with oxime, oxime ether, amidine, and hydrazine substituted at the 3-position in patents WO2012136724A1, EP2684879A1, and WO2014033244A2. The insecticidal activity of these compounds was generally moderate. In 2021, Holmes, M et al. disclosed a series of pyridinopyrimidinone metronidazole compounds with a 3-alkynylphenyl group at the 3-position in patent WO2021151034A1. Bioactivity tests showed that most compounds exhibited excellent insecticidal activity, with some compounds showing activity as low as 0.4%. μ g·mL -1 At certain concentrations, these compounds still exhibit a 100% lethality against Lepidoptera such as diamondback moth and fall armyworm. Some compounds also show activity against aphids and planthoppers, significantly enhancing the insecticidal spectrum and activity. From 2024 to 2025, Qingdao Qingyuan Compounds Co., Ltd. disclosed pyridinidone metronidazole compounds with structures containing a benzo[a]-heterocyclic ring, a diynyl group, a pyrazole, and a benzo[a]-dioxane heterocycle at the 3-position in patents CN120441570A, CN120904195A, CN120774913A, CN120774911A, CN120774912A, and CN120682223A. Some of these compounds show good control activity against agricultural pests such as Lepidoptera, Homoptera, and Acari. They are characterized by broad spectrum, high efficiency, and strong systemic activity, effectively controlling resistant pests and possessing certain commercial value. Among them, the compound "chlorfenapyr" has been granted a provisional name by ISO. It is a novel chemically structured patented insecticide independently developed by Qingyuan, exhibiting no cross-resistance with existing insecticides. It possesses excellent penetration ability and a certain degree of systemic conductivity, effectively controlling lepidopteran pests such as the rice stem borer and rice leaf roller that have developed resistance to traditional pesticides. The creation of chlorfenapyr marks a significant breakthrough for Qingyuan in the field of rice resistant pest control, and it is expected to become a core force in the rice insecticide market in the future.

[0011] Our research team also conducted extensive research and modification on the 3-position of pyridopyrimidine ketone metronidazole compounds. First, patent CN113292557A disclosed pyridopyrimidine ketone metronidazole compounds with an indole derivative at the 3-position. These compounds exhibited good insecticidal activity against white-backed planthoppers and broad bean aphids, with some compounds showing activity at 10... μ g·mL -1 At the specified concentration, the mortality rate against both white-backed planthopper and broad bean aphid was 100%. Subsequently, patent CN113651811A disclosed pyridopyrimidine ketone metronidazole compounds with an isoxazole unit at the 3-position. These compounds exhibit excellent control efficacy against rice planthoppers, and a compound named "isoxamethonium pyrimidine" was created and named by the National Pesticide Standardization Technical Committee. This compound has a 2 μ g·mL -1 At the specified concentration, the mortality rate against white-backed planthoppers remained 100%. To broaden the insecticidal spectrum and enhance the insecticidal activity of the compound, our research team disclosed a pyridopyrimidine ion compound containing a 1,2,4-oxadiazole structure at the 3-position in patent CN117720535A in 2024. The created "oxadiazole pyrimidine" compound exhibits excellent insecticidal activity against rice stem borers, reaching 5... μ g·mL -1 The lethality rate at the concentration is still 95%, and it has insecticidal activity against both hemiptera and lepidopteran pests.

[0012] For pyrido[1,2- a Studies on the 9-position substitution of pyrimidinone mesoionic skeletons have found that the insecticidal activity of compounds significantly decreases when groups other than the methyl group are introduced. In 2011, Holyoke CW et al. of Corteva (formerly DuPont) disclosed a method for preparing a class of mesoionic compounds and their application as insecticides in patent WO2011017342A2. These compounds exhibit good insecticidal activity, with some compounds showing a 100% lethality against diamondback moth, fall armyworm, and cotton aphid at a concentration of 10 mg / L. Structure-activity relationship studies have shown that in pyrido[1,2- a The compound exhibits optimal insecticidal activity against diamondback moth and fall armyworm when the 1-position of the pyrimidine ring is substituted with a 2-chlorothiazol-5-ylmethyl group and the 9-position is substituted with a methyl group. This effect is only effective when the 1-position is 2-chlorothiazol-5-yl, a phenomenon DuPont refers to as the "magic methyl effect." Based on this, DuPont developed dichlorothiapyrimidine, which possesses insecticidal activity against both hemiptera and lepidopteran pests.

[0013] Amide groups, due to their unique electronic structure and biological activity mechanisms, have become important pharmacodynamic groups in the design of green pesticide molecules. Compounds containing amide structures often possess broad biological activities such as antibacterial, insecticidal, and antiviral activity, and their synthesis and biological activity research have always been a hot topic in pesticide chemistry research. Over the past few decades, a variety of amide derivatives with significant biological activity and unique mechanisms of action have been developed, such as fungicides targeting succinate dehydrogenase and insecticides targeting ryneline receptors (RyRs). These compounds stand out due to their high efficiency, low toxicity, and safety for non-target organisms. Amide insecticides are the most market-focused insecticide class after neonicotinoid insecticides, and also the fastest-growing insecticide class in recent years. Their ability to reduce environmental impact and target specificity make them even more attractive. Therefore, amide derivatives will provide a sustainable and effective solution for pest management in the foreseeable future.

[0014] In 2021, Wang Qingmin et al. disclosed a class of isoxazoline derivatives containing amide structures, their preparation methods, and their applications in controlling pests and plant pathogens in patent CN115246825A. Combining the "intermediate derivatization method," they discovered for the first time that derivatives based on the conversion of the cyano group in the highly active molecule DP-9 reported by DuPont into carboxylic acids and amides exhibit good activity against diamondback moth, armyworm, fall armyworm, cotton bollworm, corn borer, mosquito larvae, fleas, mites, ticks, and inhibit plant pathogens. This invention lays the foundation for the creation of novel, broad-spectrum, and highly effective insecticides and possesses significant inventiveness.

[0015] In 2022, Shi Jianjun et al. disclosed a series of [unclear text - possibly related to patent CN115477615A] containing [unclear text - possibly related to patent CN115477615A]. N This invention relates to 3-(benzimidazole-2-yl)phenyl)amide compounds, their preparation methods, and their insecticidal applications. It begins with a pyridine-imidazolium-bipyridine structure, which is electron-isolated to form an alkylbenzimidazole-biphenyl structure. An amide group is introduced at the meta position of the intermediate benzene ring, followed by appropriate structural modifications. The invention's preparation method is simple and convenient, and results show that most compounds can be prepared within 200 days. μ g·mL -1 At certain concentrations, they exhibit certain insecticidal activity. Some compounds have a mortality rate of over 85% against armyworms, over 85% against alfalfa aphids, and over 85% against rice planthoppers.

[0016] In summary, addressing the severe, difficult-to-control, and highly resistant pests in agricultural production, coupled with a lack of effective pesticides, this study focuses on the design and synthesis of mesoionic compounds, addressing the key scientific challenge of constructing novel lead molecules for highly efficient and low-risk pest control. Specifically, it examines pyrido[1,2-] a Based on the excellent insecticidal activity of pyrimidine metronid compounds, research was conducted on pyridine compounds containing amide structures [1,2-]. aThe design, synthesis, and insecticidal activity studies of pyrimidine metronid compounds have been conducted, introducing amide structures with excellent biological activity into pyridine[1,2-]pyrimidines. a The pyrimidine structure is located at the para and meta positions of the 3-phenyl group. Bioactivity screening results indicate that it exhibits good insecticidal activity and a broad spectrum of control, providing a theoretical basis for the creation and research of novel green interionic insecticides. Summary of the Invention

[0017] To address the aforementioned problems in the prior art, this invention provides a class of pyrido[1,2-]pyridines containing amide structures. a [A pyrimidine mesonotropic derivative and its preparation method. The compound exhibits excellent control effects against pests such as the pea aphid, white-backed planthopper, diamondback moth, and fall armyworm.]

[0018] Another object of the present invention is to provide a composition containing the above-mentioned compound or its stereoisomer or its salt.

[0019] Another object of the present invention is to provide the use of the above-mentioned compound or its stereoisomer, or its salt, or the composition thereof.

[0020] Another object of the present invention is to provide a method for controlling agricultural pests using the above-mentioned compound or its stereoisomer, or its salt, or the composition thereof.

[0021] To achieve the above objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides a pyrido[1,2-] amide-containing pyrido[1,2-] a Pyrimidine mesonotropic derivatives, including compounds having the general formula (I) or its stereoisomers, salts or solvates thereof, the structural formula of which is as follows: (I) Where X represents a nitrogen atom or a carbon atom; R 1 It is independently selected from one or more of hydrogen, deuterium, 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); R 2 It is independently selected from one or more of hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, amino, mercapto, any substituted or unsubstituted alkyl, any substituted or unsubstituted alkoxy, any substituted or unsubstituted alkenyl, any substituted or unsubstituted cycloalkyl, and any substituted or unsubstituted aryl. R 3It is independently selected from one or more of the following: alkyl group (either substituted or unsubstituted), alkoxy group (either substituted or unsubstituted), alkenyl group (either substituted or unsubstituted), alkynyl group (either substituted or unsubstituted), cycloalkyl group (either substituted or unsubstituted), aryl group (either substituted or unsubstituted), and heteroaryl group (either substituted or unsubstituted); R 4 It is independently selected from one or more of hydrogen, alkyl (either substituted or unsubstituted), alkoxy (either substituted or unsubstituted), alkenyl (either substituted or unsubstituted), alkynyl (either substituted or unsubstituted), cycloalkyl (either substituted or unsubstituted), aryl (either substituted or unsubstituted), and heteroaryl (either substituted or unsubstituted). R 5 It is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, cyano, and any substituted or unsubstituted alkyl group.

[0022] Preferably, R 1 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; R 2 Independently selected from hydrogen, deuterium, halogen, cyano, 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; R 3 Independently selected from substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkenyl, substituted or unsubstituted C1-C6 ynyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C 15 One or more of aryl, substituted or unsubstituted C5-C6 heteroaryl groups; R 4 Independently selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkenyl, substituted or unsubstituted C1-C6 alkynyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C 15 One or more of aryl, substituted or unsubstituted C5-C6 heteroaryl groups.

[0023] R 5 It is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, cyano, and C1-C6 alkyl; The substitution refers to the substitution by at least one of the halogens.

[0024] More preferably, R1 Independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, pyrazolyl, pyrrolyl, furanyl, thiophene, thiazolyl, benzopyrrolyl, pyridazine, pyrimidine, pyrazine, -CH2CH2CN, -CHCNCH3, -CH2CH2CH2CN, -CH2CHCNCH3, -CHCNCH2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHClCH3, -CH2CH2CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3, -CHBrCH2CH3 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; R 3 Independently selected from methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, propenyl, -CH2F, -CHF2, -CF3, -CH2Cl, -CHCl2, -CCl3, -CH2Br, -CHBr2, -CBr3, -CH2CH2Cl, -CH2CH2Br, -CH2CH2F, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ... , , , , , , , , , , , , , , .

[0025] Preferred derivative compounds include compounds A1-A50 listed below.

[0026] Secondly, the present invention provides the pyrido[1,2-] ... a Methods for preparing pyrimidine mesonotropic derivatives include: Preferably, it further includes: Most preferably, it includes: or Thirdly, the present invention provides a composition comprising pyrido[1,2-] amide-containing pyrido[1,2-]a The composition may be a pyrimidine mesonotropic derivative or its stereoisomer, or its salt, and an adjuvant, fungicide, insecticide or herbicide available in agriculture; the formulation of the composition may be 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).

[0027] Fourthly, the present invention provides pyrido[1,2-] ... a The use of pyrimidine mesonotropic derivatives or their stereoisomers, or their salts, or the composition thereof in the preparation of pesticides for controlling agricultural pests and diseases; wherein the agricultural pests and diseases are hemiptera and lepidopteran pests. Preferably, the agricultural pests and diseases are aphids, rice planthoppers, diamondback moths, and fall armyworms.

[0028] Fifthly, the present invention provides a method for preventing and controlling agricultural pests and diseases, wherein the compound or its stereoisomer, or its salt, or the composition thereof acts on the harmful substance or its habitat; preferably, the agricultural pests and diseases are hemiptera and lepidopteran pests; more preferably, the agricultural pests and diseases are aphids, rice planthoppers, diamondback moths, and fall armyworms.

[0029] In a sixth aspect, the present invention provides a method for protecting plants from agricultural pests and diseases, comprising inducing the pests to react with the amide-containing pyridine[1,2- a The method steps of contacting the pyrimidine mesonotropic derivative or its stereoisomer, its salt or its solvate, or the composition thereof.

[0030] The beneficial effects of this invention are: Excellent insecticidal activity. The compounds provided by this invention exhibit excellent insecticidal activity against pests such as aphids, rice planthoppers, diamondback moths, and fall armyworms. Most of the compounds are effective at low doses (1... μ The compound still exhibits high insecticidal activity under conditions of g / mL, therefore the compound provided by this invention can improve the problem of high-dose application and fundamentally reduce the cost of application and pest resistance.

[0031] 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) compounds are intended for C1, C2, C3, C4, C5, C6, C7, C8, C9, and C6. 10 Alkyl group. 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.

[0032] "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 2-6 The 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.

[0033] The term "cycloalkyl" refers to cycloalkyl groups, including mono-, di-, or polycyclic systems. 3-7 The term cycloalkyl refers to 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.

[0034] 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.

[0035] The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine, and iodine.

[0036] 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, but 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).

[0037] The term "alkoxy group" refers to an alkyl group that is attached to the remainder of a molecule by an oxygen atom, wherein the alkyl group has the meaning as described in this invention. The alkoxy group contains 1-20 carbon atoms. Examples of alkoxy groups include, but are not limited to, methoxy (-OCH3), ethoxy (-OCH2CH3), 1-propoxy (-OCH2CH2CH3), 2-propoxy (-OCH(CH3)2), and 1-butoxy (-OCH2CH2CH2CH3).

[0038] The term "substituted" refers to the substitution of any one or more hydrogen atoms on a specified atom or group with a selected specified group, provided that the substitution does not exceed the general valence of the specified atom. Unless otherwise specified, substituents are named to the central structure. For example, it can be understood that when (cycloalkyl)alkyl is a possible substituent, the connection point of the substituent to the central structure is in the alkyl moiety, and the substituent group includes, but is not limited to, halogen atoms.

[0039] The term "solvent" refers to an association formed by one or more solvent molecules with the compounds of the present invention. Solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and aminoethanol. Specific implementation methods 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.

[0040] Example 1: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylcyclopropanoamide)phenyl)-4-oxo-4 H -pyridyl[1,2- a Pyrimidine-1-onium-2-ol (A1): (1) Preparation of methyl 2-(3-(cyclopropanecarboxamido)phenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (1.01 g, 9.99 mmol) were added to a 100 mL round-bottom flask. Cyclopropylformyl chloride (1.23 g, 11.80 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.91 g of a colorless oil, with a yield of 90.2%.

[0041] (2) 2-(3-( N Preparation of dimethyl methylcyclopropane)phenyl)malonate: 1.9 g (8.15 mmol) of methyl 2-(3-(cyclopropanecarboxamido)phenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 1.17 g (48.87 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated, and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 1.7 g of a colorless oil, with a yield of 71.65%.

[0042] (3) 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%.

[0043] (4) 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylcyclopropanoamide)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A1): 2-(3-( N Dimethyl methylcyclopropane (1.0 g, 3.29 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (741.6 mg, 3.29 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 150 mg of yellow solid, yield 9.8%.

[0044] Example 2: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(3-( N (-methylcyclopropanamide)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A2): Steps (1) and (2) are the same as steps (1) and (2) in Example 1. (3) 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 , 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 10.8 g of a pale yellow solid, with a yield of 48.72%.

[0045] (4) 1-((2-chlorothiazol-5-yl)methyl))-9-methyl-3-(3-( N (-methylcyclopropanoamide)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A2): 2-(3-(N Dimethyl methylcyclopropane (1.0 g, 3.29 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (787.7 mg, 3.29 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 132 mg of yellow solid, yield 8.4%.

[0046] Example 3: 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylcyclopropanoamide)phenyl)-4-oxo-4 H -pyridyl[1,2- a Pyrimidine-1-onium-2-ol (A3): Steps (1) to (2) are the same as steps (1) to (2) in Example 1. (3) 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%.

[0047] (4) 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylcyclopropanoamide)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A3): 2-(3-( N Dimethyl methylcyclopropane (1.0 g, 3.28 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N-((6-chloropyridin-3-yl)methyl)pyridin-2-amine (716.2 mg, 3.28 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 194.2 mg of yellow solid, yield 12.9%.

[0048] Example 4: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A4): (1) Preparation of methyl 2-(3-acetaminophenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (1.19 g, 9.99 mmol) were added to a 100 mL round-bottom flask. Acetyl chloride (0.78 g, 11.80 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.61 g of a colorless oil, with a yield of 85.6%.

[0049] (2) 2-(3-( N Preparation of dimethyl methyl acetamidophenyl malonate: 1.6 g (7.72 mmol) of methyl 2-(3-acetamidophenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 1.11 g (46.33 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 1.81 g of a colorless oil, with a yield of 83.5%.

[0050] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A4): 2-(3-(N Dimethyl methyl methacrylate (1.0 g, 3.58 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (808.1 mg, 3.58 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 118.3 mg of yellow solid, yield 7.49%.

[0051] Example 5: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(3-( N (-methylacetamide)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A5): Steps (1) and (2) are the same as steps (1) and (2) in Example 4. Step (3) is the same as step (3) in Example 2. (4) 1-((2-chlorothiazol-5-yl)methyl))-9-methyl-3-(3-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A5): 2-(3-( N Dimethyl methyl methacrylate (1.0 g, 3.58 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (787.7 mg, 3.58 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 168.5 mg of yellow solid, yield 10.3%.

[0052] Example 6: 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Pyrimidine-1-onthium-2-ol (A6): Steps (1) and (2) are the same as steps (1) and (2) in Example 4. Step (3) is the same as step (3) in Example 3. (4) 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A6): 2-(3-( N Dimethyl methyl methacrylate (1.0 g, 3.58 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((6-chloropyridin-3-yl)methyl)pyridin-2-amine (716.2 mg, 3.58 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 176.4 mg of yellow solid, yield 11.3%.

[0053] Example 7: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-Methylpropionamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A7): (1) Preparation of methyl 2-(3-propionylaminophenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (1.19 g, 9.99 mmol) were added to a 100 mL round-bottom flask. Propionyl chloride (0.924 g, 11.80 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.92 g of a colorless oil, with a yield of 95.6%.

[0054] (2) 2-(3-( N Preparation of dimethyl methylpropionamide (M-methylpropionamide)phenyl)malonate: 1.9 g (8.59 mmol) of methyl 2-(3-propamidophenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 1.24 g (51.52 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated, and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 2.20 g of a colorless oil, with a yield of 87.34%.

[0055] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-( N (-Methylpropionamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A7): 2-(3-( N Dimethyl methylpropionamide (1.0 g, 3.41 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (808.1 mg, 3.58 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 288.5 mg of yellow solid, yield 18.6%.

[0056] Example 8: 3-(3-( N (-Methylpropionamido)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A8): Steps (1) and (2) are the same as steps (1) and (2) in Example 7. (3) 3-(3-( N (-Methylpropionamido)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A8): 2-(3-( NDimethyl 3-amino-3-methylpyridine (0.5 g, 1.70 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask. 2-Amino-3-methylpyridine (408.6 mg, 1.70 mmol) was added to the system under stirring at room temperature. The mixture was heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 128.6 mg of yellow solid, with a yield of 16.1%.

[0057] Example 9: 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-Methylpropionamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Pyrimidine-1-onthium-2-ol (A9): Steps (1) and (2) are the same as steps (1) and (2) in Example 7. Step (3) is the same as step (3) in Example 3. (4) 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-Methylpropionamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A9): 2-(3-( N Dimethyl propionylamino(phenyl)malonate (0.5 g, 1.70 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((6-chloropyridin-3-yl)methyl)pyridin-2-amine (372.7 mg, 1.70 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 152.2 mg of yellow solid, yield 19.9%.

[0058] Example 10: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylisobutyramido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A10): (1) Preparation of methyl 2-(3-isobutyrylaminophenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (0.92 g, 9.08 mmol) were added to a 100 mL round-bottom flask, and isobutyryl chloride (1.06 g, 9.99 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.62 g of a colorless oil, with a yield of 75.83%.

[0059] (2) 2-(3-( N Preparation of dimethyl methylisobutyramide (Methylisobutyramide)phenyl)malonate: 1.62 g (6.89 mmol) of methyl 2-(3-isobutamidophenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 0.83 g (34.43 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 1.43 g of a pale yellow oil, with a yield of 70.81%.

[0060] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-( N (-methylisobutyramido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A10): 2-(3-( N Dimethyl (-methylisobutyramido)phenyl)malonate (0.5 g, 1.70 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.38 g, 1.70 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 60.65 mg of yellow solid, yield 7.82%.

[0061] Example 11: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(3-( N(-methylisobutyramide)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onyl-2-ol (A11): Steps (1) and (2) are the same as steps (1) and (2) in Example 10. Step (3) is the same as step (3) in Example 2. (4) 1-((2-chlorothiazol-5-yl)methyl))-9-methyl-3-(3-( N (-methylisobutyramido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A11): 2-(3-( N Dimethyl (-methylisobutyramido)phenyl)malonate (0.5 g, 1.70 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (408.6 mg, 1.70 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 55.2 mg of yellow solid, yield 6.91%.

[0062] Example 12: 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylisobutyramido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Pyrimidine-1-onium-2-ol (A12): Steps (1) and (2) are the same as steps (1) and (2) in Example 10. Step (3) is the same as step (3) in Example 3. (4) 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylisobutyramido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A12): 2-(3-( N Dimethyl (-methylisobutyrylamino)phenyl)malonate (0.5 g, 1.70 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N-((6-chloropyridin-3-yl)methyl)pyridin-2-amine (374.72 mg, 1.70 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 51.2 mg of yellow solid, yield 6.69%.

[0063] Example 13: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylbutyramido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A13): (1) Preparation of methyl 2-(3-butyrylaminophenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (0.92 g, 9.08 mmol) were added to a 100 mL round-bottom flask, and butyryl chloride (1.05 g, 9.99 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.65 g of a colorless oil, with a yield of 77.23%.

[0064] (2) 2-(3-( N Preparation of dimethyl (-methylbutamido)phenyl)malonate: 1.65 g (7.01 mmol) of methyl 2-(3-butamidophenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 0.84 g (35.06 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 1.51 g of a pale yellow oil, with a yield of 70.06%.

[0065] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-( N (-methylbutyramido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A13): 2-(3-(N Dimethyl (-methylbutamido)phenyl)malonate (0.5 g, 1.63 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.63 g, 1.63 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 77.5 mg of yellow solid, yield 10.16%.

[0066] Example 14: 3-(3-( N (-Methylbutyramido)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A14): Steps (1) and (2) are the same as steps (1) and (2) in Example 13. (3) 3-(3-(N-methylbutamido)phenyl)-9-methyl-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A14): 2-(3-( N Dimethyl (-methylbutamido)phenyl)malonate (0.5 g, 1.63 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask. 2-Amino-3-methylpyridine (389.99 mg, 1.63 mmol) was added to the system under stirring at room temperature. The mixture was heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 59.6 mg of a yellow solid, with a yield of 7.59%.

[0067] Example 15: 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylbutyramido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Pyrimidine-1-onyl-2-ol (A15): Steps (1) and (2) are the same as steps (1) and (2) in Example 13. Step (3) is the same as step (3) in Example 3. (4) 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylbutyramido)phenyl)-4-oxo-4 H -pyridyl[1,2- aPreparation of pyrimidine-1-onium-2-olate (A15): 2-(3-( N Dimethyl (-methylbutyrylamino)phenyl)malonate (0.5 g, 1.63 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((6-chloropyridin-3-yl)methyl)pyridin-2-amine (374.72 mg, 1.63 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 58.65 mg of yellow solid, yield 7.79%.

[0068] Example 16: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylmethoxyacetamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A16): (1) Preparation of methyl 2-(3-methoxyacetamidophenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (0.92 g, 9.08 mmol) were added to a 100 mL round-bottom flask, and methoxyacetyl chloride (1.07 g, 9.99 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.41 g of a colorless oil, with a yield of 65.45%.

[0069] (2) 2-(3-( N Preparation of dimethyl methylmethoxyacetamido)phenyl)malonate: 1.41 g (5.94 mmol) of methyl 2-(3-methoxyacetamoxyphenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 0.71 g (29.71 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated, and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 1.49 g of a pale yellow oil, with a yield of 81.05%.

[0070] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-( N (-methylmethoxyacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A16): 2-(3-( N Dimethyl methoxyacetamyl)phenyl)malonate (0.5 g, 1.62 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.36 g, 1.62 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 71.55 mg of yellow solid, yield 9.40%.

[0071] Example 17: 3-(3-(2-methoxy- N (-methylacetamido)phenyl)-9-methyl-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A17): Steps (1) and (2) are the same as steps (1) and (2) in Example 16. (3) 3-(3-(2-methoxy- N (-methylacetamido)phenyl)-9-methyl-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A17): 2-(3-( N Dimethyl 3-amino-3-methylpyridine (387.5 mg, 1.62 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask. 2-Amino-3-methylpyridine (387.5 mg, 1.62 mmol) was added to the system under stirring at room temperature. The mixture was heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 68.69 mg of yellow solid, with a yield of 8.76%.

[0072] Example 18: 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylmethoxyacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2-a Pyrimidine-1-onium-2-olate (A18): Steps (1) and (2) are the same as steps (1) and (2) in Example 16. Step (3) is the same as step (3) in Example 3. (4) 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylmethoxyacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A18): 2-(3-( N Dimethyl methoxyacetamido)phenyl)malonate (0.5 g, 1.62 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((6-chloropyridin-3-yl)methyl)pyridin-2-amine (355.09 mg, 1.62 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 78.21 mg of yellow solid, yield 10.41%.

[0073] Example 19: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(2-methoxyacetamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A19): Step (1) is the same as step (1) in Example 16. (2) Preparation of dimethyl 2-(3-(2-methoxyacetamido)phenyl)malonate: 1.20 g (5.06 mmol) of methyl 2-(3-methoxyacetamidophenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 0.71 g (29.71 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated, and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to obtain 1.41 g of a pale yellow oil, with a yield of 94.41%. This step is the same reaction as step (2) in Example 16, but this step produces the unmethylated product, while step (2) in Example 16 produces the methylated product.

[0074] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(2-methoxyacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A19): Dimethyl 2-(3-(2-methoxyacetamido)phenyl)malonate (0.5 g, 1.69 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.38 g, 1.69 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 81.02 mg of yellow solid, yield 10.47%.

[0075] Example 20: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(3-(2-methoxyacetamide)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A20): Step (1) is the same as step (1) in Example 16. Step (2) is the same as step (2) in Example 19. Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl))-9-methyl-3-(3-(2-methoxyacetamyl)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A20): Dimethyl 2-(3-(2-methoxyacetamido)phenyl)malonate (0.5 g, 1.69 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (405.91 mg, 1.69 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 74.55 mg of yellow solid, yield 9.35%.

[0076] Example 21: 1-((6-chloropyridin-3-yl)methyl)-3-(3-(2-methoxyacetamido)phenyl)-4-oxo-4 H-pyridyl[1,2- a Pyrimidine-1-onthium-2-ol (A21): Step (1) is the same as step (1) in Example 16. Step (2) is the same as step (2) in Example 19. Step (3) is the same as step (3) in Example 1. (4) 1-((6-chloropyridin-3-yl)methyl)-3-(3-(2-methoxyacetamyl)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A21): Dimethyl 2-(3-(2-methoxyacetamido)phenyl)malonate (0.5 g, 1.69 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((6-chloropyridin-3-yl)methyl)pyridin-2-amine (371.96 mg, 1.69 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 82.1 mg of yellow solid, yield 10.75%.

[0077] Example 22: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylcyclobutyramido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A22): (1) Preparation of methyl 2-(3-cyclobutyrylaminophenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (0.92 g, 9.08 mmol) were added to a 100 mL round-bottom flask, and butyryl chloride (1.18 g, 9.99 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.48 g of a colorless oil, with a yield of 65.91%.

[0078] (2) 2-(3-( N Preparation of dimethyl methylcyclobutamido)phenyl)malonate: 1.48 g (5.98 mmol) of methyl 2-(3-cyclobutamidophenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 0.72 g (29.926 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated, and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 1.02 g of a pale yellow oil, with a yield of 61.02%.

[0079] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-( N (-methylcyclobutyramido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A22): 2-(3-( N Dimethyl methylcyclobutamido)phenyl)malonate (0.5 g, 1.63 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.63 g, 1.63 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 92.33 mg of yellow solid, yield 12.26%.

[0080] Example 23: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(3-( N (-methylcyclobutyramide)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-olate (A23): Steps (1) and (2) are the same as steps (1) and (2) in Example 22. Step (3) is the same as step (3) in Example 2. (4) 1-((2-chlorothiazol-5-yl)methyl))-9-methyl-3-(3-( N (-methylcyclobutyramido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A23): 2-(3-(N Dimethyl 2-methylcyclobutamido)phenyl)malonate (0.5 g, 1.57 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (375.32 mg, 1.57 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 93.56 mg of yellow solid, yield 12.07%.

[0081] Example 24: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(2-methoxyacrylamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A24): (1) Preparation of methyl 2-(3-acryloylaminophenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (0.92 g, 9.08 mmol) were added to a 100 mL round-bottom flask, and acryloyl chloride (0.92 g, 9.99 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.43 g of a colorless oil, with a yield of 71.83%.

[0082] (2) 2-(3-( N Preparation of dimethyl methacrylamidoyl)phenyl)malonate: 1.43 g (6.52 mmol) of methyl 2-(3-acrylamidophenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 0.78 g (32.61 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated, and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 1.19 g of a pale yellow oil, with a yield of 62.63%.

[0083] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(N (-methacrylamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A24): 2-(3-( N Dimethyl methacrylamidoyl)phenyl)malonate (0.5 g, 1.63 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.63 g, 1.63 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 92.99 mg of yellow solid, yield 9.39%.

[0084] Example 25: 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methacrylamide)phenyl)-4-oxo-4 H -pyridyl[1,2- a Pyrimidine-1-onium-2-ol (A25): Steps (1) and (2) are the same as steps (1) and (2) in Example 24. Step (3) is the same as step (3) in Example 3. (4) 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methacrylamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A25): 2-(3-( N Dimethyl methacryloylamino(phenyl)malonate (0.5 g, 1.62 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((6-chloropyridin-3-yl)methyl)pyridin-2-amine (355.09 mg, 1.62 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 102.59 mg of yellow solid, yield 13.37%.

[0085] Example 26: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylbenzamido)phenyl)-4-oxo-4 H-pyrido[1,2- a Pyrimidine-1-onium-2-ol (A26): (1) Preparation of methyl 2-(3-benzoylaminophenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (0.92 g, 9.08 mmol) were added to a 100 mL round-bottom flask, and benzoyl chloride (1.4 g, 9.99 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.66 g of a colorless oil, with a yield of 67.88%.

[0086] (2) 2-(3-( N Preparation of dimethyl (-methylbenzamido)phenyl)malonate: 1.66 g (6.16 mmol) of methyl 2-(3-benzamidophenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 0.74 g (30.82 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 1.58 g of a colorless oil, with a yield of 75.09%.

[0087] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazol-5-yl)methyl)-3-(3-( N (-methylbenzamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A26): 2-(3-( N Dimethyl (-methylbenzamido)phenyl)malonate (0.5 g, 1.46 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N-((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (330.58 mg, 1.46 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 106.5 mg of yellow solid, yield 14.46%.

[0088] Example 27: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(3-( N (-methylbenzamide)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A27): Steps (1) and (2) are the same as steps (1) and (2) in Example 26. Step (3) is the same as step (3) in Example 2. (4) 1-((2-chlorothiazol-5-yl)methyl))-9-methyl-3-(3-( N (-methylbenzamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A27): 2-(3-( N Dimethyl (-methylbenzamido)phenyl)malonate (0.5 g, 1.48 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (351.12 mg, 1.46 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 101.77 mg of yellow solid, yield 13.44%.

[0089] Example 28: 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylbenzamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Pyrimidine-1-onthium-2-ol (A28): Steps (1) and (2) are the same as steps (1) and (2) in Example 26. Step (3) is the same as step (3) in Example 3. (4) 1-((6-chloropyridin-3-yl)methyl)-3-(3-( N (-methylbenzamido)phenyl)-4-oxo-4 H-pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A28): 2-(3-( N Dimethyl (-methylbenzamido)phenyl)malonate (0.5 g, 1.46 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((6-chloropyridin-3-yl)methyl)pyridin-2-amine (321.76 mg, 1.46 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 99.95 mg of yellow solid, yield 13.73%.

[0090] Example 29: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(nicotinamide)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A29): (1) Preparation of methyl 2-(3-nicotinamide phenyl)acetate: Methyl 2-(3-aminophenyl)acetate (1.5 g, 9.08 mmol) and triethylamine (0.92 g, 9.08 mmol) were added to a 100 mL round-bottom flask, and nicotinic acid chloride (1.41 g, 9.99 mmol) was added dropwise to the system under stirring at room temperature. The flask was then sealed with a drying tube and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.01 g of a colorless oil, with a yield of 41.15%.

[0091] (2) Preparation of dimethyl 2-(3-(nicotinamide)phenyl)malonate: 1.01 g (3.74 mmol) of methyl 2-(3-nicotinamide phenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 6 mL of tetrahydrofuran was added to the system, and 0.45 g (18.68 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to 100 °C and refluxed for 6–10 h. After the reaction was completed, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 60 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 0.50 g of a pale yellow oil, with a yield of 40.75%.

[0092] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazolyl-5-yl)methyl)-3-(3-(nicotinamide)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A29): Dimethyl 2-(3-(nicotinamide)phenyl)malonate (0.5 g, 1.52 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.34 g, 1.52 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 41.12 mg of yellow solid, yield 5.51%.

[0093] Example 30: 1-((2-chlorothiazol-5-yl)methyl)-3-(4-(cyclopropanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A30): (1) Preparation of dimethyl 2-(4-aminophenyl)malonate: p-Aniline (1.5 g, 6.85 mmol), 2-pyridinecarboxylic acid (0.169 mg, 1.37 mmol), cuprous iodide (130.43 mg, 0.68 mmol), and cesium carbonate (5.6 g, 17.12 mmol) were added to a 200 mL Schlenk flask. Dimethyl malonate (1.81 g, 13.7 mmol) was added to the system under a nitrogen atmosphere, along with 50 mL of dried 1,4-dioxane as a solvent. After the addition was complete, the system was heated to 90 °C and reacted for 8–12 h. After the reaction was complete, the system temperature was lowered to room temperature, and the reaction was quenched by adding 100 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (100 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.22 g of a colorless oil, with a yield of 79.8%.

[0094] (2) Preparation of dimethyl 2-(4-(cyclopropanocarboxamide)phenyl)malonate: Dimethyl 2-(4-aminophenyl)malonate (1.22 g, 5.47 mmol) and triethylamine (0.55 g, 5.47 mmol) were added to a 100 mL round-bottom flask. Cyclopropyl chloride (0.63 g, 6.01 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.15 g of a colorless oil, with a yield of 72.23%.

[0095] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(4-(cyclopropanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A30): Dimethyl 2-(4-(cyclopropanocarboxamide)phenyl)malonate (0.5 g, 1.72 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.39 g, 1.72 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 132.22 mg of yellow solid, yield 15.85%.

[0096] Example 31: 3-(4-(cyclopropaneformamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-olate (A31): Steps (1) and (2) are the same as steps (1) and (2) in Example 30. (3) 3-(4-(cyclopropanecarbamate)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A31): Dimethyl 2-(4-(cyclopropanocarboxamide)phenyl)malonate (0.5 g, 1.72 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask. 2-Aminopyridine (0.161 g, 1.72 mmol) was added to the system under stirring at room temperature. The mixture was heated to 165 °C and reacted for 12–24 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 112.2 mg of a yellow solid, with a yield of 14.43%.

[0097] Example 32: 1-((2-chlorothiazol-5-yl)methyl)-3-(4-(ethanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-olate (A32): Step (1) is the same as step (1) in Example 30. (2) Preparation of dimethyl 2-(4-(acetylcarboxamide)phenyl)malonate: Dimethyl 2-(4-aminophenyl)malonate (1.2 g, 5.38 mmol) and triethylamine (0.54 g, 5.38 mmol) were added to a 100 mL round-bottom flask. Acetyl chloride (0.46 g, 5.91 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.28 g of a colorless oil, with a yield of 89.76%.

[0098] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(4-(ethanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A32): Dimethyl 2-(4-(acetylcarboxamide)phenyl)malonate (0.5 g, 1.88 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.43 g, 1.88 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 133.66 mg of yellow solid, with a yield of 16.61%.

[0099] Example 33: 3-(4-(ethaneformamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onyl-2-ol (A33): Steps (1) and (2) are the same as steps (1) and (2) in Example 32. (3) 3-(4-(ethanecarbamoyl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A33): Dimethyl 2-(4-(acetylcarboxamide)phenyl)malonate (0.5 g, 1.88 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask. 2-Aminopyridine (0.177 g, 1.88 mmol) was added to the system under stirring at room temperature. The mixture was heated to 165 °C and reacted for 12–24 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 99.52 mg of a yellow solid, with a yield of 17.88%.

[0100] Example 34: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(ethanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A34): (1) Preparation of dimethyl 2-(3-aminophenyl)malonate: m-Iodoaniline (1.5 g, 6.85 mmol), 2-pyridinecarboxylic acid (0.169 mg, 1.37 mmol), cuprous iodide (130.43 mg, 0.68 mmol), and cesium carbonate (5.6 g, 17.12 mmol) were added to a 200 mL Schlenk flask. Dimethyl malonate (1.81 g, 13.7 mmol) was added to the system under a nitrogen atmosphere, and 50 mL of dry 1,4-dioxane was added as a solvent. After the addition was complete, the system was heated to 90 °C and reacted for 8–12 h. After the reaction was complete, the system temperature was lowered to room temperature, and the reaction was quenched by adding 100 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (100 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.19 g of a colorless oil, with a yield of 77.84%.

[0101] (2) Preparation of dimethyl 2-(3-(acetylcarboxamide)phenyl)malonate: Dimethyl 2-(3-aminophenyl)malonate (1.2 g, 5.38 mmol) and triethylamine (0.54 g, 5.38 mmol) were added to a 100 mL round-bottom flask. Acetyl chloride (0.46 g, 5.91 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.25 g of a colorless oil, with a yield of 87.66%.

[0102] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(ethanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A34): Dimethyl 2-(3-(acetylcarboxamide)phenyl)malonate (0.5 g, 1.88 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.43 g, 1.88 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 113.65 mg of yellow solid, yield 14.12%.

[0103] Example 35: 1-((2-chlorothiazol-5-yl)methyl)-3-(4-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A35): (1) Preparation of methyl 2-(4-acetaminophenyl)acetate: 1.5 g (9.08 mmol) of methyl 2-(4-aminophenyl)acetate and 0.92 g (9.08 mmol) of triethylamine were added to a 100 mL round-bottom flask. Acetyl chloride (0.78 g, 9.99 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.34 g of a colorless oil, with a yield of 71.21%.

[0104] (2) 2-(4-( N Preparation of dimethyl methyl acetamidophenyl malonate: 1.34 g (6.47 mmol) of methyl 2-(4-acetamidophenyl)acetate and 30 mL of dimethyl carbonate were added to a 250 mL three-necked round-bottom flask. 0.78 g (32.33 mmol) of 60% sodium hydride was added under ice bath conditions. The mixture was heated to reflux for 6–10 h. After the reaction was complete, 20 mL of anhydrous methanol was added to quench the reaction. The solvent was concentrated, and 100 mL of water was added. The mixture was extracted with ethyl acetate (3 × 100 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 1.51 g of a colorless oil, with a yield of 83.61%.

[0105] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazol-5-yl)methyl)-3-(4-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2- a Preparation of pyrimidine-1-onium-2-olate (A35): 2-(4-( N Dimethyl methyl methacrylate (0.5 g, 1.79 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (404.05 mg, 1.79 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 114.93 mg of yellow solid, yield 14.56%.

[0106] Example 36: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(4-( N (-methylacetamide)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A36): Steps (1) and (2) are the same as steps (1) and (2) in Example 35. Step (3) is the same as step (3) in Example 2. (4) 1-((2-chlorothiazol-5-yl)methyl))-9-methyl-3-(4-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyridyl[1,2- aPreparation of pyrimidine-1-onium-2-olate (A36): 2-(4-( N Dimethyl methyl methacrylate (0.5 g, 1.79 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (429.16 mg, 1.79 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 105.4 mg of yellow solid, yield 12.94%.

[0107] Example 37: 3-(4-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A37): Steps (1) and (2) are the same as steps (1) and (2) in Example 35. (3) 3-(4-( N (-methylacetamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A37): 2-(-( N Dimethyl 2-methylacetamidoyl)phenyl)malonate (0.5 g, 1.79 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask. 2-Aminopyridine (168.49 mg, 1.79 mmol) was added to the system under stirring at room temperature. The mixture was heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 96.3 mg of a yellow solid, with a yield of 17.39%.

[0108] Example 38: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(cyclopropanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-olate (A38): Step (1) is the same as step (1) in Example 34. (2) Preparation of dimethyl 2-(3-(cyclopropanocarboxamide)phenyl)malonate: Dimethyl 2-(3-aminophenyl)malonate (1.2 g, 5.38 mmol) and triethylamine (0.54 g, 5.38 mmol) were added to a 100 mL round-bottom flask, and cyclopropionyl chloride (0.62 g, 5.91 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.07 g of a colorless oil, with a yield of 68.33%.

[0109] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(cyclopropanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A38): Dimethyl 2-(4-(cyclopropanocarboxamide)phenyl)malonate (0.5 g, 1.72 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.387 g, 1.72 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 101.33 mg of yellow solid, yield 13.03%.

[0110] Example 39: 1-((2-chlorothiazol-5-yl)methyl)-9-methyl-3-(3-(cyclopropanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A39): Steps (1) and (2) are the same as steps (1) and (2) in Example 38. Step (3) is the same as step (3) in Example 2. (4) 1-((2-chlorothiazo-5-yl)methyl)-9-methyl-3-(3-(cyclopropanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A39): Dimethyl 2-(4-(cyclopropanocarboxamide)phenyl)malonate (0.5 g, 1.72 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature.N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.411 g, 1.72 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 89.9 mg of yellow solid, yield 11.22%.

[0111] Example 40: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-bromo-4-(cyclopropanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A40): (1) Preparation of dimethyl 2-(4-aminophenyl)malonate: 2-Bromo-4-iodoaniline (1.5 g, 5.03 mmol), 2-pyridinecarboxylic acid (0.124 mg, 1.01 mmol), cuprous iodide (95.89 mg, 0.50 mmol), and cesium carbonate (2.5 g, 12.59 mmol) were added to a 200 mL Schlenk flask. Dimethyl malonate (1.33 g, 10.07 mmol) was added to the system under a nitrogen atmosphere, along with 50 mL of dried 1,4-dioxane as a solvent. After the addition was complete, the system was heated to 90 °C and reacted for 8–12 h. After the reaction was complete, the system temperature was lowered to room temperature, and the reaction was quenched by adding 100 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (100 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.18 g of a colorless oil, with a yield of 77.57%.

[0112] (2) Preparation of dimethyl 2-(3-bromo-4-(cyclopropanocarboxamide)phenyl)malonate: Dimethyl 2-(3-bromo-4-aminophenyl)malonate (1.18 g, 3.91 mmol) and triethylamine (0.40 g, 3.91 mmol) were added to a 100 mL round-bottom flask. Cyclopropyl chloride (0.50 g, 4.30 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.24 g of a colorless oil, with a yield of 85.76%.

[0113] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazol-5-yl)methyl)-3-(3-bromo-4-(cyclopropanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A40): Dimethyl 2-(3-bromo-4-(cyclopropanocarboxamide)phenyl)malonate (0.5 g, 1.35 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazo-5-yl)methyl)pyridine-2-amine (0.32 g, 1.35 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 75.6 mg of yellow solid, with a yield of 10.53%.

[0114] Example 41: 3-(3-bromo-4-(cyclopropanecarbamate)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onium-2-ol (A41): Steps (1) and (2) are the same as steps (1) and (2) in Example 40. (3) 3-(3-bromo-4-(cyclopropanecarbamate)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A41): Dimethyl 2-(3-bromo-4-(cyclopropanocarboxamide)phenyl)malonate (0.5 g, 1.35 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask. 2-Aminopyridine (0.127 g, 1.35 mmol) was added to the system under stirring at room temperature. The mixture was heated to 165 °C and reacted for 12–24 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 96.8 mg of a yellow solid, with a yield of 17.91%.

[0115] Example 42: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-bromo-4-(ethanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A42): Step (1) is the same as step (1) in Example 40. (2) Preparation of dimethyl 2-(3-bromo-4-(acetylcarboxamide)phenyl)malonate: Dimethyl 2-(3-bromo-4-aminophenyl)malonate (1.2 g, 3.97 mmol) and triethylamine (0.40 g, 3.97 mmol) were added to a 100 mL round-bottom flask. Acetyl chloride (0.34 g, 4.37 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.11 g of a colorless oil, with a yield of 81.2%.

[0116] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-bromo-4-(ethanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A42): Dimethyl 2-(3-bromo-4-(acetylcarboxamide)phenyl)malonate (0.5 g, 1.45 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.35 g, 1.45 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 86.7 mg of yellow solid, yield 11.80%.

[0117] Example 43: 3-(3-bromo-4-(ethanecarbamoyl)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onyl-2-ol (A43): Steps (1) and (2) are the same as steps (1) and (2) in Example 42. (3) 3-(3-bromo-4-(ethanecarbamoyl)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A43): Dimethyl 2-(3-bromo-4-(ethoxycarboxamide)phenyl)malonate (0.5 g, 1.45 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask. 2-Aminopyridine (0.137 g, 1.45 mmol) was added to the system under stirring at room temperature. The mixture was heated to 165 °C and reacted for 12–24 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 106.53 mg of a yellow solid, with a yield of 19.6%.

[0118] Example 44: 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(2,2,2-trifluoroacetamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A44): Step (1) is the same as step (1) in Example 34. (2) Preparation of dimethyl 2-(3-(2,2,2-trifluoroacetamide)phenyl)malonate: Dimethyl 2-(3-aminophenyl)malonate (1.15 g, 5.15 mmol) and triethylamine (0.52 g, 5.15 mmol) were added to a 100 mL round-bottom flask. 2,2,2-trifluoroacetyl chloride (0.75 g, 5.67 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was complete, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.06 g of a colorless oil, with a yield of 64.45%.

[0119] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(2,2,2-trifluoroacetamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A44): Dimethyl 2-(4-(2,2,2-trifluoroacetamide)phenyl)malonate (0.5 g, 1.57 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N-((2-chlorothiazo-5-yl)methyl)pyridine-2-amine (0.353 g, 1.57 mmol), heated to 165 °C and reacted for 24-48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 101.2 mg of yellow solid, yield 13.44%.

[0120] Example 45: 1-((2-chlorothiazo-5-yl)methyl)-3-(6-(cyclopropanecarbamate)pyridin-3-yl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A45): (1) Preparation of dimethyl 2-(6-aminopyridin-3-yl)malonate: 5-Iodopyridine-2-amine (1.5 g, 6.82 mmol), 2-pyridinecarboxylic acid (0.168 mg, 1.36 mmol), cuprous iodide (129.84 mg, 0.68 mmol), and cesium carbonate (5.57 g, 17.04 mmol) were added to a 200 mL Schlenk flask. Dimethyl malonate (1.80 g, 13.64 mmol) was added to the system under a nitrogen atmosphere, along with 50 mL of dried 1,4-dioxane as a solvent. After the addition was complete, the system was heated to 90 °C and reacted for 8–12 h. After the reaction was complete, the system temperature was lowered to room temperature, and the reaction was quenched by adding 100 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (100 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.08 g of a colorless oil, with a yield of 70.65%.

[0121] (2) Preparation of dimethyl 2-(4-(6-(cyclopropanecarbamoyl)pyridin-3-yl)malonate: Dimethyl 2-(6-aminopyridin-3-yl)malonate (1.08 g, 4.82 mmol) and triethylamine (0.49 g, 4.82 mmol) were added to a 100 mL round-bottom flask. Cyclopropyl chloride (0.554 g, 6.01 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.23 g of a colorless oil, with a yield of 87.36%.

[0122] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(4-(6-(cyclopropanecarbamoyl)pyridin-3-yl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A45): Dimethyl 2-(4-(6-(cyclopropanecarbamoyl)pyridin-3-yl)malonate (0.5 g, 1.71 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazo-5-yl)methyl)pyridine-2-amine (0.386 g, 1.71 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 106.6 mg of yellow solid, yield 13.73%.

[0123] Example 46: 1-((2-chlorothiazo-5-yl)methyl)-9-methyl-3-(6-(cyclopropanecarbamoyl)pyridin-3-yl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A46): Steps (1) and (2) are the same as steps (1) and (2) in Example 44. Step (3) is the same as step (3) in Example 2. (4) 1-((2-chlorothiazo-5-yl)methyl)-9-methyl-3-(4-(6-(cyclopropanecarbamoyl)pyridin-3-yl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A46): Dimethyl 2-(4-(6-(cyclopropanecarbamoyl)pyridin-3-yl)malonate (0.5 g, 1.71 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (0.386 g, 1.71 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 99.3 mg of yellow solid, yield 12.41%.

[0124] Example 47: 1-((2-chlorothiazol-5-yl)methyl)-3-(3-(cyclobutanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2-a Pyrimidine-1-onthium-2-ol (A47): Step (1) is the same as step (1) in Example 34. (2) Preparation of dimethyl 2-(3-(cyclobutyroxycarboxamide)phenyl)malonate: Dimethyl 2-(3-aminophenyl)malonate (1.15 g, 5.13 mmol) and triethylamine (0.52 g, 5.13 mmol) were added to a 100 mL round-bottom flask, and cyclobutyryl chloride (0.67 g, 5.64 mmol) was added dropwise to the system under stirring at room temperature. The flask was then sealed with a drying tube and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.37 g of a colorless oil, with a yield of 87.2%.

[0125] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(3-(cyclobutanecarboxamido)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A47): Dimethyl 2-(3-(cyclobutyroxycarboxamide)phenyl)malonate (0.5 g, 1.64 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.37 g, 1.64 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 117.4 mg of yellow solid, yield 15.35%.

[0126] Example 48: 3-(3-(cyclobutanecarbamate)phenyl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A48): Step (1) is the same as step (1) in Example 34. Step (2) is the same as step (2) in Example 47. (3) 3-(3-(cyclobutanecarbamate)phenyl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A48): Dimethyl 2-(3-(cyclobutyroxycarboxamide)phenyl)malonate (0.5 g, 1.64 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask. 2-Aminopyridine (0.15 g, 1.64 mmol) was added to the system under stirring at room temperature. The mixture was heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 112.76 mg of yellow solid, with a yield of 20.53%.

[0127] Example 49: 1-((2-chlorothiazo-5-yl)methyl)-3-(6-(acetamido)pyridin-3-yl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A49): Step (1) is the same as step (1) in Example 45. (2) Preparation of dimethyl 2-(4-(6-(cyclopropanecarbamoyl)pyridin-3-yl)malonate: Dimethyl 2-(6-aminopyridin-3-yl)malonate (1.2 g, 5.35 mmol) and triethylamine (0.54 g, 5.35 mmol) were added to a 100 mL round-bottom flask. Acetyl chloride (0.46 g, 5.89 mmol) was added dropwise to the system under stirring at room temperature. The flask was stoppered and reacted at room temperature for 1 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was evaporated, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, mixed, and separated by column chromatography to obtain 1.08 g of a colorless oil, with a yield of 75.79%.

[0128] Step (3) is the same as step (3) in Example 1. (4) 1-((2-chlorothiazo-5-yl)methyl)-3-(4-(6-(cyclopropanecarbamoyl)pyridin-3-yl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A49): Dimethyl 2-(4-(6-(cyclopropanecarbamoyl)pyridin-3-yl)malonate (0.5 g, 1.88 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)pyridine-2-amine (0.42 g, 1.88 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 99.6 mg of yellow solid, yield 12.4%.

[0129] Example 50: 1-((2-chlorothiazo-5-yl)methyl)-9-methyl-3-(6-(acetamido)pyridin-3-yl)-4-oxo-4 H -pyrido[1,2- a Pyrimidine-1-onthium-2-ol (A50): Steps (1) and (2) are the same as steps (1) and (2) in Example 49. Step (3) is the same as step (3) in Example 2. (4) 1-((2-chlorothiazo-5-yl)methyl)-9-methyl-3-(4-(6-(acetamido)pyridin-3-yl)-4-oxo-4 H -pyrido[1,2- a Preparation of pyrimidine-1-onium-2-olate (A50): Dimethyl 2-(4-(6-(acetamido)pyridin-3-yl)malonate (0.5 g, 1.71 mmol) and xylene (20 mL) were added to a 100 mL three-necked round-bottom flask, and the mixture was stirred at room temperature. N -((2-chlorothiazol-5-yl)methyl)-3-methylpyridin-2-amine (0.386 g, 1.71 mmol), heated to 165 °C and reacted for 24–48 h. After the reaction was completed, the mixture was cooled to room temperature, dissolved, mixed with silica gel, and separated by column chromatography to obtain 91.0 mg of yellow solid, yield 10.97%.

[0130] The compound's nuclear magnetic resonance hydrogen spectrum ( 1 H NMR and carbon spectroscopy 13 The C NMR data are shown in Table 1.

[0131] Table 1. Spectral data of compounds A1-A50 in Examples

[0132] Compound insecticidal activity test Example 1: Determination of the bioactivity of the target compound in controlling the pea aphid in the room.

[0133] 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 the TW-80 stock solution yielded concentrations of 100.0, 10.0, and 1.0 g / L. μ Test solutions of g / mL and other concentrations.

[0134] Select more than 50 pea aphid nymphs and transfer them to a disposable plastic bowl containing a broad bean seedling. The seedling was fixed with clean quartz sand, and a small amount of water was added to keep the sand moist to prevent the seedling from drying out. Let it stand for 30 minutes to allow the aphids to stabilize and attach to the seedling. Spray with 4 mL of test solution, cover with a homemade breathable plastic cup, and seal the opening with breathable gauze or a perforated lid. A TW-80 solution containing DMSO was used as a blank control. Each group was tested in triplicate. The treated broad bean aphids were placed in a greenhouse (temperature 26±2 ℃, humidity 75±5%, light / dark = 16 / 8h), and the number of dead aphids was recorded after 48 h. The lethality rate and corrected lethality 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 pruning aphid

[0135] Insecticidal activity results showed that the compounds had good activity against pea aphids, with some compounds showing activity at 100... μ g / mL and 10 μ At a concentration of g / mL, the mortality rate against the pea aphid was 100%, with compound A4 showing a high mortality rate of 1 g / mL. μ Even at a concentration of g / mL, the mortality rate against the pea aphid is still around 73%.

[0136] Example 2: Determination of the bioactivity of the target compound in controlling white-backed planthoppers indoors.

[0137] 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 the TW-80 stock solution yielded concentrations of 100.0, 10.0, and 1.0 g / L. μ Test solutions of g / mL and other concentrations.

[0138] Approximately 50 white-backed planthoppers of uniform size (2nd-3rd instar) were collected and transferred to disposable plastic bowls containing 6-7 rice seedlings. The rice seedlings were fixed with clean quartz sand, and a small amount of water was added to keep the quartz sand moist to prevent the rice seedlings from drying out. The bowls were left to stand for 30 minutes to allow the planthoppers to stabilize and attach to the seedlings. 4 mL of the test solution was sprayed, with a TW-80 solution containing DMSO as a blank control. Each group was tested in triplicate. The treated white-backed planthoppers were placed in a greenhouse (temperature 26±2 ℃, humidity 75±5%, light / dark = 16 / 8h), and the number of dead planthoppers was recorded after 48 h. The lethality rate and corrected lethality 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 rates of compounds A1-A50 against white-backed planthoppers in the examples.

[0139] Insecticidal activity results showed that the compounds exhibited good activity against white-backed planthoppers, with most compounds showing activity at 100 mg / L. μ At a concentration of g / mL, the mortality rate against white-backed planthoppers was 100%, and some compounds showed a mortality rate of 10 g / mL. μ The mortality rate against white-backed planthoppers remained 100% at a concentration of g / mL, with compound A34 showing the highest mortality rate at 1 g / mL. μ Even at a concentration of g / mL, the mortality rate against white-backed planthoppers is still around 68%.

[0140] Example 3: Indoor bioactivity assay of target compound for controlling diamondback moth.

[0141] 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 the TW-80 stock solution yielded concentrations of 200.0, 100.0, and 10.0 g / L. μ Test solutions of g / mL and other concentrations.

[0142] Cabbage leaves were immersed in solutions with different insecticide concentrations for 30 seconds, while control leaves were treated with a TW-80 solution containing DMSO. After drying the leaves in petri dishes (10 cm in diameter) at room temperature for 2 hours, 15 second-instar larvae were selected and placed inside. The TW-80 solution containing DMSO served as a blank control, and each concentration was repeated three times. The petri dishes were then covered and placed in an incubator (temperature 26±2 ℃, humidity 75±5%, light / dark = 16 / 8h). Results were checked after 48 h. The lethality rate and corrected lethality 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 diamondback moth

[0143] Insecticidal activity results showed that the compound had good activity against diamondback moth, and the compound was effective at 200... μ At a concentration of g / mL, the lethality against diamondback moth was 100%. μ At a concentration of g / mL, the lethality against diamondback moth remained 100%, with compound A2 showing a high mortality rate at 10 g / mL. μ Even at a concentration of g / mL, the mortality rate against diamondback moth is still around 63%.

[0144] Example 4: Indoor bioactivity assay of target compound for controlling fall armyworm.

[0145] 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 the TW-80 stock solution yielded concentrations of 500.0, 200.0, and 100.0 g / L. μ Test solutions of g / mL and other concentrations.

[0146] Third-instar fall armyworms with consistent physiological states, reared indoors, were selected. Half the volume of feed was added to each well of a 24-well plate beforehand. Depending on the test concentration, 100 mg / L of feed was added to each well. μ L's test solution. After the test solution dried, one test worm was picked from each well and tested using the stomach poison method, with TW-80 solution containing DMSO as a blank control. Each dose was repeated in triplicate. The 24-well plate was covered after treatment and placed in a temperature incubator (temperature 26±2 ℃, humidity 75±5%, light / dark = 16 / 8h). The results were checked after 48 h. The lethality and corrected lethality were calculated as follows, and the activity data are shown in Table 5: Mortality rate = (Number of dead insects) / (Total number of insects treated) × 100 Corrected lethality = (treatment lethality - blank lethality) / (1 - blank lethality) × 100 Table 5. Lethality of the compounds in the examples against fall armyworm

[0147] Insecticidal activity results showed that the compounds exhibited good activity against fall armyworm, with some compounds showing activity at 500 μL. μ g / mL and 200 μ At a concentration of g / mL, the lethality against fall armyworm was 100%, with compound A2 showing the highest lethality at 100 g / mL. μ At a concentration of g / mL, compound A4 still has a lethality of about 70% against the fall armyworm. μ Even at a concentration of g / mL, the mortality rate against fall armyworm is still around 75%.

Claims

1. A pyrido[1,2-] ... a Pyrimidine mesonotropic derivatives, characterized in that, This includes compounds having the structure shown in general formula (I), or their stereoisomers, salts, or solvates thereof, as follows: (I) Where X represents a nitrogen atom or a carbon atom; R 1 It is independently selected from one or more of hydrogen, deuterium, 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); R 2 It is independently selected from one or more of hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, amino, mercapto, any substituted or unsubstituted alkyl, any substituted or unsubstituted alkoxy, any substituted or unsubstituted alkenyl, any substituted or unsubstituted cycloalkyl, and any substituted or unsubstituted aryl. R 3 It is independently selected from one or more of the following: alkyl group (either substituted or unsubstituted), alkoxy group (either substituted or unsubstituted), alkenyl group (either substituted or unsubstituted), alkynyl group (either substituted or unsubstituted), cycloalkyl group (either substituted or unsubstituted), aryl group (either substituted or unsubstituted), and heteroaryl group (either substituted or unsubstituted); R 4 It is independently selected from one or more of hydrogen, alkyl (either substituted or unsubstituted), alkoxy (either substituted or unsubstituted), alkenyl (either substituted or unsubstituted), alkynyl (either substituted or unsubstituted), cycloalkyl (either substituted or unsubstituted), aryl (either substituted or unsubstituted), and heteroaryl (either substituted or unsubstituted). R 5 It is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, cyano, and any substituted or unsubstituted alkyl group.

2. The pyrido[1,2-]pyrido[ ... a Pyrimidine mesonotropic derivatives, characterized in that: R 1 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; R 2 Independently selected from hydrogen, deuterium, halogen, cyano, 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; R 3 Independently selected from substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkenyl, substituted or unsubstituted C1-C6 ynyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C 15 One or more of aryl, substituted or unsubstituted C5-C6 heteroaryl groups; R 4 Independently selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkenyl, substituted or unsubstituted C1-C6 alkynyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C 15 One or more of aryl, substituted or unsubstituted C5-C6 heteroaryl groups. R 5 It is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, cyano, and C1-C6 alkyl; The substitution refers to the substitution by at least one of the halogens.

3. The pyrido[1,2-]pyrido[ ... a Pyrimidine mesonotropic derivatives, characterized in that: R 1 Independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl, pyridyl, pyrazolyl, pyrrolyl, furanyl, thiophene, thiazolyl, benzopyrrolyl, pyridazine, pyrimidine, pyrazine, -CH2CH2CN, -CHCNCH3, -CH2CH2CH2CN, -CH2CHCNCH3, -CHCNCH2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHClCH3, -CH2CH2CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3, -CHBrCH2CH3 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; R 3 Independently selected from methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, propenyl, -CH2F, -CHF2, -CH2Cl, -CHCl2, -CCl3, -CH2Br, -CHBr2, -CBr3, -CH2CH2Cl, -CH2 CH2Br, -CH2 CH2F, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ... , , , , , , , , , , , , , , .

4. The pyrido[1,2-]pyrido[ ... a Pyrimidine mesonotropic derivatives, characterized in that, Selected from the following specific compounds: 。 5. The pyrido[1,2-]pyrido[]pyridyl ... a A method for preparing pyrimidine mesonotropic derivatives, characterized in that, include: 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: 。 6. A composition, characterized in that... The pyrido[1,2-]pyrido[ ... a The composition comprises pyrimidine mesonotropic derivatives and agricultural adjuvants; 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).

7. The pyrido[1,2-]pyridinium benzo[1,2-]pyridinium benzo[2 ... a The use of pyrimidine metronid derivatives, or the composition of claim 6, in the prevention and control of agricultural pests and diseases, wherein the agricultural pests and diseases are hemiptera and lepidopteran pests; wherein the agricultural pests are aphids, white-backed planthoppers, diamondback moths, and fall armyworms.

8. A method for preventing and controlling agricultural pests and diseases, characterized in that: The pyrido[1,2-] amide-containing structure of any one of claims 1-4 is used to make the pyrido[1,2-] a The pyrimidine metronid derivative, or the composition of claim 6, is applied to the harmful substance or its living environment; the agricultural pests are hemiptera and lepidopteran pests; the agricultural pests are aphids, white-backed planthoppers, diamondback moths, and fall armyworms.

9. A method for protecting plants from agricultural pests and diseases, comprising causing the pest to react with a pyridine containing an amide structure as described in any one of claims 1-4. a The method steps of contacting the pyrimidine mesonotropic derivative or the composition of claim 6.

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