Pyrido[1,2-a]pyrimidinone derivatives containing sulfonamide units, their preparation methods and applications

Abstract

The present invention relates to the field of compound preparation, specifically to pyrido[1,2-a]pyrimidinone derivatives containing a sulfonamide unit. It also relates to a preparation method of the pyrido[1,2-a]pyrimidinone derivatives containing a sulfonamide unit, and the application of the pyrido[1,2-a]pyrimidinone derivatives containing a sulfonamide unit in controlling plant bacterial diseases such as rice bacterial blight, rice bacterial leaf streak and citrus canker. The present invention has good biological activity against plant bacterial diseases and low production cost.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticides, and in particular to a class of pyrido[1,2-a]pyrimidone derivatives containing sulfonamide units, and also relates to a preparation method of the pyrido[1,2-a]pyrimidone derivatives containing sulfonamide units, and application of the pyrido[1,2-a]pyrimidone derivatives containing sulfonamide units in resisting plant bacterial diseases such as rice bacterial leaf blight, rice bacterial leaf streak and citrus canker. Background Art

[0002] Rice is susceptible to infection by a large number of pathogenic microorganisms, which can lead to serious yield reduction. Among them, Xanthomonas oryzae and Xanthomonas oryzae are bacterial diseases of rice caused by the corresponding Xanthomonas oryzae. They are also the two most widespread and most harmful bacterial diseases in the growth process of rice. Bacterial diseases of rice occur all over the world, but they are relatively serious in my country. The disease is prevalent in all major rice-growing areas in China, with the most serious incidence in East China, South China and Central China. The occurrence of bacterial diseases generally reduces rice production by 10%-20%. In severe cases, it leads to difficulty in heading and yield losses of more than 50%, causing huge economic losses to my country's rice production every year.

[0003] Currently, the commercial antimicrobial agents used to control rice bacterial leaf blight are mainly chlorothalonil, thiophanate-methyl and agricultural streptomycin. Due to their long residual time and high toxicity, the long-term use of these pesticides has caused irreversible damage to the environment and has led to different degrees of drug resistance in pathogens. Therefore, finding and developing new green pesticides with high efficiency and low risk for controlling rice bacterial leaf blight has become an important issue in controlling rice bacterial leaf blight.

[0004] Mesoionic compounds are an important class of skeletons. They not only have unique physical and chemical properties, but also have a variety of biological activities, such as antibacterial, insecticidal, antiviral and anti-inflammatory activities. The inventors introduced the biologically active natural products vanillin, diaryl ether, thiazole and oxazole structural units into the mesoionic structure, designed and synthesized a series of pyrido[1,2-a]pyrimidinone mesoionic derivatives, and tested the activity of the target compounds against the rice bacterial blight pathogen. The results showed that most of the target compounds had good activity against the rice bacterial blight pathogen.

[0005] In addition, sulfonamide compounds have a broad spectrum of antibacterial activity, such as anti-Gram-negative bacteria, Gram-positive bacteria and antifungal activity. However, through reviewing the literature on sulfonamide compounds against plant pathogens, it was found that there are few reports on the activity of sulfonamide compounds against plant pathogens, especially the research on rice bacterial blight and rice leaf streak pathogen. Summary of the invention

[0006] In view of this, the present invention provides pyrido[1,2-a]pyrimidinone derivatives containing a sulfonamide unit. The present invention has good biological activity against plant bacterial diseases, and the reagents and drugs used in the preparation route are widely sourced, the preparation process is simple, and the yield of the target product is relatively high.

[0007] Another object of the present invention is to provide a method for preparing the pyrido[1,2-a]pyrimidinone derivatives containing a sulfonamide unit.

[0008] Still another object of the present invention is to provide the application of the pyrido[1,2-a]pyrimidinone derivatives containing a sulfonamide unit in the preparation of medicaments for preventing and treating plant bacterial diseases such as rice bacterial blight.

[0009] The pyrido[1,2-a]pyrimidinone derivatives containing a sulfonamide unit of the present invention have the general formula shown in formula (C):

[0010]

[0011] Wherein: R 1 independently selected from one or more of optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted epoxyalkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl; R 2 independently selected from one or more of hydrogen, deuterium, halogen, nitro, cyano, trifluoromethyl, formamido, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted alkyl, and optionally substituted or unsubstituted aryl.

[0012] In some embodiments, R 1 independently selected from one or more of C1-C12 alkyl, C1-C12 alkenyl, substituted or unsubstituted C6-C15 aryl, and substituted or unsubstituted C5-C6 heteroaryl; R 2 independently selected from one or more of hydrogen, deuterium, halogen, nitro, cyano, trifluoromethyl, formamido, C1-C12 alkoxy, C1-C12 alkyl, substituted or unsubstituted C6-C15 aryl, and substituted or unsubstituted C5-C6 heteroaryl.

[0013] In some embodiments, the pyrido[1,2-a]pyrimidinone mesoionic derivatives containing a sulfonamide unit are one of the following compounds:

[0014] Compound C1: 1-(cyclopropylmethyl)-3-((4-bromophenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0015] Compound C2: 1-(Cyclopropylmethyl)-3-((4-((4-acetamidophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0016] Compound C3: 1-Ethyl-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0017] Compound C4: 1-(Cyclopropylmethyl)-3-((4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0018] Compound C5: 1-(Cyclopropylmethyl)-4-oxo-3-((4-tolylpiperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0019] Compound C6: 1-(Cyclopropylmethyl)-4-oxo-3-((4-(tert-butyl)phenylpiperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0020] Compound C7: 1-(Cyclopropylmethyl)-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0021] Compound C8: 1-(Cyclopropylmethyl)-4-oxo-3-((4-cyanophenylpiperazin-1-yl)nitro)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0022] Compound C9: 1-(Cyclopropylmethyl)-3-((4-((3-bromophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0023] Compound C10: 1-(Cyclopropylmethyl)-3-((4-((2,5-dichlorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0024] Compound C11: 1-(Cyclopropylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0025] Compound C12: 1-(pyridin-2-ylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0026] Compound C13: 1-(pyridin-2-ylmethyl)-3-((4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0027] Compound C14: 1-(pyridin-2-ylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0028] Compound C15: 1-(pyridin-2-ylmethyl)-3-((4-((2,5-dichlorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0029] Compound C16: 1-(cyclopropylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0030] Compound C17: 1-(cyclopropylmethyl)-3-((4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0031] Compound C18: 1-benzyl-3-((4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0032] Compound C19: 1-(cyclopropylmethyl)-3-((4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0033] Compound C20: 1-(cyclopropylmethyl)-3-((4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0034] Compound C21: 1-(Cyclopropylmethyl)-3-((4-((4-chloro-3-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0035] Compound C22: 1-Propyl-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0036] Compound C23: 1-Propyl-3-((4-((4-bromophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0037] Compound C24: 1-((2-Chlorothiazol-5-yl)methyl)-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0038] Compound C25: 1-((6-Chloropyridin-3-yl)methyl)-4-oxo-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate.

[0039] A preparation method of a pyrido[1,2-a]pyrimidinone mesoionic derivative containing a sulfonamide unit provided by the present invention comprises the following steps:

[0040] (1) Using malonic acid and 2,4,6-trichlorophenol as reaction raw materials, adding a reaction solvent, heating under reflux for 4 - 6 h. After the reaction is completed, slowly drop the reaction system into ice water, stir well. After the temperature drops to room temperature, filter to collect the white solid to obtain the intermediate bis(2,4,6-trichlorophenyl)-malonate

[0041]

[0042] (2) Using 2-aminopyridine as a reaction raw material, adding a reaction solvent, reacting with differently substituted aldehydes under heating and reflux conditions to form a Schiff base, and obtaining the intermediate N-substituted pyridin-2-amine after the Schiff base reacts with a reducing agent

[0043] (3) Using 2-aminopyridine as a reaction raw material, adding an acid-binding agent, a catalyst and a reaction solvent, and reacting with differently substituted chlorides under heating and reflux conditions to obtain the intermediate N-substituted pyridin-2-amine

[0044] (4) Using N-substituted pyridin-2-amine and bis(2,4,6-trichlorophenyl)-malonate as reaction raw materials, adding a reaction solvent, and reacting under the condition of heating to reflux to obtain the intermediate 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate

[0045] (5) Under the ice bath condition, phosphorus oxychloride is slowly added dropwise to the solution of N,N-dimethylformamide to generate the vislmer reagent first, and then the N,N-dimethylformamide solution of the intermediate 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate is slowly added to the reaction system. The reaction system is transferred to 25 - 50 °C for reaction for 3 - 6 h. After the reaction is completed, the reaction system is slowly poured into ice water, and a basic pH regulator is added to adjust the pH to neutral. The solid is collected by filtration to obtain the intermediate 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate

[0046] (6) Using tert-butyl piperazine-1-carboxylate as the reaction raw material, adding an acid-binding agent and a reaction solvent, and carrying out a substitution reaction with differently substituted benzenesulfonyl chlorides under the ice bath condition to obtain differently substituted intermediate tert-butyl phenylsulfonylpiperazine-1-carboxylate

[0047] (7) Using differently substituted tert-butyl piperazine-1-carboxylate as the reaction raw material, adding a reaction solvent, and reacting with trifluoroacetic acid at room temperature to obtain the intermediate 1-(substituted phenylsulfonyl)piperazine

[0048]

[0049] (8) Using 1-(substituted phenylsulfonyl)piperazine as the reaction raw material, adding a reaction solvent, an acid-binding agent, and a reducing agent, and reacting with 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate at room temperature to obtain the target product 1-substituted-3-((substituted phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate

[0050] (9) Using N-substituted pyridin-2-amine and bis(2,4,6-trichlorophenyl)-malonate as reaction raw materials, adding a reaction solvent, and reacting under the condition of heating to reflux to obtain the intermediate 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate

[0051] (10) Under ice bath conditions, phosphorus oxychloride was slowly added dropwise to a solution of N,N-dimethylformamide to first generate the vislmer reagent, and then a solution of intermediate D: 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate in N,N-dimethylformamide was slowly added to the reaction system. The reaction system was then transferred to 25 - 50 °C for reaction for 3 - 6 h. After the reaction was completed, the reaction system was slowly poured into ice water, and a basic pH regulator was added to adjust the pH to neutral. The solid was collected by filtration to obtain intermediate 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate

[0052] (11) Using tert-butyl piperazine-1-carboxylate as the reaction raw material, an acid-binding agent and a reaction solvent were added. Under ice bath conditions, a substitution reaction was carried out with differently substituted benzenesulfonyl chlorides to obtain differently substituted intermediate tert-butyl phenylsulfonylpiperazine-1-carboxylate

[0053] (12) Using differently substituted tert-butyl piperazine-1-carboxylate as the reaction raw material, a reaction solvent was added, and the reaction was carried out with trifluoroacetic acid at room temperature to obtain intermediate 1-(substituted phenylsulfonyl)piperazine

[0054] (13) Using 1-(substituted phenylsulfonyl)piperazine as the reaction raw material, a reaction solvent, an acid-binding agent, and a reducing agent were added, and the reaction was carried out with 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate at room temperature to obtain the target product 1-substituted-3-((substituted phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate

[0055]

[0056] In some embodiments, in step (1), the reaction solvent is phosphorus oxychloride or oxalyl chloride; in step (2), the reaction solvent is 1,2-dichloroethane or methanol, and the reducing agent is sodium borohydride or sodium triacetoxyborohydride.

[0057] In some embodiments, in step (3), the acid-binding agent is N,N-diisopropylethylamine, triethylamine, or 1,8-diazabicycloundec-7-ene, the catalyst is potassium iodide, sodium iodide, or tetrabutylammonium bromide, and the reaction solvent is xylene or toluene.

[0058] In some embodiments, in step (4), the reaction solvent is xylene or toluene; in step (5), the basic pH regulator is anhydrous potassium carbonate or sodium bicarbonate; in step (6), the acid-binding agent is triethylamine, N,N-diisopropylethylamine, or 1,8-diazabicyclo[5.4.0]undec-7-ene, and the reaction solvent is dichloromethane, ethanol, or methanol; in step (7), the reaction solvent is dichloromethane or acetonitrile; in step (8), the reaction solvent is dichloromethane or methanol, the acid-binding agent is triethylamine, N,N-diisopropylethylamine, or 4-dimethylaminopyridine, and the reducing agent is sodium triacetoxyborohydride or sodium borohydride.

[0059] In some embodiments, the preparation method of the pyrido[1,2-a]pyrimidinone mesoionic derivative containing a sulfonamide unit of the present invention has the following synthetic route:

[0060] (1) Using malonic acid and 2,4,6-trichlorophenol as reaction raw materials, phosphorus oxychloride as the reaction solvent, heating under reflux for 4 - 6 h. After the reaction is completed, slowly drop the reaction system into ice water and stir well; after the temperature drops to room temperature, filter to collect the white solid to obtain the intermediate bis(2,4,6-trichlorophenyl)-malonate;

[0061]

[0062] (2) Using 2-aminopyridine as the reaction raw material, 1,2-dichloroethane as the reaction solvent, reacting with differently substituted aldehydes under heating and reflux conditions to form a Schiff base, and reducing the Schiff base with sodium borohydride to obtain the intermediate N-substituted pyridin-2-amine;

[0063]

[0064] (3) Using 2-aminopyridine as the reaction raw material, N,N-diisopropylethylamine as the acid-binding agent, potassium iodide as the catalyst, and xylene as the reaction solvent, reacting with differently substituted chlorides under heating and reflux conditions to obtain the intermediate N-substituted pyridin-2-amine;

[0065]

[0066] (4) Using N-substituted pyridin-2-amine and bis(2,4,6-trichlorophenyl)-malonate as reaction raw materials, xylene as the reaction solvent, reacting under heating and reflux conditions to obtain the intermediate 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0067]

[0068] (5) Using N-substituted pyridin-2-amine and bis(2,4,6-trichlorophenyl) malonate as reaction raw materials, xylene as the reaction solvent, and reacting under the condition of heating to reflux to obtain the intermediate 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0069]

[0070] (6) Under ice bath conditions, phosphorus oxychloride was slowly added dropwise to a solution of N,N-dimethylformamide to first generate the Vilsmeier reagent, and then a solution of N,N-dimethylformamide of 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate was slowly added to the reaction system. The reaction system was transferred to 50 °C and reacted for 3 h. After the reaction was completed, the reaction system was slowly poured into ice water, and anhydrous potassium carbonate was added to adjust the pH to neutral. The solid was collected by filtration to obtain the intermediate 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0071]

[0072] (7) Under ice bath conditions, phosphorus oxychloride was slowly added dropwise to a solution of N,N-dimethylformamide to first generate the Vilsmeier reagent, and then a solution of N,N-dimethylformamide of 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate was slowly added to the reaction system. The reaction system was transferred to 50 °C and reacted for 3 h. After the reaction was completed, the reaction system was slowly poured into ice water, and anhydrous potassium carbonate was added to adjust the pH to neutral. The solid was collected by filtration to obtain the intermediate 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0073]

[0074] (8) Using tert-butyl piperazine-1-carboxylate as the reaction raw material, triethylamine as the acid-binding agent, and dichloromethane as the reaction solvent, and carrying out a substitution reaction with differently substituted benzenesulfonyl chlorides under ice bath conditions to obtain differently substituted intermediate tert-butyl benzenesulfonylpiperazine-1-carboxylate;

[0075]

[0076] (9) Using differently substituted tert-butyl piperazine-1-carboxylate as the reaction raw material, dichloromethane as the reaction solvent, and reacting with trifluoroacetic acid at room temperature to obtain the intermediate 1-(substituted benzenesulfonyl)piperazine;

[0077]

[0078] (10) Using 1-(substituted benzenesulfonyl)piperazine as the reaction raw material, dichloromethane as the reaction solvent, triethylamine as the acid-binding agent, and sodium triacetoxyborohydride as the reducing agent, reacting with 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate under room temperature conditions to obtain the target product 1-substituted-3-((substituted phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0079]

[0080] (11) Using 1-(substituted benzenesulfonyl)piperazine as the reaction raw material, dichloromethane as the reaction solvent, triethylamine as the acid-binding agent, and sodium triacetoxyborohydride as the reducing agent, reacting with 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate under room temperature conditions to obtain the target product 1-substituted-3-((substituted phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate;

[0081]

[0082] On the other hand, the present invention provides a composition comprising at least one of the derivatives described in the present invention.

[0083] Furthermore, the composition described in the present invention comprises agriculturally acceptable excipients.

[0084] On the other hand, the present invention provides the use of a sulfonamide unit-containing pyrido[1,2-a]pyrimidinone mesoionic derivative or a composition thereof in the preparation of an agent for plant bacterial diseases.

[0085] Furthermore, the plant bacterial diseases described in the present invention include Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola, or Xanthomonas axonopodis pv. citri.

[0086] The present invention introduces a sulfonamide structural unit onto the pyrido[1,2-a]pyrimidinone mesoionic structure, and prepares a series of sulfonamide-containing pyrido[1,2-a]pyrimidinone mesoionic derivatives. The antibacterial activities of the synthesized compounds against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola, and Xanthomonas axonopodis pv. citri are tested, and the bioactivity screening results show that some compounds have good antibacterial activities against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola, and Xanthomonas axonopodis pv. citri. Detailed Embodiments

[0087] The present invention discloses pyrido[1,2-a]pyrimidinone mesoionic derivatives containing sulfonamide units, their preparation methods and applications. Those skilled in the art can draw on the content of this article and appropriately improve process parameters to achieve them. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The methods and applications of the present invention have been described through preferred embodiments. Relevant personnel can obviously make changes or appropriate alterations and combinations to the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0088] Example 1: Preparation method of 1-(cyclopropylmethyl)-3-(((4-bromophenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound number: C1), comprising the following steps:

[0089] Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0090] (1) Dissolve 2-methylmalonic acid (10 mmol) and 2,4,6-trichlorophenol (20 mmol) in phosphorus oxychloride (30 mL), heat under reflux for 4 - 6 h. After the reaction is completed, slowly drop the reaction system into 200 mL of ice water with magnetic stirring, and stir well. After the temperature drops to room temperature, filter to collect the white solid to obtain the intermediate bis(2,4,6-trichlorophenyl)-2-methylmalonate.

[0091] Preparation of N-(cyclopropylmethyl)pyridin-2-amine (Intermediate 2):

[0092] (2) Dissolve 2-aminopyridine (20.0 mmol) and cyclopropanecarbaldehyde (24.0 mmol) in 30 mL of DCE, heat under reflux, monitor the reaction by TLC. When the raw materials are completely reacted, cool the reaction system to room temperature, then add sodium borohydride (40.0 mmol) to the reaction system in batches, react at room temperature for 4 - 6 h. After the reaction is completed, remove the solvent under reduced pressure, add water for washing, extract with ethyl acetate, dry over anhydrous sodium sulfate, concentrate and separate and purify by column chromatography to obtain 1.68 g of a yellow liquid, yield: 56.6%.

[0093] (3) Preparation of 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3):

[0094] Dissolve N-(cyclopropylmethyl)pyridin-2-amine (10.0 mmol) and bis(2,4,6-trichlorophenyl)-2-methylmalonate (10.0 mmol) in 15 mL of xylene, reflux for 4 - 6 h, monitor the reaction progress by TLC. After the reaction is completed, stop the reaction, remove the solvent, and purify by column chromatography to obtain 1.88 g of a yellow solid with a yield of 86.9% and a melting point of 173 - 175 °C.

[0095] (4) Preparation of 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 4):

[0096] Add 15 mL of N,N-dimethylformamide to a 100 mL three-necked flask, slowly drop phosphorus oxychloride (24.0 mmol) under ice bath conditions, react for 30 min under ice bath, then slowly add 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate to the reaction system, warm up to 50 °C and react for 4 hours. After the reaction is completed, slowly add the reaction system to ice water and stir, add potassium carbonate to adjust the pH to 7 - 8, stir overnight, precipitate a yellow solid, filter by suction, and dry to obtain 1.72 g of a yellow solid with a yield of 88.1%.

[0097] (5) Preparation of tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0098] Dissolve 1-Boc piperazine (5.0 mmol) and triethylamine (7.5 mmol) in 20 mL of dichloromethane, slowly add 4-bromobenzenesulfonyl chloride (6.0 mmol) under ice bath conditions, then transfer to room temperature for reaction, monitor the reaction progress by TLC. After the reaction is completed, stop the reaction, remove the solvent, and recrystallize from methanol to obtain 1.52 g of a white solid with a yield of 75.0% and a melting point of 84 - 86 °C.

[0099] (6) Preparation of 1-((4-bromophenyl)sulfonyl)piperazine (Intermediate 6):

[0100] Dissolve tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate (1.0 mmol) in 10 mL of dichloromethane, then add 1 mL of trifluoroacetic acid to the reaction system, react at room temperature, monitor the reaction by TLC. After the raw materials are reacted, concentrate under reduced pressure to remove dichloromethane, and finally obtain a white solid. The obtained intermediate can be used in the next step without purification.

[0101] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-bromophenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C1):

[0102] Dissolve 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (1.0 mmol) and 1-((4-bromophenyl)sulfonyl)piperazine (1.0 mmol) in 20 mL of dichloromethane, and then successively add triethylamine (1.5 mmol) and sodium triacetoxyborohydride (1.5 mmol) to the reaction system. Monitor the reaction system by TLC until the raw materials are completely converted, stop the reaction, add water for washing, collect the organic layer, and dry it over anhydrous magnesium sulfate; concentrate the reaction mixture under reduced pressure to obtain a crude product as a yellow solid, and then recrystallize it with methanol to obtain 0.21 g of a yellow solid, yield: 46.2%, melting point: 204 - 205 °C.

[0103] Example 2: Synthesis of 1-(cyclopropylmethyl)-3-((4-((4-acetamidophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C2), which comprises the following steps:

[0104] Steps (1)-(4) are the same as those in steps (1)-(4) of Example 1 in terms of methods and conditions, and will not be elaborated here.

[0105] (5) Preparation of tert-butyl 4-((4-acetamidophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0106] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 4-acetamidobenzenesulfonyl chloride, and will not be elaborated here.

[0107] (6) Preparation of 1-((4-acetamidophenyl)sulfonyl)piperazine (Intermediate 6):

[0108] The method and conditions are the same as those in step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 4-((4-acetamidophenyl)sulfonyl)piperazine-1-carboxylate, and will not be elaborated here.

[0109] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((4-acetamidophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target compound C2):

[0110] The method and conditions are the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine is replaced with an equimolar amount of 1-((4-acetamidophenyl)sulfonyl)piperazine, and will not be elaborated here.

[0111] Example 3: Preparation of 1-ethyl-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C3), including the following steps:

[0112] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0113] Synthesized by the method and conditions of step (1) in Example 1.

[0114] (2) Preparation of N-ethylpyridin-2-amine (Intermediate 2)

[0115] The method and conditions are the same as those in step (2) of Example 1, except that cyclopropanecarbaldehyde is replaced with an equimolar amount of acetaldehyde, which will not be elaborated here.

[0116] (3) Preparation of 1-ethyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3)

[0117] The method and conditions are the same as those in step (3) of Example 1, except that N-(cyclopropylmethyl)pyridin-2-amine is replaced with an equimolar amount of N-ethylpyridin-2-amine, which will not be elaborated here.

[0118] (4) Preparation of 1-ethyl-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 4):

[0119] The method and conditions are the same as those in step (4) of Example 1, except that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate is replaced with an equimolar amount of 1-ethyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0120] (5) Preparation of tert-butyl 4-((4-fluorophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5)

[0121] Synthesized by the method and conditions of step (5) in Example 1, except that 4-acetamidobenzenesulfonyl chloride is replaced with an equimolar amount of 4-fluorobenzenesulfonyl chloride, which will not be elaborated here..

[0122] (6) Preparation of 1-((4-fluorophenyl)sulfonyl)piperazine (Intermediate 6)

[0123] The method and conditions are the same as those in step (6) of Example 1, except that tert-butyl 4-((4-acetamidophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 4-((4-fluorophenyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0124] (7) Preparation of 1-ethyl-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (target compound C3)

[0125] The method and conditions are the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate are replaced with an equimolar amount of 1-((4-fluorophenyl)sulfonyl)piperazine and 1-ethyl-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0126] Example 4: Preparation of 1-(cyclopropylmethyl)-3-((4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (compound number C4), including the following steps:

[0127] Steps (1)-(4) are the same as those in steps (1)-(4) of Example 1, which will not be elaborated here.

[0128] (5) Preparation of tert-butyl 4-((4-methoxyphenyl)sulfonyl)piperazine-1-carboxylate (intermediate 5):

[0129] Synthesized by the same method and conditions as in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 4-methoxybenzenesulfonyl chloride.

[0130] (6) Preparation of 1-((4-methoxyphenyl)sulfonyl)piperazine (intermediate 6):

[0131] Synthesized by the same method and conditions as in step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 4-((4-methoxyphenyl)sulfonyl)piperazine-1-carboxylate

[0132] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (target compound C4):

[0133] Synthesized by the method and conditions of step (7) in Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((4-methoxyphenyl)sulfonyl)piperazine.

[0134] Example 5: Preparation of 1-(cyclopropylmethyl)-3-((4-((4-tolyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C5), which comprises the following steps:

[0135] Steps (1)-(4) were synthesized by the method and conditions of steps (1)-(4) in Example 1.

[0136] (5) Preparation of tert-butyl 4-((4-tolyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0137] Synthesized by the method and conditions of step (5) in Example 1, except that 4-bromobenzenesulfonyl chloride was replaced with an equimolar amount of 4-methylbenzenesulfonyl chloride.

[0138] (6) Preparation of 1-((4-tolyl)sulfonyl)piperazine (Intermediate 6):

[0139] Synthesized by the method and conditions of step (6) in Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate was replaced with an equimolar amount of tert-butyl 4-((4-tolyl)sulfonyl)piperazine-1-carboxylate

[0140] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((4-tolyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C5):

[0141] Synthesized by the method and conditions of step (7) in Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((4-tolyl)sulfonyl)piperazine.

[0142] Example 6: Preparation of 1-(cyclopropylmethyl)-4-oxo-3-((4-(tert-butyl)phenylpiperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C6), which comprises the following steps:

[0143] Steps (1)-(4) were synthesized by the method and conditions of steps (1)-(4) in Example 1.

[0144] (5) Preparation of tert-butyl 4-((4-(tert-butyl)phenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0145] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 4-(tert-butyl)benzenesulfonyl chloride, which will not be elaborated here.

[0146] (6) Preparation of 1-((4-(tert-butyl)phenyl)sulfonyl)piperazine (Intermediate 6):

[0147] The method and conditions are the same as those in step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 4-((4-(tert-butyl)phenyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0148] (7) Preparation of 1-(cyclopropylmethyl)-4-oxo-3-((4-(tert-butyl)phenylpiperazin-1-yl)methyl)-

[0149] 4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C6):

[0150] Synthesized under the same method and conditions as in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine is replaced with an equimolar amount of 1-((4-(tert-butyl)phenyl))sulfonyl)piperazine.

[0151] Example 7: Preparation of 1-(cyclopropylmethyl)-4-oxo-3-((4-(nitrophenyl)piperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C7), including the following steps:

[0152] Steps (1)-(4) are synthesized under the same method and conditions as steps (1)-(4) of Example 1.

[0153] (5) Preparation of tert-butyl 4-((4-(nitrophenyl))sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0154] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 4-nitrobenzenesulfonyl chloride, which will not be elaborated here.

[0155] (6) Preparation of 1-((4-nitrophenyl)sulfonyl)piperazine (Intermediate 6):

[0156] The method and conditions are the same as those in step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 4-((4-nitrophenyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0157] (7) Preparation of 1-(cyclopropylmethyl)-4-oxo-3-((4-(nitrophenyl)piperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C7):

[0158] The method and conditions were the same as those in Step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((4-nitrophenyl)sulfonyl)piperazine, which will not be elaborated here.

[0159] Example 8: Preparation of 1-(cyclopropylmethyl)-4-oxo-3-((4-(cyanophenyl)piperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C8), including the following steps:

[0160] Steps (1)-(4) were synthesized in the same method and conditions as Steps (1)-(4) of Example 1.

[0161] (5) Preparation of tert-butyl 4-((4-(cyanophenyl))sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0162] The method and conditions were the same as those in Step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride was replaced with an equimolar amount of 4-cyanobenzenesulfonyl chloride, which will not be elaborated here.

[0163] (6) Preparation of 1-((4-cyanophenyl)sulfonyl)piperazine (Intermediate 6):

[0164] The method and conditions were the same as those in Step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate was replaced with an equimolar amount of tert-butyl 4-((4-cyanophenyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0165] (7) Preparation of 1-(cyclopropylmethyl)-4-oxo-3-((4-(cyanophenyl)piperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C8):

[0166] The method and conditions were the same as those in Step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((4-cyanophenyl)sulfonyl)piperazine, which will not be elaborated here.

[0167] Example 9: Preparation of 1-(cyclopropylmethyl)-3-((4-((3-bromophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C9), including the following steps:

[0168] Steps (1)-(4) are synthesized by the same methods and conditions as those in steps (1)-(4) of Example 1.

[0169] (5) Preparation of tert-butyl 4-((3-bromophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0170] It is synthesized by the same methods and conditions as in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 3-bromobenzenesulfonyl chloride.

[0171] (6) Preparation of 1-((3-bromophenyl)sulfonyl)piperazine (Intermediate 6):

[0172] It is synthesized by the same methods and conditions as in step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 4-((3-bromophenyl)sulfonyl)piperazine-1-carboxylate.

[0173] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((3-bromophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C9):

[0174] The methods and conditions are the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine is replaced with an equimolar amount of 1-((3-bromophenyl)sulfonyl)piperazine, which will not be elaborated here.

[0175] Example 10: Preparation of 1-(cyclopropylmethyl)-3-((4-((2,5-dichlorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C10), including the following steps:

[0176] Steps (1)-(4) are synthesized by the same methods and conditions as those in steps (1)-(4) of Example 1.

[0177] (5) Preparation of tert-butyl 1-((2,5-dichlorophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0178] The methods and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 2,5-dichlorobenzenesulfonyl chloride, which will not be elaborated here.

[0179] (6) Preparation of 1-((2,5-dichlorophenyl)sulfonyl)piperazine (Intermediate 6):

[0180] Synthesized by the method and conditions in step (6) of Example 1, with the difference that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate was replaced with an equimolar amount of tert-butyl 4-((2,5-dichlorophenyl)sulfonyl)piperazine-1-carboxylate

[0181] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((2,5-dichlorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (target compound C10):

[0182] The method and conditions were the same as those in step (7) of Example 1, with the difference that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((2,5-dichlorophenyl)sulfonyl)piperazine, which will not be elaborated here.

[0183] Example 11: Preparation of 1-(cyclopropylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (compound number C11), including the following steps:

[0184] Steps (1)-(4) were synthesized by the method and conditions in steps (1)-(4) of Example 1.

[0185] (5) Preparation of tert-butyl 4-((4-(fluorophenyl))sulfonyl)piperazine-1-carboxylate (intermediate 5):

[0186] The method and conditions were the same as those in step (5) of Example 1, with the difference that 4-bromobenzenesulfonyl chloride was replaced with an equimolar amount of 4-fluorobenzenesulfonyl chloride.

[0187] (6) Preparation of 1-((4-fluorophenyl)sulfonyl)piperazine (intermediate 6):

[0188] The method and conditions were the same as those in step (6) of Example 1, with the difference that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate was replaced with an equimolar amount of tert-butyl 4-((4-fluorophenyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0189] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (target compound C11):

[0190] The method and conditions were the same as those in step (7) of Example 1, with the difference that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((4-fluorophenyl)sulfonyl)piperazine, which will not be elaborated here.

[0191] Example 12: Preparation of 1-(pyridin-2-ylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C12), including the following steps:

[0192] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0193] Synthesized by the method and conditions of step (1) in Example 1.

[0194] (2) Preparation of N-(pyridin-2-ylmethyl)pyridin-2-amine (Intermediate 2):

[0195] Synthesized by the method and conditions of step (2) in Example 1, with the difference that cyclopropanecarbaldehyde is replaced by an equimolar amount of pyridinecarbaldehyde.

[0196] (3) Preparation of 1-(pyridin-2-ylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3)

[0197] The method and conditions are the same as those in step (3) of Example 1, with the difference that N-(cyclopropylmethyl)pyridin-2-amine is replaced by an equimolar amount of N-(pyridin-2-ylmethyl)pyridin-2-amine, which will not be elaborated here.

[0198] (4) Preparation of 1-(pyridin-2-ylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 4):

[0199] The method and conditions are the same as those in step (4) of Example 1, with the difference that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate is replaced by an equimolar amount of 1-(pyridin-2-ylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0200] (5) Preparation of tert-butyl 4-(phenylsulfonyl)piperazine-1-carboxylate (Intermediate 5)

[0201] The method and conditions are the same as those in step (5) of Example 1, with the difference that 4-bromobenzenesulfonyl chloride is replaced by an equimolar amount of benzenesulfonyl chloride, which will not be elaborated here.

[0202] (6) Preparation of 1-phenylsulfonylpiperazine (Intermediate 6)

[0203] The method and conditions are the same as those in step (6) of Example 1, except that tert-butyl 1-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 4-(phenylsulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0204] (7) Preparation of 1-(pyridin-2-ylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C12)

[0205] The method and conditions are the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate are replaced with an equimolar amount of 1-phenylsulfonylpiperazine and 1-(pyridin-2-ylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0206] Example 13: Preparation of 1-(pyridin-2-ylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C13), including the following steps:

[0207] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0208] The method and conditions are the same as those in step (1) of Example 1, which will not be elaborated here.

[0209] (2) Preparation of N-(pyridin-2-ylmethyl)pyridin-2-amine (Intermediate 2):

[0210] The method and conditions are the same as those in step (2) of Example 1, except that cyclopropanecarbaldehyde is replaced with an equimolar amount of pyridinecarbaldehyde, which will not be elaborated here.

[0211] (3) Preparation of 1-(pyridin-2-ylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3):

[0212] The method and conditions are the same as those in step (3) of Example 1, except that N-(cyclopropylmethyl)pyridin-2-amine is replaced with an equimolar amount of N-(pyridin-2-ylmethyl)pyridin-2-amine, which will not be elaborated here.

[0213] (4) Preparation of 1-(pyridin-2-ylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 4):

[0214] The method and conditions are the same as those in Step (4) of Example 1, except that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate is replaced with an equimolar amount of 1-(pyridin-2-ylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0215] (5) Preparation of tert-butyl 4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5)

[0216] The method and conditions are the same as those in Step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 3-(trifluoromethyl)benzenesulfonyl chloride, which will not be elaborated here.

[0217] (6) Preparation of 1-((3-(trifluoromethyl)phenyl)sulfonyl)piperazine (Intermediate 6)

[0218] The method and conditions are the same as those in Step (6) of Example 1, except that tert-butyl 1-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 4-(phenylsulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0219] (7) Preparation of 1-(pyridin-2-ylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C13)

[0220] The method and conditions are the same as those in Step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate are replaced with an equimolar amount of 1-((3-(trifluoromethyl)phenyl)sulfonyl)piperazine and 1-(pyridin-2-ylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate.

[0221] Example 14: Preparation of 1-(pyridin-2-ylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C14), including the following steps:

[0222] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0223] The method and conditions are the same as those in step (1) of Example 1.

[0224] (2) Preparation of N-(pyridin-2-ylmethyl)pyridin-2-amine (Intermediate 2):

[0225] The method and conditions are the same as those in step (2) of Example 1, except that cyclopropanecarbaldehyde is replaced with an equimolar amount of pyridinecarbaldehyde, which will not be elaborated here.

[0226] (3) Preparation of 1-(pyridin-2-ylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3):

[0227] The method and conditions are the same as those in step (3) of Example 1, except that N-(cyclopropylmethyl)pyridin-2-amine is replaced with an equimolar amount of N-(pyridin-2-ylmethyl)pyridin-2-amine, which will not be elaborated here.

[0228] (4) Preparation of 1-(pyridin-2-ylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 4):

[0229] The method and conditions are the same as those in step (4) of Example 1, except that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate is replaced with an equimolar amount of 1-(pyridin-2-ylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0230] (5) Preparation of tert-butyl 4-((4-fluorophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0231] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 4-fluorobenzenesulfonyl chloride, which will not be elaborated here.

[0232] (6) Preparation of 1-((4-fluorophenyl)sulfonyl)piperazine (Intermediate 6):

[0233] The method and conditions are the same as those in step (6) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate tert-butyl ester is replaced with an equimolar amount of 1-((4-fluorophenyl)sulfonyl)piperazine-1-carboxylate tert-butyl ester, which will not be elaborated here.

[0234] (7) Preparation of 1-(pyridin-2-ylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C14)

[0235] The method and conditions were the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate were replaced with equimolar amounts of 1-((4-fluorophenyl)sulfonyl)piperazine and 1-(pyridin-2-ylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0236] Example 15: Preparation of 1-(pyridin-2-ylmethyl)-3-((4-((2,5-dichlorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C15), including the following steps:

[0237] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0238] The method and conditions were the same as those in step (1) of Example 1, which will not be elaborated here.

[0239] (2) Preparation of N-(pyridin-2-ylmethyl)pyridin-2-amine (Intermediate 2):

[0240] Synthesized under the same method and conditions as in step (2) of Example 1, except that cyclopropanecarbaldehyde was replaced with equimolar amount of pyridinecarbaldehyde, which will not be elaborated here.

[0241] (3) Preparation of 1-(pyridin-2-ylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3):

[0242] The method and conditions were the same as those in step (3) of Example 1, except that N-(cyclopropylmethyl)pyridin-2-amine was replaced with equimolar amount of N-(pyridin-2-ylmethyl)pyridin-2-amine, which will not be elaborated here.

[0243] (4) Preparation of 1-(pyridin-2-ylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 4):

[0244] The method and conditions are the same as those in step (4) of Example 1, except that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate is replaced with an equimolar amount of 1-(pyridin-2-ylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0245] (5) Preparation of tert-butyl 1-((2,5-dichlorophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5)

[0246] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 2,5-dichlorobenzenesulfonyl chloride, which will not be elaborated here.

[0247] (6) Preparation of 1-((2,5-dichlorophenyl)sulfonyl)piperazine (Intermediate 6):

[0248] The method and conditions are the same as those in step (6) of Example 1, except that tert-butyl 1-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 1-((2,5-dichlorophenyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0249] (7) Preparation of 1-(pyridin-2-ylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C15):

[0250] The method and conditions are the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate are replaced with an equimolar amount of 1-((2,5-dichlorophenyl)sulfonyl)piperazine and 1-(pyridin-2-ylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0251] Example 16: Preparation of 1-(cyclopropylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C16), including the following steps:

[0252] Steps (1)-(4) are synthesized by the same method and conditions as steps (1)-(4) of Example 1.

[0253] (5) Preparation of tert-butyl 4-(phenylsulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0254] The method and conditions were the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride was replaced with an equimolar amount of 4-phenylsulfonyl chloride, which will not be elaborated here.

[0255] (6) Preparation of 1-phenylsulfonylpiperazine (Intermediate 6):

[0256] Synthesized according to the method and conditions in step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate was replaced with an equimolar amount of tert-butyl 1-phenylsulfonylpiperazine-1-carboxylate

[0257] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-

[0258] 4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C16):

[0259] The method and conditions were the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-phenylsulfonylpiperazine, which will not be elaborated here.

[0260] Example 17: Preparation of 1-(cyclopropylmethyl)-3-((4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C17), including the following steps:

[0261] Steps (1)-4) were synthesized according to the method and conditions in steps (1)-(4) of Example 1.

[0262] (5) Preparation of tert-butyl 4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0263] The method and conditions were the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride was replaced with an equimolar amount of 3-trifluoromethylbenzenesulfonyl chloride, which will not be elaborated here.

[0264] (6) Preparation of 1-((3-(trifluoromethyl)phenyl)sulfonyl)piperazine (Intermediate 6):

[0265] The method and conditions were the same as those in step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate was replaced with an equimolar amount of tert-butyl 4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0266] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C17):

[0267] The method and conditions were the same as those in Step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((3-(trifluoromethyl)phenyl)sulfonyl)piperazine, which will not be elaborated here.

[0268] Example 18: Preparation of 1-benzyl-3-((4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C18), including the following steps:

[0269] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0270] The method and conditions were the same as those in Step (1) of Example 1, which will not be elaborated here.

[0271] (2) Preparation of N-benzylpyridin-2-amine (Intermediate 2):

[0272] The method and conditions were the same as those in Step (2) of Example 1, except that cyclopropanecarbaldehyde was replaced with an equimolar amount of benzaldehyde, which will not be elaborated here.

[0273] (3) Preparation of 1-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3):

[0274] Synthesized under the same method and conditions as in Step (3) of Example 1, except that N-(cyclopropylmethyl)pyridin-2-amine was replaced with an equimolar amount of N-benzylpyridin-2-amine.

[0275] (4) Preparation of 1-benzyl-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 4):

[0276] The method and conditions were the same as those in Step (4) of Example 1, except that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate was replaced with an equimolar amount of 1-benzyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0277] (5) Preparation of tert-butyl 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5)

[0278] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 3-(trifluoromethyl)-4-chlorobenzenesulfonyl chloride, which will not be elaborated here.

[0279] (6) Preparation of 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine (Intermediate 6):

[0280] The method and conditions are the same as those in step (6) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine-1-carboxylic acid tert-butyl ester is replaced with an equimolar amount of 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine-1-carboxylic acid tert-butyl ester, which will not be elaborated here.

[0281] (7) Preparation of 1-benzyl-3-((4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C18):

[0282] The method and conditions are the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate are replaced with an equimolar amount of 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine and 1-benzyl-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0283] Example 19: Preparation of 1-(cyclopropylmethyl)-3-((4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C19), including the following steps:

[0284] Steps (1)-(4) are the same as those in steps (1)-(4) of Example 1, which will not be elaborated here.

[0285] (5) Preparation of 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine-1-carboxylic acid tert-butyl ester (Intermediate 5)

[0286] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 3-(trifluoromethyl)-4-chlorobenzenesulfonyl chloride, which will not be elaborated here.

[0287] (6) Preparation of 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine (Intermediate 6):

[0288] The method and conditions were the same as those in Step (6) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine-1-carboxylic acid tert-butyl ester was replaced with an equimolar amount of 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine-1-carboxylic acid tert-butyl ester, which will not be elaborated here.

[0289] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C19):

[0290] The method and conditions were the same as those in Step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazine, which will not be elaborated here.

[0291] Example 20: Preparation of 1-(cyclopropylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C20), including the following steps:

[0292] Steps (1)-(4) were the same as those in Steps (1)-(4) of Example 1, which will not be elaborated here.

[0293] (5) Preparation of 4-((4-fluorophenyl)sulfonyl)piperazine-1-carboxylic acid tert-butyl ester (Intermediate 5):

[0294] The method and conditions were the same as those in Step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride was replaced with an equimolar amount of 4-fluorobenzenesulfonyl chloride, which will not be elaborated here.

[0295] (6) Preparation of 1-((4-methylphenyl)sulfonyl)piperazine (Intermediate 6):

[0296] The method and conditions were the same as those in Step (6) of Example 1, except that 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylic acid tert-butyl ester was replaced with an equimolar amount of 4-((4-fluorophenyl)sulfonyl)piperazine-1-carboxylic acid tert-butyl ester, which will not be elaborated here.

[0297] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C20):

[0298] The method and conditions were the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((4-fluorophenyl)sulfonyl)piperazine, which will not be elaborated here.

[0299] Example 21: Preparation of 1-(cyclopropylmethyl)-3-((4-((4-chloro-3-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C21), including the following steps:

[0300] Steps (1)-(4) were synthesized by the same method and conditions as steps (1)-(4) of Example 1.

[0301] (5) Preparation of tert-butyl 1-((4-chloro-3-fluorophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0302] The method and conditions were the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride was replaced with an equimolar amount of 4-chloro-3-fluorobenzenesulfonyl chloride, which will not be elaborated here.

[0303] (6) Preparation of 1-((4-chloro-3-fluorophenyl)sulfonyl)piperazine (Intermediate 6):

[0304] The method and conditions were the same as those in step (6) of Example 1, except that tert-butyl 1-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate was replaced with an equimolar amount of tert-butyl 1-((4-chloro-3-fluorophenyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0305] (7) Preparation of 1-(cyclopropylmethyl)-3-((4-((4-chloro-3-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C21):

[0306] The method and conditions were the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine was replaced with an equimolar amount of 1-((4-chloro-3-fluorophenyl)sulfonyl)piperazine, which will not be elaborated here.

[0307] Example 22: Preparation of 1-propyl-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C22), including the following steps:

[0308] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0309] The method and conditions are the same as those in step (1) of Example 1, and will not be elaborated here.

[0310] (2) Preparation of N-propylpyridin-2-amine (Intermediate 2):

[0311] The method and conditions are the same as those in step (2) of Example 1, except that cyclopropanecarbaldehyde is replaced by an equimolar amount of propionaldehyde, and will not be elaborated here.

[0312] (3) Preparation of 1-propyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3):

[0313] The method and conditions are the same as those in step (3) of Example 1, except that N-(cyclopropylmethyl)pyridin-2-amine is replaced by an equimolar amount of N-propylpyridin-2-amine, and will not be elaborated here.

[0314] (4) Preparation of 1-propyl-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 4):

[0315] The method and conditions are the same as those in step (4) of Example 1, except that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate is replaced by an equimolar amount of 1-propyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, and will not be elaborated here.

[0316] (5) Preparation of tert-butyl 4-((4-nitrophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0317] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced by an equimolar amount of 4-nitrobenzenesulfonyl chloride, and will not be elaborated here.

[0318] (6) Preparation of 1-((4-nitrophenyl)sulfonyl)piperazine (Intermediate 6):

[0319] The method and conditions are the same as those in step (6) of Example 1, except that 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced by an equimolar amount of 4-((4-nitrophenyl)sulfonyl)piperazine-1-carboxylate, and will not be elaborated here.

[0320] (7) Preparation of 1-propyl-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C22):

[0321] The method and conditions were the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate were replaced with equimolar amounts of 1-((4-nitrophenyl)sulfonyl)piperazine and 1-propyl-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0322] Example 23: Preparation of 1-propyl-3-((4-((4-tolyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C23), including the following steps:

[0323] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0324] The method and conditions were the same as those in step (1) of Example 1, which will not be elaborated here.

[0325] (2) Preparation of N-propylpyridin-2-amine (Intermediate 2):

[0326] The method and conditions were the same as those in step (2) of Example 1, except that cyclopropanecarbaldehyde was replaced with equimolar amount of propionaldehyde, which will not be elaborated here.

[0327] (3) Preparation of 1-propyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3):

[0328] The method and conditions were the same as those in step (3) of Example 1, except that N-(cyclopropylmethyl)pyridin-2-amine was replaced with equimolar amount of N-propylpyridin-2-amine, which will not be elaborated here.

[0329] (4) Preparation of 1-propyl-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 4):

[0330] The method and conditions were the same as those in step (4) of Example 1, except that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate was replaced with equimolar amount of 1-propyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0331] (5) Preparation of tert-butyl 4-((4-(tolyl))sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0332] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 4-methylbenzenesulfonyl chloride, which will not be elaborated here.

[0333] (6) Preparation of 1-((4-tolyl)sulfonyl)piperazine (Intermediate 6):

[0334] The method and conditions are the same as those in step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 4-((4-tolyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0335] (7) Preparation of 1-propyl-3-((4-((4-bromophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C23):

[0336] The method and conditions are the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate are replaced with an equimolar amount of 1-((4-tolyl)sulfonyl)piperazine and 1-propyl-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0337] Example 24: Preparation of 1-((2-chlorothiazol-5-yl)methyl)-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C24), comprising the following steps:

[0338] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0339] The method and conditions are the same as those in step (1) of Example 1, which will not be elaborated here.

[0340] (2) Preparation of N-((2-chlorothiazol-5-yl)methyl)pyridin-2-amine (Intermediate 2):

[0341] 2-Aminopyridine (20.0 mmol), 2-chloro-5-(chloromethyl)thiazole (20.0 mmol), N,N-diisopropylethylamine (40 mmol), potassium iodide (0.2 mmol) and 50 mL of xylene were mixed in a 250 mL three-necked flask and reacted at 80 °C for 6 - 10 h. After the reaction, the reaction mixture was concentrated under reduced pressure, triturated with silica gel, and separated by column chromatography to obtain 1.82 g of a light yellow solid with a yield of 40.3%.

[0342] (3) Preparation of 1-((2-chlorothiazol-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3):

[0343] The method and conditions were the same as those in Step (3) of Example 1, except that N-(cyclopropylmethyl)pyridin-2-amine was replaced with an equimolar amount of N-((2-chlorothiazol-5-yl)methyl)pyridin-2-amine, which will not be elaborated here.

[0344] (4) Preparation of 1-((2-chlorothiazol-5-yl)methyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-1-olate (Intermediate 4):

[0345] The method and conditions were the same as those in Step (4) of Example 1, except that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate was replaced with an equimolar amount of 1-((2-chlorothiazol-5-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidinium salt, which will not be elaborated here.

[0346] (5) Preparation of tert-butyl 4-((4-nitrophenyl)sulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0347] The method and conditions were the same as those in Step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride was replaced with an equimolar amount of 4-nitrobenzenesulfonyl chloride, which will not be elaborated here.

[0348] (6) Preparation of 1-((4-nitrophenyl)sulfonyl)piperazine (Intermediate 6):

[0349] The method and conditions were the same as those in Step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate was replaced with an equimolar amount of tert-butyl 4-((4-nitrophenyl)sulfonyl)piperazine-1-carboxylate, which will not be elaborated here.

[0350] (7) Preparation of 1-((2-chlorothiazol-5-yl)methyl)-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C24):

[0351] The method and conditions were the same as those in Step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate were replaced with equimolar amounts of 1-((4-nitrophenyl)sulfonyl)piperazine and 1-((2-chlorothiazol-5-yl)methyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, which will not be elaborated here.

[0352] Example 25: Preparation of 1-((6-chloropyridin-3-yl)methyl)-4-oxo-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Compound No. C25), including the following steps:

[0353] (1) Preparation of bis(2,4,6-trichlorophenyl)-2-methylmalonate (Intermediate 1):

[0354] The method and conditions were the same as those in Step (1) of Example 1, which will not be elaborated here.

[0355] (2) Preparation of N-((6-chloropyridin-3-yl)methyl)pyridin-2-amine (Intermediate 1):

[0356] The method and conditions were the same as those in Step (2) of Example 24, except that 2-chloro-5-chloromethylthiazole was replaced with equimolar amount of 2-chloro-5-chloromethylpyridine, which will not be elaborated here.

[0357] (3) Preparation of 1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Intermediate 3):

[0358] The method and conditions were the same as those in Step (3) of Example 1, except that N-(cyclopropylmethyl)pyridin-2-amine was replaced with equimolar amount of N-((6-chloropyridin-3-yl)methyl)pyridin-2-amine, which will not be elaborated here.

[0359] (4) Preparation of 1-((6-chloropyridin-3-yl)methyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-1-olate (Intermediate 4):

[0360] The method and conditions are the same as those in step (4) of Example 1, except that 1-(cyclopropylmethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate is replaced with an equimolar amount of 1-((6-chloropyridin-3-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidinium salt, which will not be elaborated here.

[0361] (5) Preparation of tert-butyl 4-(phenylsulfonyl)piperazine-1-carboxylate (Intermediate 5):

[0362] The method and conditions are the same as those in step (5) of Example 1, except that 4-bromobenzenesulfonyl chloride is replaced with an equimolar amount of 4-phenylsulfonyl chloride, which will not be elaborated here.

[0363] (6) Preparation of 1-phenylsulfonylpiperazine (Intermediate 6):

[0364] The method and conditions are the same as those in step (6) of Example 1, except that tert-butyl 4-((4-bromophenyl)sulfonyl)piperazine-1-carboxylate is replaced with an equimolar amount of tert-butyl 1-phenylsulfonylpiperazine-1-carboxylate, which will not be elaborated here.

[0365] (7) Preparation of 1-((6-chloropyridin-3-yl)methyl)-4-oxo-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate (Target Compound C25):

[0366] The method and conditions are the same as those in step (7) of Example 1, except that 1-((4-bromophenyl)sulfonyl)piperazine and 1-(cyclopropylmethyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate are replaced with an equimolar amount of 1-phenylsulfonylpiperazine and 1-((6-chloropyridin-3-yl)methyl)-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-1-olate, which will not be elaborated here.

[0367] The physical and chemical properties of the pyrido[1,2-a]pyrimidinone derivatives containing sulfonamide units prepared in the above examples are shown in Table 1, and their structural formulas, nuclear magnetic resonance hydrogen spectra ( 1 HNMR), carbon spectra ( 13 CNMR) and high-resolution mass spectrometry (HRMS) data are shown in Table 2.

[0368] Table 1 Physical and Chemical Properties of Target Compounds C1 - C25 in Examples

[0369]

[0370]

[0371] Table 2 Structural formulas and spectral data of the target compounds C1 - C25 in the examples

[0372]

[0373]

[0374]

[0375]

[0376]

[0377]

[0378] Test Example 1: The indoor inhibitory activities of the target compounds against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola, and Xanthomonas citri subsp. citri are shown in Tables 3, 4, and 5 as follows.

[0379] Prepare the test compounds into NB liquid media with corresponding concentrations, and then add 40 μL of the above - prepared media containing Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc), and Xanthomonas citri subsp. citri (Xac) respectively. Incubate them on a constant - temperature shaker at 28 °C and 180 rpm for 24 - 48 h. Measure the OD value (OD 595 ) of the bacterial suspension at each concentration on an enzyme - linked immunosorbent assay (ELISA) reader. Also, measure the OD values of the NB liquid media of the corresponding concentrations of the test agents and the control agent, and correct the OD values caused by the agents themselves. The calculation formulas for the corrected OD value and the inhibition rate are as follows:

[0380] Corrected OD value = OD value of the bacterial - containing medium - OD value of the sterile medium;

[0381] Inhibition rate (%) = (OD value of the bacterial suspension in the corrected control medium - OD value of the bacterial suspension in the corrected toxic medium) / OD value of the bacterial suspension in the corrected control medium × 100;

[0382] Table 3 EC of the examples C1 - C25 against Xanthomonas oryzae pv. oryzae 50

[0383]

[0384]

[0385] TC (Thiodiazole Copper)

[0386] It can be seen from Table 3 that some compounds C1, C7, C17, C19, C21, C24, and C25 have certain antibacterial activities against Xanthomonas oryzae pv. oryzae, but the overall antibacterial activities are not high. EC 50The values were 35.1, 45.8, 47.3, 20.6, 55.2, 54.9, and 53.6 μg / mL respectively, and the antibacterial activity was better than that of the control agent thiodiazole copper (59.2 μg / mL). In some compounds, when R 2 was unchanged, the antibacterial activity when R 1 was cyclopropyl was better than that when R 1 was pyridyl, such as C17 (EC 50 : 47.3 μg / mL) > C13 (EC 50 : 127 μg / mL); C11 (EC 50 : 95.8 μg / mL) > C14 (EC 50 : 108 μg / mL); C16 (EC 50 : 81.6 μg / m / L) > C12 (EC 50 : 114 μg / m / L). When R 2 was unchanged, the antibacterial activity when R 1 was cyclopropyl was better than that when R 1 was propyl, such as C1 (EC 50 : 35.1 μg / mL) > C23 (EC 50 : 85.3 μg / mL); C7 (EC 50 : 45.8 μg / mL) > C22 (EC 50 : 74.3 μg / mL).

[0387] Table 4 EC of Examples C1 - C25 against Xanthomonas oryzae pv. oryzicola 50

[0388]

[0389]

[0390] It can be seen from Table 4 that compounds C7, C17, C19, and C24 have certain antibacterial activities against Xanthomonas oryzae pv. oryzicola, and the EC 50 values were 37.5, 28.8, 25.6, and 25.3 μg / mL respectively, all exceeding that of the control agent thiodiazole copper (58.1 μg / mL).

[0391] Table 5. EC of Examples C1 - C25 against Xanthomonas axonopodis pv. citri 50

[0392]

[0393]

[0394] It can be seen from Table 5 that the antibacterial activities of some target compounds against Xanthomonas citri subsp. citri are better than those of the control agents. Among them, the target compound C25 (EC 50 : 21.3 μg / mL) has good antibacterial activity against Xanthomonas citri subsp. citri, which is better than that of the control agent thiodiazole copper (EC 50 : 40.8 μg / mL).

[0395] It can be seen from Tables 3, 4 and 5 that the antibacterial activities of this type of derivatives against Xanthomonas oryzae pv. oryzae are more significant. Especially for compound C19, a pot experiment on living plants will be carried out on it.

[0396] Test Example 2: Pot experiment on living plants of Xanthomonas oryzae pv. oryzae with highly active compounds

[0397] Protective effect of pot experiment on living plants of Xanthomonas oryzae pv. oryzae

[0398] Compound C19, which has good activity against Xanthomonas oryzae pv. oryzae, and the control agent thiodiazole copper were respectively prepared into medicated solutions with a concentration of 200 μg / mL using 0.1% Tween 20 solution, and sprayed on the leaf surfaces of rice until liquid droplets dripped down. After 24 h, at a position 1 - 2 cm away from the leaf tip of the rice leaf, cut off the leaf tip with scissors dipped in Xanthomonas oryzae pv. oryzae bacterial solution, and soak the wound in the bacterial solution for about 10 s. At the same time, set a clear water control without medicament and a bacterial solution control. There are 30 rice seedlings in each treatment. Check the disease incidence 14 days after applying the medicine, record the lesion length of the rice leaf, and calculate its disease index and control effect. The results are shown in Table 6.

[0399] Control effect (%) = (lesion length of the control group - lesion length of the treatment group) / lesion length of the control group × 100

[0400] Table 6. Protective activities of compounds against Xanthomonas oryzae pv. oryzae at a concentration of 200 mg / L -1

[0401]

[0402] It can be seen from Table 6 that when the concentration of compound C19 is 200 μg / mL, the indoor living plant protection activities against Xanthomonas oryzae pv. oryzae are 43.1% respectively. Among them, the protection activity of compound C19 against Xanthomonas oryzae pv. oryzae is equivalent to that of thiodiazole copper.

[0403] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be regarded as the protection scope of the present invention.​

Claims

1. A pyrido[1,2-a]pyrimidinone mesoionic derivative containing a sulfonamide unit, characterized in that, Its structural formula is shown in formula (C): Wherein: R 1 is independently selected from one or more of C1-C 12 alkyl, unsubstituted C6-C 15 aryl, unsubstituted C5-C6 heteroaryl; R 2 is independently selected from one or more of hydrogen, deuterium, halogen, nitro, cyano, trifluoromethyl, formamido, C1-C 12 alkoxy, C1-C 12 alkyl.

2. A pyrido[1,2-a]pyrimidinone mesoionic derivative containing a sulfonamide unit, characterized in that, It is one of the following compounds: Compound C1: 1-(Cyclopropylmethyl)-3-((4-bromophenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C2: 1-(Cyclopropylmethyl)-3-((4-((4-acetamidophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C3: 1-Ethyl-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C4: 1-(Cyclopropylmethyl)-3-((4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C5: 1-(Cyclopropylmethyl)-4-oxo-3-((4-tolylpiperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C6: 1-(Cyclopropylmethyl)-4-oxo-3-((4-(tert-butyl)phenylpiperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C7: 1-(Cyclopropylmethyl)-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C8: 1-(Cyclopropylmethyl)-4-oxo-3-((4-cyanophenylpiperazin-1-yl)nitro)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C9: 1-(Cyclopropylmethyl)-3-((4-((3-bromophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C10: 1-(Cyclopropylmethyl)-3-((4-((2,5-dichlorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C11: 1-(Cyclopropylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C12: 1-(Pyridin-2-ylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C13: 1-(Pyridin-2-ylmethyl)-3-((4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C14: 1-(pyridin-2-ylmethyl)-3-((4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C15: 1-(pyridin-2-ylmethyl)-3-((4-((2,5-dichlorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C16: 1-(cyclopropylmethyl)-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C17: 1-(cyclopropylmethyl)-3-((4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C18: 1-benzyl-3-((4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C19: 1-(cyclopropylmethyl)-3-((4-((4-chloro-3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C20: 1-(cyclopropylmethyl)-3-((4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C21: 1-(cyclopropylmethyl)-3-((4-((4-chloro-3-fluorophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C22: 1-propyl-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C23: 1-propyl-3-((4-((4-bromophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C24: 1-((2-chlorothiazol-5-yl)methyl)-3-((4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate; Compound C25: 1-((6-chloropyridin-3-yl)methyl)-4-oxo-3-((4-(phenylsulfonyl)piperazin-1-yl)methyl)-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate.

3. A composition comprising the derivative according to claim 1 or 2.

4. The preparation method of a pyrido[1,2-a]pyrimidinone mesoionic derivative containing a sulfonamide unit according to claim 1, characterized in that, Comprising the following steps: (1) Using malonic acid and 2,4,6-trichlorophenol as reaction raw materials, adding a reaction solvent, heating under reflux for 4 - 6 h. After the reaction is completed, slowly drip the reaction system into ice water, stir well. After the temperature drops to room temperature, filter to collect the white solid to obtain the intermediate bis(2,4,6-trichlorophenyl)-malonate (2) Using 2-aminopyridine as a reaction raw material, adding a reaction solvent, and reacting with aldehydes with different substituents under heating and reflux conditions to form Schiff bases, and obtaining intermediate N-substituted pyridin-2-amines after the Schiff bases are reacted with a reducing agent. (3) Using 2-aminopyridine as a reaction raw material, adding an acid-binding agent, a catalyst and a reaction solvent, and reacting with differently substituted chlorides under the condition of heating under reflux to obtain an intermediate N-substituted pyridin-2-amine (4) Using N-substituted pyridin-2-amine and bis(2,4,6-trichlorophenyl)-malonate as reaction raw materials, adding a reaction solvent, and reacting under the condition of heating to reflux to obtain intermediate 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate (5) Under ice bath conditions, phosphorus oxychloride was slowly added dropwise to a solution of N,N-dimethylformamide to first generate a vislmer reagent, and then a solution of N,N-dimethylformamide of intermediate 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate was slowly added to the reaction system. The reaction system was then transferred to 25 - 50 °C for reaction for 3 - 6 h. After the reaction was completed, the reaction system was slowly poured into ice water, and a basic pH regulator was added to adjust the pH to neutral. The solid was collected by filtration to obtain intermediate 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate (6) Using tert-butyl piperazine-1-carboxylate as a reaction raw material, adding an acid-binding agent and a reaction solvent, and carrying out a substitution reaction with differently substituted benzenesulfonyl chlorides under an ice bath condition to obtain differently substituted intermediate tert-butyl benzenesulf (7) Using differently substituted tert-butyl piperazine-1-carboxylate as a reaction raw material, adding a reaction solvent, and reacting with trifluoroacetic acid at room temperature to obtain the intermediate 1-(substituted phenylsulfonyl)piperazine (8) Using 1-(substituted benzenesulfonyl)piperazine as the reaction raw material, adding a reaction solvent, an acid-binding agent, and a reducing agent, reacting with 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate under room temperature conditions to obtain the target product 1-substituted-3-((substituted phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate (9) Using N-substituted pyridin-2-amine and bis(2,4,6-trichlorophenyl)-malonate as reaction raw materials, adding a reaction solvent, and reacting under the condition of heating to reflux to obtain intermediate 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate (10) Under ice bath conditions, phosphorus oxychloride was slowly added dropwise to a solution of N,N-dimethylformamide to first generate the vislmer reagent, and then an N,N-dimethylformamide solution of intermediate D: 1-substituted-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate was slowly added to the reaction system. The reaction system was then transferred to 25 - 50 °C for reaction for 3 - 6 h. After the reaction was completed, the reaction system was slowly poured into ice water, and a basic pH regulator was added to adjust the pH to neutral. The solid was collected by filtration to obtain intermediate 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate (11) Using tert-butyl piperazine-1-carboxylate as the reaction raw material, adding an acid-binding agent and a reaction solvent, and carrying out a substitution reaction with differently substituted benzenesulfonyl chlorides under an ice bath condition to obtain differently substituted intermediate tert-butyl benzenesulfonyl piperazine-1-carboxylate (12) Using differently substituted tert-butyl piperazine-1-carboxylate as a reaction raw material, adding a reaction solvent, and reacting with trifluoroacetic acid at room temperature to obtain the intermediate 1-(substituted phenylsulfonyl)piperazine (13) Using 1-(substituted benzenesulfonyl)piperazine as a reaction raw material, adding a reaction solvent, an acid-binding agent, and a reducing agent, reacting with 1-substituted-3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate under room temperature conditions to obtain the target product 1-substituted-3-((substituted phenylsulfonyl)piperazin-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-ium-2-phenolate 5. The preparation method according to claim 4, characterized in that, In step (1), the reaction solvent is phosphorus oxychloride or oxalyl chloride; in step (2), the reaction solvent is 1,2-dichloroethane or methanol, and the reducing agent is sodium borohydride or sodium triacetoxyborohydride.

6. The preparation method according to claim 4, wherein In step (3), the acid-binding agent is N,N-diisopropylethylamine, triethylamine or 1,8-diazabicycloundec-7-ene, the catalyst is potassium iodide, sodium iodide or tetrabutylammonium bromide, and the reaction solvent is xylene or toluene.

7. The preparation method according to claim 4, characterized in that, In step (4), the reaction solvent is xylene or toluene; in step (5), the basic pH regulator is anhydrous potassium carbonate or sodium bicarbonate, in step (6), the acid-binding agent is triethylamine, N,N-diisopropylethylamine or 1,8-diazabicycloundec-7-ene, and the reaction solvent is dichloromethane, ethanol or methanol; in step (7), the reaction solvent is dichloromethane or acetonitrile; in step (8), the reaction solvent is dichloromethane or methanol, the acid-binding agent is triethylamine, N,N-diisopropylethylamine or 4-dimethylaminopyridine, and the reducing agent is sodium triacetoxyborohydride or sodium borohydride.

8. Use of the sulfonamide unit-containing pyrido[1,2-a]pyrimidinone mesoionic derivative according to claim 1 or 2 or the composition according to claim 3 in the preparation of an agent for controlling plant bacterial diseases.

9. The application according to claim 8, wherein The agent is used for controlling Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola or Xanthomonas axonopodis pv. citri.

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