Pyrido[1,2-a]pyrimidinone derivatives containing a beta-styryl group, processes for their preparation and uses thereof

Abstract

This invention belongs to the field of chemical synthesis technology, specifically relating to pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl groups, their preparation methods, and applications. This invention provides a pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl groups, which exhibits extremely high insecticidal activity against pests, has a broad insecticidal spectrum, and has broad application prospects in the preparation of insecticides. Furthermore, the preparation method of this pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl groups has the advantages of readily available raw materials, mild reaction conditions, and high yield, making it very suitable for large-scale industrial production.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology. More specifically, it relates to pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl groups, their preparation methods, and applications. Background Technology

[0002] Neonicotinic insecticides, represented by imidacloprid, have rapidly become an important part of the global pesticide market due to their advantages such as high efficiency, broad spectrum, and high selectivity. However, with the widespread, long-term, and unrestricted use of neonicotinic insecticides, problems of pest resistance and bee toxicity have gradually emerged (Han Minghui, Fang Hongji, Wang Yuanping, Wang Hexing, Jiang Qingwu. Study on pollution, human exposure and harmful effects of neonicotinic pesticides [J]. Shanghai Journal of Preventive Medicine, 2021, 33(06):534-543.DOI:10.19428 / j.cnki.sjpm.2021.20818.).

[0003] Plant essential oils can also be used as insecticides, and their environmental and human health impacts are superior to those of synthetic insecticides. Cinnamon essential oil, as one of the best plant essential oils, has had its active ingredient cinnamaldehyde repeatedly proven to have good insecticidal activity. However, most plant essential oils, including cinnamon essential oil, have a slow onset of action and lower insecticidal activity than synthetic pesticides, thus limiting their widespread adoption.

[0004] Therefore, given the increasingly stringent environmental impact of pesticide use, it is of great significance to research more efficient pesticides that require smaller dosages. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the defects and shortcomings of existing commonly used pesticides, such as pests developing resistance, high toxicity, easy residues, and slow action, and to provide a pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl group that is highly effective against pests and requires a small dosage.

[0006] Another object of the present invention is to provide a method for preparing the pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl group.

[0007] Another object of the present invention is to provide the use of the β-phenylpropenyl pyrido[1,2-a]pyrimidinone derivatives in insecticides.

[0008] Another object of the present invention is to provide an insecticide comprising a pyrido[1,2-a]pyrimidinone derivative containing the β-phenylpropenyl group.

[0009] The above-mentioned objective of this invention is achieved through the following technical solution:

[0010] A pyrido[1,2-a]pyrimidinone derivative containing a β-phenylpropenyl group has the molecular structure shown in formula (I):

[0011] ;

[0012] Among them, R1 is selected from C 1~5 Alkyl, phenyl, halophenyl, halogenated C 1~3 Alkyl-substituted phenyl, benzyl, or halogenated C 1~3 Alkyl-substituted benzyl group; R2 is selected from hydrogen, halogen or C 1~6 Alkyl group; R3 is selected from hydrogen, halogen, or halogenated C. 1~6 Alkyl or C 1~6 alkoxy group; R4 is selected from hydrogen or C 1~6 alkyl.

[0013] Preferably, R1 is selected from C 1~3 Alkyl, phenyl, chlorophenyl, fluoromethane-substituted phenyl, benzyl, or fluoromethane-substituted benzyl; R2 is selected from hydrogen, halogen, or C. 1~6 Alkyl; R3 is selected from hydrogen, halogen, fluoromethyl or C 1~3 alkoxy group; R4 is selected from hydrogen or C 1~3 alkyl.

[0014] More preferably, wherein R1 is selected from methyl, phenyl, 3,5-dichlorophenyl, 3-(trifluoromethyl)phenyl, benzyl or 3-(trifluoromethyl)benzyl; R2 is selected from hydrogen, bromine, methyl, pentyl or hexyl; R3 is selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl or methoxy; and R4 is selected from hydrogen or methyl.

[0015] More preferably, wherein R1 is selected from 3,5-dichlorophenyl, 3-(trifluoromethyl)phenyl, benzyl or 3-(trifluoromethyl)benzyl; R2 is selected from hydrogen or bromine; R3 is selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl or methoxy; and R4 is selected from hydrogen.

[0016] More preferably, R1 is selected from benzyl, 3,5-dichlorophenyl, 3-(trifluoromethyl)phenyl or 3-(trifluoromethyl)benzyl; R2 is selected from hydrogen; R3 is selected from hydrogen, fluorine, chlorine or trifluoromethyl; R4 is selected from hydrogen.

[0017] This invention also provides a method for preparing the pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl groups, wherein intermediate compound h and intermediate compound c are dissolved in toluene or xylene, reacted completely at 100-110°C, and then post-treated to obtain target compound l:

[0018] ;

[0019] The definitions of R1 to R4 are consistent with those described above.

[0020] Preferably, the reaction takes 3 to 6 hours to complete.

[0021] Preferably, the molar mass ratio of intermediate compound h to intermediate compound c is 1 to 3:1.

[0022] Preferably, the post-processing includes the following steps: after the reaction is completed, column chromatography gradient separation is performed to obtain the target compound l.

[0023] Furthermore, the intermediate compound h can be prepared in-house or purchased.

[0024] Furthermore, when R1 is selected from C 1~5 Alkyl, phenyl, benzyl or halogenated C 1~3 When the benzyl group is substituted with an alkyl group, the synthetic route for the intermediate compound h is as follows:

[0025]

[0026] Specifically, the following steps are included:

[0027] S1. Sodium was added to anhydrous ethanol and completely dissolved. Diethyl malonate was added and reacted for 1-2 h. Compound d was added and reacted fully at 70-80 °C. After post-treatment, compound e was obtained.

[0028] S2. Dissolve compound e obtained in step S1 in a mixed solvent of dichloromethane:methanol (V:V=1~12:1), react it with sodium hydroxide at room temperature, and then perform post-treatment to obtain compound f;

[0029] S3. Add water to the compound f obtained in step S2, add an acidic reagent to adjust the pH to 2-3, react fully at room temperature, and then perform post-treatment to obtain compound g;

[0030] S4. Add 2,4,6-trichlorophenol and phosphorus oxychloride to compound g obtained in step S3, react completely at 100~106 °C, and then perform post-treatment to obtain intermediate compound h.

[0031] Preferably, in step S1, the time for the full reaction is 1 to 2 hours.

[0032] Preferably, in step S1, the post-processing includes the following steps: after the reaction is completed, filter to remove solid impurities, evaporate the reaction solution to dryness, and obtain compound e.

[0033] Preferably, in step S1, the molar mass ratio of sodium metal: diethyl malonate: compound d is 1:1:1~1.5.

[0034] Preferably, in step S2, the time for the full reaction is 3 to 5 hours.

[0035] Preferably, in step S2, the molar mass ratio of compound e to sodium hydroxide is 1:2~4.

[0036] Preferably, in step S2, the post-processing includes the following steps: after the reaction is completed, the reaction solution is evaporated to obtain compound f.

[0037] Preferably, in step S3, the acidic reagent is hydrochloric acid, nitric acid, sulfuric acid, or acetic acid.

[0038] More preferably, in step S3, the acidic reagent is hydrochloric acid.

[0039] Preferably, in step S3, the time for the complete reaction is 0.5 to 1 hour.

[0040] Preferably, in step S3, the post-processing includes the following steps: extracting the residue with ethyl acetate, drying the organic layer with anhydrous MgSO4, and concentrating it to obtain compound g.

[0041] Preferably, in step S4, the time for the complete reaction is 3 to 4 hours.

[0042] Preferably, in step S4, the molar mass ratio of compound g to 2,4,6-trichlorophenol is 1:1~2.

[0043] Preferably, in step S4, the post-processing includes the following steps: after the reaction is complete, the entire reaction system is poured into an ice-water mixture, and after a period of time, a viscous substance precipitates out. The viscous substance is transferred to a round-bottom flask, anhydrous ethanol is added, the mixture is stirred at room temperature, and filtered to obtain intermediate compound h.

[0044] Furthermore, when R1 is selected from halophenyl or haloC 1~3 When the alkyl group replaces the phenyl group, the synthetic route for the intermediate compound h is as follows:

[0045]

[0046] Specifically, the following steps are included:

[0047] S1. R5-substituted phenylacetic acid was dissolved in toluene or xylene, thionyl chloride catalyst was added, and the reaction was carried out at 100-110 °C for 3-4 h. Methanol was added, and the reaction was carried out at 55-65 °C until complete. After post-treatment, compound d was obtained.

[0048] S2. Dimethyl carbonate and tetrahydrofuran are added sequentially, followed by slow addition of sodium hydride in batches. Compound d obtained in step S1 is then added dropwise. The mixture is allowed to react fully at 60-68 °C. After post-treatment, compound e is obtained.

[0049] S3. Dissolve compound e obtained in step S2 in anhydrous ethanol, react it with sodium hydroxide at room temperature, and then perform post-treatment to obtain compound f;

[0050] S4. Add water to the compound obtained in step S3, add an acidic reagent to adjust the pH to 2-3, react fully at room temperature, and then perform post-treatment to obtain compound g;

[0051] S5. Dissolve compound g obtained in step S4 in dichloromethane, add dimethylformamide and oxaloyl chloride, react at room temperature for 1-2 h, add 2,4,6-trichlorophenol and react until complete, then post-process to obtain intermediate compound h;

[0052] R5 is selected from halogens or halogenated C. 1~3 The alkyl group, R5 together with the phenyl group it is attached to, forms R1.

[0053] Preferably, in step S1, the time for the full reaction is 3 to 4 hours.

[0054] Preferably, in step S1, the post-processing includes the following steps: after the reaction is complete, the reaction solution is evaporated to dryness, extracted with ethyl acetate, and the organic layer is dried with anhydrous MgSO4 or anhydrous Na2SO4 and desolventized under reduced pressure to obtain compound d.

[0055] Preferably, in step S1, the molar mass ratio of R5-substituted phenylacetic acid to thionyl chloride is 1:1~3.

[0056] Preferably, in step S2, the time for the full reaction is 6 hours.

[0057] Preferably, in step S2, the molar mass ratio of compound d to sodium hydride is 1:4.

[0058] Preferably, in step S2, the post-treatment includes the following steps: after the reaction is completed, the reaction solution is evaporated to dryness, extracted with ethyl acetate, diethyl ether or dichloromethane, and the organic layer is dried with anhydrous MgSO4 or anhydrous Na2SO4 and desolventized under reduced pressure to obtain compound e.

[0059] Preferably, in step S3, the time for the full reaction is 3 to 6 hours.

[0060] Preferably, in step S3, the molar mass ratio of compound e to sodium hydroxide is 1:1~2.

[0061] Preferably, in step S3, the post-processing includes the following steps: after the reaction is completed, desolvation is performed under reduced pressure to obtain compound f.

[0062] Preferably, in step S4, the acidic reagent is hydrochloric acid, nitric acid, sulfuric acid, or acetic acid.

[0063] More preferably, in step S4, the acidic reagent is hydrochloric acid.

[0064] Preferably, in step S4, the time for the complete reaction is 0.5 to 1 hour.

[0065] Preferably, in step S4, the molar mass ratio of compound g to 2,4,6-trichlorophenol is 1:1~2.

[0066] Preferably, in step S4, the post-treatment includes the following steps: After the reaction is complete, the mixture is extracted with ethyl acetate, and the organic layer is dried and concentrated with anhydrous MgSO4 or anhydrous Na2SO4 to obtain compound g.

[0067] Preferably, in step S5, the time for the complete reaction is 2 hours.

[0068] Preferably, in step S5, the molar mass ratio of compound g to 2,4,6-trichlorophenol is 1:2.

[0069] Preferably, in step S5, the post-processing includes the following steps: after the reaction is completed, desolvation is performed under reduced pressure, ethanol is added to the residue to dissolve it, the residue is placed in a refrigerator overnight to precipitate a white solid, and the intermediate compound h is obtained by filtration.

[0070] Furthermore, intermediate compound c can be prepared in-house or purchased.

[0071] Furthermore, the synthetic route for the intermediate compound c is shown below:

[0072]

[0073] Furthermore, when R2 is selected from hydrogen, and R3 is selected from hydrogen, halogen, or halogenated C. 1~6 Alkyl or C 1~6 When alkoxy is involved, the synthetic route for intermediate compound c specifically includes the following steps:

[0074] Under a protective gas atmosphere and at room temperature, R4-substituted 2-aminopyridine and compound a were added, along with anhydrous sodium sulfate and acetic acid. The reaction was carried out for 3-6 h to obtain compound b. Anhydrous ethanol was added, and sodium borohydride was slowly added in batches. After the reaction was completed, the intermediate compound c was obtained.

[0075] Preferably, the protective gas includes helium, neon, argon, and nitrogen.

[0076] More preferably, the protective gas is argon.

[0077] Preferably, the time for the complete reaction is 4 hours.

[0078] Preferably, the post-processing includes the following steps: after the reaction is completed, acetic acid is added to quench the reaction; the reaction solution is extracted with ethyl acetate; the organic layer is dried and concentrated with anhydrous MgSO4 or anhydrous Na2SO4; and the residue is separated by column chromatography to obtain compound c.

[0079] Preferably, the molar mass ratio of R4-substituted 2-aminopyridine to compound a is 1:1 to 2.5.

[0080] Furthermore, when R2 is selected from halogen or C 1~6 When alkyl and R3 is selected from hydrogen, the synthetic route of intermediate compound c specifically includes the following steps:

[0081] Under a protective gas atmosphere and at room temperature, R4-substituted 2-aminopyridine was dissolved in anhydrous ethanol, and ferric sulfate and compound a were added. The mixture was reacted at 40-50 °C for 2-6 h to obtain compound b. Sodium borohydride was added slowly in batches, and the mixture was allowed to react fully at room temperature. After post-treatment, intermediate compound c was obtained.

[0082] Preferably, the protective gas includes helium, argon, neon, and nitrogen.

[0083] More preferably, the protective gas is nitrogen.

[0084] Preferably, the time for the complete reaction is 4 hours.

[0085] Preferably, the post-processing includes the following steps: the reaction solution is extracted with ethyl acetate, the organic layer is dried and concentrated with anhydrous MgSO4 or anhydrous Na2SO4, and the residue is separated by column chromatography to obtain compound c.

[0086] Preferably, the molar mass ratio of R4-substituted 2-aminopyridine:compound a:ferric sulfate is 1:1~1.5:0.4~0.5.

[0087] Furthermore, the present invention also provides the application of the pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl group as an insecticide.

[0088] Preferably, the insecticide kills pests including Aedes albopictus, German cockroach, and housefly.

[0089] Furthermore, the present invention also provides an insecticide comprising the pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl groups.

[0090] The present invention has the following beneficial effects:

[0091] The pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl group of the present invention exhibits extremely high insecticidal activity against pests and has a broad insecticidal spectrum, showing great application prospects in the preparation of insecticides; furthermore, the preparation method of the pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl group has the advantages of readily available raw materials, mild reaction conditions, and high yield, making it very suitable for large-scale industrial production. Detailed Implementation

[0092] The present invention will be further illustrated below with reference to specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in this technical field.

[0093] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0094] Among them, the β-phenylpropenyl pyrido[1,2- a The synthetic route for the pyrimidinone derivative (i.e., compounds 1l-40l) is as follows:

[0095]

[0096]

[0097] or

[0098]

[0099] Example 1: Synthesis of intermediates 1c-11c

[0100] The synthetic route for the intermediate compound 1c-11c is as follows:

[0101]

[0102]

[0103] Specifically, the following steps are included:

[0104] S1. Under argon protection and at room temperature, add 1.88 g (20 mmol, 1 eq) of R4-substituted 2-aminopyridine, 20 mL of benzene, and 3 g of anhydrous sodium sulfate to a 100 mL round-bottom flask equipped with a stirrer. Then slowly add dropwise cinnamaldehyde (compound a) (25 mmol, 1.25 eq) dissolved in 10 mL of cinnamaldehyde with different benzene ring substitutions, and 5 drops of acetic acid. Stir at room temperature for 6 h. After the reaction is complete, filter, and evaporate the filtrate to dryness to obtain compound b. Without purification, immediately add compound b to the next reaction. Add compound b and 30 mL of anhydrous ethanol to a 100 mL round-bottom flask, and after complete dissolution, weigh 2.9 g of sodium borohydride and add it in batches. Stir at room temperature for 4 h, and add 1 mL of acetic acid to quench the reaction. Evaporate the reaction solution to dryness, and separate the residue by column chromatography with petroleum ether:ethyl acetate = 8:1 (v / v) as the eluent to obtain intermediates 1c-7c.

[0105] S2. Under nitrogen protection and at room temperature, using anhydrous ethanol as solvent, R4-substituted 2-aminopyridine and ferric sulfate were added, followed by dropwise addition of cinnamaldehyde with different α-substitutions (compound a). The reaction was carried out at 50°C for 3 h to obtain compound b. After the reaction was completed, sodium borohydride was slowly added in batches, and the reaction was carried out at room temperature for 4 h. The reaction was then quenched by adding acetic acid. The reaction solution was extracted with ethyl acetate, the organic layer was dried and concentrated with anhydrous MgSO4, and the residue was separated by column chromatography to obtain intermediates 8c-11c.

[0106] Example 2 Synthesis of target compound ll-26l

[0107] The synthetic route for the target compound 1l-26l is as follows:

[0108]

[0109]

[0110] S1. Cut a sodium block (0.46 g, 20 mmol, 1 eq) with a knife and remove the surface oxide layer. Add the sodium block to a 50 mL flask and immediately add 30 mL of anhydrous ethanol. Stir at room temperature until the sodium block is completely dissolved. Add diethyl malonate (3.2 g, 20 mmol, 1 eq) and stir at room temperature for 1 h. Then weigh compound d (25 mmol) and add it to the reaction system. Heat the system to 80 °C and react for 2 h. Monitor the reaction progress using TLC (petroleum ether:ethyl acetate = 8:1). After the reaction is complete, filter to remove solid impurities and evaporate the reaction solution to dryness to obtain compound e.

[0111] S2. Compound e (20 mmol, 1 eq) was placed in a 250 mL round-bottom flask and 100 mL of dichloromethane:methanol (V:V=9:1) solvent and sodium hydroxide (3.2 g, 80 mmol, 4 eq) were added. The mixture was stirred at room temperature for 5 h, and the reaction progress was monitored by TLC (petroleum ether:ethyl acetate=8:1). After the reaction was completed, the reaction mixture was evaporated to dryness to obtain compound f.

[0112] S3. Add 50 mL of water to compound f (15 mmol, 1 eq), and slowly add 1 M hydrochloric acid to adjust the pH to 2. Add 150 mL of water to the residue, extract with ethyl acetate (50 mL × 3), wash the organic phase three times with 100 mL of saturated sodium chloride solution, dry to anhydrous sodium sulfate, and evaporate the solvent to obtain compound g.

[0113] S4. Compound g (15 mmol, 1 eq), 2,4,6-trichlorophenol (5.9 g, 30 mmol, 2 eq), and 30 mL of phosphorus oxychloride were added to a 100 mL round-bottom flask and stirred under reflux at 106 °C for 4 h. After the reaction was complete, the entire reaction system was poured into a 300 mL ice-water mixture, and a viscous substance precipitated after a period of time. The viscous substance was transferred to a 100 mL round-bottom flask, 60 mL of anhydrous ethanol was added, and the mixture was stirred at room temperature for 1 h. The mixture was then filtered to obtain intermediate h.

[0114] S5. Weigh intermediate h (5 mmol, 1 eq) and intermediate c (5 mmol, 1 eq) into a 100 mL three-necked flask. Use 30 mL of toluene as the reaction solvent. First, heat to 80 °C, then to 90 °C after half an hour. Thereafter, increase the temperature by 10 °C every half hour until the temperature reaches 110 °C. React for 6 h. After the reaction is complete, perform gradient separation by column chromatography. The eluents are petroleum ether:ethyl acetate = 1:1 (v / v) and ethyl acetate:methanol = 15:1 (v / v) in sequence to obtain 1-26 L of the target product.

[0115] Example 3 Synthesis of target compounds 27l-40l

[0116] The synthetic route for the target compound 27l-40l is as follows:

[0117]

[0118]

[0119] S1: 25 mmol (1 eq) of R5-substituted phenylacetic acid, 75 mmol (3 eq) of thionyl chloride, and 20 mL of toluene were added to a 100 mL round-bottom flask. The mixture was refluxed at 110 °C for 4 h. After the reaction, the reaction solution was evaporated to dryness. The resulting acyl chloride was slowly added dropwise to a round-bottom flask containing 50 mL of methanol. The mixture was refluxed at 65 °C for 3 h. After the reaction, the reaction solution was evaporated to dryness, and 100 mL of water and ethyl acetate (50 mL × 3) were added. The mixture was extracted separately. The organic phase was washed three times with 100 mL of saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and dissolved under reduced pressure. The residue was separated by column chromatography (petroleum ether:ethyl acetate = 10:1) to give compound d.

[0120] S2: Add 20 mL of dimethyl carbonate and 20 mL of tetrahydrofuran to a 250 mL round-bottom flask, then slowly add sodium hydride (7.2 g, 30 mmol, 1.5 eq) in portions. After the addition is complete, slowly add compound d (20 mmol, 1 eq). Reflux at 68 °C for 6 h, and monitor the reaction progress by TLC (petroleum ether:ethyl acetate = 5:1). After the reaction is complete, evaporate the reaction solution to dryness, add 150 mL of water and (50 mL × 3) ethyl acetate to the reaction residue, and extract by separation. Wash the organic phase three times with 100 mL of saturated sodium chloride solution, dry to anhydrous magnesium sulfate, and remove solvent under reduced pressure to obtain compound e.

[0121] S3: Compound e (15 mmol, 1 eq) and 50 mL of anhydrous ethanol were added to a 100 mL round-bottom flask. The mixture was stirred slowly at room temperature for 10 min until completely dissolved. Then, sodium hydroxide (2.3 g, 60 mmol, 3 eq) was added, and the mixture was stirred at room temperature for 6 h. The reaction progress was monitored by TLC (petroleum ether: ethyl acetate = 10:1). After the reaction was completed, the solvent was removed under reduced pressure to obtain compound f.

[0122] S4: Add 50 mL of water to compound f (15 mmol, 1 eq), slowly add 1 M hydrochloric acid dropwise under ice bath to adjust the pH to 2-3, and react at room temperature for 1 h. Then add 150 mL of water, extract with ethyl acetate (50 mL × 3), wash the organic phase three times with 100 mL of saturated sodium chloride solution, dry to anhydrous sodium sulfate, and remove solvent under reduced pressure to obtain compound g.

[0123] S5: Add compound g (10 mmol, 1 eq), 25 mL of dichloromethane, and 1 mL of DMF to a 100 mL round-bottom flask equipped with a stir bar, then slowly add 2 mL of oxaloyl chloride. After stirring at room temperature for 2 h, add 2,4,6-trichlorophenol (3.94 g, 20 mmol, 2 eq) in batches and continue stirring at room temperature for 2 h. After the reaction is complete, desolvate under reduced pressure, add 100 mL of ethanol to the residue, and place in a refrigerator overnight to precipitate a white solid. Filter to obtain intermediate compound h.

[0124] S6: Weigh intermediate compound h (5 mmol, 1 eq) and intermediate compound c (5 mmol, 1 eq) into a 100 mL three-necked flask. Use 30 mL of toluene as the reaction solvent. First, heat to 80 °C, then to 90 °C after half an hour. Thereafter, increase the temperature by 10 °C every half hour until the temperature reaches 110 °C. React for 6 h. After the reaction is complete, perform gradient separation by column chromatography. The eluents are petroleum ether:ethyl acetate = 1:1 (v / v) and ethyl acetate:methanol = 15:1 (v / v) in sequence to obtain 27-40 L of the target product.

[0125] The mass spectrometry data and molecular structures of the 40 target compounds (1-40 μL) are as follows:

[0126] 1-Cinnamyl-3-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onthiol (1l):

[0127] Yellow soil, (yield: 37.2%), mp: 124-125 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.24 (dd, J = 6.9, 1.6 Hz, 1H), 8.23 ​​(ddd, J = 8.8, 7.0, 1.7 Hz, 1H), 7.78 (dt, J = 9.0, 0.9 Hz, 1H), 7.51 – 7.43 (m, 1H), 7.43 – 7.36 (m, 2H), 7.29 (t, J = 7.7Hz, 2H), 7.24 – 7.19 (m, 1H), 6.57 – 6.51 (m, 1H), 6.35 (dt, J = 16.1, 5.2 Hz,1H), 5.33 – 4.78 (m, 2H), 1.94 (s, 3H). 13C NMR (151 MHz, DMSO) δ 159.44,154.09, 145.92, 142.80, 136.56, 131.73, 131.04, 129.00, 128.14, 126.76,124.13, 116.37, 114.84, 88.34, 44.00, 11.03. HRMS (ESI): Extract masscalculated for C 18 H 16 N₂O₂[M + H] + Found: 293.1291; Found: 293.1299.

[0128] (E)-1-(3-(4-chlorophenyl)allyl)-3-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (2l):

[0129] Yellow soil, (yield: 31.2%), mp: 111-112 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.24 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 8.23 ​​(ddd, J = 8.8, 7.0, 1.7 Hz, 1H),7.90 – 7.67 (m, 1H), 7.47 (td, J = 6.9, 1.1 Hz, 1H), 7.44 – 7.39 (m, 2H), 7.37– 7.29 (m, 2H), 6.56 – 6.46 (m, 1H), 6.39 (dt, J = 16.2, 5.1 Hz, 1H), 5.17 –4.93 (m, 2H), 1.94 (s, 3H). 13 C NMR (151 MHz, DMSO) δ 159.43, 154.10, 145.93,142.83, 135.57, 132.49, 131.03, 130.27, 128.97, 128.49, 125.24, 116.40,114.84, 88.34, 43.94, 11.02. HRMS (ESI): Extract mass calculated forC 18 H 15ClN2O2[M + 2H] + Found: 328.0822

[0130] (E)-1-(3-(4-bromophenyl)allyl)-3-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onthiol (3l):

[0131] Yellow soil, (yield: 37.4%), mp: 136-137 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.23 (dd, J = 6.9, 1.6 Hz, 1H), 8.22 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H), 7.76 (dt, J = 9.0, 0.9 Hz, 1H), 7.50 – 7.44 (m, 3H), 7.38 – 7.32 (m, 2H), 6.53 – 6.45(m, 1H), 6.40 (dt, J = 16.2, 5.0 Hz, 1H), 5.21 – 4.84 (m, 2H), 1.94 (s, 3H). 13 CNMR (151 MHz, DMSO) δ 159.43, 154.11, 145.92, 142.83, 135.92, 131.88, 131.03,130.32, 129.70, 129.21, 128.81, 125.33, 121.06, 116.40, 114.84, 88.35, 43.95,11.02. Extract mass calculated for C 18 H 15 BrF3N2O2[M + H] + : 371.0396; Found:371.0381.

[0132] 1-Cinnamyl-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidine-1-on-2-ol (4l):

[0133] Yellow soil, (yield: 60.6%), mp: 146-147 ℃; 1 H NMR (600 MHz, DMSO-d 6)δ 9.32 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.29 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H),7.83 (dt, J = 9.1, 1.0 Hz, 1H), 7.78 – 7.62 (m, 2H), 7.50 (td, J = 6.9, 1.1 Hz,1H), 7.44 – 7.37 (m, 2H), 7.34 – 7.27 (m, 4H), 7.27 – 7.19 (m, 1H), 7.19 –7.13 (m, 1H), 6.66 – 6.57 (m, 1H), 6.39 (dt, J = 16.1, 5.3 Hz, 1H), 5.12 (d, J =5.3 Hz, 2H). 13 C NMR (151 MHz, DMSO) δ 158.67, 153.78, 146.52, 143.69, 136.60,135.96, 131.94, 131.50, 131.23, 129.01, 128.17, 127.35, 126.78, 125.69,124.08, 116.59, 114.96, 94.00, 44.22. HRMS (ESI): Extract mass calculated forC 23 H 18 N₂O₂[M + H] + Found: 355.1447; Found: 355.1442.

[0134] (E)-1-(3-(4-chlorophenyl)allyl)-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (5l):

[0135] Yellow soil, (yield: 60.3%), mp: 134-135℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.32 (dd, J = 6.9, 1.6 Hz, 1H), 8.28 (ddd, J= 8.9, 7.0, 1.7 Hz, 1H), 7.89 –7.75 (m, 1H), 7.75 – 7.67 (m, 2H), 7.50 (td, J = 7.0, 1.1 Hz, 1H), 7.46 – 7.40(m, 2H), 7.37 – 7.27 (m, 4H), 7.18 – 7.11 (m, 1H), 6.63 – 6.53 (m, 1H), 6.49– 6.38 (m, 1H), 5.11 (d, J = 5.1 Hz, 2H). 13 C NMR (151 MHz, DMSO) δ 158.66,153.79, 148.07, 146.53, 143.71, 137.38, 135.94, 135.61, 132.52, 131.50,131.22, 130.48, 128.99, 128.51, 127.35, 125.69, 125.19, 116.62, 114.97,112.25, 108.43, 93.99, 44.15. HRMS (ESI): Extract mass calculated forC 23 H 17 ClN2O2[M + H] + Found: 389.1137; Found: 389.1161.

[0136] (E)-1-(3-(4-bromophenyl)allyl)-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (6l):

[0137] Yellow soil, (yield: 48.9%), mp: 154-155 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.32 (dd, J = 6.9, 1.6 Hz, 1H), 8.28 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.73 – 7.66 (m, 2H), 7.53 – 7.45 (m, 3H), 7.40 – 7.34 (m, 2H),7.30 (t, J= 7.8 Hz, 2H), 7.16 (tt, J = 7.2, 1.3 Hz, 1H), 6.64 – 6.55 (m, 1H), 6.53 – 6.38 (m, 1H), 5.10 (d, J = 5.1 Hz, 2H). 13 C NMR (151 MHz, DMSO) δ 158.65,153.79, 146.54, 143.71, 135.97, 135.95, 132.58, 131.90, 131.50, 131.22,130.52, 129.75, 128.83, 127.99, 127.34, 125.69, 125.30, 122.98, 121.08,116.62, 114.99, 93.97, 44.16. HRMS (ESI): Extract mass calculated forC 23 H 17 BrF3N2O3[M + H] + Found: 433.0552; Found: 433.0557.

[0138] (E)-1-(3-(4-fluorophenyl)allyl)-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (7l):

[0139] Yellow soil, (yield: 56.7%), mp: 156-157 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.32 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.29 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H),7.81 (dt, J = 9.1, 1.0 Hz, 1H), 7.76 – 7.67 (m, 2H), 7.55 – 7.42 (m, 3H), 7.41 – 7.22 (m, 2H), 7.19 – 7.05 (m, 3H), 6.69 – 6.51 (m, 1H), 6.35 (dt, J = 16.0, 5.2 Hz, 1H), 5.10 (d, J = 5.2 Hz, 2H).13 C NMR (151 MHz, DMSO) δ 162.93, 161.31,157.46, 155.28, 153.78, 146.53, 143.69, 135.97, 131.49, 131.22, 130.68,128.74, 128.69, 127.34, 125.68, 124.01, 124.00, 116.60, 115.90, 115.76,114.98, 93.98, 44.16. HRMS (ESI): Extract mass calculated for C 23 H 17 FN2O2[M +H] + Found: 373.1353; Found: 373.1379.

[0140] (E)-4-oxo-3-phenyl-1-(3-(3-(trifluoromethyl)phenyl)allyl)-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (8l):

[0141] Yellow soil, (yield: 57.1%), mp: 188-189 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.33 (dd, J = 6.9, 1.6 Hz, 1H), 8.29 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H), 7.89 –7.61 (m, 6H), 7.62 – 7.42 (m, 3H), 7.31 (t, J = 7.7 Hz, 2H), 7.22 – 7.07 (m,1H), 6.79 – 6.46 (m, 1H), 5.23 – 5.04 (m, 2H). 13C NMR (151 MHz, DMSO) δ158.65, 153.82, 146.58, 143.71, 137.87, 135.98, 131.47, 131.23, 130.42,130.05, 129.87, 127.34, 126.67, 125.67, 124.45, 124.42, 123.43, 123.41,123.12, 116.62, 115.05, 93.99, 44.11, 40.58. HRMS (ESI): Extract masscalculated for C 24 H 17 F3N2O2[M + H] + Found: 423.1321; Found: 423.1316.

[0142] (E)-1-(3-(4-methoxyphenyl)allyl)-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (9l):

[0143] Yellow soil, (yield: 55.4%), mp: 177-178 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.31 (dd, J = 6.9, 1.6 Hz, 1H), 8.29 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H), 7.83 (d, J = 9.0 Hz, 1H), 7.78 – 7.63 (m, 2H), 7.50 (td, J = 6.9, 1.0 Hz, 1H), 7.37 – 7.27(m, 4H), 7.26 – 7.08 (m, 1H), 6.97 – 6.76 (m, 2H), 6.58 (dd, J = 16.2, 1.6 Hz, 1H), 6.22 (dt, J = 16.1, 5.4 Hz, 1H), 5.08 (d, J = 5.4 Hz, 2H), 3.73 (s, 3H). 13CNMR (151 MHz, DMSO) δ 159.42, 158.67, 153.76, 146.49, 143.65, 135.98, 131.73,131.48, 131.23, 129.23, 128.08, 127.34, 125.68, 121.43, 116.56, 114.97,114.44, 94.01, 55.57, 44.28. HRMS (ESI): Extract mass calculated for C 24 H 20 N₂O₃[M + H] + Found: 385.1553; Found: 385.1546.

[0144] (E)-1-(2-methyl-3-phenylallyl)-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (10l):

[0145] Yellow soil, (yield: 37.6%), mp: 124-125 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.33 (dd, J = 6.9, 1.6 Hz, 1H), 8.30 (ddd, J = 8.8, 6.9, 1.7 Hz, 1H), 7.79 –7.63 (m, 3H), 7.52 (t, J = 7.0 Hz, 1H), 7.31 (td, J = 7.7, 3.9 Hz, 4H), 7.25 –7.14 (m, 4H), 6.26 (s, 1H), 5.03 (s, 2H), 1.90 (s, 3H). 13C NMR (151 MHz, DMSO)δ 158.84, 153.78, 146.75, 143.71, 137.19, 135.99, 132.57, 131.53, 131.25,129.70, 129.23, 128.58, 128.21, 127.34, 126.99, 125.69, 124.75, 116.72,115.11, 99.99, 93.84, 48.88, 16.13. HRMS (ESI): Extract mass calculated forC 24 H 20 N₂O₂[M + H] + Found: 369.1604; Found: 369.1629.

[0146] (E)-1-(2-benzylethyl)-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (11l):

[0147] Yellow soil, (yield: 38.5%), mp: 156-157 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.33 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 8.32 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H),7.76 – 7.58 (m, 3H), 7.52 (td, J = 6.9, 1.1 Hz, 1H), 7.35 – 7.27 (m, 4H), 7.23– 7.12 (m, 4H), 6.21 (s, 1H), 5.07 (s, 2H), 2.35 – 2.16 (m, 2H), 1.56 (q, J =7.5, 7.1 Hz, 2H), 1.31 – 1.22 (m, 4H), 0.90 – 0.75 (m, 3H). 13C NMR (151 MHz, DMSO) δ 158.78, 153.74, 146.74, 143.70, 137.15, 136.69, 135.99, 131.57,131.25, 128.87, 128.67, 127.35, 127.08, 125.71, 124.98, 116.71, 115.11,93.88, 47.45, 31.85, 29.55, 27.75, 22.18, 14.29. HRMS (ESI): Extract masscalculated for C 28 H 28 N₂O₂[M + H] + Found: 425.2230; Found: 425.2226.

[0148] (E)-1-(2-benzylethyl)-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (12l):

[0149] Yellow soil, (yield: 41.2%), mp: 121-122 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.33 (dd, J = 6.9, 1.7 Hz, 1H), 8.30 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H), 7.86 –7.60 (m, 3H), 7.60 – 7.45 (m, 1H), 7.35 – 7.25 (m, 4H), 7.23 – 7.12 (m, 4H),6.22 (s, 1H), 5.06 (s, 2H), 2.50 (p, J = 1.8 Hz, 1H), 2.32 – 2.17 (m, 2H), 1.54(ddd, J = 12.2, 10.1, 6.4 Hz, 2H), 1.33 – 1.15 (m, 7H). 13C NMR (151 MHz, DMSO) δ158.78, 153.73, 146.74, 143.70, 137.15, 136.71, 135.99, 133.34, 132.11,131.99, 131.57, 131.25, 131.21, 128.87, 128.67, 127.34, 127.08, 125.71,125.07, 116.71, 115.11, 93.87, 47.46, 31.31, 29.52, 29.27, 28.03, 22.45,14.35. HRMS (ESI): Extract mass calculated for C 29 H 30 N₂O₂[M + H] + : 439.2386;Found: 439.2363.

[0150] (Z)-1-(2-bromo-3-phenylallyl)-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (13l):

[0151] Yellow soil, (yield: 42.3%), mp: 132-133 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.35 (ddd, J = 14.3, 6.8, 1.6 Hz, 1H), 8.40 (dddd, J = 55.3, 8.8, 7.0, 1.7 Hz,1H), 7.79 (d, J = 9.0 Hz, 1H), 7.69 (ddt, J = 20.6, 6.3, 1.4 Hz, 2H), 7.62 – 7.52(m, 2H), 7.47 – 7.26 (m, 6H), 7.24 – 7.11 (m, 2H), 5.41 (d, J = 32.5 Hz, 2H). 13CNMR (151 MHz, DMSO) δ 157.90, 157.39, 153.15, 146.05, 145.47, 143.57, 135.24,134.58, 131.49, 131.20, 130.61, 128.69, 128.52, 128.03, 126.78, 125.15,118.84, 116.62, 114.30, 93.10, 83.48, 49.52, 32.24. HRMS (ESI): Extract masscalculated for C 23 H 17 BrN2O2[M + H] + Found: 433.0552; Found: 433.0558.

[0152] 1-Cinnamyl-9-methyl-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidine-1-onyl-2-ol (14l):

[0153] Yellow soil, (yield: 37.4%), mp: 171-172 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.33 (s, J = 6.9, 1.7 Hz, 1H), 7.77 – 7.63 (m, 3H), 7.52 (t, J = 7.0 Hz, 1H), 7.31 (td, J = 7.7, 3.9 Hz, 4H), 7.25 – 7.14 (m, 4H), 6.55 (s, 1H), 6.25 (s,1H), 5.33 (s, 2H), 1.95 (s, 3H). 13 C NMR (151 MHz, DMSO) δ 157.87, 154.54,146.77, 144.00, 137.76, 137.20, 134.68, 131.07, 130.43, 130.06, 128.89,129.91, 128.89, 128.29, 126.50, 124.45, 124.24, 122.99, 116.86, 115.25,92.22, 44.41, 33.21. Extract mass calculated for C 24 H20 N₂O₂[M + H] + Found: 369.1604; Found: 369.1635.

[0154] 3-Benzyl-1-cinnamyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onthium-2-ol (15l):

[0155] Yellow soil, (yield: 49.2%), mp: 176-177 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.25 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.24 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H),7.79 (dt, J = 9.0, 1.0 Hz, 1H), 7.48 (td, J = 6.9, 1.1 Hz, 1H), 7.42 – 7.35 (m,2H), 7.35 – 7.31 (m, 2H), 7.29 (dd, J = 8.4, 6.9 Hz, 2H), 7.25 – 7.16 (m, 3H), 7.13 – 7.06 (m, 1H), 6.55 (dt, J = 16.1, 1.7 Hz, 1H), 6.35 (dt, J = 16.1, 5.2 Hz,1H), 5.22 – 4.92 (m, 2H), 3.79 (s, 2H). 13 C NMR (151 MHz, DMSO) δ 159.39,154.31, 146.31, 143.17, 142.56, 136.53, 134.03, 131.88, 131.31, 128.99,128.85, 128.25, 128.15, 127.63, 127.11, 126.76, 126.18, 125.74, 124.94,124.10, 116.49, 114.93, 93.07, 44.09, 30.98. HRMS (ESI): Extract masscalculated for C 24 H 20 N₂O₂[M + H] +Found: 369.1604; Found: 369.1649.

[0156] (E)-3-benzyl-1-(3-(4-chlorophenyl)allyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (16l):

[0157] Yellow soil, (yield: 50.7%), mp: 138-139 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.24 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 8.23 ​​(ddd, J = 8.9, 7.0, 1.7 Hz, 1H),7.76 (dt, J = 9.1, 1.0 Hz, 1H), 7.47 (td, J = 6.9, 1.1 Hz, 1H), 7.43 – 7.37 (m,2H), 7.37 – 7.28 (m, 4H), 7.23 – 7.14 (m, 2H), 7.14 – 7.05 (m, 1H), 6.53 (dt, J = 16.1, 1.7 Hz, 1H), 6.38 (dt, J = 16.2, 5.2 Hz, 1H), 5.10 – 4.98 (m, 2H), 3.79 (s, 2H). 13 C NMR (151 MHz, DMSO) δ 159.37, 154.33, 146.33, 143.20, 142.53,135.53, 132.52, 131.21, 130.43, 128.97, 128.84, 128.48, 128.35, 128.25,127.94, 127.76, 127.49, 125.74, 125.20, 116.52, 114.94, 93.05, 44.03, 30.96.HRMS (ESI): Extract mass calculated for C 24 H 19 ClN2O2[M + H] + : 403.1214; Found:403,1210.

[0158] (E)-3-benzyl-1-(3-(4-bromophenyl)allyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (17l):

[0159] Yellow soil, (yield: 46.4%), mp: 145-146 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.25 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 8.24 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H),7.77 (dt, J = 9.1, 1.0 Hz, 1H), 7.51 – 7.44 (m, 3H), 7.37 – 7.30 (m, 4H), 7.21 – 7.16 (m, 2H), 7.11 – 7.06 (m, 1H), 6.55 – 6.47 (m, 1H), 6.40 (dt, J = 16.1,5.1 Hz, 1H), 5.17 – 4.93 (m, 2H), 3.78 (s, 2H). 13 C NMR (151 MHz, DMSO) δ159.37, 154.33, 146.35, 143.20, 142.54, 135.90, 131.89, 131.21, 130.47,129.52, 128.84, 128.81, 128.25, 125.74, 125.32, 121.08, 116.52, 114.96,93.02, 44.03, 31.40, 30.97, 22.51, 14.40. HRMS (ESI): Extract mass calculated for C 24 H 19 BrN2O2[M + H] + Found: 447.0709; Found: 447.0706.

[0160] (E)-3-benzyl-1-(3-(4-fluorophenyl)allyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (18l):

[0161] Yellow soil, (yield: 49.5%), mp: 150-151 ℃;1 H NMR (600 MHz, DMSO- d 6)δ 9.24 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.24 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H),7.77 (dt, J = 9.1, 1.0 Hz, 1H), 7.53 – 7.38 (m, 3H), 7.38 – 7.25 (m, 2H), 7.25 – 7.16 (m, 2H), 7.16 – 7.06 (m, 3H), 6.54 (dt, J = 16.1, 1.7 Hz, 1H), 6.39 –6.21 (m, 1H), 5.12 – 4.97 (m, 2H), 3.78 (s, 2H). 13 C NMR (151 MHz, DMSO) δ162.93, 161.31, 158.65, 146.53, 143.69, 135.97, 133.23, 133.21, 131.49,131.23, 130.67, 128.74, 128.69, 127.34, 125.68, 124.01, 123.99, 116.60,115.91, 115.76, 114.99, 93.98, 44.16, 41.16. HRMS (ESI): Extract masscalculated for C 24 H 19 FN2O2[M + H] + Found: 387.1510; Found: 387.1508.

[0162] (E)-3-benzyl-4-oxo-1-(3-(3-(trifluoromethyl)phenyl)allyl)-4H-pyrido[1,2-a]pyrimidin-1-onthiol (19l):

[0163] Yellow soil, (yield: 49.2%), mp: 179-180℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.24 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 8.24 (ddd, J= 8.8, 7.0, 1.7 Hz, 1H),7.77 (dt, J = 9.1, 1.0 Hz, 1H), 7.53 – 7.37 (m, 3H), 7.37 – 7.28 (m, 2H), 7.28 – 7.16 (m, 2H), 7.16 – 7.03 (m, 3H), 6.54 (dt, J = 16.2, 1.7 Hz, 1H), 6.30 (dt, J = 16.2, 5.2 Hz, 1H), 5.17 – 5.00 (m, 2H), 3.78 (s, 2H). 13 C NMR (151 MHz, DMSO) δ 162.36, 160.74, 158.82, 153.76, 145.76, 142.62, 141.97, 132.58,130.63, 130.07, 128.27, 128.17, HRMS (ESI): Extract mass calculated for C 25 H 19 F3N2O2[M + H] + Found: 437.1478; Found: 437.1466.

[0164] (E)-3-benzyl-1-(3-(4-methoxyphenyl)allyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (20l):

[0165] Yellow soil, (yield: 50.6%), mp: 168-169 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.54 – 8.94 (m, 1H), 8.23 ​​(ddd, J = 8.9, 7.0, 1.7 Hz, 1H), 7.78 (dt, J = 9.1, 0.9 Hz, 1H), 7.46 (td, J = 6.9, 1.1 Hz, 1H), 7.32 (td,J = 7.5, 6.9, 1.7 Hz, 4H),7.19 (t, J = 7.7 Hz, 2H), 7.09 (td, J = 7.2, 1.3 Hz, 1H), 6.87 – 6.72 (m, 2H), 6.50 (d, J = 1.6 Hz, 1H), 6.17 (d, J = 16.1 Hz, 1H), 5.11 – 4.96 (m, 2H), 3.75(d, J = 41.7 Hz, 5H). 13 C NMR (151 MHz, DMSO) δ 159.42, 159.40, 154.30, 146.29,143.14, 142.56, 131.67, 131.19, 129.17, 128.84, 128.25, 128.07, 125.74,121.45, 116.46, 114.94, 114.43, 93.09, 55.56, 44.15, 30.97. HRMS (ESI):Extract mass calculated for C 25 H 22 N₂O₃[M + H] + Found: 399.1709; Found: 399.1725.

[0166] (E)-3-benzyl-1-(2-methyl-3-phenylallyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onyl-2-ol (21l):

[0167] Yellow soil, (yield: 34.2%), mp: 123-124 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.25 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 8.25 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H),7.69 (dt, J = 9.0, 0.9 Hz, 1H), 7.49 (td, J = 7.0, 1.1 Hz, 1H), 7.35 – 7.27 (m,4H), 7.19 (td,J = 7.7, 1.9 Hz, 5H), 7.11 – 7.06 (m, 1H), 6.16 (d, J = 2.0 Hz,1H), 5.00 (s, 2H), 3.80 (s, 2H), 1.87 (d, J = 1.3 Hz, 3H). 13 C NMR (151 MHz, DMSO) δ 159.58, 154.29, 146.52, 143.21, 142.57, 137.10, 132.64, 131.25,129.17, 128.76, 128.59, 128.25, 126.99, 125.74, 124.69, 116.63, 115.06,92.91, 48.74, 30.97, 16.09. HRMS (ESI): Extract mass calculated for C 25 H 22 N₂O₂[M + H] + Found: 383.1760; Found: 383.1773.

[0168] (E)-3-Benzyl-1-(2-Benzyleneethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onthiol (22l):

[0169] Yellow soil, (yield: 30.7%), mp: 146-147 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.26 (dd, J = 6.9, 1.6 Hz, 1H), 8.27 (ddd, J = 8.8, 6.9, 1.7 Hz, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.49 (t, J = 6.9 Hz, 1H), 7.37 – 7.26 (m, 4H), 7.26 – 7.03 (m,6H), 6.16 (s, 1H), 5.05 (s, 2H), 3.80 (s, 2H), 2.27 – 2.12 (m, 2H), 1.51 (dd, J = 9.8, 5.6 Hz, 2H), 1.23 (d, J= 4.1 Hz, 4H), 0.82 (q, J = 3.7, 2.9 Hz, 3H). 13 CNMR (151 MHz, DMSO) δ 159.52, 154.24, 146.51, 143.21, 142.57, 137.06, 136.87,131.29, 128.81, 128.75, 128.68, 128.22, 127.10, 126.65, 125.73, 125.23,124.66, 116.62, 115.06, 112.03, 92.94, 47.36, 31.84, 30.98, 29.43, 27.76,22.15, 14.27. HRMS (ESI): Extract mass calculated for C 29 H 30 N₂O₂[M + H] + :439.2386; Found: 439.2366.

[0170] (E)-3-benzyl-1-(2-benzylethyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onthiol (23l):

[0171] Yellow soil, (yield: 30.2%), mp: 118-119 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.25 (dd, J = 6.9, 1.6 Hz, 1H), 8.27 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H), 7.64 (dd, J = 9.0, 1.1 Hz, 1H), 7.49 (td, J = 7.0, 1.1 Hz, 1H), 7.34 – 7.28 (m, 4H), 7.22– 7.16 (m, 3H), 7.14 (dd, J= 7.8, 1.2 Hz, 2H), 7.11 – 7.07 (m, 1H), 6.16 (s,1H), 5.05 (s, 2H), 3.80 (s, 2H), 2.35 – 2.01 (m, 2H), 1.68 – 1.42 (m, 2H),1.35 – 1.02 (m, 7H), 0.82 (t, J = 7.0 Hz, 3H). 13 C NMR (151 MHz, DMSO) δ 159.52,154.23, 146.50, 143.21, 142.57, 137.07, 136.87, 131.28, 128.81, 128.75,128.67, 128.22, 127.10, 125.74, 125.24, 116.62, 115.06, 92.94, 47.36, 31.28,30.97, 29.44, 29.25, 28.02, 22.43, 14.34. HRMS (ESI): Extract mass calculated for C 30 H 32 N₂O₂[M + H] + Found: 453.2543; Found: 453.2549.

[0172] (Z)-3-benzyl-1-(2-bromo-3-phenylallyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onyl-2-ol (24l):

[0173] Yellow soil, (yield: 40.2%), mp: 136-137 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.29 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 8.31 (ddd, J = 8.9, 7.1, 1.7 Hz, 1H),7.77 (dt, J = 9.0, 0.9 Hz, 1H), 7.63 – 7.45 (m, 3H), 7.45 – 7.26 (m, 5H), 7.19(t, J = 7.6 Hz, 2H), 7.12 (s, 2H), 5.38 (d, J= 25.5 Hz, 2H), 3.80 (s, 2H). 13 C NMR(151 MHz, DMSO) δ 159.21, 154.26, 146.46, 143.67, 142.44, 135.11, 131.52,130.05, 129.82, 129.54, 129.26, 128.79, 128.69, 128.63, 128.26, 128.12,128.01, 125.76, 119.51, 117.06, 114.87, 92.67, 49.94, 30.96. HRMS (ESI):Extract mass calculated for C 24 H 19 BrN2O2[M + H] + Found: 447.0709; Found: 447.0737.

[0174] 3-Benzyl-1-cinnamyl-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-on-2-ol (25l):

[0175] Yellow soil, (yield: 27.2%), mp: 165-166 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.26 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 7.69 (dt, J = 9.0, 0.9 Hz, 1H), 7.49 (td, J = 7.0, 1.1 Hz, 1H), 7.35 – 7.27 (m, 4H), 7.19 (td, J = 7.7, 1.9 Hz, 5H), 7.11– 7.06 (m, 1H), 6.40 (d, J = 2.0 Hz, 1H), 6.10 (d, J = 2.0 Hz, 1H), 5.10 (s, 2H), 3.73 (s, 2H), 1.77 (d, J = 1.3 Hz, 3H). 13C NMR (151 MHz, DMSO) δ 159.88, 154.26,146.52, 143.21, 142.57, 137.20, 132.64, 131.25, 129.19, 129.06, 128.86,128.84, 128.82, 128.42, 128.25, 127.62, 126.99, 125.54, 124.99, 116.53,115.16, 92.61, 49.04, 31.07, 16.39. Extract mass calculated for C 25 H 22 N₂O₂[M + H] + Found: 383.1681; Found: 383.1698.

[0176] 1-Cinnamyl-4-oxo-3-(3-(trifluoromethyl)benzyl)-4H-pyrido[1,2-a]pyrimidine-1-onthiol (26l):

[0177] Yellow soil, (yield: 58.7%), mp: 169-170 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.34 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.32 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H),8.19 (m, 1H), 8.15 – 8.09 (m, 1H), 7.85 (dt, J = 9.1, 0.9 Hz, 1H), 7.59 – 7.46(m, 3H), 7.44 – 7.38 (m, 2H), 7.33 – 7.26 (m, 2H), 7.26 – 7.19 (m, 1H), 6.74– 6.53 (m, 1H), 6.40 (dt, J = 16.1, 5.2 Hz, 1H), 5.23 – 5.03 (m, 2H). 13C NMR(151 MHz, DMSO) δ 158.70, 154.00, 146.68, 144.16, 137.20, 136.61, 134.70,131.95, 131.60, 129.01, 128.39, 128.29, 128.18, 127.17, 126.79, 126.04,124.24, 123.93, 122.01, 116.82, 115.13, 99.99, 92.63, 44.33. HRMS (ESI):Extract mass calculated for C 25 H 19 F3N2O2[M-CH] + Found: 423.1321; Found: 423.1338.

[0178] (E)-1-(3-(4-chlorophenyl)allyl)-4-oxo-3-(3-(trifluoromethyl)phenyl)-4H-pyrido[1,2-a]pyrimidine-1-onthiol (27l):

[0179] Yellow soil, (yield: 46.8%), mp: 161-162 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.34 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.32 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H),8.18 (dd, J = 2.3, 1.3 Hz, 1H), 8.12 (dq, J = 7.7, 1.0 Hz, 1H), 7.83 (dt, J = 9.0,0.9 Hz, 1H), 7.58 – 7.51 (m, 2H), 7.52 – 7.47 (m, 1H), 7.46 – 7.41 (m, 2H),7.38 – 7.33 (m, 2H), 6.65 – 6.59 (m, 1H), 6.47 – 6.40 (m, 1H). 13C NMR (151MHz, DMSO) δ 158.67, 154.01, 146.68, 144.19, 137.18, 135.61, 134.69, 132.52,131.59, 130.46, 128.99, 128.51, 128.38, 128.30, 128.17, 127.16, 126.04,125.03, 124.24, 122.01, 116.84, 115.14, 92.62, 44.26. HRMS (ESI): Extractmass calculated for C 24 H 16 ClF3N2O2[M + H] + Found: 457.0867; Found: 457.0899.

[0180] (E)-1-(3-(4-bromophenyl)allyl)-4-oxo-3-(3-(trifluoromethyl)phenyl)-4H-pyrido[1,2-a]pyrimidine-1-onthiol (28l):

[0181] Yellow soil, (yield: 54.6%), mp: 166-167 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.34 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 8.32 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H),8.18 (q, J = 1.8, 1.4 Hz, 1H), 8.12 (dt, J = 7.9, 1.4 Hz, 1H), 7.83 (dt, J = 9.0,0.9 Hz, 1H), 7.59 – 7.45 (m, 5H), 7.41 – 7.33 (m, 2H), 6.60 (dt, J = 16.1, 1.7Hz, 1H), 6.45 (dt, J = 16.2, 5.1 Hz, 1H), 5.18 – 5.01 (m, 2H). 13C NMR (151 MHz, DMSO) δ 158.67, 154.01, 146.68, 144.18, 137.17, 135.96, 134.69, 131.90,131.60, 130.53, 128.83, 128.38, 128.30, 128.18, 127.13, 126.04, 125.13,124.23, 121.99, 121.10, 116.84, 115.13, 92.62, 44.27. Extract mass calculated for C 24 H 16 BrF3N2O2[M + H] + Found: 501.0426; Found: 501.0420.

[0182] (E)-1-(3-(4-fluorophenyl)allyl)-4-oxo-3-(3-(trifluoromethyl)phenyl)-4H-pyrido[1,2-a]pyrimidine-1-onthiol (29l):

[0183] Yellow soil, (yield: 47.5%), mp: 154-155 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.34 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.32 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H),8.18 (h, J = 0.9 Hz, 1H), 8.12 (dt, J = 7.9, 1.2 Hz, 1H), 7.84 (dt, J = 9.0, 0.9Hz, 1H), 7.59 – 7.36 (m, 5H), 7.19 – 7.05 (m, 2H), 6.63 (dt, J = 16.2, 1.7 Hz, 1H), 6.35 (dt, J = 16.2, 5.2 Hz, 1H), 5.11 (d, J = 5.8 Hz, 2H). 13C NMR (151 MHz, DMSO) δ 161.31, 158.68, 154.00, 146.68, 144.17, 137.19, 134.69, 133.23,131.59, 130.69, 128.75, 128.70, HRMS (ESI): Extractmass calculated for C 24 H 16 F4N2O2[M + H] + Found: 441.1227; Found: 441.1222.

[0184] (E)-4-oxo-3-(3-(trifluoromethyl)phenyl)-1-(3-(3-(trifluoromethyl)phenyl)allyl)-4H-pyrido[1,2-a]pyrimidine-1-onthiol (30l):

[0185] Yellow soil, (yield: 43.5%), mp: 149-150 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.34 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.32 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H),8.29 – 8.07 (m, 2H), 7.83 (dt, J = 9.0, 0.9 Hz, 1H), 7.58 – 7.46 (m, 3H), 7.45– 7.39 (m, 2H), 7.37 – 7.33 (m, 2H), 6.69 – 6.24 (m, 2H), 5.12 (d, J = 5.1 Hz, 2H). 13C NMR (151 MHz, DMSO) δ 158.67, 154.04, 146.72, 144.20, 137.86, 137.20,134.68, 131.57, 130.42, 130.06, 129.89, 129.81, 128.39, 128.29, 126.50,126.04, 124.44, 124.24, 123.44, 123.41, 121.99, 116.86, 115.20, 92.62, 44.21.HRMS (ESI): Extract mass calculated for C 25 H 16 F6N2O2[M + H] + Found: 491.1195; Found: 491.1174.

[0186] (E)-1-(3-(4-methoxyphenyl)allyl)-4-oxo-3-(3-(trifluoromethyl)phenyl)-4H-pyrido[1,2-a]pyrimidine-1-onyl-2-ol (31l):

[0187] Yellow soil, (yield: 49.4%), mp: 180-181 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.33 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.32 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H),8.18 (ddt, J = 1.9, 1.3, 0.7 Hz, 1H), 8.15 – 8.08 (m, 1H), 7.86 (dt, J = 9.1, 1.0Hz, 1H), 7.59 – 7.45 (m, 3H), 7.38 – 7.29 (m, 2H), 6.91 – 6.81 (m, 2H), 6.64– 6.53 (m, 1H), 6.22 (dt, J = 16.1, 5.5 Hz, 1H), 5.10 (d, J = 5.4 Hz, 2H), 3.73 (s, 3H). 13C NMR (151 MHz, DMSO) δ 159.44, 158.70, 158.70, 157.57, 153.98,146.66, 144.13, 137.20, 134.70, 131.75, 131.59, 129.24, HRMS (ESI): Extract mass calculated for C 25 H 19 F3N2O3[M + H] + Found: 453.1427; Found: 453.1425.

[0188] (Z)-1-(2-bromo-3-phenylallyl)-4-oxo-3-(3-(trifluoromethyl)phenyl)-4H-pyrido[1,2-a]pyrimidine-1-onyl-2-ol (32l):

[0189] Yellow soil, (yield: 27.3%), mp: 169-170 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.38 (ddd, J = 6.8, 1.7, 0.6 Hz, 1H), 8.39 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H),8.18 (d, J = 1.8 Hz, 1H), 8.13 (dd, J = 7.9, 1.4 Hz, 1H), 7.81 (dt, J = 9.0, 0.8Hz, 1H), 7.63 – 7.48 (m, 5H), 7.40 – 7.29 (m, 3H), 7.20 (s, 1H), 5.42 (d, J =37.0 Hz, 2H). 13C NMR (151 MHz, DMSO) δ 158.52, 153.97, 146.77, 144.67, 137.06,135.16, 134.68, 131.90, 129.29, 129.12, 128.69, 128.63, 128.61, 128.42,128.35, 128.34, 128.21, 127.11, 122.09, 119.19, 117.40, 115.04, 92.36, 50.22.HRMS (ESI): Extract mass calculated for C 24 H 16 BrF3N2O3[M + H] + : 501.0426; Found: 501.0394.

[0190] 1-Cinnamyl-9-methyl-4-oxo-3-(3-(trifluoromethyl)phenyl)-4H-pyrido[1,2-a]pyrimidine-1-onyl-2-ol (33l):

[0191] Yellow soil, (yield: 35.4%), mp: 172-173 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.33 (dd, J = 6.9, 1.6 Hz, 1H), 7.77 – 7.63 (m, 3H), 7.52 (t, J = 7.0 Hz, 1H), 7.31 (td, J = 7.7, 3.9 Hz, 3H), 7.25 – 7.14 (m, 4H), 6.52 (s, 1H), 6.25 (s,1H), 5.33 (s, 2H), 1.91 (s, 3H). 13C NMR (151 MHz, DMSO) δ 157.84, 153.88,146.76, 143.73, 137.19, 135.99, 135.99, 135.44, 132.57, 132.01, 131.53,131.25, 130.10, HRMS (ESI): Extract masscalculated for C 25 H 19 F3N2O2[M + H] + Found: 437.1478; Found: 437.1499.

[0192] 1-Cinnamyl-3-(3,5-dichlorophenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onthiol (34l):

[0193] Yellow soil, (yield: 40.2%), mp: 165-166 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.32 (dd, J = 6.9, 0.6 Hz, 1H), 8.29 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H), 7.83 (dt, J = 9.1, 1.0 Hz, 1H), 7.78 – 7.62 (m, 1H), 7.44 – 7.37 (m, 2H), 7.34 – 7.27(m, 4H), 7.19 – 7.13 (m, 2H), 6.66 – 6.57 (m, 1H), 6.39 (dt, J = 16.1, 5.3 Hz, 1H), 5.12 (d, J = 5.3 Hz, 2H). 13C NMR (151 MHz, DMSO) δ 157.67, 154.78, 146.52,143.69, 136.60, 135.66, 133.36, 132.90, 131.94, 131.50, 131.23, 130.49,129.95, 129.01, 128.17, 127.35, 126.28, 125.29, 124.08, 116.59, 114.96,94.00, 44.02. HRMS (ESI): Extract mass calculated for C 23 H 16 Cl2N2O2[M + H] + :423.0669; Found: 423.0673.

[0194] (E)-1-(3-(4-chlorophenyl)allyl)-3-(3,5-dichlorophenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onyl-2-ol (35l):

[0195] Yellow soil, (yield: 51.3%), mp: 164-165℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.22 (dd, J = 6.9, 1.6 Hz, 1H), 8.18 (ddd, J = 8.7, 7.0, 1.7 Hz, 1H), 7.89 –7.75 (m, 1H), 7.74 – 7.67 (m, 2H), 7.50 (td, J = 7.0, 1.1 Hz, 1H), 7.37 – 7.27(m, 4H), 7.17 – 7.11 (m, 1H), 6.63 – 6.53 (m, 1H), 6.49 – 6.38 (m, 1H), 5.11(d, J = 5.1 Hz, 2H). 13C NMR (151 MHz, DMSO) δ 158.86, 153.99, 148.37, 146.53,142.73, 137.38, 135.94, 135.84, 135.64, 132.62, 131.53, 131.22, 130.48,128.89, 128.50, 127.35, 125.72, 125.19, 116.62, 114.92, 112.25, 93.93, 44.66.HRMS (ESI): Extract mass calculated for C 23 H 15 Cl3N2O2[M + H] + : 457.0278; Found: 457.0267.

[0196] (E)-1-(3-(4-bromophenyl)allyl)-3-(3,5-dichlorophenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-1-onthiol (36l).

[0197] Yellow soil, (yield: 48.9%), mp: 184-185 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.32 (dd, J = 6.9, 1.6 Hz, 1H), 8.28 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.73 – 7.66 (m, 2H), 7.53 – 7.45 (m, 2H), 7.40 – 7.34 (m, 2H),7.30 (t, J = 7.8 Hz, 1H), 7.16 (tt, J = 7.2, 1.3 Hz, 1H), 6.64 – 6.55 (m, 1H), 6.53 – 6.38 (m, 1H), 5.10 (d, J = 5.1 Hz, 2H). 13C NMR (151 MHz, DMSO) δ 158.65,153.79, 146.54, 143.71, 135.97, 135.95, 133.10, 131.90, 131.50, 131.22,130.52, 129.75, 128.83, 127.34, 125.69, 125.30, 124.61, 121.08, 118.26,116.62, 114.99, 93.97, 44.76. HRMS (ESI): Extract mass calculated forC 23 H 15 Br2Cl2N2O2[M + H] + Found: 500.9773; Found: 500.9765.

[0198] (E)-3-(3,5-dichlorophenyl)-1-(3-(4-fluorophenyl)allyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onthiol (37l):

[0199] Yellow soil, (yield: 46.7%), mp: 186-187 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.32 (ddd, J = 6.9, 1.7, 0.6 Hz, 1H), 8.29 (ddd, J = 8.9, 7.0, 1.7 Hz, 1H),7.81 (dt, J = 9.1, 1.0 Hz, 1H), 7.76 – 7.67 (m, 2H), 7.55 (dt, J = 15.7, 5.2 Hz,1H), 7.41 – 7.22 (m, 2H), 7.19 – 7.05 (m, 3H), 6.69 – 6.51 (m, 1H), 6.35 (dt, J = 16.0, 5.2 Hz, 1H), 5.10 (d, J = 5.2 Hz, 2H). 13C NMR (151 MHz, DMSO) δ 158.67,154.01, 146.68, 144.19, 137.18, 135.61, 134.69, 133.25, 132.52, 131.59,130.46, 129.78, 128.99, 128.51, 128.30, 127.16, 126.04, 125.03, 122.01,116.84, 115.14, 92.62, 44.26. HRMS (ESI): Extract mass calculated forC 23 H 15 FCl2N2O2[M + H] + Found: 441.0571; Found: 441.0566.

[0200] (E)-3-(3,5-dichlorophenyl)-4-oxo-1-(3-(3-(trifluoromethyl)phenyl)allyl)-4H-pyrido[1,2-a]pyrimidine-1-onthiol (38l):

[0201] Yellow soil, (yield: 41.1%), mp: 188-189 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.34 (dd, J = 6.9, 1.6 Hz, 1H), 8.29 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H), 7.89 –7.61 (m, 4H), 7.60 – 7.42 (m, 3H), 7.31 (t, J = 7.7 Hz, 1H), 7.22 – 7.07 (m,1H), 6.69 – 6.67 (m, 1H), 6.61 – 6.59 (m, 1H), 5.21 – 5.09 (m, 2H). 13C NMR(151 MHz, DMSO) δ 158.85, 153.85, 146.58, 143.31, 137.87, 135.94, 131.47,131.43, 130.42, 130.05, 129.88, 127.24, 126.77, 125.67, 124.46, 123.72,123.43, 123.34, 116.22, 115.99, 115.55, 93.99, 43.91. HRMS (ESI): Extractmass calculated for C 24 H 15 Cl2F3N2O2[M + H] + Found: 491.0542; Found: 491.0562.

[0202] (E)-3-(3,5-dichlorophenyl)-1-(3-(4-methoxyphenyl)allyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onyl-2-ol (39l):

[0203] Yellow soil, (yield: 35.4%), mp: 187-188 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.31 (dd, J = 6.9, 1.6 Hz, 1H), 8.29 (ddd, J = 8.8, 7.0, 1.7 Hz, 1H), 7.83 (d, J = 9.0 Hz, 1H), 7.76 – 7.61 (m, 2H), 7.50 (td, J = 6.9, 1.0 Hz, 1H), 7.37 – 7.29(m, 4H), 7.26 – 7.08 (m, 1H), 6.97 – 6.76 (m, 2H), 6.58 (dd, J = 16.2, 1.6 Hz, 1H), 6.22 (dt, J = 16.1, 5.4 Hz, 1H), 5.08 (d, J = 5.4 Hz, 2H), 3.73 (s, 3H). 13CNMR (151 MHz, DMSO) δ 159.42, 158.67, 153.76, 146.49, 143.65, 135.98, 134.12,131.73, 131.48, 131.23, 129.23, 128.08, 127.34, 125.68, 124.03, 121.43,118.69, 116.56, 114.97, 114.44, 112.90, 94.01, 55.57, 44.28. HRMS (ESI):Extract mass calculated for C 24 H 18 Cl2N2O3[M + H] + Found: 453.0773; Found: 453.0769.

[0204] 1-Cinnamyl-3-(3,5-dichlorophenyl)-9-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-1-onthiol (40l):

[0205] Yellow soil, (yield: 34.4%), mp: 171-172 ℃; 1 H NMR (600 MHz, DMSO- d 6)δ 9.32 (s, J = 6.9, 1.7 Hz, 1H), 7.77 – 7.63 (m, 3H), 7.52 (t, J = 7.0 Hz, 1H), 7.31 (td, J = 7.7, 3.9 Hz, 2H), 7.25 – 7.14 (m, 4H), 6.36 (s, 1H), 6.26 (s, 1H), 5.03 (s, 2H), 1.90 (s, 3H). 13C NMR (151 MHz, DMSO) δ 158.63, 154.63, 146.33,143.29, 135.97, 133.28, 131.49, 131.22, 130.68, 128.79, 128.69, 127.64,125.68, 125.64, 124.01, 124.00, 121.16, 116.61, 115.90, 115.56, 114.94,93.95, 44.16, 31.66. HRMS (ESI): Extract mass calculated for C 24 H 18 Cl2N2O2[M +H] + Found: 437.0824;

[0206] Experimental Example 1: Determination of the bioactivity of pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl groups against houseflies.

[0207] 1. Experimental Objective

[0208] The toxic activity of compounds 1l-40l prepared in this invention against houseflies was determined.

[0209] 2. Test methods

[0210] The toxic activity of a compound against houseflies was determined using the feed-mixing poison method. The prepared stock solution of the test compound was diluted to a suitable concentration with acetone. 1 g of granulated sugar was weighed and placed in a glass tube with a diameter of 2 cm and a length of 5 cm. 1 mL of the prepared test compound solution was added to the glass tube, ensuring the liquid covered the sugar. After the acetone in the glass tube had evaporated, houseflies were stunned with ether and then placed inside the glass tube. The opening of the glass tube was sealed with gauze. Each experiment was repeated three times, with 10 houseflies per replicate. The average of the three results was taken. The glass tube was then placed in an artificial climate chamber with a temperature of (25 ± 1)℃, a relative humidity of 60%–75%, and a photoperiod of L:D = 14 h:10 h. Housefly mortality was investigated after 24 hours. Acetone was set as a blank control group. Mortality rate and corrected mortality rate were calculated. Based on these results, a series of compound concentration gradients (5 concentrations) prepared according to the embodiments of this invention were selected and tested in the same manner. Mortality rate and corrected mortality rate were calculated, and the correlation coefficient and median lethal concentration (LC50) were calculated using the logarithm of the drug concentration and the probability value of the corrected mortality rate. 50 The cinnamaldehyde treatment group was set as the negative control group, and the imidacloprid treatment group was set as the positive control group.

[0211] 3. Test Results

[0212] The results of the compound activity against houseflies are shown in Table 1. At a concentration of 20 µg / mL, most of the compounds 1-40L showed toxic effects on houseflies. Among them, compounds 26L, 27L, 30L, 34L, 35L, and 38L resulted in a mortality rate of 50% or higher in houseflies. In particular, compounds 26L, 30L, 34L, 35L, and 38L resulted in a mortality rate of 100% in houseflies.

[0213] Further determination of the compound's LC50 for houseflies 50 The values ​​and results are shown in Table 2, for compounds 26l, 27l, 30l, 34l, and 35l. 50 The values ​​were 3.255 μg / mL, 2.488 μg / mL, 1.512 μg / mL, and 1.828 μg / mL, respectively, all significantly lower than the LC50 of imidacloprid. 50 The values ​​show that compounds 26l, 27l, 30l, 34l, and 35l have very good insecticidal activity against houseflies, even better than imidacloprid.

[0214] Table 1. Activity results of the compounds against houseflies (20 µg / mL)

[0215]

[0216] Note: Data in the same column with the same letter after it indicates no significant difference (5%).

[0217] Table 2. Results of toxicity assays of the compounds against houseflies.

[0218]

[0219] Experimental Example 2: Determination of the bioactivity of pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl groups against Aedes albopictus mosquitoes.

[0220] 1. Experimental Objective

[0221] The toxic activity of compound 1I-40I prepared in this invention against Aedes albopictus larvae was determined.

[0222] 2. Test methods

[0223] The toxic activity of the compound against Aedes albopictus larvae was determined using the immersion method. 1 mL of the prepared stock solution of the test compound was added to disposable plastic cups, followed by 99 mL of overnight tap water. Ten 3rd instar larvae of uniform size were screened using a mesh screen and placed in the cups. The cups were then placed in a rearing room at 25 °C and 60%–70% relative humidity. Each experiment was repeated three times, with 10 larvae per replicate. The average of the three results was taken. After 24 hours, the number of dead larvae was counted. Acetone was used as a blank control group. The mortality rate and corrected mortality rate were calculated. Based on these results, a series of concentration gradients (5 concentrations) of the compound prepared in this embodiment were selected and tested using the same method. The mortality rate and corrected mortality rate were calculated, and the correlation coefficient and median lethal concentration (LC50) were calculated using the logarithm of the drug concentration and the probability value of the corrected mortality rate. 50 Acetone-treated feed was set as the blank control group, cinnamaldehyde-treated feed as the negative control group, and imidacloprid-treated feed as the positive control group.

[0224] 3. Test Results

[0225] The activity results of the compounds against Aedes albopictus larvae are shown in Table 3. Compounds 1-40L all showed toxic effects on Aedes albopictus larvae at a concentration of 5 µg / mL. Among them, compounds 15L, 17L, 18L, 24L, 26L, 27L, 28L, 29L, 30L, 32L, 34L, 35L, 36L, and 38L resulted in a mortality rate of over 50% for Aedes albopictus larvae. In particular, compounds 15L, 26L, 28L, 29L, 34L, 35L, and 38L resulted in a mortality rate of 100% for Aedes albopictus larvae.

[0226] Further determination of the LC50 of the compound against Aedes albopictus larvae 50 The values ​​and results are shown in Table 4, for compounds 26l, 28l, 29l, 34l, and 35l. 50 The values ​​were 0.447 μg / mL, 1.622 μg / mL, 1.103 μg / mL, 0.524 μg / mL, and 0.745 μg / mL, respectively, all significantly lower than the LC50 of imidacloprid. 50 The values ​​show that compounds 26l, 28l, 29l, 34l, and 35l have very good biological activity against Aedes albopictus larvae, even better than imidacloprid.

[0227] Table 3 shows the activity results of the compounds against Aedes albopictus larvae (5 µg / mL).

[0228]

[0229] Note: Data in the same column with the same letter after it indicates no significant difference (5%).

[0230] Table 4. Results of toxicity assays of the compounds against Aedes albopictus larvae.

[0231]

[0232] Experimental Example 3: Determination of the bioactivity of pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl groups against German cockroaches.

[0233] 1. Experimental Objective

[0234] The toxic activity of compound 1I-40I prepared in this invention against German cockroaches was determined.

[0235] 2. Test methods

[0236] The toxic activity of the compound against German cockroaches was determined using the drop method. The compound was diluted with acetone to prepare a 1 mg / mL test solution. After stunning the test insects with carbon dioxide, they were laid flat on filter paper. Using a microsyringe, 1 μL of the test solution was dropped onto the thoracic plate. After the acetone had completely evaporated, the test insects were placed in a clean 250 mL Erlenmeyer flask, and the flask opening was sealed with gauze. After 24 hours of normal rearing, the mortality rate of the German cockroaches was recorded. Each experiment was conducted in triplicate, with 10 German cockroaches per replicate. The average of the three results was taken. Acetone was used as a blank control. The mortality rate and corrected mortality rate were calculated. Based on these results, a series of concentration gradients (5 concentrations) of the compound prepared in the embodiments of this invention were selected, and the same method was used to determine the mortality rate and corrected mortality rate. The correlation coefficient and median lethal concentration (LD50) were calculated by comparing the logarithm of the drug concentration with the probability value of the corrected mortality rate. 50 .

[0237] 3. Test Results

[0238] The activity results of the compounds against German cockroaches are shown in Table 5. Compound 1I-40I showed toxicity to German cockroaches at a concentration of 1 µg / head. Among them, the mortality rate of German cockroaches after treatment with compounds 15l, 17l, 26l, 28l, 30l, 34l, 35l and 38l was higher than 50%, especially after treatment with compounds 26l, 34l and 35l, the mortality rate of German cockroaches reached 100%.

[0239] Further determination of the LD50 of the compound against German cockroaches 50 The values ​​are shown in Table 6. The LD values ​​of compound 26l are... 50 The value was 0.242 μg / head, which is similar to the LD50 of imidacloprid. 50 Similar values; LD values ​​of 34L and 35L 50 The values ​​were 0.142 μg / head and 0.171 μg / head, respectively, both significantly lower than the LD50 of imidacloprid. 50The values ​​show that compounds 34l and 35l have very good insecticidal activity against German cockroaches, even better than imidacloprid.

[0240] Table 5 shows the activity results of the compounds against the German cockroach (1 μg / cockroach).

[0241]

[0242] Note: Data in the same column with the same letter after it indicates no significant difference (5%).

[0243] Table 6. Results of toxicity assays of compounds against German cockroaches.

[0244]

[0245] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A pyrido[1,2-a]pyrimidinone derivative containing a β-phenylpropenyl group, characterized in that, The pyrido[1,2-a]pyrimidinone derivatives containing β-phenylpropenyl groups have any one of the structures shown in 12l, 15l, 17l, 18l, 24l, 26l, 27l, 28l, 29l, 30l, 32l, 34l, 35l, 36l, and 38l; The molecular structures of 12l, 15l, 17l, 18l, 24l, and 26l are shown in formula (Ⅰ): The R1~R4 corresponding to the 12l, 15l, 17l, 18l, 24l, and 26l structures are shown in the table below: The molecular structures of 27l, 28l, 29l, 30l, 32l, 34l, 35l, 36l, and 38l are shown in formula (Ⅰ'): ； The R2~R5 values ​​corresponding to the structures 27l, 28l, 29l, 30l, 32l, 34l, 35l, 36l, and 38l are shown in the table below: 。 2. The method for preparing the pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl group according to claim 1, characterized in that, Compounds h and c were dissolved in toluene or xylene and reacted completely at 100–110 °C. After post-treatment, the target compound l was obtained. ； The definitions of R1 to R4 are consistent with those in the corresponding structures of 12l, 15l, 17l, 18l, 24l, 26l, 27l, 28l, 29l, 30l, 32l, 34l, 35l, 36l, and 38l.

3. The method for preparing the pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl group according to claim 2, characterized in that, The reaction takes 3 to 6 hours to complete.

4. The method for preparing the pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl group according to claim 2, characterized in that, The molar mass ratio of compound h to compound c is 1 to 3:

1.

5. The use of the β-phenylpropenyl pyrido[1,2-a]pyrimidinone derivative of claim 1 in the preparation of insecticides.

6. The application according to claim 5, characterized in that, The insecticide kills pests including Aedes albopictus, German cockroaches, or houseflies.

7. An insecticide, characterized in that, It comprises the pyrido[1,2-a]pyrimidinone derivative containing β-phenylpropenyl group as described in claim 1, or a pharmaceutically acceptable salt thereof.

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