A C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative and its synthesis method

Abstract

The present invention discloses a C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative and a synthesis method thereof, belonging to the field of organic photocatalytic synthesis technology. In view of the problems that the current preparation of C3 fluoroalkylated pyrido 4H-[1,2-a]pyrimidin-4-one derivatives has a narrow substrate range, low product yield, and the use of toxic solvents is unfriendly to the environment, graphite phase carbon nitride (g-C3N4) is used as a photocatalyst. Under room temperature and air conditions, blue light LED irradiation, 4H-pyrido[1,2-a]pyrimidin-4-one compound and sodium fluoroalkylsulfinate are reacted in dimethyl carbonate solvent for 24 hours to prepare C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivatives. Visible light-induced catalytic C-H bond functionalization reaction of heterocyclic compounds is a mild, environmentally friendly and sustainable synthetic strategy. Graphitic carbon nitride (g‑C3N4) is an inorganic non-metallic polymer semiconductor material that responds to visible light and has the advantages of simple preparation, low price, high chemical and thermal stability, and green environmental protection.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic photocatalytic synthesis, and particularly relates to a C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative and a synthesis method thereof. Background Art

[0002] 4H-pyrido[1,2-a]pyrimidin-4-one derivatives are important heterocyclic backbones for many drug molecules. C3-substituted 4H-pyrido[1,2-a]pyrimidin-4-one derivatives exhibit diverse biological activities, including as inhibitors of endothelial cell dysfunction and smooth muscle cell activators, regulators of platelet activation and aggregation, anti-inflammatory and anti-tuberculosis agents, anti-allergic agents, efflux pump inhibitors, and acetylcholinesterase and antipsychotic drugs. At present, the functionalization of the C3 position of 4H-pyrido[1,2-a]pyrimidin-4-one mainly includes: palladium acetate-catalyzed C3 aromatic substitution (RSCAdv.2015,5,36171–36174; J.Org.Chem.2015,80,8482–8488); silver nitrate-catalyzed C3 dialkyl phosphite substitution (AsianJ.Org.Chem.2021,10,1660–1664); oxidant (I2, PIFA, K2S2O8)-catalyzed C3 aromatic sulfide (selenium) substitution, etc. (AsianJ.Org.Chem.2021,10,2911–2915; Synlett 2018,29,116–120; RSC Adv. 2021, 11, 10258–10263; Adv. Synth. Catal. 2021, 363, 2148–2156); photosensitizer-promoted photocatalytic C3 aryl substitution (The Journal of Organic Chemistry, 2023, 88, 13: 9537–9542). However, the above-mentioned C3 functionalization methods have the following disadvantages: harsh reaction conditions, the need to add noble metal catalysts, strong oxidants, and the addition of photosensitizers that cause environmental pollution.

[0003] trifluoromethyl (-CF3), difluoromethyl (-CF2H), perfluoroalkyl (C3F7, C6F 13 、C8F 17) and other groups have strong electron-withdrawing properties, lipophilicity, and stable CF bonds. Introducing them into organic heterocyclic molecules can greatly improve the pharmaceutical properties of the compounds and significantly change the solubility, metabolic stability, and bioavailability of the compounds. In 2023, Liu Shaohua's research group at Guangdong Pharmaceutical University used electrochemical oxidation to synthesize C3-halogenated or trifluoromethane-substituted pyrido-4H-[1,2-a]pyrimidin-4-one derivatives. However, this method has the disadvantages of using toxic acetone as an organic solvent and a narrow substrate range of fluoroalkylation reagents (European Journal of Organic Chemistry, 2023, 26(29), e202300268). Summary of the Invention

[0004] In response to the current problems in the preparation of C3 fluoroalkylated pyrido 4H-[1,2-a]pyrimidin-4-one derivatives, such as narrow substrate range, low yield, and environmentally unfriendly use of toxic solvents, the present invention provides a C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative and a photocatalytic synthesis method thereof.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] A C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative, wherein the structure (I) of the C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative is as follows:

[0007]

[0008] R 1 =H, 6-methyl, 7-methyl, 8-methyl, 7-fluoro, 7-chloro, 7-bromo, 7-ester, 7-CF3; R 2 = methyl, ethyl, phenyl, p-chlorophenyl; R f =CHF2, CF3, C3F7, C6F 13 、C8F 17 .

[0009] A method for preparing C3-fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivatives has been developed. Using graphitic carbon nitride (g-C3N4) as a photocatalyst, the 4H-pyrido[1,2-a]pyrimidin-4-one compound reacts with sodium fluoroalkylsulfinate in an organic solvent for 24 hours under 455-460 nm LED blue light in air at room temperature to prepare C3-fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivatives. Visible light-induced catalytic C-H bond functionalization of heterocyclic compounds is a mild, environmentally friendly, and sustainable synthetic strategy. Graphitic carbon nitride (g-C3N4) is a visible light-responsive inorganic non-metallic polymer semiconductor material with advantages such as simple preparation, low cost, high chemical and thermal stability, and environmental friendliness.

[0010] Furthermore, the 4H-pyrido[1,2-a]pyrimidin-4-one compound is represented by the following structural formula II:

[0011]

[0012] Among them, R 1 =H, 6-methyl, 7-methyl, 8-methyl, 7-fluoro, 7-chloro, 7-bromo, 7-ester, 7-CF3; R 2 = methyl, ethyl, phenyl, p-chlorophenyl;

[0013] The sodium fluoroalkylsulfinate is shown as compound III:

[0014] R f SO2Na(III)

[0015] Among them, R f For difluoromethyl (CHF2), trifluoromethyl (CF3), perfluoropropyl (C3F7), perfluorohexyl (C6F 13 ), perfluorooctyl (C8F 17 ).

[0016] Furthermore, the ratio of the photocatalyst to the 4H-pyrido[1,2-a]pyrimidin-4-one compound is 15 mg:0.2 mmol. The catalyst can be reused more than 5 times.

[0017] Furthermore, the molar ratio of 4H-pyrido[1,2-a]pyrimidin-4-one to sodium fluoroalkylsulfinate is 1:1.5 to 1:2.5, preferably 1:2.

[0018] Furthermore, the organic solvent is one of acetonitrile, ethanol, 1,2-dichloroethane, dichloromethane, N,N-dimethylformamide, dimethyl sulfoxide, and dimethyl carbonate, among which dimethyl carbonate is preferred.

[0019] Furthermore, the wavelength of the blue light LED is 455-460 nm, and the light intensity is 8-12 W, preferably 10 W.

[0020] The present invention also proposes a reasonable reaction mechanism. Under 455-460nm blue light irradiation, the substrate NaSO2R f (2) Single-electron oxidation is carried out on VB under the action of catalyst g-C3N4 to generate free radical intermediate SO2R f (5) by releasing SO2 and converting it into free radicals R f Then, R f Reacts with substrate 1 to obtain the corresponding free radical intermediate 6. On the other hand, oxygen in the air is reduced on CB to obtain O2 ·- Intermediate 6 in O2 ·- Under the action of , the target product 3 is transformed through hydrogen atom transfer.

[0021]

[0022] Compared with the prior art, the present invention has the following advantages:

[0023] Using graphitic carbon nitride (g-C3N4) as a photocatalyst, dimethyl carbonate (DMC) as a solvent, and 4H-pyrido[1,2-a]pyrimidin-4-one and sodium fluoroalkylsulfinate as raw materials, a blue light reaction was conducted at room temperature for 24 hours to prepare C3-fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one and its derivatives in high yields. This method offers advantages such as simplicity, mild conditions, high yields, and reusable catalysts, making it feasible for industrial production and providing an important reference for the photocatalytic CH functionalization of other heterocyclic compounds. Furthermore, the prepared C3-fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivatives exhibited inhibitory activity against colon cancer HCT116 cells and cervical cancer HeLa cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The present invention provides a roadmap for the photocatalytic synthesis of C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivatives.

[0025] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of 7-chloro-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one.

[0026] Figure 3 This is the carbon NMR spectrum of 7-chloro-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one.

[0027] Figure 4 These are the XRD patterns of freshly prepared g-C3N4 and recycled g-C3N4.

[0028] Figure 5 These are the SEM images of freshly prepared g-C3N4 and recycled g-C3N4.

[0029] Figure 6 This is the single crystal diffraction pattern of 7-bromo-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. DETAILED DESCRIPTION

[0030] To gain a deeper understanding of the present invention, we will provide a comprehensive and detailed description thereof. However, the present invention has various implementations and is not limited to the specific examples listed herein. These examples are presented to enhance a comprehensive understanding of the present disclosure.

[0031] Synthesis of g-C3N4: In a muffle furnace, urea was heated to 550°C at a rate of 2°C per minute and calcined for 3 hours. After the reaction, the temperature was cooled to room temperature and the light yellow solid was ground to obtain g-C3N4. (Synthesis method refers to the literature Organic Letters, 2021, 23(12): 4843-4848, catalyst characterization see attached Figure 4 and attached Figure 5 )

[0032] Comparative Example:

[0033] The following control experimental groups 1 to 20 all react according to the following reaction equation

[0034]

[0035] The specific operation steps are as follows: 15 mg of the catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol), sodium trifluoromethanesulfinate (0.4 mmol), and 1 mL of dimethyl carbonate were added to a 10 mL reaction tube in sequence. The reaction was allowed to proceed at room temperature under 455-460 nm blue light for 24 hours. After the reaction, the mixture was cooled to room temperature and the yield was analyzed by crude NMR spectroscopy.

[0036]

[0037] Experiments 1 to 5 in the table above examined the effects of photocatalysis on the reaction. When Rhodamine 6G was used as the catalyst, the reaction barely occurred. When Ru(bpy) 3 Cl 2 · 6H 2 O, Rhodamine B, and Eosin Y were used as the catalyst, the product yield was only 36-60%. However, using g-C 3 N 4 as the catalyst significantly improved the product yield, reaching 75%. This demonstrates that g-C 3 N 4 possesses a superior catalytic effect.

[0038] Experiments 6 to 15 in the table above investigated the effect of the reaction medium on the reaction. Using g-C3N4 as a photocatalyst, the effects of different solvents on the reaction yield were investigated. When the reaction solvents were ethyl acetate (EtOAc), water (H2O), tetrahydrofuran (THF), and 2-methyltetrahydrofuran (2-MeTHF), the reaction yield was very low. However, when acetonitrile (MeCN), ethanol (EtOH), 1,2-dichloroethane (DCE), dichloromethane (CH2Cl2), N,N-dimethylformamide (DMF), etc. were used as reaction solvents, the yield increased. Surprisingly, when the green solvent dimethyl carbonate (DMC) was used, the yield of the target product was the highest, reaching 87%. Therefore, DMC was selected as the optimal reaction solvent.

[0039] Experiments 16 and 17 in the table above investigated the effect of light power on the response. The experiments showed that 10W was the optimal light power. Lowering the power to 8W resulted in a lower yield. Increasing the power to 12W also resulted in a decreasing yield.

[0040] Experiments 18 to 20 in the table above investigated the effects of the absence of a photocatalyst, the absence of light, and nitrogen on the reaction. The experiments showed that the reaction could not occur without a photocatalyst, the absence of light, and the presence of nitrogen.

[0041] The synthetic route of the C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative provided by the present invention is as follows: Figure 1 shown.

[0042] In a 10 mL reaction tube, 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol), sodium fluoroalkylsulfinate (0.4 mmol), and 1 mL of dimethyl carbonate were added in sequence. The reaction was allowed to proceed under blue light at room temperature for 24 h. After the reaction was complete, the catalyst was transferred to a 20 mL centrifuge tube for recovery (see attached for catalyst recovery characterization). Figure 4 and attached Figure 5 ), the upper mixed solution was dried by rotary evaporation and purified by column chromatography to obtain a C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative.

[0043] The experiment of inhibiting the viability of colon cancer HCT116 cells and cervical cancer HeLa cells by the C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivatives provided by the present invention mainly comprises the following steps:

[0044] Antitumor activity was tested using HCT116 and HeLa cancer cells. The cytotoxicity of C3-fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivatives was investigated using the CCK-8 assay. HCT116 and HeLa cancer cells were cultured in DMEM medium supplemented with 10% fetal bovine serum and 1% dual-antibody (penicillin and streptomycin). Well-growing cells were digested and counted. 50,000 cells were plated per well of a 96-well plate. Blank, control, and experimental groups were plated in triplicate. After cell attachment, the culture medium was discarded and the cells were washed three times with PBS. 100 μL of culture medium was added to the blank and control groups. A mixture of 10 μL of the prepared 0.5 mmol / mL sample and 90 μL of culture medium was added to the experimental group wells, resulting in a drug concentration of 50 μmol / mL per well. After 24 hours of culture, the liquid in all wells was discarded, and the cells were washed three times with PBS. 10 μL of CCK-8 reagent and 90 μL of culture medium were added to each well and cultured for 2-4 hours. The absorbance of each well was measured by a microplate reader, and the cell viability value was calculated according to the following formula:

[0045] Cell viability (%) = [A(average absorbance of experimental group) - A(average absorbance of blank group)] / [A(average absorbance of control group) - A(average absorbance of blank group)] × 100%

[0046] The present invention will be further described below with reference to specific Preparation Examples 1 to 20:

[0047] Example 1

[0048] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f =CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover and use in the next cycle. The supernatant was dried and purified by column chromatography to obtain a light yellow solid, 2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, with a yield of 83%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 31% and 10%, respectively. The target product has the following structural formula:

[0049]

[0050] Mp = 131-132 ° C; NMR and mass spectrometry data: 1H NMR (500MHz, CDCl3): δ9.10(d,J=7.5Hz,1H),7.85(s,1H),7.70(d,J=9.0Hz,1H),7.46(s,2H),7.40(s,3H),7.23(s,1H); 13 C NMR (126MHz, CDCl3): δ163.8,154.3,149.5,137.9,128.6,127.0,126.7,125.7,123.6,121.5,119.3,115.8,111.7,102.9(q,J=30.6Hz),99.7; 19 F NMR (471MHz, CDCl3): δ-55.5ppm; HRMS: calcd for C 15 H 10 F3N2O[M+H] + 291.0667, found 291.0661.

[0051] Example 2

[0052] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =6-CH3,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f =CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The upper mixed solution was spin-dried and column chromatography was performed to obtain a light yellow solid 6-methyl-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one with a yield of 79%. This derivative was used to inhibit the viability of colon cancer HCT116 cells and cervical cancer HeLa cells, showing inhibition rates of 37% and 21%, respectively. The target product has the following structural formula:

[0053]

[0054] Mp = 150-151 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ7.54(t,J=7.0Hz,1H),7.44(t,J=7.5Hz,3H),7.39(s,2H),7.19(s,1H),6.76(t,J=7.5Hz,1H),3.05(s,1H); 13C NMR (126MHz, CDCl3): δ162.4,158.4,152.0,143.9,137.6,136.7,128.5,12 7.0,126.9,124.4,123.7,121.5,118.7,104.3,104.2(q,J=30.3Hz),23.6; 19 F NMR (471MHz, CDCl3): δ-56.1ppm; HRMS: calcd for C 16 H 12 F3N2O[M+H] + 305.0823,found 305.0828.

[0055] Example 3

[0056] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-CH3,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f =CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The upper mixed solution was spin-dried and column chromatography was performed to obtain a light yellow solid, 7-methyl-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, with a yield of 81%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 19% and 17%, respectively. The target product has the following structural formula:

[0057]

[0058] Mp = 139-141 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ8.91(s,1H),7.71(d,J=7.0Hz,1H),7.63(d,J=9.0Hz,1H),7.47(s,2H),7.39(s,3H),2.43(s,3H); 13 C NMR (126MHz, CDCl3): δ163.3,154.3,148.4,140.6,138.0,128.5,127.0,126.9,126.4,125.1,124.2,123.7,121.6,102.5(q,J=30.8Hz),13.1; 19F NMR (471MHz, CDCl3): δ-55.4ppm; HRMS: calcd for C 16 H 12 F3N2O[M+H] + 305.0823,found 305.0827.

[0059] Example 4

[0060] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =8-CH3,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f =CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover the catalyst for the next cycle. The upper mixed solution was spin-dried and purified by column chromatography to obtain a light yellow solid 8-methyl-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one with an 82% yield. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 43% and 24%, respectively. The target product has the following structural formula:

[0061]

[0062] Mp = 134-135 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ8.97(t,J=7.5Hz,1H),7.46(t,J=8.5Hz,3H),7.38(s,3H)7.04(t,J=7.5Hz,1H),2.45(s,3H); 13 C NMR (126MHz, CDCl3): δ164.0,154.4,150.7,149.4,138.1,130.0,128.5,127.8,127.0,126.9,126.6,126.0,123.9,101.9(q,J=29.3Hz),20.6; 19 F NMR (471MHz, CDCl3): δ-55.2ppm; HRMS: calcd for C 16 H 12 F3N2O[M+H] + 305.0823,found 305.0820.

[0063] Example 5

[0064] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-F,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f =CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover and use in the next cycle. The upper mixed solution was spin-dried and purified by column chromatography to obtain a light yellow solid, 7-fluoro-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, with a yield of 76%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 38% and 27%, respectively. The target product has the following structural formula:

[0065]

[0066] Mp = 157-158 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ8.99(t,J=3.3Hz,1H),7.75-7.73(m,2H),7.46(t,J=8.0Hz,2H),7.41(t,J=6.0Hz,3H); 13 C NMR (126MHz, CDCl3): δ164.5,155.7,154.8,153.7,148.5,138.6,131.2,131.0,129.8,12 8.7,128.2,128.1,128.0,126.7,124.5,122.3,120.1,114.3,114.0,103.8(q,J=30.7Hz); 19 F NMR (471MHz, CDCl3): δ-55.6, -129.8ppm; HRMS: calcd for C 15 H9F4N2O[M+H] + 330.0231,found330.0236.

[0067] Example 6

[0068] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-Cl,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, Rf =CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to be recovered for the next cycle. The supernatant was dried and purified by column chromatography to obtain a yellow solid, 7-chloro-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, with a yield of 78%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 36% and 22%, respectively. The target product has the following structural formula:

[0069]

[0070] Mp = 162-163 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ9.20 (s, 1H), 7.88-7.85 (m, 1H), 7.57 (d, J = 9.5Hz, 1H), 7.47 (t, J = 4.0Hz, 2H), 7.40 (t, J = 7.5Hz, 3H); 13 C NMR (126MHz, CDCl3): δ163.8,153.4,148.0,141.1,137.5,128.9,127.8,127.2,12 7.0,126.9,126.6,126.4,125.6,123.4,121.2,119.1,111.1,103.6(q,J=30.6Hz); 19 F NMR (471MHz, CDCl3): δ-55.7ppm; HRMS: calcd for C 15 H9ClF3N2O[M+H] + 325.0227,found 325.0224.

[0071] Example 7

[0072] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-Br,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f=CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The supernatant was dried and purified by column chromatography to obtain a yellow solid, 7-bromo-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, with a yield of 79%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 72% and 68%, respectively. The target product has the following structural formula:

[0073]

[0074] Mp = 163-165 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ9.20 (s, 1H), 7.88-7.86 (m, 1H), 7.57 (d, J = 9.5Hz, 1H), 7.47 (d, J = 7.5Hz, 2H), 7.41 (d, J = 7.5Hz, 3H); 13 C NMR (126MHz, CDCl3): δ163.8,153.4,148.0,141.1,137.5,128.9,127.8,127.2,127.1,126.9,126.6,126.4,123.4,121.2,111.1,103.4,99.5; 19 F NMR (471MHz, CDCl3): δ-55.7ppm; HRMS: calcd for C 15 H9BrF3N2O[M+H] + 368.9772,found 368.9768.

[0075] Single crystal data CCDC-2324195:C 15 H8BrF3N2O; Mr=369.14,Triclinic,space group P-1, T=150.00K;Z=4;Reflections collected / unique,20616 / 9878,R int =0.0475, R1=0.0363, wR2=0.1086; GOF=1.040.

[0076] Example 8

[0077] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-CF3,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f =CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The supernatant was dried and purified by column chromatography to obtain a white solid, 2-phenyl-3,7-bis(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, with a yield of 78%. This derivative was tested for inhibition of colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 38% and 24%, respectively. The target product has the following structural formula:

[0078]

[0079] Mp = 155-157 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ9.37 (s, 1H), 7.90-7.88 (m, 1H), 7.75 (d, J = 9.0Hz, 1H), 7.49 (d, J = 6.0Hz, 2H), 7.44-7.40 (m, 3H); 13 C NMR (126MHz, CDCl3): δ165.7,154.9,150.5,138.2,133.8,128.2,128.0,12 7.0,124.2,123.3,122.0,121.2,120.6,119.8,119.0,105.5(q,J=31.0Hz); 19 F NMR (471MHz, CDCl3): δ-55.9,-63.2ppm; HRMS: calcd for C 16 H9F6N2O[M+H] + 359.0641,found 359.0645.

[0080] Example 9

[0081] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-CO2Et,R 2 =Ph), sodium trifluoromethanesulfinate (0.3mmol, R f=CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The upper mixed solution was spin-dried and purified by column chromatography to obtain a yellow solid, 4-oxo-2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-7-carboxylic acid ethyl ester, with a yield of 80%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, showing inhibition rates of 28% and 21%, respectively. The target product has the following structural formula:

[0082]

[0083] Mp = 164-165 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ9.62(s,1H),8.13(t,J=9.5Hz,1H),8.03(t,J=6.0Hz,2 H),7.63(t,J=9.0Hz,1H),7.44-7.42(m,4H),6.88(s,1H),4.41-4.36(m,3H); 13 C NMR (126MHz, CDCl3): δ163.6,163.0,162.4,158.4,151.2,138.4,137.5,13 6.7,134.9,131.4,131.3,131.0,130.1,128.9,127.5,126.5,120.4,100.7; 19 F NMR (471MHz, CDCl3): δ-55.8ppm; HRMS: calcd for C 18 H 14 F3N2O3[M+H] + 363.0878,found 363.0881.

[0084] Example 10

[0085] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =4-ClC6H4), sodium trifluoromethanesulfinate (0.4mmol, R f=CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover the catalyst for the next cycle. The upper mixed solution was spin-dried and purified by column chromatography to obtain a yellow solid 2-(4-chlorophenyl)-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one with a yield of 73%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, showing inhibition rates of 24% and 20%, respectively. The target product has the following structural formula:

[0086]

[0087] Mp = 175-177 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ9.11(d,J=8.5Hz,1H),7.88(t,J=8.7Hz,1H),7.69(d,J=9Hz,1H),7.43(d,J=8.5Hz,2H),7.38(t,J=8.5Hz,2H),7.26(t,J=7Hz,1H); 13 C NMR (126MHz, CDCl3): δ162.6,159.7,154.2,149.6,138.0,136.3,135.4,134.9,128.5 ,128.0,127.7,126.8,125.7,123.5,121.4,115.9,114.3,102.8(q,J=25.2Hz),98.8; 19 F NMR (471MHz, CDCl3): δ-55.4ppm; HRMS: calcd forC 15 H9ClF3N2O[M+H] + 325.0233,found 325.0230.

[0088] Example 11

[0089] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =CH3), sodium trifluoromethanesulfinate (0.4mmol, R f=CF3) and 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 445nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover the catalyst for the next cycle. The supernatant was dried and purified by column chromatography to yield a yellow solid, 2-methyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, in a 73% yield. This derivative was tested for inhibition of colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 19% and 17%, respectively. Mp = 123-124°C. The target product has the following structural formula:

[0090]

[0091] NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ9.04 (d, J = 7.5Hz, 1H), 7.84 (t, J = 8.5Hz, 1H), 7.59 (d, J = 8.5Hz, 1H), 7.20 (d, J = 6.75Hz, 1H), 2.59 (d, J = 2.5Hz, 3H); 13 C NMR (126MHz, CDCl3): δ164.1, 153.5, 149.7, 137.7, 126.8, 126.6, 125.0, 124.4, 122.3, 115.5, 103.3 (q, J = 30.6Hz), 28.7, 23.7, 23.6; 19 F NMR (471MHz, CDCl3): δ-56.6ppm; HRMS: calcdfor C 10 H8F3N2O[M+H] + 229.0510,found 229.0515.

[0092] Example 12

[0093] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-CH3,R 2 =CH3), sodium trifluoromethanesulfinate (0.4mmol, R f=CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 445nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover and use in the next cycle. The upper mixed solution was spin-dried and purified by column chromatography to obtain a yellow solid, 2,7-dimethyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, with a yield of 68%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 19% and 21%, respectively. The target product has the following structural formula:

[0094]

[0095] Mp = 155-157 ° C; NMR and mass spectrometry data are as follows: 1 H NMR (500MHz, CDCl3): δ8.84 (s, 1H), 7.70-7.67 (m, 1H), 7.51 (d, J = 9.0Hz, 1H), 2.58 (s, 3H), 2.41 (s, 3H); 13 C NMR (126MHz, CDCl3): δ163.4, 153.5, 148.5, 140.5, 126.0, 124.4 (q, J = 12.4Hz), 122.4, 102.9 (q, J = 30.8Hz), 28.7, 23.6, 17.4; 19 F NMR (471MHz, CDCl3): δ-56.5ppm; HRMS: calcd forC 11 H 10 F3N2O[M+H] + 243.0667,found 243.0671.

[0096] Example 13

[0097] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =C2H5), sodium trifluoromethanesulfinate (0.4mmol, R f=CF3), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 460nm) for 24 hours. After the reaction was completed, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The upper mixed solution was spin-dried and column chromatography was performed to obtain a yellow oily liquid 2-ethyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one with a yield of 70%. The derivative was used to inhibit the viability of colon cancer HCT116 cells and cervical cancer HeLa cells, showing inhibition rates of 20% and 24%, respectively. The results showed that the derivative had a certain inhibitory effect on the two cancer cells mentioned above at the cellular level. The target product has the following structural formula:

[0098]

[0099] NMR and mass spectrometry data: δ9.03 (d, J = 7.0 Hz, 1H), 7.80 (t, J = 9.0 Hz, 1H), 7.59 (d, J = 9.0 Hz, 1H), 7.59-7.19 (m, 1H), 2.80 (t, J = 3.5 Hz, 2H), 1.74-1.69 (m, 3H); 13 C NMR (126MHz, CDCl3): δ168.8,167.1,160.7,154.9,151.5,150.8,138.4,134 .3,127.7,126..1,125.4,124.7,123.3,116.1,111.0,104.2(q,J=30.8Hz); 19 F NMR (471MHz, CDCl3): δ-56.2ppm; HRMS: calcd for C 11 H 10 F3N2O[M+H] + 243.0667,found 243.0672.

[0100] Example 14

[0101] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =Ph), sodium difluoromethanesulfinate (0.3mmol, R f=CHF2), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 460nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover the catalyst for the next cycle. The upper mixed solution was spin-dried and purified by column chromatography to obtain a light yellow solid 2-phenyl-3-(difluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one with a yield of 69%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 23% and 18%, respectively. The target product has the following structural formula:

[0102]

[0103] Mp = 78-80 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ9.08(d,J=8.5Hz,1H),7.81(t,J=9.0Hz 1H),7.68(d,J=10.5Hz,1H),7.56(s,2H),7.43(s,3H),7.19(s,1H),6.76(t,J=67.0Hz 1H); 13 C NMR (126MHz, CDCl3): δ163.7,155.3,149.8,137.1,136.2,129.0,127.8,127.4,126.6,125.7,115.3,112.4,110.0,105.6(q,J=28.4Hz); 19 F NMR (471MHz, CDCl3): δ-112.1ppm; HRMS: calcd for C 15 H 11 F2N2O[M+H] + 273.0761,found273.0766.

[0104] Example 14

[0105] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-F,R 2 =Ph), sodium difluoromethanesulfinate (0.3mmol, R f=CHF2), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (12W, 460nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover and use in the next cycle. The upper mixed solution was spin-dried and column chromatography was performed to obtain a light yellow oily liquid 7-fluoro-2-phenyl-3-(difluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one with a yield of 75%. This derivative was tested in the inhibition of colon cancer HCT116 cells and cervical cancer HeLa cells, showing inhibition rates of 17% and 22%, respectively. The target product has the following structural formula:

[0106]

[0107] NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ8.99 (s, 1H), 7.72 (d, J = 7.5Hz, 2H), 7.56 (t, J = 5.0Hz 2H), 7.45 (s, 3H), 6.76 (t, J = 66.7Hz 1H); 13 C NMR (126MHz, CDCl3): δ164.3,155.8,153.3,148.8,137.0,130.6,130.3,130.2,128.9 ,128.8,128.7,128.5,115.6,114.1,113.7,113.2,110.9,106.5(q,J=28.3Hz),99.7; 19 F NMR (471MHz, CDCl3): δ-112.3,-130.6ppm; HRMS: calcd for C 15 H 10 F3N2O[M+H] + 291.0667,291.0672.

[0108] Example 15

[0109] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-Cl,R 2 =Ph), sodium difluoromethanesulfinate (0.3mmol, R f=CHF2), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (8W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The upper mixed solution was spin-dried and column chromatography was performed to obtain a light yellow solid 7-chloro-2-phenyl-3-(difluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one with a yield of 81%. This derivative was used to inhibit the viability of colon cancer HCT116 cells and cervical cancer HeLa cells, showing inhibition rates of 38% and 20%, respectively. The target product has the following structural formula:

[0110]

[0111] Mp = 139-140 ° C; NMR and mass spectrometry data are as follows: 1 H NMR (500MHz, CDCl3): δ9.19 (d, J = 2.5Hz, 1H), 7.82 (d, J = 2.5Hz, 1H), 7.58-7.56 (m, 2H), 7.45 (d, J = 3.1Hz, 3H), 1.19 (s, 1H); 13 CNMR (126MHz, CDCl3): δ163.6,154.3,148.3,140.3,135.9,129.2,127.9,127.5,126.7,114.0,112.1,110.7,110.2,106.3; 19 F NMR (471MHz, CDCl3): δ-112.3ppm; HRMS: calcd forC 15 H9F2N2O[M+H] + 306.0293,found 306.0297.

[0112] Example 16

[0113] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =CH3), sodium difluoromethanesulfinate (0.3mmol, R f=CHF2), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (8W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover the catalyst for the next cycle. The upper mixed solution was spin-dried and purified by column chromatography to obtain a light yellow solid, 2-methyl-3-(difluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one, with a yield of 77%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 15% and 19%, respectively. The target product has the following structural formula:

[0114]

[0115] Mp = 129-131 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ8.99 (d, J = 7Hz, 1H), 7.79 (t, J = 8.5Hz, 1H), 7.60 (d, J = 9.5Hz, 1H), 7.17 (t, J = 6.5Hz, 1H), 2.61 (s, 3H); 13 CNMR (126MHz, CDCl3): δ164.9,164.6,162.8,162.6,156.4,155.7,149.6,149.0,136.9,127.5,126.7, 125.1,122.7,115.2,113.5,111.6,111.1,109.7,109.0,106.2(t,J=24.2Hz),103.8,23.6,22.7,21.8; 19 F NMR (471MHz, CDCl3): δ-114.0,-116.5ppm; HRMS: calcd for C 10 H8F2N2O[M+H] + 210.0526,found 210.0531.

[0116] Example 17

[0117] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =C2H5), sodium difluoromethanesulfinate (0.3mmol, R f=CHF2), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (8W, 455nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The upper mixed solution was spin-dried and column chromatography was performed to obtain a light yellow oily liquid 2-ethyl-3-(difluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one with a yield of 79%. This derivative was used to inhibit the viability of colon cancer HCT116 cells and cervical cancer HeLa cells, showing inhibition rates of 17% and 19%, respectively. The target product has the following structural formula:

[0118]

[0119] NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ6.50(t,J=9.5Hz,1H),6.27(d,J=9.5Hz,1H),6.17(s,1H),5 .25(d,J=22.5Hz,1H),2.90-2.85(m,1H),2.70-2.64(m,1H),2.41(t,J=7.5Hz,3H); 13 C NMR (126MHz, CDCl3): δ166.4,160.1,150.9,134.8,127.5,123.2,122.9,114.4,11 2.5,110.5,109.8,109.6,103.3,47.3(q,J=17.2Hz),39.2,38.3,28.7,20.1,12.7; 19 F NMR (471MHz, CDCl3): δ-125.2,-130.1ppm; HRMS: calcd forC 11 H 10 F2N2O[M+H] + 224.0683,found224.0687.

[0120] Example 18

[0121] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-CH3,R 2 =Ph), sodium perfluoropropylsulfinate (0.5mmol, R f=C3F7), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (8W, 460nm) for 24 hours. After completion of the reaction, the catalyst was transferred to a 20mL centrifuge tube to recover and use in the next cycle. The supernatant was dried and purified by column chromatography to obtain a white solid, 7-methyl-2-phenyl-3-(perfluoropropyl)-4H-pyrido[1,2-a]pyrimidin-4-one, with a yield of 72%. This derivative was tested in an inhibition assay for colon cancer HCT116 cells and cervical cancer HeLa cells, demonstrating inhibition rates of 54% and 30%, respectively. The target product has the following structural formula:

[0122]

[0123] Mp = 187-189 ° C; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ8.92 (s, 1H), 7.74 (d, J = 9.0Hz, 1H), 7.64 (d, J = 9.0Hz, 1H), 7.35 (t, J = 3.5Hz, 3H), 7.29 (t, J = 3.3Hz, 2H), 2.43 (s, 3H); 13 C NMR (126MHz, CDCl3): δ165.3,148.4,141.0,138.6,127.6,126.8,126.7,126.1,125.1,124.2,118.1,108.5,101.2; 19 F NMR (471MHz, CDCl3): δ-80.4,-102.0,-122.5ppm; HRMS:calcd for C 18 H 12 F7N2O[M+H] + 405.0760,found 405.0764.

[0124] Example 19

[0125] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-CH3,R 2 =Ph), sodium perfluorohexylsulfinate (0.5mmol, R f =C6F 13), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 460nm) for 24 hours. After the reaction was completed, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The upper mixed solution was spin-dried and column chromatography was performed to obtain a white solid 7-methyl-2-phenyl-3-(perfluorohexyl)-4H-pyrido[1,2-a]pyrimidin-4-one with a yield of 71%. The derivative was used to inhibit the viability of colon cancer HCT116 cells and cervical cancer HeLa cells, showing inhibition rates of 23% and 60%, respectively. The target product structure is as follows:

[0126]

[0127] Mp = 209-211 ° C; NMR and mass spectrometry data: 1 HNMR (500MHz, CDCl3): δ8.93 (s, 1H), 7.75-7.73 (m, 1H), 7.64 (d, J = 9.0Hz, 1H), 7.35 (t, J = 3.5Hz, 3H), 7.29 (d, J = 4.0Hz, 2H), 2.43 (s, 3H); 13 C NMR (126MHz, CDCl3): δ165.4,154.3,148.4,141.0,138.7,127.6,126.8,126. 7,126.0,125.1,124.3,117.3,115.0,101.4(q,J=22.3Hz),99.5,28.7,17.5; 19 F NMR (471MHz, CDCl3): δ-80.8,-101.4,-118.3,-121.9,-122.6,-126.1ppm; HRMS:calcd forC 21 H 12 F 13 N2O[M+H] + 555.0664,found 555.0668.

[0128] Example 20

[0129] 15 mg of catalyst g-C3N4, 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =7-CH3,R 2 =Ph), sodium perfluorooctanesulfinate (0.5mmol, R f =C8F 17), 1mL dimethyl carbonate. The reaction was carried out at room temperature under blue light (10W, 460nm) for 24 hours. After the reaction was completed, the catalyst was transferred to a 20mL centrifuge tube to recover for the next cycle. The upper mixed solution was spin-dried and column chromatography was used to obtain a white solid 7-methyl-2-phenyl-3-(perfluorooctyl)-4H-pyrido[1,2-a]pyrimidin-4-one with a yield of 65%. The derivative was used to inhibit the viability of colon cancer HCT116 cells and cervical cancer HeLa cells, showing inhibition rates of 8% and 28%, respectively. The target product structure is as follows:

[0130]

[0131] Mp>250℃; NMR and mass spectrometry data: 1 H NMR (500MHz, CDCl3): δ8.93 (s, 1H), 7.75-7.73 (m, 1H), 7.64 (d, J = 9.0Hz, 1H), 7.35 (t, J = 3.0Hz, 3H), 7.19 (s, 2H), 3.13 (s, 3H); 13 C NMR (126MHz, CDCl3): δ154.3,148.4,141.0,138.7,127.6,126.8,126.7,126.0,125.1,124.3,17.5; 19 FNMR (471MHz, CDCl3): δ-80.7,-101.4,-118.2,-121.6,-121.9,-122.7,-126.1ppm; HRMS:calcd for C 23 H 12 F 17 N2O[M+H] + 655.0600,found 655.0667.

[0132] In order to further demonstrate the superiority of the method of the present invention, the following photosensitizers are selected as catalyst comparison examples:

[0133] Comparative Example 1

[0134] In a 10 mL reaction tube, catalyst Ru(bpy)3Cl2·6H2O (0.01 mmol, 5 mol%), 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f=CF3), 1 mL of dimethyl carbonate. The reaction was allowed to proceed at room temperature under blue light (10 W, 455 nm) for 24 h. After completion, the catalyst was transferred to a 20 mL centrifuge tube for recovery and reuse in the next cycle. The supernatant was purified by column chromatography to afford 2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a light yellow solid in a 60% yield.

[0135] Comparative Example 2

[0136] In a 10 mL reaction tube, catalyst Rhodamine 6G (0.01 mmol, 5 mol%), 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f =CF3), 1 mL of dimethyl carbonate. The reaction was carried out at room temperature under blue light (10 W, 455 nm) for 24 h. After completion of the reaction, the catalyst was transferred to a 20 mL centrifuge tube to be recovered for the next cycle. TLC analysis of the upper mixed solution revealed no target product.

[0137] Comparative Example 3

[0138] In a 10 mL reaction tube, catalyst Rhodamine B (0.01 mmol, 5 mol%), 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f =CF3), 1 mL of dimethyl carbonate. The reaction was allowed to proceed at room temperature under blue light (10 W, 455 nm) for 24 h. After completion, the catalyst was transferred to a 20 mL centrifuge tube for recovery and reuse in the next cycle. The supernatant was purified by column chromatography to afford 2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a light yellow solid in a 45% yield.

[0139] Comparative Example 4

[0140] In a 10 mL reaction tube, catalyst Eosin Y (0.01 mmol, 5 mol%), 4H-pyrido[1,2-a]pyrimidin-4-one (0.2 mmol, R 1 =H,R 2 =Ph), sodium trifluoromethanesulfinate (0.4mmol, R f=CF3), 1 mL of dimethyl carbonate. The reaction was allowed to proceed at room temperature under blue light (10 W, 455 nm) for 24 h. After completion, the catalyst was transferred to a 20 mL centrifuge tube for recovery and reuse in the next cycle. The supernatant was purified by column chromatography to afford 2-phenyl-3-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a light yellow solid in a 36% yield.

[0141] Any matters not described in detail in this specification are prior art known to those skilled in the art. Although the above description of the present invention is based on specific embodiments to facilitate understanding of the present invention by those skilled in the art, it should be understood that the present invention is not limited to the scope of the specific embodiments. As long as various modifications are within the spirit and scope of the present invention as defined and determined by the appended claims, such modifications will be obvious to those skilled in the art, and all inventions and creations utilizing the concepts of the present invention are protected.

Claims

1. A method for preparing a C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative, characterized by: Using graphitic carbon nitride as a photocatalyst, 4H-pyrido[1,2-a]pyrimidin-4-one compounds reacted with sodium fluoroalkylsulfinate in an organic solvent under room temperature and air conditions under blue LED irradiation for 24 h to prepare C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivatives. The structure (I) of the C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative is as follows: （I） R 1 = H, 6-methyl, 7-methyl, 8-methyl, 7-fluoro, 7-chloro, 7-bromo, 7-ester, 7-CF3; R 2 = methyl, ethyl, phenyl, p-chlorophenyl; R f = CHF2、CF3、C3F7、C6F 13 、C8F 17 ; The 4H-pyrido[1,2-a]pyrimidin-4-one compound is shown in the following structural formula II: (II) Among them, R 1 = H, 6-methyl, 7-methyl, 8-methyl, 7-fluoro, 7-chloro, 7-bromo, 7-ester, 7-CF3; R 2 = methyl, ethyl, phenyl, p-chlorophenyl; The sodium fluoroalkylsulfinate is shown as compound III: (III) Among them, R f is difluoromethyl, trifluoromethyl, perfluoropropyl, perfluorohexyl, or perfluorooctyl; The organic solvent is one of acetonitrile, ethanol, 1,2-dichloroethane, dichloromethane, N,N-dimethylformamide, dimethyl sulfoxide, and dimethyl carbonate; The blue light LED has a wavelength of 455-460 nm and a light intensity of 8-12 W.

2. The method for preparing a C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative according to claim 1, characterized in that: The amount ratio of the photocatalyst to the 4H-pyrido[1,2-a]pyrimidin-4-one compound was 15 mg:0.2 mmol.

3. The method for preparing a C3 fluoroalkylated 4H-pyrido[1,2-a]pyrimidin-4-one derivative according to claim 1, characterized in that: The molar ratio of the 4H-pyrido[1,2-a]pyrimidin-4-one to sodium fluoroalkylsulfinate is 1:1.5 to 1:2.5.

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