Green synthesis method of polycyclic quinazolinone derivative with antiviral activity

Abstract

The invention provides a green synthesis method of a polycyclic quinazolinone derivative with antiviral activity, which comprises the following steps: mixing a compound with a structure as shown in a formula (I), a photocatalyst, a hydrogen atom transfer reagent and a solvent, and reacting under sunlight or blue light irradiation conditions to obtain a compound with antiviral activity as shown in a formula (II). According to the method provided by the invention, reaction conversion can be completed under the condition of using blue light (467 nm) with longer wavelength or sunlight, and the dosage of the photocatalyst is only 0.2 mol%, so that the catalytic efficiency is high; meanwhile, a specific photocatalyst is selected, so that the yield is increased, and reactants are clean and pollution-free; and the method is suitable for large-scale production, and has a good application prospect and a good research value.

Description

Technical Field

[0001] The invention relates to the field of drug synthesis, and in particular to a green synthesis method of polycyclic quinazolinone derivatives with antiviral activity. Background Art

[0002] Polycyclic quinazolinone and its derivatives are an important class of nitrogen-containing heterocyclic structures and are also important skeletons of many natural alkaloids. The reported polycyclic quinazolinones all have various biological activities, such as: the natural products and drug molecules containing polycyclic quinazolinone skeletons shown in the following structural formulas have antiviral activity, antibacterial activity, anticancer activity, antidepressant activity, or anti-Alzheimer's disease activity, etc.

[0003]

[0004] Therefore, the synthesis method of polycyclic quinazolinone and its derivatives is favored by many drug synthesis researchers; especially in recent years, the free radical cascade reaction triggered by photochemical, electrochemical induction or peroxide, metal salt and other conditions has become a popular research method for preparing polycyclic quinazolinone derivatives (Org. Lett. 2023, 25, 1683-1688; Chem. Commun., 2018, 54, 10160-10163). Although there are many reports on the synthesis method of polycyclic quinazolinone and its derivatives, it is summarized as follows:

[0005] Path A: The functional group-activated small molecule RX undergoes homolysis under metal catalysts, peroxides or ultraviolet conditions to generate R-based free radicals, which then add to the alkenyl double bond of the N-alkyl-substituted quinazolinone QN to generate the intermediate Int-I, which then undergoes cyclization to obtain the polycyclic quinazolinone product QN-1.

[0006] Path B: Under 420 nm violet light, the protonated N-alkyl-substituted quinazolinone QN under acidic conditions is reduced by a single electron by an excited photosensitizer to give the intermediate Int-II, which then undergoes an intramolecular free radical cycloaddition to the side chain double bond to give the polycyclic quinazolinone product QN-2.

[0007] Path B (Path C): N-alkyl substituted quinazolinone QN via heavy metal compound SmI 2 The catalytic reaction was carried out to obtain the cycloquinazolinone product QN-3.

[0008]

[0009] From the above reactions, it can be seen that these current methods all have certain shortcomings and cannot meet the requirements of green chemistry. For example, some of these reactions require harsh conditions such as high temperature, some require the use of oxidants or catalysts containing heavy metals, some use equivalent amounts of peroxides, organic acids or have poor atom economy, etc. Therefore, it is of great significance to develop a synthetic method with mild conditions and green environmental protection. Summary of the invention

[0010] In view of this, the technical problem to be solved by the present invention is to provide a green synthesis method for polycyclic quinazolinone derivatives with antiviral activity. The method provided by the present invention not only has mild reaction conditions and is environmentally friendly, but also has wide applicability to substrates.

[0011] Compared with the prior art, the present invention provides a green synthesis method of polycyclic quinazolinone derivatives with antiviral activity. The method provided by the present invention is to mix a compound with a structure of formula (I), a photocatalyst, a hydrogen atom transfer reagent and a solvent, and react under sunlight or blue light irradiation conditions to obtain a compound with a structure of formula (II) with antiviral activity. It is found through experiments that the method provided by the present invention can complete the conversion of the reaction under the use of longer wavelength blue light (467nm) or sunlight, and the amount of the photocatalyst is only 0.2mol%, and the catalytic efficiency is high; at the same time, the use of a specific photocatalyst not only improves the yield, but also makes the reactants clean and pollution-free; and the amplified reaction yield is not significantly reduced, which is suitable for large-scale production and has good application prospects and research value. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 This is the hydrogen spectrum of the compound prepared in Example 1 of the present invention;

[0013] Figure 2 This is the carbon spectrum of the compound prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0014] The present invention provides a method for preparing a polycyclic quinazolinone derivative having antiviral activity, comprising: mixing a compound having a structure of formula (I), a photocatalyst, a hydrogen atom transfer reagent and a solvent, and reacting the mixture under sunlight or blue light to obtain a compound having a structure of formula (II), which is a polycyclic quinazolinone derivative having antiviral activity;

[0015]

[0016] in,

[0017] Said n is 0, 1, 2 or 3;

[0018] The R 1 is hydrogen;

[0019] The R 2 is hydrogen, C6-C12 aryl, C1-C6 alkyl or halogen;

[0020] The R 3 is hydrogen, C6-C12 aryl, C1-C6 alkyl or halogen;

[0021] The R 4 is hydrogen, C1-C6 alkyl or halogen;

[0022] R is hydrogen, C1-C3 alkyl with substituents, C1-C3 alkyl without substituents, C1-C3 alkoxy, halogen or amino;

[0023] The photocatalyst is one or more of 4DPIPN, 4CzIPN and 3CzCIIPN.

[0024]

[0025] The hydrogen atom transfer reagent is a sulfur- and nitrogen-containing organic compound or a salt of a sulfur- and nitrogen-containing organic compound.

[0026] According to the present invention, the R 2 Preferably, R 3 Preferably, R 4 Preferably, it is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl or fluorine; R is preferably hydrogen, methyl, ethyl, propyl, trifluoromethyl, trifluoroethyl, fluorine, chlorine, bromine, methoxy, ethoxy or amino, wherein R can be at any position of the benzene ring where it is located, and there can be 1, 2 or 3 R substituents on the benzene ring; More preferably, the compound of formula (II) has the following structure:

[0027]

[0028] In addition, it should be noted that the dashed line structure in the box selected in the following compounds of formula (I) and formula (II) described in the present invention may be a benzene ring; it may not be a benzene ring. If it is not a benzene ring, it is only the alkyl group of the solid line part.

[0029]

[0030] According to the present invention, the compound of formula (I), a photocatalyst, a hydrogen atom transfer agent and a solvent are mixed and reacted under sunlight or blue light irradiation to obtain a compound of formula (II); wherein, the present invention preferably further adds an additive, and the additive is preferably one or more of water, formic acid, acetic acid, benzoic acid and p-toluenesulfonic acid, more preferably water or formic acid; wherein, the wavelength of the blue light is preferably 465-470nm, more preferably 20w 467nm blue light source; the molar ratio of the compound with formula (I) structure to the additive is preferably 1: (1-8), more preferably 1: (5-7); the molar ratio of the compound with formula (I) structure to the photocatalyst is preferably 1: (0.001-0.005), more preferably 1: (0.002-0.003); the molar ratio of the compound with formula (I) structure to the hydrogen atom transfer reagent is preferably 1: (0.01-0.05), more preferably 1: (0.02-0.04); the amount ratio of the compound with formula (I) structure to the solvent is preferably 1mmol: (8-20)mL, more preferably 1mmol: (10-15)mL.

[0031] According to the present invention, the photocatalyst is preferably one or more of 4DPIPN and 4CzIPN; the hydrogen atom transfer reagent is preferably one or more of 2-mercaptobenzoic acid methyl ester, 4-mercaptobenzoic acid methyl ester, 2-methoxybenzenethiol, triethylamine, diisopropylethylamine, triethylenediamine, thiolate and thiol; more preferably one or more of 2-mercaptobenzoic acid methyl ester, 4-mercaptobenzoic acid methyl ester and 2-methoxybenzenethiol; the solvent is preferably DMSO, DMF, THF and CH 3 CN, more preferably DMSO or DMF.

[0032] According to the present invention, there is no special requirement for the mixing method, and any method known to those skilled in the art can be used. The reaction is preferably carried out under a nitrogen atmosphere. The method for providing the nitrogen atmosphere is to remove the air in the reaction solution and the reaction bottle by filling with nitrogen, so that the nitrogen fills the entire reaction system. The reaction time is preferably 6 to 20 hours, more preferably 8 to 15 hours. The reaction temperature is preferably 20 to 30° C., more preferably 25 to 28° C. After the reaction is completed, the present invention preferably adds saturated salt water and an organic solvent for extraction, and extracts the aqueous phase 2 to 3 times, and combines the organic phases for distillation and concentration to obtain a compound of formula (II), wherein the organic solvent for extraction is preferably ethyl acetate. The present invention also preferably purifies the obtained concentrate again by column chromatography to obtain a high-purity compound of formula (II), wherein the column chromatography washing machine is preferably petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably (3 to 5):1.

[0033] The present invention provides a green synthesis method for polycyclic quinazolinone derivatives with antiviral activity. The method provided by the present invention is to react a compound with a structure of formula (I), a photocatalyst, an additive, a hydrogen atom transfer reagent and a solvent mixture under sunlight or blue light irradiation conditions to obtain a compound with a structure of formula (II) with antiviral activity. The results show that the method provided by the present invention can complete the reaction conversion under the use of longer wavelength blue light (465-470nm) or sunlight, and the amount of photocatalyst used is only 0.2mol%, with high catalytic efficiency; at the same time, a specific photocatalyst is selected and additive water is added during the reaction, which not only improves the yield, but also makes the reactants clean and pollution-free; and the amplified reaction yield is not significantly reduced, which is suitable for large-scale production and has good application prospects and research value.

[0034] The following will be described clearly and completely in conjunction with the technical solutions of the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0035] All chemicals and solvents were commercially available and used without further purification. Analytical thin layer chromatography (TLC) was performed on silica gel plates (GF254) using UV light (254 nm). For flash chromatography, 200-300 mesh silica gel (Qingdao, China) was used. Recording was at 400 MHz 1 H NMR spectrum. Relative to DMSO-d6 (δ = 2.50 ppm), CDCl 3 (δ=7.26ppm), Acteone-d 6 and CF 3 COOD (δ = 11.5 ppm), chemical shifts are in ppm. Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), integral and coupling constant J (Hz). 13 C NMR spectra were recorded at 100 MHz with complete proton decoupling. 6 (δ=39.6ppm), CDCl 3 (δ=77.2ppm), 200Acteone-d 6 (δ=29.8 ppm), chemical shifts are reported in ppm. 19 F NMR was recorded at 376 MHz. High resolution mass spectra (HRMS) were recorded on a Bruker Apex IV FTMS spectrometer.

[0036] The reaction substrates involved in this embodiment are shown in Table 1:

[0037] Table 1: Substrates involved in the embodiments of the present invention

[0038]

[0039]

[0040]

[0041] The substrates involved in the present invention are prepared according to the methods disclosed in the prior art:

[0042] (a) Synthesis of 1a-1af and lah-laq 1 The references used are as follows: Xiao, H.-X.; Li, P.-P.; Pan, B.; Liang, W.; Du, F.; Yu, Y. Photoinduced, Silver (I)-Mediated Synthesis of Ester-Substituted Fused Quinazolinones via Cascade Alkoxycarbonylation / Cyclization of Heterocycles Bearing Unactivated Alkenes. J. Org. Chem. 2023, 88, 5861-5874. The synthesis reaction equation is:

[0043]

[0044] (b) The synthesis method of substrate lag is as follows: Prasanth, K.; Anandhan, R. (2020). Visible-Light Induced Copper (I)-Catalyzed Oxidative Cyclization of o-Aminobenzamides with Methanol and Ethanol via HAT. Org. Biomol. Chem. 2020, 18, 9601-9605.

[0045] 2013, 20, 794-814. The reaction equation is:

[0046]

[0047] (c) The method for synthesizing the brominated compound is as follows: Nikas, SP; D'Souza, M.; Makriyannis, A. Enantioselective Synthesis of (10S)- and (10R)-Methyl-anandamides. Tetrahedron, 2012, 68, 6329-6337. The reaction equation is as follows:

[0048]

[0049] Example 1

[0050]

[0051] Substrate 1a (0.2 mmol, 1.0 equiv), photocatalyst 0.0004 mmol 4DPAIPN (0.2 mol%), hydrogen atom transfer reagent 0.004 mmol methyl 2-mercaptobenzoate (2.0 mol%) and solvent DMSO (2.0 mL) were added to a schlenk sealed tube and mixed. The reaction solution was heated with 20 w The mixture was irradiated with a 467 nm blue LED lamp at room temperature (25° C.) for 12 hours. After the reaction was completed, saturated saline and ethyl acetate were added to the mixture for extraction, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined, and the obtained organic phases were dried over anhydrous sodium sulfate, and then concentrated by reduced pressure distillation to remove the solvent to obtain a yellow oily substance. The yellow oily substance was separated by column chromatography, and column chromatography was performed using a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 3:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated and dried to obtain 24.8 mg of a polycyclic quinazolinone derivative having a structure of formula 2a, with a yield of 67%. Its chemical structure is:

[0052]

[0053] Characterization data: White solid, its hydrogen spectrum is as follows Figure 1 As shown, Figure 1 The hydrogen spectrum of the compound prepared in Example 1 of the present invention; the carbon spectrum is as follows Figure 2 As shown, Figure 2 This is the carbon spectrum of the compound prepared in Example 1 of the present invention.

[0054] 1 H NMR (400 MHz, CDCl 3)δ8.19 (d, J=8.0Hz, 1H), 7.67-7.61 (m, 1H), 7.58 (d, J=8.1Hz, 1H), 7.35 (t, J=7.5Hz, 1H), 4.21 (dt, J=14.0, 6.0Hz, 1H), 3.88- 3.83 (m, 1H), 2.99 (d, J=7.5Hz, 1H), 2.06 (dd, J=13.2, 6.7Hz, 1H), 1.98-1.89 (m, 2H), 1.60-1.53 ​​(m, 1H), 1.43 (d, J=7.0Hz, 3H);

[0055] 13 C NMR (100 MHz, CDCl 3 ): δ=174.0, 152.3, 139.1, 134.4, 133.2, 130.0, 128.4, 128.2, 125.2, 125.0, 124.9, 124.5, 118.9, 107.6.

[0056] Embodiments 2 to 16

[0057] The preparation method and substrate are consistent with those in Example 1. In Examples 2 to 13, when the amount of each raw material used is the same, the type of photocatalyst, the type of hydrogen atom transfer reagent or the reaction solvent is changed respectively to obtain methyl-6,7,8,9-tetrahydro-11 hydrogen-pyrido[2,1-b]quinazolin-11-one; Example 14, under the reaction conditions of Example 1, 5.0 equiv of water as an additive is added to prepare methyl-6,7,8,9-tetrahydro-11 hydrogen-pyrido[2,1-b]quinazolin-11-one. Example 1 Under the reaction conditions of Example 1, 5.0 equiv of formic acid was added as an additive to prepare methyl-6,7,8,9-tetrahydro-11 hydrogen-pyrido [2,1-b] quinazolin-11-one. Example 16, based on the reaction conditions of Example 1, changed the amount of the catalyst to 0.02 mol% to obtain methyl-6,7,8,9-tetrahydro-11 hydrogen-pyrido [2,1-b] quinazolin-11-one; the reaction results are shown in Table 1, which is a summary of the reaction conditions and yields of Examples 1 to 16.

[0058] Table 1

[0059]

[0060] Among them, ArSH, ArSH-1 and ArSH-2 are methyl 2-mercaptobenzoate, 2-methoxythiophenol and methyl 4-mercaptobenzoate, respectively.

[0061] It can be seen from the table that the photocatalysts 4DPAIPN, 4CzIPN and 3CzClIPN have good catalytic effects, the reaction effects of ArSH, ArSH-1 and ArSH-2 among the hydrogen atom transfer agents are better, and the reaction effects of DMSO, THF and DMF as reaction solvents are better. It can be seen from Example 14 that after adding N water as an additive, the reaction yield is significantly improved.

[0062] Embodiment 17

[0063] 0.2 mmol of substrate 1b, 0.0004 mmol of 4DPAIPN (0.2 mol%) of photocatalyst, 0.004 mmol of methyl 2-mercaptobenzoate (2.0 mol%) of hydrogen atom transfer reagent, 1 mmol of water (5 equiv) of additive and DMSO (2.0 mL) of solvent were added into a schlenk sealed tube and mixed. Under nitrogen atmosphere, the reaction solution was irradiated with a 20 W 467 nm blue light LED lamp at room temperature for 12 hours. After the reaction, saturated brine and ethyl acetate were added to the mixed solution for extraction, and the aqueous phase was extracted three times with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to obtain a yellow oil. The yellow oil was separated by column chromatography using a mixed solution of petroleum ether (PE) and ethyl acetate EA (PE / EA=3 / 1) as an eluent for column chromatography. The eluate containing the target compound was collected, the solvent was evaporated and dried to obtain 38.3 mg of white solid 2b with a yield of 84%.

[0064]

[0065] Characterization data: white solid, (38.3 mg, 84%).

[0066] 1 H NMR (400 MHz, CDCl 3 ): δ7.53 (t, J=8.0Hz, 1H), 7.47 (d, J=8.0Hz, 1H), 7.16 (d, J=7.6Hz, 1H), 4.21-4.14 (m, 1H), 3.91-3.85 (m, 1H), 3 .04-2.87(m, 1H), 2.87(s, 3H), 2.11-2.08(m, 1H), 2.03-1.96(m, 2H), 1.66-1.59(m, 1H), 1.48(d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3): δ162.8, 158.1, 148.9, 140.7, 133.1, 128.6, 124.9, 118.7, 42.0, 35.4, 27.6, 23.1, 20.3, 19.5.

[0067] Embodiment 18

[0068] According to the preparation method of Example 17, only different substrates were changed to obtain a series of polycyclic quinazolinone derivatives, and the results and characterization data are as follows:

[0069]

[0070] Characterization data: white solid (39.7 mg, yield 87%).

[0071] 1 H NMR (400 MHz, CDCl 3 ): δ8.10 (d, J=8.0Hz, 1H), 7.55 (d, J=7.6Hz, 1H), 7.31-7.26 (m, 1H), 4.29-4.23 (m, 1H), 3.98-3.91 (m, 1H), 3. 04-2.98 (m, 1H), 2.60 (s, 3H), 2.15-2.13 (m, 1H), 2.04-1.97 (m, 2H), 1.60-1.58 (m, 1H), 1.51 (d, J=6.8Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ162.6, 156.9, 145.9, 135.3, 134.4, 125.5, 124.2, 120.0, 41.9, 35.7, 27.8, 20.6, 19.1, 17.1.

[0072]

[0073] Characterization data: white solid, (33.7 mg, yield 74%).

[0074] 1 H NMR (400 MHz, CDCl 3 ): δ8.13 (d, J=8.0Hz, 1H), 7.44 (s, 1H), 7.27-7.23 (m, 1H), 4.31-4.24 (m, 1H), 3.94-3.87 (m, 1H) ), 3.04-3.00 (m, 1H), 2.48 (s, 3H), 2.11-1.97 (m, 3H), 1.66-1.61 (m, 1H), 1.49 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl3 ): δ162.1, 158.5, 147.5, 144.9, 127.7, 126.4, 117.8, 42.0, 35.4, 27.6, 21.8, 20.2, 19.4.

[0075]

[0076] Characterization data: white solid, (39.7 mg, yield 82%).

[0077] 1 H NMR (400 MHz, CDCl 3 ): δ7.87(s, 1H), 7.36(s, 1H), 4.27-4.21(m, 1H), 3.96-3.89(m, 1H), 2.99-2.96(m, 1H), 2.55(s, 3H), 2.41(s, 3H), 2.12-1.96(m, 3H), 1.58-1.56(m, 1H), 1.48(d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ162.6, 156.0, 136.0, 135.4, 135.1, 123.5, 119.8, 99.9, 41.9, 35.6, 27.9, 21.3, 20.7, 19.1, 17.0.

[0079]

[0080] Characterization data: white solid, (31.6 mg, yield 68%).

[0081] 1 H NMR (400 MHz, CDCl 3 ): δ7.63-7.60 (m, 1H), 7.43 (d, J=8.0Hz, 1H), 7.08-7.03 (m, 1H), 4.26-4.20 (m, 1H), 3.93-3 .86 (m, 1H), 3.08-2.99 (m, 1H), 2.15-1.98 (m, 3H), 1.68-1.62 (m, 1H), 1.49 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3): δ162.4, 159.7 (J=16.0Hz), 159.2 (J=4.0Hz), 149.3, 134.2 (d, J=10.5Hz), 1 22.5, 112.4 (d, J=21.2Hz), 109.9 (d, J=6.2Hz), 42.0, 35.4, 27.4, 20.1, 19.4; 19 F NMR (376 MHz, CDCl 3 ): δ-111.3; HRMS(ESI)m / zcalcd for C 13 H 13 FN 2 O[M+H + ]: 233.1085, found 233.1077.

[0082]

[0083] Characterization data: white solid, (34.3 mg, yield 74%).

[0084] 1 H NMR (400 MHz, CDCl 3 ): δ8.03 (d, J=8.0Hz, 1H), 7.45-7.40 (m, 1H), 7.37-7.27 (m, 1H), 4.28-4.22 (m, 1H), 3.99-3 .92 (m, 1H), 3.13-3.08 (m, 1H), 2.13-2.00 (m, 3H), 1.66-1.64 (m, 1H), 1.52 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.4, 159.2, 157.9, 155.4,

[0085] 137.1 (d, J=11.7Hz), 125.9 (d, J=7.6Hz), 122.0 (d, J=4.4Hz), 119.2 (d, J=19.1Hz), 42.4, 35.7, 27.5, 20.1, 19.6; 19 F NMR (376 MHz, CDCl 3 ): δ-126.4.

[0086]

[0087] Characterization data: white solid, (32.3 mg, yield 65%).

[0088] 1 H NMR (400 MHz, CDCl3 ): δ8.21 (d, J=2.4Hz, 1H), 7.63 (dd, J=8.4, 2.4Hz, 1H), 7.57 (d, J=8.4Hz, 1H), 4.30-4.24 (m, 1H), 3.96-3.88 (m, 1H), 3.04-2.99 (m, 1H), 2.15-2.11 (m, 1H), 2.03-2.00 (m, 2H), 1.68-1.62 (m, 1H), 1.49 (d, J=6.8Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.2, 158.7, 145.9, 134.4, 131.6, 128.5, 125.8, 121.1, 42.3, 35.5, 27.5, 20.1, 19.3; HRMS (ESI) m / z calcd for C 13 H 14 C1N 2 O[M+H + ]: 249.0789, found 249.0787.

[0089]

[0090] Characterization data: white solid, (41.7 mg, yield 74%).

[0091] 1 H NMR (400 MHz, CDCl 3 ): δ8.55 (d, J=4.0Hz, 1H), 7.90 (dd, J=8.0, 4.0Hz, 1H), 7.73 (d, J=8.0Hz, 1H), 4.32-4.26 (m, 1H), 3 .98-3.91(m, 1H), 3.08-3.03(m, 1H), 2.17-2.01(m, 3H), 1.70-1.63(m, 1H), 1.51(d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.6,

[0092] 160.7, 149.5, 130.1 (d, J=8.0Hz), 127.9 (d, J=27.3Hz), 124.6 (d, J=3.2Hz), 124.5 (d, J=4.7Hz), 122.4, 119.9, 42.4, 35.7, 27.4, 20.1, 19.3; 19 F NMR (376 MHz, CDCl 3)δ-62.1; HRMS (ESI)m / z calcd for C 14 H 14 F 3 N 2 O[M+H + ]: 283.1053, found 283.1057.

[0093]

[0094] Characterization data: white solid, (41.4 mg, 85% yield).

[0095] 1 H NMR (400 MHz, CDCl 3 ): δ7.61-7.56(m, 2H), 7.33-7.29(m, 1H), 4.32-4.25(m, 1H), 3.97-3.92(m, 1H), 3.91(s, 3H), 3 .04-2.99(m, 1H), 2.13-2.11(m, 1H), 2.02-1.97(m, 2H), 1.66-1.60(m, 1H), 1.48(d, J=7.2, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ162.0, 157.7, 156.0, 142.1, 128.3, 124.4, 120.7, 105.6, 55.7, 42.1, 35.2, 27.6, 20.2, 19.4; HRMS (ESI) m / zcalcd for C14H17N2O 2 [M+H + ]: 245.1285, found 245.1284.

[0096]

[0097] Characterization data: white solid, (38.6 mg, yield 79%).

[0098] 1 H NMR (400 MHz, CDCl 3 ): δ7.85 (d, J=8.0Hz, 1H), 7.35 (t, J=8.0Hz, 1H), 7.15 (d, J=8.0Hz, 1H), 4.22-4.17 (m, 1H), 4.0 4-3.97(m, 4H), 3.18-3.17(m, 1H), 2.13-1.96(m, 3H), 1.67-1.65(m, 1H), 1.53(d, J=7.2Hz, 3H); 13C NMR (100 MHz, CDCl 3 ): δ162.1, 157.8, 154.0, 138.2, 126.2, 121.3, 118.0, 113.8, 56.3, 42.6, 35.7, 27.6, 20.1; HRMS (ESI) m / z calcd forC14H17N2O 2 [M+H + ]: 245.1285, found 245.1281.

[0099]

[0100] Characterization data: white solid, (45.7 mg, yield 83%).

[0101] 1 H NMR (400 MHz, CDCl 3 ): δ7.50 (s, 1H), 6.98 (s, 1H), 4.24-4.17 (m, 1H), 3.95 (s, 6H), 3.92-3.83 (m, 1H) , 2.98-2.92(m, 1H), 2.06-1.90(m, 3H), 1.56-1.54(m, 1H), 1.42(d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.5, 157.2, 154.8, 148.6, 143.7, 113.4, 107.0, 105.4, 56.2, 42.1, 35.3, 27.6, 20.2, 19.5.

[0102]

[0103] Characterization data: white solid, (31.7 mg, yield 69%). 1 H NMR (400 MHz, CDCl 3 ): δ8.04 (dd, J=8.4Hz, 1H), 6.76-6.71 (m, 2H), 4.27-4.20 (m, 1H), 4.17 (s, 2H), 3.91-3.8 5 (m, 1H), 2.99-2.96 (m, 1H), 2.11-1.94 (m, 3H), 1.66-1.60 (m, 1H), 1.46 (d, J=6.8Hz, 3H). 13 C NMR (100 MHz, CDCl 3): δ161.8, 158.9, 151.9, 149.4, 128.3, 115.1, 111.7, 108.2, 41.8, 35.4, 27.7, 20.2, 19.6; HRMS (ESI) m / z calcd for C 13 H 16 N 3 O[M+H + ]: 230.1288, found 230.1290.

[0104]

[0105] Characterization data: white solid, (37.4 mg, yield 82%).

[0106] 1 H NMR (400 MHz, CDCl 3 ): δ8.27-8.25(m, 1H), 7.73-7.69(m, 1H), 7.64(d, J=8.0Hz, 1H), 7.44-7.40(m, 1H), 4.19-4.12(m, 1H ), 4.05-4.00 (m, 1H), 2.87-2.84 (m, 1H), 2.20-1.95 (m, 4H), 1.76-1.69 (m, 2H), 1.06 (t, J=7.6Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ162.3, 157.9, 147.4, 134.0, 126.7, 126.5, 126.0, 120.1, 42.2, 41.9, 26.6, 23.9, 20.1, 11.5; HRMS (ESI) m / z calcd for C14H17N2O[M+H + ]: 229.1335, found 229.1337.

[0107]

[0108] Characterization data: white solid, (51.6 mg, yield 89%).

[0109] 1 H NMR (400 MHz, CDCl 3): δ8.28 (dd, J=8.0, 1.2Hz, 1H), 7.73-7.69 (m, 2H), 7.46-7.42 (m, 1H), 7.33-7.23 (m, 5H), 4.20-4.15 (m, lH), 3. 95-3.93(m, 1H), 3.72-3.68(m, 1H), 3.19-3.17(m, 1H), 2.90-2.84(m, 1H), 1.96-1.88(m, 3H), 1.58-1.56(m, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ162.2, 157.1, 147.3, 139.5, 134.2, 129.2, 128.4, 126.8, 126.6, 126.3, 120.2, 42.1, 42.1, 39.2, 23.8, 20.0; HRMS (ESI) m / z calcd for C 19 H 19 N 2 O[M+H + ]: 291.1492, found 291.1487.

[0110]

[0111] Characterization data: white solid, (58.2 mg, yield 91%).

[0112] 1 H NMR (400 MHz, CDCl 3 ): δ8.28 (dd, J=8.0, 1.6Hz, 1H), 7.74-7.69 (m, 2H), 7.45-7.41 (m, 1H), 7.17 (d, J=8.0Hz, 2H), 6.88-6.84 (m, 2H), 4.19-4.13 (m, 1H), 3.9 7-3.92 (m, 1H), 3.80 (s, 3H), 3.60 (dd, J=13.6, 4.0Hz, 1H), 3.15-3.13 (m, 1H), 2.88-2.82 (m, 1H), 2.01-1.85 (m, 3H), 1.60-1.56 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ162.3, 158.1, 157.2, 147.3, 134.0, 131.4, 130.2, 126.8, 126.6, 126.1, 120.2, 113.8, 55.2, 42.3, 42.2, 38.4, 23.8, 20.1; HRMS (ESI) m / z calcd for C 20H 21 N 2 O 2 [M+H + ]: 321.1598, found 321.1592.

[0113]

[0114] Characterization data: white solid, (34.8 mg, yield 87%).

[0115] 1 H NMR (400 MHz, CDCl 3 ): δ8.29-8.27(m, 1H), 7.76-7.66(m, 2H), 7.46-7.42(m, 1H), 4.31-4.24(m, 1H), 4.04-3.9 7 (m, 1H), 3.37-3.28 (m, 1H), 2.52-2.46 (m, 1H), 1.91-1.85 (m, 1H), 1.49 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ162.3, 161.0, 149.2, 134.0, 126.9, 126.3, 126.1, 120.6, 44.5, 38.7, 28.5, 17.1.

[0116]

[0117] Characterization data: white solid, (36.0 mg, yield 84%).

[0118] 1 H NMR (400 MHz, CDCl 3 ): δ7.57-7.53(m, 2H), 7.18-7.16(m, 1H), 4.25-4.19(m, 1H), 4.00-3.93(m, 1H), 3.35- 3.24 (m, 1H), 2.88 (s, 3H), 2.50-2.45 (m, 1H), 1.88-1.83 (m, 1H), 1.47 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.9, 161.7, 150.9, 140.9, 133.1, 128.8, 125.1, 119.1, 44.5, 38.7, 28.4, 22.9, 17.2.

[0119]

[0120] Characterization data: white solid, (41.0 mg, yield 90%).

[0121] 1 H NMR (400 MHz, CDCl 3 ): δ8.13 (d, J=8.0Hz, 1H), 7.56 (d, J=7.6Hz, 1H), 7.31 (t, J=7.6Hz, 1H), 4.30-4.23 (m, 1H), 4.02-3.97 (m, 1H), 3.36-3.27 (m, 1H), 2.62 (s, 3H), 2.50-2.45 (m, 1H), 1.88-1.82 (m, 1H), 1.48 (d, J=7.2, Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.4, 160.9, 147.9, 135.5, 134.6, 125.5, 124.0, 120.5, 44.4, 38.7, 28.7, 17.4, 17.2.

[0122]

[0123] Characterization data: white solid, (42.4 mg, 93% yield). 1 H NMR (400 MHz, CDCl 3 ): δ8.15 (d, J=8.0Hz, 1H), 7.48 (s, 1H), 7.25 (d, J=8.0Hz, 1H), 4.29-4.22 (m, 1H), 4.02-3. 95 (m, 1H), 3.34-3.28 (m, 1H), 2.52-2.45 (m, 4H), 1.89-1.84 (m, 1H), 1.47 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ162.4, 160.9, 149.3, 145.0, 127.7, 126.6, 126.0, 118.1, 44.4, 38.6, 28.5, 21.8.17.1.

[0124]

[0125] Characterization data: white solid, (42.6 mg, yield 88%).

[0126] 1 H NMR (400 MHz, CDCl 3): δ7.91(s, 1H), 7.38(s, 1H), 4.28-4.22(m, 1H), 4.00-3.95(m, 1H), 3.32-3.26(m, 1H), 2.57 (s, 3H), 2.49-2.44 (m, 1H), 2.42 (s, 3H), 1.86-1.81 (m, 1H), 1.46 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ162.4, 160.9, 149.3, 144.9, 127.7, 126.6, 126.1, 118.1, 44.4, 38.7, 28.5, 21.8, 17.1.

[0127]

[0128] Characterization data: white solid, (37.0 mg, yield 85%).

[0129] 1 H NMR (400 MHz, CDCl 3 ): 1 H NMR (400MHz,) δ7.66-7.60 (m, 1H), 7.46 (d, J=8.0Hz, 1H), 7.09-7.04 (m, 1H), 4.29-4.22 (m, 1H), 4 .02-3.94(m, 1H), 3.34-3.28(m, 1H), 2.53-2.46(m, 1H), 1.90-1.84(m, 1H), 1.47(d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ163.2, 162.7, 160.1, 158.1 (d, J=3.3Hz), 151.6, 134.2 (d, J=10.0Hz), 122.8 (d, J=4.0Hz), 112.6 (d, J=20.7Hz), 110.4 (d, J=6.5Hz), 44.5, 38.8, 28.2, 17.0; 19 F NMR (376MHz, CDCl3): δ-111.0.

[0130]

[0131] Characterization data: white solid, (28.5 mg, yield 61%). 1 H NMR (400 MHz, CDCl 3): δ8.20(s, 1H), 7.63-7.58(m, 2H), 4.28-4.22(m, 1H), 4.03-3.94(m, 1H), 3. 34-3.24(m, 1H), 2.52-2.46(m, 1H), 1.89-1.84(m, 1H), 1.46(d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ162.6, 159.9, 147.8, 134.3, 131.8, 128.6, 125.6, 121.7, 44.6, 38.7, 28.5, 17.0.

[0132]

[0133] Characterization data: white solid, (38.6 mg, yield 84%).

[0134] 1 H NMR (400 MHz, CDCl 3 ): δ7.65-7.60(m, 2H), 7.34-7.28(m, 1H), 4.30-4.24(m, 1H), 4.04-3.96(m, 1H), 3.91(s, 3 H), 3.33-3.28 (m, 1H), 2.51-2.47 (m, 1H), 1.90-1.87 (m, 1H), 1.47 (dd, J=7.2, 2.0Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ160.8, 160.1, 157.9, 143.9, 128.4, 124.2, 121.3, 105.8, 55.7, 44.5, 38.4, 28.7, 17.2; HRMS (ESI) m / z calcd for C 13 H 15 N 2 O 2 [M+H + ]: 231.1128, found 231.1122.

[0135]

[0136] Characterization data: white solid, (39.1 mg, yield 85%).

[0137] 1 H NMR (400 MHz, CDCl 3): δ7.78 (d, J=8.0Hz, 1H), 7.30 (t, J=8.0Hz, 1H), 7.09 (d, J=8.0Hz, 1H), 4.20-4.14 (m, 1H), 4.00-3.95 (m, 1H), 3.92 (s, 3H), 3.33-3.31 (m, 1H), 2.42-2.38 (m, 1H), 1.83-1.77 (m, 1H), 1.42 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.7, 160.7, 154.1, 126.2, 121.6, 117.5, 113.7, 56.1, 44.5, 38.8, 28.3, 17.6; HRMS(ESI)m / zcalcd for C 13 H 15 N 2 O 2 [M+H+]: 231.1128, found 231.1121.

[0138]

[0139] Characterization data: white solid, (45.2 mg, 87% yield).

[0140] 1 H NMR (400 MHz, CDCl 3 ): δ7.52 (s, 1H), 7.03 (s, 1H), 3.94-3.90 (m, 1H), 3.92 (s, 6H), 3.28-3.19 (m, 1H), 2.45-2.37 (m, 1H), 1.82-1.77 (m, 1H), 1.40 (d, J=7.0Hz, 3H); 13 CNMR (100MHz, CDCl 3 ): δ161.1, 160.3, 154.6, 148.5, 145.4, 113.7, 107.4, 105.3, 56.2, 56.2, 44.6, 38.6, 28.6, 17.1.

[0141]

[0142] Characterization data: white solid, (36.5 mg, yield 80%).

[0143] 1 H NMR (400 MHz, CDCl 3): δ8.30-8.28 (m, 1H), 7.73-7.69 (m, 2H), 7.46-7.42 (m, 1H), 4.29-4.23 (m, 1H), 4.07-3.99 (m, 1H), 3.26-3.2 2 (m, lH), 2.48-2.44 (m, lH), 2.12-2.11 (m, 1H), 1.95-1.90 (m, 1H), 1.57-1.51 (m, 3H), 1.02 (t, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.9, 161.0, 149.3, 134.0, 127.0, 126.3, 126.1, 120.7, 44.8, 43.8, 34.4, 34.3, 26.2, 20.5, 14.0; HRMS (ESI) m / z calcd for C 14 H 17 N 2 O[M+H + ]: 229.1335, found 229.1333.

[0144]

[0145] Characterization data: white solid, (41.0 mg, yield 76%).

[0146] 1 H NMR (400 MHz, CDCl 3 ): δ8.28 (dd, J=8.0Hz, 2.4Hz, 1H), 7.72-7.69 (m, 2H), 7.46-7.42 (m, 1H), 4.29-4.22 (m, 1H), 4.06-4.00 (m, 1H), 3.25-3.19 (m, 1H), 2.4 8-2.44(m, 1H), 2.17-2.10(m, 1H), 1.95-1.90(m, 1H), 1.61-1.54(m, 1H), 1.51-1.43(m, 2H), 1.41-1.30(m, 6H), 0.90(t, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.9, 161.0, 149.3, 134.0, 126.9, 126.3, 126.1, 120.7, 44.8, 44.0, 32.3, 31.7, 29.2, 27.2, 26.2, 22.6, 14.0; HRMS (ESI) m / zcalcd for C 17 H 23 N2 O[M+H + ]: 271.1805, found 271.1807.

[0147]

[0148] Characterization data: white solid, (50.2 mg, yield 91%).

[0149] 1 H NMR (400 MHz, CDCl 3 ): δ8.28(d, J=8.0Hz, 1H), 7.74-7.72(m, 2H), 7.47-7.43(m, 1H), 7.31-7.27(m, 2H), 7.25-7.22(m, 3H), 4.08- 4.01(m, 1H), 3.96-3.89(m, 1H), 3.54-3.50(m, 2H), 2.90-2.84(m, 1H), 2.29-2.21(m, 1H), 2.00-1.90(m, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ160.9, 160.8, 149.1, 138.4, 134.0, 128.9, 128.6, 126.9, 126.6, 126.3, 120.1, 45.4, 44.6, 37.9, 25.5; HRMS (ESI) m / z calcd for C 18 H 17 N 2 O[M+H + ]: 277.1335, found 277.1330.

[0150]

[0151] Characterization data: white solid, (35.6 mg, yield 78%).

[0152] 1 H NMR (400 MHz, CDCl 3 ): δ8.28 (dd, J=8.0Hz, 1.2Hz, 1H), 7.72-7.69 (m, 2H), 7.46-7.42 (m, 1H), 4.23-4.16 (m, 1H), 4.09-4.02 (m, 1H), 3.27 -3.22 (m, lH), 2.53-2.48 (m, 1H), 2.30-2.26 (m, 1H), 2.1-2.07 (m, 1H), 1.12 (d, J=4.0Hz, 3H), 0.91 (d, J=4.0Hz, 3H); 13C NMR (100 MHz, CDCl 3 ): δ161.2, 161.0, 149.3, 134.0, 127.0, 126.2, 126.0, 120.6, 49.6, 45.1, 29.6, 20.7, 20.6, 17.3; HRMS (ESI) m / z calcd for C 14 H 17 N 2 O[M+H + ]:229.1335, found229.1336.

[0153]

[0154] Characterization data: white solid, (35.5 mg, yield 83%).

[0155] 1 H NMR (400 MHz, CDCl 3 ): δ8.28 (dd, J=8.0Hz, 1.2Hz, 1H), 7.72-7.68 (m, 2H), 7.46-7.42 (m, 1H), 4.83-4.79 (m, 1H), 3.46 -3.40 (m, 1H), 2.19-2.14 (m, 1H), 2.06-1.98 (m, 1H), 1.50 (d, J = 7.2Hz, 3H), 1.48 (d, J = 7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ161.8, 160.7, 149.3, 134.0, 126.9, 126.3, 126.1, 121.1, 53.1, 36.6, 36.5, 18.7, 16.6; HRMS(ESI)m / zcalcd for C 13 H 15 N 2 O[M+H + ]: 215.1179, found 215.1177.

[0156]

[0157] Characterization data: white solid, (19.3 mg, 45% yield). 1 H NMR (400 MHz, CDCl 3): δ8.28 (d, J=8.8Hz, 1H), 7.73-7.68 (m, 2H), 7.44-7.40 (m, 1H), 4.12 (t, J=6.8Hz, 2H), 2.10 (t, J=6.8Hz, 2H), 1.25 (s, 3H), 1.24 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ164.9, 161.1, 149.5, 134.0, 127.1, 126.3, 126.0, 120.7, 43.4, 43.1, 35.4, 25.9, 21.9, 21.9.

[0158]

[0159] Characterization data: white solid, (19.3 mg, 45% yield). 1 H NMR (400 MHz, CDCl 3 ): δ8.26 (dd, J=8.0Hz, 1.2Hz, 1H), 7.74-7.69 (m, 1H), 7.61 (d, J=8.0Hz, 1H), 7.44-7.41 (m, 1H), 4.39-4.33 (m, 1H), 3 .86-3.79 (m, 1H), 3.14-3.08 (m, 1H), 2.65-2.58 (m, 1H), 2.17-2.11 (m, 2H), 1.62-1.59 (m, 1H), 1.15 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ162.1, 154.4, 147.3, 134.1, 126.5, 126.3, 126.0, 120.3, 42.2, 40.1, 30.1, 26.1, 21.1; HRMS(ESI)m / z calcd forC 13 H 15 N 2 O[M+H + ]: 215.1179, found 215.1177.

[0160]

[0161] Characterization data: white solid, (13.1 mg, 25% yield). 1 H NMR (400 MHz, CDCl 3): δ8.62 (d, J=7.6Hz, 1H), 8.43 (d, J=8.0Hz, 1H), 7.79-7.78 (m, 2H), 7.54-7.50 (m, 1H), 7.44-7.42 (m, 2H), 7.37-7.35 (m, 1H), 1.65 (s, 6H); 13 C NMR (100 MHz, CDCl 3 ): δ164.6, 147.6, 138.3, 137.8, 134.3, 127.3, 126.8, 126.6, 126.5, 122.4, 121.4, 117.2, 45.1, 26.7.

[0162]

[0163] Characterization data: white solid, (25.7 mg, 49% yield).

[0164] 1 H NMR (400 MHz, CDCl 3 ): δ8.35 (dd, J=8.0, 1.2Hz, 1H), 8.22 (d, J=8.0Hz, 1H), 7.77-7.73 (m, 1H), 7.65-7.63 (m, 1H), 7. 49-7.45 (m, 1H), 7.35-7.27 (m, 3H), 3.16-3.11 (m, 2H), 2.91-2.85 (m, 1H), 1.34 (d, J=7.2Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ160.7, 153.9, 146.2, 136.1, 134.5, 133.7, 127.5, 127.0, 126.6, 126.6, 126.5, 125.7, 124.0, 122.0, 40.8, 30.4, 17.9; HRMS (ESI) m / z calcd for C 17 H 15 N 2 O[M+H + ]: 263.1179, found 263.1178.

[0165]

[0166] Characterization data: white solid, (13.7 mg, 12% yield).

[0167] 1 H NMR (400 MHz, CDCl 3): δ8.26 (dd, J=8.0, 2.4Hz, 1H), 7.72 (dt, J=8.0, 2.4Hz, 1H), 7.64 (d, J=8.0Hz, 1H), 7.43 (t, J=8.0 Hz, 1H), 4.34 (m, 2H), 3.06-3.03 (m, 2H), 2.02-1.98 (m, 4H), 1.63-1.59 (m, 2H), 1.44-1.43 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ161.8, 159.4, 147.6, 134.1, 126.7, 126.6, 126.2, 120.3, 43.0, 35.5, 30.6, 28.6, 26.0, 24.2; HRMS (ESI) m / z calcdfor C 14 H 17 N 2 O[M+H + ]: 229.1335, found 229.1333.

[0168] Embodiment 19

[0169] 1a (10 mmol, 2.14 g), a photocatalyst 0.02 mmol 4DPAIPN (0.2 mol%), a hydrogen atom transfer reagent 0.2 mmol 2-mercaptobenzoic acid methyl ester (2.0 mol%), an additive 50 mmol water (5 equiv) and a solvent DMSO (40 mL) were added to a flask and mixed. The air was expelled from the mixed solution and nitrogen was introduced. The reaction solution under nitrogen atmosphere was irradiated with a 20 W 467 nm blue light LED lamp at room temperature for 12 hours. After the reaction was completed, saturated brine and ethyl acetate were added to the mixed solution for extraction, and the aqueous phase was extracted three times with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to obtain a yellow oil. The yellow oil was separated by column chromatography using a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 3:1 as an eluent for column chromatography. The eluent containing the target compound was collected, the solvent was evaporated and dried to obtain 1.58 g of white solid 2a, and the yield was 72%.

[0170] The above embodiments are only used to help understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing a polycyclic quinazolinone derivative having antiviral activity, comprising: The compound of formula (I), a photocatalyst, a hydrogen atom transfer agent and a solvent are mixed and reacted under sunlight or blue light to obtain a compound of formula (II), which is a polycyclic quinazolinone derivative with antiviral activity; in, Said n is 0, 1, 2 or 3; Said R1 is hydrogen; R2 is hydrogen, C6-C12 aryl, C1-C6 alkyl or halogen; R3 is hydrogen, C6-C12 aryl, C1-C6 alkyl or halogen; R4 is hydrogen, C1-C6 alkyl or halogen; R is hydrogen, C1-C3 alkyl with substituents, C1-C3 alkyl without substituents, C1-C3 alkoxy, halogen or amino; The photocatalyst is one or more of 4DPIPN, 4CzIPN and 3CzCIIPN; The hydrogen atom transfer reagent is a sulfur- and nitrogen-containing organic compound or a salt of a sulfur- and nitrogen-containing organic compound.

2. The preparation method according to claim 1, characterized in that: An additive is also added into the reaction, and the additive is one or more of water, formic acid, acetic acid, benzoic acid and p-toluenesulfonic acid.

3. The preparation method according to claim 1, characterized in that: R2 is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, phenyl or fluorine; R3 is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, phenyl or fluorine; The R4 is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, n-hexyl or fluorine.

4. The preparation method according to claim 1, characterized in that: The R is hydrogen, methyl, ethyl, propyl, trifluoromethyl, trifluoroethyl, fluorine, chlorine, bromine, methoxy, ethoxy or amino.

5. The preparation method according to claim 1, characterized in that: The molar ratio of the compound of formula (I) to the photocatalyst is 1:(0.001-0.005).

6. The preparation method according to claim 1, characterized in that: The hydrogen atom transfer reagent is one or more of 4-mercaptobenzoic acid, methyl thiosalicylate, 2-methoxythiophenol, triethylamine, diisopropylethylamine, triethylenediamine, thiol and thiolate.

7. The preparation method according to claim 1, characterized in that: The molar ratio of the compound of formula (I) to the hydrogen atom transfer reagent is 1:(0.01-0.05).

8. The preparation method according to claim 1, characterized in that: The solvent is one or more of DMSO, DMF, THF and CH3CN.

9. The preparation method according to claim 2, characterized in that: The molar ratio of the compound of formula (I) to the additive is 1:(1-8).

10. The preparation method according to claim 1, characterized in that: The compound of formula (II) has the following structure:

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