2,3-disubstituted quinazolinones and methods for their preparation

Abstract

This invention provides a 2,3-disubstituted quinazolinone compound and its preparation method, relating to the field of organic synthesis technology. The preparation method of the 2,3-disubstituted quinazolinone compound provided by this invention does not use an oxidizing agent and includes the following steps: mixing an aniline compound, a phenyl isothiocyanate compound, an indigo compound, a base, and an organic solvent, and performing a coupling addition reaction to obtain the 2,3-disubstituted quinazolinone compound. This invention can obtain 2,3-disubstituted quinazolinone compounds through a one-step coupling addition reaction. The preparation method is simple, easy to control, economical, and uses inexpensive and readily available raw materials. This invention does not use an oxidizing agent during the preparation process and has the advantage of good functional group tolerance. Furthermore, the 2,3-disubstituted quinazolinone compound prepared by this invention has a purity of 98.5%–99.9%, and has significant market potential.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a 2,3-disubstituted quinazolinone compound and its preparation method. Background Technology

[0002] 2,3-Disubstituted quinazolinone derivatives are a class of nitrogen-containing heterocyclic compounds with diverse biological and pharmaceutical activities. Due to their rich pharmacological activities, including anticancer, antibacterial, and anticonvulsant effects, many quinazolinone compounds with these activities are used as drugs in everyday life. For example, raltitrexed, which specifically inhibits thymidylate synthase (TS), is used as a first-line treatment for advanced colorectal cancer. Therefore, the synthesis of 2,3-disubstituted quinazolinones has attracted considerable attention.

[0003] Currently, the main methods for synthesizing 2,3-disubstituted quinazolinone compounds are:

[0004] Feng-Cheng Jia et al. (An-Xin Wu, et al. Divergent Synthesis of Quinazolin-4(3H)-ones and Tryptanthrins Enabled by a tert-Butyl Hydroperoxide / K3PO4-Promoted Oxidative Cyclization of Isatins at Room Temperature. Org. Lett. 2016, 18(12), 2942-2945. DOI:10.1021 / acs.orglett.6b01291) reported the generation of quinazolinone compounds, such as: indigo and benzylamidine hydrochloride, catalyzed by tert-butyl hydroperoxide and potassium phosphate.

[0005]

[0006] Meilin Liu et al. (Meilin Liu, Miaomiao Shu, Jinkun Huang, et al. Synthesis of Pyrido-Fused Quinazolinone Derivatives via Copper-Catalyzed DominoReaction. Org. Lett. 2016, 18, (4), 824-827. DOI: 10.1021 / acs.orglett.6b00113.) reported the synthesis of quinazolinone compounds, such as indigo and 2-bromopyridine, catalyzed by copper acetate and sodium bicarbonate.

[0007]

[0008] Anil Kumar Soda et al. (Indrasena Reddy Bontha, Sai Krishna Chilaka, Sridhar Madabhushi, et al. Lewis Acid-catalyzed Tandem Synthesis of Quinazoline-2,4-diones by Reaction of Isatins with Aryl / Alkyl Amines using TBHP as Oxidant. Asian J.Org.Chem, 2022, 11(7):e202200193. DOI:10.1002 / ajoc.202200193.) reported the generation of quinazoline-2,4-diones from indigo and aniline under the catalysis of bismuth trifluoromethanesulfonate and TBHP, such as:

[0009]

[0010] However, the above preparation methods have drawbacks, such as the need to use oxidants and the limited range of substrates. Summary of the Invention

[0011] The purpose of this invention is to provide a 2,3-disubstituted quinazolinone compound and its preparation method. The preparation method provided by this invention does not use an oxidizing agent and has a wide range of substrate options.

[0012] To achieve the objectives of this invention, the following technical solutions are provided:

[0013] A method for preparing 2,3-disubstituted quinazolinone compounds without using an oxidizing agent includes the following steps:

[0014] A aniline compound, a phenyl isothiocyanate compound, an indigo compound, a base reagent, and an organic solvent are mixed and subjected to a coupling addition reaction to obtain the 2,3-disubstituted quinazolinone compound.

[0015] The aniline compounds have the structure shown in Formula I:

[0016]

[0017] The phenyl isothiocyanate compound has the structure shown in Formula II:

[0018]

[0019] The indigo compounds have the structure shown in Formula III:

[0020]

[0021] Wherein, R1 is -H, a halogen group, or an alkyl group having 1 to 3 carbon atoms;

[0022] R2 is -H, a halogen group, a nitro group, an alkyl group with 1 to 3 carbon atoms, or an alkoxy group with 1 to 3 carbon atoms;

[0023] R3 is -H, a halogen group, an alkyl group with 1 to 3 carbon atoms, or an alkoxy group with 1 to 3 carbon atoms. Preferably, the aniline compound is aniline, 2-iodoaniline, 4-methylaniline, 4-iodoaniline, 4-fluoroaniline, 4-chloroaniline, or 2,4,6-trimethylaniline.

[0024] Preferably, the phenyl isothiocyanate compound is phenyl isothiocyanate, 2-fluorophenyl thioisocyanate, 2-chlorophenyl thioisocyanate, 2-bromophenyl thioisocyanate, 4-nitrophenyl thioisocyanate, 4-ethylphenyl thioisocyanate, or 4-methoxyphenyl thioisocyanate.

[0025] Preferably, the indigo compound is indigo, 5-methyl indigo, 5-isopropyl indigo, 5-methoxy indigo, 5-fluoro indigo, 6-methoxy indigo, or 7-methyl indigo.

[0026] Preferably, the alkaline reagent is an inorganic base and / or an organic base;

[0027] The inorganic base is one or more of potassium carbonate, cesium carbonate, potassium hydroxide, and dipotassium hydrogen phosphate; the organic base is 1,8-diazabicyclo[5.4.0]undec-7-ene or triethylenediamine.

[0028] Preferably, the organic solvent includes one of dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, tetrahydrofuran, dichloromethane, and ethanol.

[0029] Preferably, the molar ratio of the aniline compound, the phenyl isothiocyanate compound, and the indigo compound is 1:1:1 to 2;

[0030] The molar ratio of the phenyl isothiocyanate compound to the base reagent is 1:1 to 2;

[0031] The ratio of the organic solvent to the phenyl isothiocyanate compound is 1–2 L: 0.1–1 mol.

[0032] Preferably, the coupling addition reaction is carried out at a temperature of 10–60°C for a time of 6–24 hours.

[0033] This invention also provides 2,3-disubstituted quinazolinone compounds prepared by the preparation method described above, having the structure shown in Formula IV or Formula V:

[0034]

[0035] Wherein, R1 is defined as in Equation I; R2 is defined as in Equation II; and R3 is defined as in Equation III.

[0036] Preferably, the 2,3-disubstituted quinazolinone compound is:

[0037]

[0038]

[0039] This invention provides a method for preparing 2,3-disubstituted quinazolinone compounds without using an oxidizing agent, comprising the following steps: mixing an aniline compound, a phenyl isothiocyanate compound, an indigo compound, a base reagent, and an organic solvent, and performing a coupling addition reaction to obtain the 2,3-disubstituted quinazolinone compound; wherein the aniline compound has the structure shown in Formula I; the phenyl isothiocyanate compound has the structure shown in Formula II; and the indigo compound has the structure shown in Formula III; wherein R1 is -H, a halogen group, or an alkyl group having 1 to 3 carbon atoms; R2 is -H, a halogen group, a nitro group, an alkyl group having 1 to 3 carbon atoms, or an alkoxy group having 1 to 3 carbon atoms; and R3 is -H, a halogen group, an alkyl group having 1 to 3 carbon atoms, or an alkoxy group having 1 to 3 carbon atoms. This invention does not use an oxidizing agent in its preparation process. 2,3-Disubstituted quinazolinone compounds can be obtained through a one-step coupling addition reaction. The preparation method is simple, easy to control, economical, uses inexpensive and readily available raw materials, and operates under mild conditions. Furthermore, substrates with various electron-withdrawing and electron-donating groups on the benzene ring of the 2,3-disubstituted quinazolinone compounds prepared by this invention can participate in the reaction, exhibiting good functional group tolerance. The purity of the 2,3-disubstituted quinazolinone compounds prepared by this invention is 98.5%–99.9%, making it highly valuable for market promotion.

[0040] Detailed Implementation

[0041] This invention provides a method for preparing 2,3-disubstituted quinazolinone compounds without using an oxidizing agent, comprising the following steps:

[0042] A aniline compound, a phenyl isothiocyanate compound, an indigo compound, a base reagent, and an organic solvent are mixed and subjected to a coupling addition reaction to obtain the 2,3-disubstituted quinazolinone compound.

[0043] The aniline compounds have the structure shown in Formula I:

[0044]

[0045] The phenyl isothiocyanate compound has the structure shown in Formula II:

[0046]

[0047] The indigo compounds have the structure shown in Formula III:

[0048]

[0049] Wherein, R1 is -H, a halogen group, or an alkyl group having 1 to 3 carbon atoms;

[0050] R2 is -H, a halogen group, a nitro group, an alkyl group with 1 to 3 carbon atoms, or an alkoxy group with 1 to 3 carbon atoms;

[0051] R3 is -H, a halogen group, an alkyl group with 1 to 3 carbon atoms, or an alkoxy group with 1 to 3 carbon atoms.

[0052] In this invention, unless otherwise specified, all raw materials used in the preparation are preferably commercially available products known to those skilled in the art or prepared using methods known to those skilled in the art.

[0053] In this invention, the aniline compound has the structure shown in Formula I, where R1 is -H, a halogen group, or an alkyl group having 1 to 3 carbon atoms; the halogen group is preferably -I, -F, or -Cl; and the alkyl group having 1 to 3 carbon atoms is preferably methyl, ethyl, or propyl.

[0054] In this invention, the aniline compound is preferably aniline, 2-iodoaniline, 4-methylaniline, 4-iodoaniline, 4-fluoroaniline, 4-chloroaniline or 2,4,6-trimethylaniline.

[0055] In this invention, the phenyl isothiocyanate compound has the structure shown in Formula II, where R2 is -H, a halogen group, a nitro group, an alkyl group with 1 to 3 carbon atoms, or an alkoxy group with 1 to 3 carbon atoms; the halogen group is preferably -F, -Cl, or -Br; the alkyl group with 1 to 3 carbon atoms is preferably methyl, ethyl, or propyl; and the alkoxy group with 1 to 3 carbon atoms is preferably methoxy, ethoxy, or propoxy.

[0056] In this invention, the phenyl isothiocyanate compound is preferably phenyl isothiocyanate, 2-fluorophenyl thioisocyanate, 2-chlorophenyl thioisocyanate, 2-bromophenyl thioisocyanate, 4-nitrophenyl thioisocyanate, 4-ethylphenyl thioisocyanate or 4-methoxyphenyl thioisocyanate.

[0057] In this invention, the indigo compounds have the structure shown in Formula III, where R3 is -H, a halogen group, an alkyl group with 1 to 3 carbon atoms, or an alkoxy group with 1 to 3 carbon atoms; the halogen group is preferably -F; the alkyl group with 1 to 3 carbon atoms is preferably methyl, ethyl, or propyl; the propyl group is preferably isopropyl; and the alkoxy group with 1 to 3 carbon atoms is preferably methoxy, ethoxy, or propoxy.

[0058] In this invention, the indigo compounds are preferably indigo, 5-methyl indigo, 5-isopropyl indigo, 5-methoxy indigo, 5-fluoro indigo, 6-methoxy indigo, or 7-methyl indigo.

[0059] In this invention, the alkaline reagent preferably includes an inorganic base and / or an organic base; the inorganic base is preferably one or more of potassium carbonate, cesium carbonate, potassium hydroxide, and dipotassium hydrogen phosphate, more preferably potassium carbonate and cesium carbonate; when the inorganic base is preferably potassium carbonate and cesium carbonate, the molar ratio of potassium carbonate and cesium carbonate is preferably 1:1 to 2, more preferably 1:1. In this invention, the organic base is preferably 1,8-diazabicyclo[5.4.0]undec-7-ene or triethylenediamine. The alkaline reagent of this invention serves as a catalyst.

[0060] In this invention, the organic solvent preferably includes one of dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, tetrahydrofuran, dichloromethane and ethanol, and more preferably dimethyl sulfoxide.

[0061] In this invention, the molar ratio of the aniline compound, the phenyl isothiocyanate compound, and the indigo compound is 1:1:1 to 2, more preferably 1:1:1; the molar ratio of the phenyl isothiocyanate compound to the base is preferably 1:1 to 2, more preferably 1:2; the ratio of the amount of organic solvent to the phenyl isothiocyanate compound is preferably 1 to 2 L: 0.1 to 1 mol, more preferably 1 L: 0.1 mol; and the molar ratio of the aniline compound to the base reagent is preferably 1:1 to 2, more preferably 1:2.

[0062] The present invention does not impose any particular limitation on the mixing method of the aniline compounds, phenyl isothiocyanate compounds, indigo compounds, alkaline reagents and organic solvents; they can be mixed uniformly in a manner known in the art.

[0063] In this invention, the temperature of the coupling addition reaction is preferably 10–60°C, more preferably 25–40°C; the time is preferably 6–24 h, more preferably 12–16 h; the coupling addition reaction is preferably carried out under stirring conditions; this invention does not have a special limitation on the stirring rate, as long as the coupling addition reaction proceeds smoothly; the coupling addition reaction is preferably carried out under light conditions; this invention does not have a special limitation on the light conditions, as long as the coupling addition reaction proceeds smoothly, preferably white light, purple light, yellow light, or green light.

[0064] In this invention, after the coupling addition reaction is completed, the coupling addition reaction product is preferably purified; the purification method is preferably column chromatography; the eluent used in the column chromatography is preferably a mixed solvent of petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate in the mixed solvent is preferably 4-6:1, more preferably 5:1. This invention does not impose any special limitations on the column chromatography method; any method well known to those skilled in the art can be used. This invention utilizes petroleum ether and ethyl acetate as eluents for purification, which can yield 2,3-disubstituted quinazolinone compounds with high purity.

[0065] This invention also provides 2,3-disubstituted quinazolinone compounds prepared by the preparation method described above, having the following structure:

[0066]

[0067] Wherein, R1 is preferably defined as in Formula I; R2 is preferably defined as in Formula II; and R3 is preferably defined as in Formula III.

[0068] In this invention, the 2,3-disubstituted quinazolinone compound is preferably:

[0069]

[0070]

[0071] In this invention, the purity of the 2,3-disubstituted quinazolinone compound is preferably 98.5–99.9 wt.%.

[0072] To further illustrate the present invention, the 2,3-disubstituted quinazolinone compounds and their preparation methods provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0073] Example 1

[0074] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0075]

[0076] 0.1 mmol phenyl isothiocyanate, 0.1 mmol aniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 78% and a purity of 99.9%.

[0077] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0078] 1 H NMR(400MHz, CDCl3, ppm) δ8.19(d,J=7.9Hz,1H),7.64(dq,J=15.3,7.1Hz,4H),7.57-7.49(m,3 H),7.42(d,J=7.0Hz,2H),7.35-7.30(m,2H),7.27(s,1H),7.10(t,J=7.4Hz,1H),5.96(s,1H);

[0079] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.6,148.6,146.4,137.8,134.8,134.5,130.9,130.3,129.1,128.9,127.2,125.7,124.1,123.7,120.9,118.4;

[0080] MS(EI,70eV)m / z 313,236,221,195,166.

[0081] Example 2

[0082] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0083]

[0084] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 2-iodoaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 30% and a purity of 99.9%.

[0085] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0086] 1 H NMR (400MHz, CDCl3, ppm) δ8.70(d,J=8.3Hz,1H),8.21(d,J=7.9Hz,1H),7.68(t,J=7.1Hz,4H),7.62-7.53(m, 2H),7.48(d,J=7.9Hz,2H),7.40(t,J=7.8Hz,1H),7.30(t,J=7.5Hz,1H),6.79(t,J=7.6Hz,1H),6.62(s,1H);

[0087] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.5,148.2,146.2,138.8,138.7,134.8,134.5 ,131.1,130.4,129.4,129.0,127.3,125.7,125.1,124.1,121.6,118.7,90.2;

[0088] MS(EI,70eV)m / z 439,312,282,235,221.

[0089] Example 3

[0090] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0091]

[0092] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 4-methylaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 35% and a purity of 99.9%.

[0093] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0094] 1H NMR (400MHz, CDCl3, ppm) δ8.16 (d, J = 8.0Hz, 1H), 7.66-7.61 (m, 1H), 7.52 (d, J = 8.4Hz, 3H), 7.42(d,J=8.0Hz,2H),7.32-7.22(m,5H),7.07(t,J=7.9Hz,1H),6.03(s,1H),2.47(s,3H);

[0095] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.6,148.5,146.52140.5,137.9,134.7,13 1.8,131.5,128.9,128.7,127.2,125.6,124.0,123.6,120.8,118.5,21.4;

[0096] MS(EI,70eV)m / z 327,311,283,250,235.

[0097] Example 4

[0098] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0099]

[0100] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 4-iodoaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 32% and a purity of 99.9%.

[0101] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0102] 1 H NMR (400MHz, CDCl3, ppm) δ8.18(d,J=7.9Hz,1H),8.01(d,J=8.2Hz,2H),7.69(t,J=7.6Hz,1H),7. 55(d,J=7.6Hz,3H),7.36(t,J=7.7Hz,2H),7.32-7.26(m,2H),7.19(d,J=8.2Hz,2H),5.92(s,1H);

[0103] 13C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.3,148.4,145.9,140.1,137.6,134.9,134.3,131.0,129.0,127.2,125.72,124.3,123.9,121.0,118.2,96.4;

[0104] MS(EI,70eV)m / z 439,346,319,311,282.

[0105] Example 5

[0106] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0107]

[0108] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 4-iodoaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 35% and a purity of 99.9%.

[0109] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0110] 1 H NMR (400MHz, CDCl3, ppm) δ8.20 (d, J=7.9Hz, 1H), 7.66 (dt, J=21.9, 7.6Hz, 6H), 7. 57-7.54(m,1H),7.43(d,J=7.1Hz,2H),7.32(dd,J=17.0,8.2Hz,3H),5.97(s,1H);

[0111] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.4,145.9,148.2,137.8,134.9,134.3,130.9,130.4,129.0,127.2,125.6,124.0,122.7,120.9,118.5,87.0;

[0112] MS(EI,70eV)m / z 439,362,347,319,312.

[0113] Example 6

[0114] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0115]

[0116] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 4-fluoroaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 26% and a purity of 99.9%.

[0117] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0118] 1 H NMR (400MHz, CDCl3, ppm) δ8.19(d,J=7.8Hz,1H),7.70(t,J=7.6Hz,1H),7.55(d,J=8.1Hz,3H),7.44( dd,J=8.6,4.9Hz,2H),7.36(t,J=8.1Hz,4H),7.31-7.27(m,1H),7.14(t,J=7.4Hz,1H),5.96(s,1H);

[0119] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ164.5,162.6,162.0,147.3(d,J=223.0Hz),137.7,134.9,131.1(d,J= 9.0Hz), 130.3 (d, J = 3.0Hz), 129.0, 127.2, 125.7, 124.2, 123.8, 120.9, 118.3, 118.0 (d, J = 23.0Hz);

[0120] MS(EI,70eV)m / z 331,239,221,212,195.

[0121] Example 7

[0122] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0123]

[0124] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 4-fluoroaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate as a base, and 1 mL dimethyl sulfoxide were added to a reaction tube. The coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1. 2,3-Disubstituted quinazolinone compounds were obtained with a yield of 16% and a purity of 99.9%.

[0125] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0126] 1 H NMR (400MHz, CDCl3, ppm) δ8.20 (d, J=7.8Hz, 1H), 7.67 (dt, J=14.9, 6.9Hz, 4H), 7.54-7.44(m,5H),7.29(d,J=14.5Hz,1H),7.05(t,J=7.8Hz,2H),5.93(s,1H);

[0127] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.5,159.4(d,J=242.0Hz),148.4,146.6,134.8,134.5,133.7(d,J= 2.0Hz),130.9,130.3,129.0,127.2,125.6,123.7,123.0(d,J=7.0Hz),118.4,115.6(d,J=23.0Hz);

[0128] MS(EI,70eV)m / z 331,254,239,221,213.

[0129] Example 8

[0130] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0131]

[0132] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 4-chloroaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 25% and a purity of 99.9%.

[0133] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0134] 1 H NMR (400MHz, CDCl3, ppm) δ8.18 (d, J=7.9Hz, 1H), 7.66 (dd, J=16.2, 8.0Hz, 3H), 7.55 (d, J=7.9Hz,3H),7.42-7.33(m,4H),7.31-7.27(m,1H),7.14(t,J=7.3Hz,1H),5.93(s,1H);

[0135] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.4,148.4,146.0,137.6,136.5,134.9,133.0,131.1,130.6,129.0,127.2,125.7,124.2,123.9,121.0,118.2;

[0136] MS(EI,70eV)m / z 347,310,255,236,228.

[0137] Example 9

[0138] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0139]

[0140] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 4-chloroaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 14% and a purity of 99.9%.

[0141] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0142] 1H NMR (400MHz, CDCl3, ppm) δ8.20 (d, J=7.9Hz, 1H), 7.68 (dq, J=14.0, 7.6, 7.1Hz, 4H), 7.53(dd,J=18.9,8.5Hz,3H),7.44(d,J=7.0Hz,2H),7.33-7.28(m,3H),5.98(s,1H);

[0143] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.4,148.2,146.1,136.4,134.9,134.4,130.9,130.4,129.0,129.0,128.89,127.2,125.6,124.0,122.1,118.5;

[0144] MS(EI,70eV)m / z 347,310,270,255,235.

[0145] Example 10

[0146] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0147]

[0148] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 2,4,6-trimethylaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 34% and a purity of 99.9%.

[0149] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0150] 1 H NMR (400MHz, CDCl3, ppm) δ8.24 (d, J = 7.9Hz, 1H), 7.70 (t, J = 7.6Hz, 1H), 7.60-7.5 5(m,3H),7.39-7.28(m,4H),7.15(s,2H),6.10(s,1H),2.43(s,3H),2.17(s,6H);

[0151] 13 C{ 1H}NMR (100MHz, CDCl3, ppm) δ161.5,148.9,146.3,140.3,138.0,136.3,134.6 ,130.5,129.6,128.9,127.3,125.6,124.0,123.5,121.0,118.3,21.3,17.6;

[0152] MS(EI,70eV)m / z 355,340,324,263,248.

[0153] Example 11

[0154] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0155]

[0156] 0.1 mmol phenyl isothiocyanate, 0.1 mmol 2,4,6-trimethylaniline, 0.1 mmol indigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 23% and a purity of 99.9%.

[0157] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0158] 1 H NMR (400MHz, CDCl3, ppm) δ8.18-8.14(m,1H),7.66(t,J=7.6Hz,2H),7.61-7.54(m,2H),7.47(d,J=7.4Hz ,2H),7.34(d,J=8.2Hz,1H),7.19(t,J=7.5Hz,1H),6.91(s,2H),5.28(s,1H),2.29(s,3H),2.17(s,6H);

[0159] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.8,149.5,147.6,136.9,135.6,135.3,134.5 ,131.7,130.8,130.1,129.0,128.8,127.1,125.6,122.90118.0,21.0,18.5;

[0160] MS(EI,70eV)m / z 355,340,324,278,262.

[0161] Example 12

[0162] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0163]

[0164] 0.1 mmol of phenyl 2-fluoroisothiocyanate, 0.1 mmol of aniline, 0.1 mmol of indigo, 0.1 mmol of potassium carbonate, 0.1 mmol of cesium carbonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube. The coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 35% and a purity of 99.9%.

[0165] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0166] 1 H NMR (400MHz, CDCl3, ppm) δ8.65(t,J=8.2Hz,1H),8.20(d,J=7.9Hz,1H),7.71-7.54(m,5H),7.42( d,J=7.1Hz,2H),7.32-7.25(m,1H),7.22-7.15(m,1H),6.99(dd,J=9.6,3.0Hz,2H),6.30(s,1H);

[0167] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.4, 152.9 (d, J = 242.0Hz), 148.3, 145.9, 134.9, 134.3, 130.9, 130.4, 128.9, 127. 3,126.4(d,J=10.0Hz),125.7,124.4(d,J=4.0Hz),124.0,123.7(d,J=8.0Hz),121.9,118.6,114.6(d,J=19.0Hz);

[0168] MS(EI,70eV)m / z 331,312,282,254,239.

[0169] Example 13

[0170] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0171]

[0172] 0.1 mmol of phenyl 2-fluoroisothiocyanate, 0.1 mmol of aniline, 0.1 mmol of indigo, 0.1 mmol of potassium carbonate, 0.1 mmol of cesium carbonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube. The coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1. The product yielded 2,3-disubstituted quinazolinone compounds with a yield of 34% and a purity of 99.9%.

[0173] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0174] 1 H NMR (400MHz, CDCl3, ppm) δ8.21(d,J=7.9Hz,1H),7.73-7.61(m,2H),7.55(d,J=7.7Hz,3H),7.46(dd,J =19.1,10.7Hz,3H),7.36(t,J=7.8Hz,2H),7.29(d,J=5.8Hz,1H),7.15(t,J=7.4Hz,1H),6.01(s,1H);

[0175] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ161.9,159.6,157.1,148.6,145.9,137.7,135.0,132.5(d,J=7.0Hz),130.7,128.9, 127.3, 126.0 (d, J = 4.0Hz), 125.7, 124.1 (d, J = 44.0Hz), 122.1 (d, J = 13.0Hz), 121.30, 118.1 (d, J = 14.0Hz), 117.8;

[0176] MS(EI,70eV)m / z 331,281,255,134,206.

[0177] Example 14

[0178] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0179]

[0180] 0.1 mmol of phenyl 2-chloroisothiocyanate, 0.1 mmol of aniline, 0.1 mmol of indigo, 0.1 mmol of potassium carbonate, 0.1 mmol of cesium carbonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube as solvents. The coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1, to obtain 2,3-disubstituted quinazolinone compounds with a yield of 38% and a purity of 99.9%.

[0181] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0182] 1 H NMR (400MHz, CDCl3, ppm) δ8.83(d,J=9.6Hz,1H),8.21(d,J=7.9Hz,1H),7.70-7.56(m,5H) ,7.44(d,J=7.3Hz,2H),7.30(dt,J=14.3,6.9Hz,3H),6.99(t,J=7.7Hz,1H),6.79(s,1H);

[0183] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.4,148.2,145.8,135.0,134.8,134.4,130.9, 130.4,129.0,128.9,127.6,127.3,125.7,124.1,123.8,123.1,121.2,118.7;

[0184] MS(EI,70eV)m / z 347,312,270,255,236.

[0185] Example 15

[0186] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0187]

[0188] 0.1 mmol of phenyl 2-bromoisothiocyanate, 0.1 mmol of aniline, 0.1 mmol of indigo, 0.1 mmol of potassium carbonate, 0.1 mmol of cesium carbonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube. The coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1. 2,3-Disubstituted quinazolinone compounds were obtained with a yield of 30% and a purity of 99.9%.

[0189] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0190] 1 H NMR (400MHz, CDCl3, ppm) δ88.83(d,J=9.8Hz,1H),8.22(d,J=8.0Hz,1H),7.72-7.64(m,3H),7.63-7.56(m ,2H),7.49-7.42(m,3H),7.38(t,J=7.2Hz,1H),7.30(t,J=7.0Hz,1H),6.93(t,J=7.7Hz,1H),6.82(s,1H);

[0191] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.5,148.2,145.9,136.1,134.8,134.4,132.2, 131.0,130.4,129.1,128.2,127.3,125.7,124.3,124.2,121.4,118.7,113.8;

[0192] MS(EI,70eV)m / z 391,312,282,235,221.

[0193] Example 16

[0194] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0195]

[0196] 0.1 mmol of 4-nitroisothiocyanate, 0.1 mmol of aniline, 0.1 mmol of indigo, 0.1 mmol of potassium carbonate, 0.1 mmol of cesium carbonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 28% and a purity of 99.9%.

[0197] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0198] 1H NMR (400MHz, CDCl3, ppm) δ8.51(d,J=8.9Hz,2H),8.16(d,J=7.9Hz,1H),7.72-7.64(m,3 H),7.51(dd,J=18.6,7.9Hz,3H),7.36-7.28(m,3H),7.13(t,J=7.4Hz,1H),5.70(s,1H);

[0199] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.2,148.7,148.3,145.2,140.5,137.4,135.3,130.7,129.0,127.2,126.0,125.9,124.6,124.2,121.3,118.0;

[0200] MS(EI,70eV)m / z 358,327,311,282,266.

[0201] Example 17

[0202] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0203]

[0204] 0.1 mmol of 4-ethylisothiocyanate, 0.1 mmol of aniline, 0.1 mmol of indigo, 0.1 mmol of potassium carbonate, 0.1 mmol of cesium carbonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube. The coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 46% and a purity of 99.9%.

[0205] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0206] 1 H NMR (400MHz, CDCl3, ppm) δ8.21(d,J=7.9Hz,1H),7.69(ddd,J=8.5,7.1,1.6Hz,1H),7.56(d,J=7.7Hz,3H),7.50(d,J=8.3Hz,2 H),7.38-7.33(m,4H),7.28(t,J=7.5Hz,1H),7.12(t,J=7.4Hz,1H),6.07(s,1H),2.82(q,J=7.6Hz,2H),1.37(t,J=7.6Hz,3H);

[0207] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.6,148.5,146.6,146.6,137.9,134.7,131.9 ,130.3,128.9,128.8,127.2,125.6,124.0,123.6,120.9,118.5,28.7,15.2;

[0208] MS(EI,70eV)m / z 341,325,312,297,249.

[0209] Example 18

[0210] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0211]

[0212] 0.1 mmol of 4-ethylisothiocyanate, 0.1 mmol of aniline, 0.1 mmol of indigo, 0.1 mmol of potassium carbonate, 0.1 mmol of cesium carbonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube. The coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography. The eluent for column chromatography was petroleum ether and ethyl acetate in a volume ratio of 6:1. The product yielded 2,3-disubstituted quinazolinone compounds with a yield of 35% and a purity of 99.9%.

[0213] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0214] 1 H NMR (400MHz, CDCl3, ppm) δ8.20(d,J=7.8Hz,1H),7.70-7.65(m,3H),7.54(d,J=8.1Hz,1H),7.44(t,J=7.5 Hz,4H),7.32-7.26(m,2H),7.18(d,J=8.4Hz,2H),5.92(s,1H),2.67-2.61(m,2H),1.24(t,J=7.6Hz,3H);

[0215] 13 C{ 1H}NMR (100MHz, CDCl3, ppm) δ162.6,148.7,146.6,140.3,135.3,134.7,134.6 ,130.8,130.2,129.1,128.3,127.2,125.6,123.5,121.2,118.4,28.3,15.7;

[0216] MS(EI,70eV)m / z 341,326,312,264,249.

[0217] Example 19

[0218] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0219]

[0220] 0.1 mmol of 4-methoxyisothiocyanate, 0.1 mmol of aniline, 0.1 mmol of indigo, 0.1 mmol of potassium carbonate, 0.1 mmol of cesium carbonate, and 1 mL of dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 48% and a purity of 99.9%.

[0221] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0222] 1 H NMR (400MHz, CDCl3, ppm) δ8.20 (d, J = 7.9Hz, 1H), 7.71-7.64 (m, 1H), 7.56 (t, J = 6.6Hz, 3H), 7 .35(dt,J=8.4,3.5Hz,4H),7.31-7.27(m,1H),7.20-7.09(m,3H),6.11(s,1H),3.93(s,3H);

[0223] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.8,160.7,148.5,146.7,137.9,134.7,13 0.1,128.9,127.2,126.6,125.6,124.0,123.6,120.8,118.4,116.1,55.7;

[0224] MS(EI,70eV)m / z 343,328,299,270,251.

[0225] Example 20

[0226] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0227]

[0228] 0.1 mmol phenyl isothiocyanate, 0.1 mmol aniline, 0.1 mmol 5-methylindigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 38% and a purity of 99.9%.

[0229] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0230] 1 H NMR (400MHz, CDCl3, ppm) δ7.98 (s, 1H), 7.63 (dt, J=15.1, 7.1Hz, 3H), 7.50 (dd, J=17.1, 8.5Hz, 4H ),7.42(d,J=7.3Hz,2H),7.32(t,J=7.9Hz,2H),7.09(t,J=7.4Hz,1H),5.94(s,1H),2.45(s,3H);

[0231] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.5,146.4,145.8,138.0,136.2,134.7,13 3.5,130.8,130.2,129.1,128.9,126.6,125.5,123.8,120.6,118.2,21.1;

[0232] MS(EI,70eV)m / z 327,250,235,220,209.

[0233] Example 21

[0234] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0235]

[0236] 0.1 mmol phenyl isothiocyanate, 0.1 mmol aniline, 0.1 mmol 5-isopropylindigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 60% and a purity of 99.9%.

[0237] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0238] 1 H NMR (400MHz, CDCl3, ppm) δ8.09 (s, 1H), 7.69-7.60 (m, 4H), 7.55 (t, J = 8.0Hz, 3H), 7.45 (d, J = 8.3Hz, 2H), 7.35(t,J=7.9Hz,2H),7.12(t,J=7.4Hz,1H),5.99(s,1H),3.06(p,J=6.9Hz,1H),1.36(d,J=6.9Hz,6H);

[0239] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.7,146.7,145.8,144.6,138.0,134.8,133.9 ,130.8,130.2,129.1,128.9,125.7,124.0,123.9,120.7,118.2,33.8,24.1;

[0240] MS(EI,70eV)m / z 355,340,312,278,263.

[0241] Example 22

[0242] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0243]

[0244] 0.1 mmol phenyl isothiocyanate, 0.1 mmol aniline, 0.1 mmol 5-methoxyindigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 56% and a purity of 99.9%.

[0245] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0246] 1 H NMR (400MHz, CDCl3, ppm) δ7.62(dd,J=14.3,7.4Hz,3H),7.56(d,J=3.0Hz,1H),7.50(dd,J=8.3,4 .6Hz,3H),7.45-7.40(m,2H),7.34-7.28(m,3H),7.08(t,J=7.4Hz,1H),5.90(s,1H),3.86(s,3H);

[0247] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.5,156.2,144.9,143.0,138.1,134.7,13 0.9,130.3,129.0,128.9,127.2,125.0,123.8,120.6,118.7,106.7,55.7;

[0248] MS(EI,70eV)m / z 343,328,299,266,251.

[0249] Example 23

[0250] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0251]

[0252] 0.1 mmol phenyl isothiocyanate, 0.1 mmol aniline, 0.1 mmol 5-fluoroindigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 45% and a purity of 99.9%.

[0253] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0254] 1H NMR (400MHz, CDCl3, ppm) δ7.81 (d, J = 8.5Hz, 1H), 7.70-7.60 (m, 3H), 7.52 (dd, J = 13.3, 6.1Hz, 3H), 7.46-7.29 (m, 5H), 7.11 (t, J = 7.3Hz, 1H), 5.97 (s, 1H);

[0255] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ161.8,160.2,157.8,145.9,145.1,137.7,134.3,130.9,130.4,129.0(d,J= 4.0Hz), 127.7 (d, J = 8.0Hz), 124.1, 123.2 (d, J = 24.0Hz), 120.9, 119.1 (d, J = 9.0Hz), 111.9 (d, J = 24.0Hz);

[0256] MS(EI,70eV)m / z 331,254,239,213,194.

[0257] Example 24

[0258] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0259]

[0260] 0.1 mmol phenyl isothiocyanate, 0.1 mmol aniline, 0.1 mmol 6-methoxyindigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 48% and a purity of 99.9%.

[0261] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0262] 1H NMR (400MHz, CDCl3, ppm) δ8.08(d,J=8.8Hz,1H),7.63(q,J=7.6Hz,3H),7.50(d,J=8.2Hz,2H),7.42(d,J=7.8Hz, 2H),7.33(t,J=7.8Hz,2H),7.10(t,J=7.4Hz,1H),6.93(s,1H),6.85(d,J=10.9Hz,1H),5.96(s,1H),3.92(s,3H);

[0263] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ165.1,162.1,150.8,147.0,137.8,134.6,13 0.8,130.2,129.1,128.9,128.7,124.1,121.0,113.9,111.9,106.5,55.6;

[0264] MS(EI,70eV)m / z 343,327,299,266,251.

[0265] Example 25

[0266] Prepare 2,3-disubstituted quinazolinone compounds with the following structures:

[0267]

[0268] 0.1 mmol phenyl isothiocyanate, 0.1 mmol aniline, 0.1 mmol 7-methylindigo, 0.1 mmol potassium carbonate, 0.1 mmol cesium carbonate, and 1 mL dimethyl sulfoxide were added to a reaction tube, and a coupling addition reaction was carried out in a photoreactor (25 °C) for 12 h. After the reaction was completed, the product was purified by column chromatography with petroleum ether and ethyl acetate in a volume ratio of 6:1 to obtain 2,3-disubstituted quinazolinone compounds with a yield of 40% and a purity of 99.9%.

[0269] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0270] 1H NMR (400MHz, CDCl3, ppm) δ8.06(d,J=7.9Hz,1H),7.61(ddd,J=23.0,14.8,7.5Hz,6H),7.42(d,J=7.5H z,2H),7.33(t,J=7.8Hz,2H),7.18(t,J=7.6Hz,1H),7.09(t,J=7.4Hz,1H),6.03(s,1H),2.60(s,3H);

[0271] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ162.9,147.1,145.2,138.2,135.2,134.6,13 3.7,130.9,130.9,129.1,128.8,124.8,123.6,123.3,120.1,118.2,17.8;

[0272] MS(EI,70eV)m / z 327,310,250,235,220.

[0273] As can be seen from the above embodiments, the present invention can obtain 2,3-disubstituted quinazolinone compounds with high purity through a one-step coupling addition reaction. The preparation method is simple, easy to control, economical, and the raw materials are inexpensive and readily available. Moreover, the present invention does not use oxidants in the preparation process, and has great market promotion value.

[0274] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing a 2,3-disubstituted quinazolinone compound, characterized in that, Without using oxidants, the following steps are included: A aniline compound, a phenyl isothiocyanate compound, an indigo compound, a base reagent, and an organic solvent are mixed and subjected to a coupling addition reaction to obtain the 2,3-disubstituted quinazolinone compound. The aniline compounds have the structure shown in Formula I: Formula I; The phenyl isothiocyanate compound has the structure shown in Formula II: Formula II; The indigo compounds have the structure shown in Formula III: Formula III; Wherein, R1 is -H, a halogen group, or an alkyl group having 1 to 3 carbon atoms; R2 is -H, a halogen group, a nitro group, an alkyl group with 1 to 3 carbon atoms, or an alkoxy group with 1 to 3 carbon atoms; R3 is -H, a halogen group, an alkyl group with 1 to 3 carbon atoms, or an alkoxy group with 1 to 3 carbon atoms; The coupling addition reaction is carried out under light conditions; The 2,3-disubstituted quinazolinone compounds have the structure shown in Formula IV or Formula V: Formula IV; Formula V; Wherein, R1 is defined as in Equation I; R2 is defined as in Equation II; and R3 is defined as in Equation III.

2. The preparation method according to claim 1, characterized in that, The aniline compounds are aniline, 2-iodoaniline, 4-methylaniline, 4-iodoaniline, 4-fluoroaniline, or 4-chloroaniline.

3. The preparation method according to claim 1, characterized in that, The phenyl isothiocyanate compounds are phenyl isothiocyanate, 2-fluorophenyl thioisocyanate, 2-chlorophenyl thioisocyanate, 2-bromophenyl thioisocyanate, 4-nitrophenyl thioisocyanate, 4-ethylphenyl thioisocyanate, or 4-methoxyphenyl thioisocyanate.

4. The preparation method according to claim 1, characterized in that, The indigo compounds are indigo, 5-methyl indigo, 5-isopropyl indigo, 5-methoxy indigo, 5-fluoro indigo, 6-methoxy indigo, or 7-methyl indigo.

5. The preparation method according to claim 1, characterized in that, The alkaline reagent is an inorganic base and / or an organic base; The inorganic base is one or more of potassium carbonate, cesium carbonate, potassium hydroxide, and dipotassium hydrogen phosphate; the organic base is 1,8-diazabicyclo[5.4.0]undec-7-ene or triethylenediamine.

6. The preparation method according to claim 1, wherein the organic solvent comprises one of dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, tetrahydrofuran, dichloromethane, and ethanol.

7. The preparation method according to any one of claims 1 to 6, wherein the molar ratio of the aniline compound, the phenyl isothiocyanate compound, and the indigo compound is 1:1:1 to 2; The molar ratio of the phenyl isothiocyanate compound to the base reagent is 1:1~2; The ratio of the organic solvent to the phenyl isothiocyanate compound is 1~2L:0.1~1mol.

8. The preparation method according to claim 1, wherein the coupling addition reaction is carried out at a temperature of 10~60℃ for 6~24h.

9. The preparation method according to claim 1, characterized in that, The 2,3-disubstituted quinazolinone compounds are: , , , , , , , , , , , , , , , , , , , , , or .

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