Preparation method of quinazolinone derivative

Abstract

The invention provides a preparation method of a quinazolinone derivative, which comprises the following step: under the catalysis of an alkali, 2-(2-bromophenyl)-2, 3-dihydroquinazolin-4 (1H)-ketone is subjected to a dehalogenation hydrogenation reaction to obtain the quinazolinone derivative. According to the method, an intermediate is obtained after NH group deprotonation and electron transfer are performed under the action of alkali, proton is obtained from the intermediate, then proton transfer hydrogenation debromination is performed to obtain the quinazolinone derivative, a target product is obtained through light and heat methods, raw material synthesis is simple, the production cost can be effectively reduced, the yield and chemical selectivity can be improved, and the method is suitable for industrial production. The method can be conveniently applied to preparation of quinazolinone derivatives.

Description

Technical Field

[0001] The present application belongs to the technical field of organic compound synthesis and relates to a method for preparing a quinazolinone derivative. Background Art

[0002] Quinazolinone skeletons are a class of fused heterocyclic compounds with potential pharmacological and biological activities. They are the basic units in natural products, agrochemicals, drugs and synthetic drugs ( Figure 1 A special type of heterocyclic framework, 2,3-dihydroquinazolin-4(1H)-one (DHQ), plays a vital role in various drugs due to its potent pharmacological and biological effects, such as anticancer, anticonvulsant, analgesic, diuretic, antihistamine, and antihypertensive activities.

[0003]

[0004] The synthetic methods of quinazolinone compounds reported so far are mainly the following:

[0005] In 2013, Dan Zhan's research group reported a method for synthesizing 2-substituted and 2,3-disubstituted quinazoline-4(3H)-ones by tandem reaction of o-aminobenzamide and aromatic aldehydes using acetylacetonatovanadium as a catalyst in air atmosphere.

[0006]

[0007] In 2023, Peng Ma's research group reported a new method for synthesizing quinazoline compounds via a Cu(I)-catalyzed cyclization / hydrodehalogenation cascade reaction using acetamide as a nitrogen source and H2O as a hydrogen source.

[0008]

[0009] In 2014, Li-XiaWang reported a copper-catalyzed method for the synthesis of 2-arylquinazolinones via a domino reaction involving C-C bond cleavage. This protocol involves intramolecular C-C bond cleavage to construct 2-arylquinazolinones, and in addition to C-C bond cleavage, this domino reaction also includes N-arylation and benzyl C-H amidation.

[0010]

[0011] In 2021, Zongbo Xie reported for the first time a facile tandem route for the synthesis of quinazolinones at room temperature using various aminobenzamides and in situ generated aldehydes as raw materials. The latter is formed by CC bond cleavage, and the entire reaction is carried out in the absence of a photocatalyst using molecular oxygen as a clean oxidant. Visible light plays multiple roles in the entire reaction process, first cleaving styrene into aldehydes, then promoting its cyclization with o-aniline, and finally promoting the dehydrogenation reaction of the cyclization intermediate.

[0012] Summary of the invention

[0013] The purpose of the embodiments of the present invention is to provide a method for preparing a quinazolinone derivative, aiming to solve the problems raised in the above background technology.

[0014] The embodiment of the present invention is implemented as follows: a method for preparing a quinazolinone derivative comprises the following steps: 2-(2-bromophenyl)-2,3-dihydroquinazolin-4(1H)-one is subjected to a dehalogenation hydrogenation reaction under base catalysis to obtain a quinazolinone derivative, and the reaction formula is as follows:

[0015]

[0016] The X group of the o-haloaniline dihydroquinoline is one of fluorine, chlorine, bromine and iodine, and the L group is oxygen or sulfur; in the o-haloaniline dihydroquinoline quinazolinone derivative, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 The radicals are each independently selected from hydrogen, halogen, substituted or unsubstituted C 1～10 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted C 1～10 One of an alkoxy group, a substituted or unsubstituted amino group, a carboxyl group, an ester group, an acyl group, a cyano group, a nitro group, a hydroxyl group, and an azido group.

[0017] Preferably, the molar ratio of the base to o-halophenyldihydroquinoline is 1 to 2:1.

[0018] Preferably, the reaction is carried out in the presence of a solvent, and the solvent is one or more of water, methanol, ethanol, acetonitrile, benzene, toluene, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide, ethylene glycol, and polyethylene glycol;

[0019] The base includes but is not limited to one or more of sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium formate, potassium formate, sodium acetate, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, potassium phosphate, and DBU.

[0020] Preferably, the reaction temperature of the thermal reaction process is 60-140° C., and the reaction time is 1-24 h.

[0021] Preferably, the reaction temperature of the photoreaction process is 10-40°C, and the reaction time is 1-48h.

[0022] The reaction light source is a white LED 6000-6500k, and the power of the light source is 1-20W.

[0023] Preferably, the reaction is carried out in air or an inert atmosphere, and the inert atmosphere is a nitrogen atmosphere or an argon atmosphere.

[0024] Preferably, after the reaction is completed, the reaction solution is extracted with ethyl acetate, the organic phase is washed with water for multiple times and dried with anhydrous magnesium sulfate, and finally the organic phase is concentrated and subjected to flash chromatography and C18 silica gel column to obtain a quinazolinone derivative.

[0025] Preferably, the concentration is carried out by one of atmospheric distillation, reduced pressure distillation and rotary evaporation.

[0026] Preferably, the post-treatment can also be performed by column chromatography purification, wherein the column chromatography uses 200-300 mesh silica gel as the separation resin and the eluent is selected from at least one of petroleum ether, n-hexane, dichloromethane, water, acetonitrile, methanol, and ethyl acetate.

[0027] Preferably, the structural formula of the quinazolinone derivative is as follows:

[0028] An example of the present invention provides a method for preparing a quinazolinone derivative. Under the action of a base, an NH group is deprotonated and an electron is transferred to obtain an intermediate. The intermediate obtains a proton and then undergoes proton transfer and hydrodebromination to obtain a quinazolinone derivative. The target product is obtained by both light and heat methods. The raw material synthesis is simple, the production cost can be effectively reduced, the yield and chemical selectivity can be improved, and the method can be conveniently applied to the preparation of quinazolinone derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The 1HNMR spectrum of compound 3a provided in Example 1 of the present invention;

[0030] Figure 2 This is the 13CNMR carbon spectrum of compound 3a prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0031] In order to make the purpose, technical solution and advantages of the present application more clear, the present application is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described here are only used to explain the present application and are not used to limit the present application.

[0032] The present application provides a method for preparing a quinazolinone derivative, which is characterized by comprising the following steps: in the presence of a base, 2-(2-halophenyl)-2,3-dihydroquinazolin-4(1H)-one is subjected to a dehalogenation hydrogenation reaction to obtain a quinazolinone derivative, and the reaction formula is as follows:

[0033]

[0034] Wherein, the X group is one of fluorine, chlorine, bromine and iodine, and the L group is oxygen or sulfur.

[0035] R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 The radicals are each independently selected from hydrogen, halogen, substituted or unsubstituted C 1～10 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted C 1～10 One of an alkoxy group, a substituted or unsubstituted amino group, a carboxyl group, an ester group, an acyl group, a cyano group, a nitro group, a hydroxyl group, and an azido group.

[0036] The temperature of the thermal reaction process is 60-140°C, and the reaction time is 1-24h. The temperature of the photoreaction process is 10-40°C, and the reaction time is 1-48h. The reaction light source is a white LED 6000-6500k, and the power of the light source is 1-20W. The reaction is carried out in air or inert atmosphere, and the inert atmosphere is a nitrogen atmosphere or an argon atmosphere.

[0037] According to the present invention, the reaction is carried out in the presence of a solvent, and the reaction is carried out in the presence of a solvent, and the solvent is one or more of water, methanol, ethanol, acetonitrile, benzene, toluene, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide, ethylene glycol, and polyethylene glycol. It should be understood that in the reaction of the present invention, the use of the above-mentioned solvent is only used to dissolve the reactants, and the solvent itself does not participate in the reaction. Therefore, as long as a solvent that can dissolve the reactants and the catalyst is selected, the above-mentioned reaction of the present application can be achieved. Although only the above-mentioned part is given as an example of a solvent in the specific embodiment of the present invention, those skilled in the art should understand that the examples are only used to explain the preferred embodiments given by the present invention, and are not used to limit the present invention. Under the enlightenment given by the examples, those skilled in the art can also obtain the present invention according to other solvents given by the present invention.

[0038] According to the present invention, the molar ratio of the base to 2-(2-bromophenyl)-2,3-dihydroquinazolin-4(1H)-one is 1 to 2:1. It should be understood that in the reaction of the present invention, the above reaction can occur according to the above molar ratio as long as the above catalyst and reactants are present. Those skilled in the art should understand that no matter in what ratio ferrocenylsulfamide and alkenylboronic acid are added, the molar ratio of the base participating in the reaction to 2-(2-bromophenyl)-2,3-dihydroquinazolin-4(1H)-one is always specific.

[0039] According to the present invention, after the reaction is completed, the reaction solution is extracted with ethyl acetate, the organic phase is washed with water for multiple times and dried with anhydrous magnesium sulfate, and finally the organic phase is concentrated and subjected to flash chromatography and C18 silica gel column to obtain a quinazolinone derivative.

[0040] In order to further understand the present invention, the method provided by the present invention is described in detail below in conjunction with embodiments, and the protection scope of the present invention is not limited by the following embodiments.

[0041] The specific implementation of the present application is described in detail below in conjunction with specific embodiments.

[0042] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0043] The specific implementation of the present invention is described in detail below in conjunction with specific embodiments.

[0044] Example 1

[0045] A method for preparing a quinazolinone derivative (Compound 2a), the structure and preparation method of which are as follows:

[0046] Method 1:

[0047]

[0048] The specific steps are as follows: weigh 2-(2-bromophenyl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 60mg) and cesium carbonate (0.2mmol, 65.2mg) into a 25mL Shrek tube, add DMF (2mL) and plug the tube, move it into a sand bath at 120°C and stir, react overnight, and track the reaction by TLC detection. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel and purified by column chromatography using an eluent with a volume ratio of petroleum ether: ethyl acetate = 5:1 to obtain pure 2-phenylquinazolin-4(3H)-one as a white solid with an isolation yield of 79%.

[0049] Method 2:

[0050]

[0051] The specific steps are as follows: weigh 2-(2-bromophenyl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 60mg), potassium tert-butoxide (0.4mmol, 44.8mg) in a 25mL quartz tube, add a magnet, add DMF (2mL) and plug the rubber stopper, place it at room temperature, irradiate with a 10W white LED, stir the mixture for 12 hours, and track the reaction by TLC detection. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel, and the eluent is a volume ratio of petroleum ether: ethyl acetate = 5:1 for column chromatography purification to obtain pure 2-phenylquinazolin-4(3H)-one as a white solid with a separation yield of 84%.

[0052] Structural identification of compound 2a:

[0053] NMR data:

[0054] 1 H NMR (500MHz, DMSO-d6) δ12.52(s,1H),8.20(d,J=7.4Hz,2H),8.17(d,J=7.8Hz,1H),7.84(t,J=7.6Hz,1H),7.75(d,J=8.1Hz,1H),7.60–7.51(m,4H).

[0055] 13C NMR (126MHz, DMSO-d6) δ162.86,152.95,149.19,135.00,133.32,131.81,129.05,128.24,127.87,126.98,126.33,121.47.

[0056] Compound 2a 1 HNMR, 13 The results of CNMR data analysis showed that the target product was correct.

[0057] Example 2

[0058] A method for preparing a quinazolinone derivative (Compound 2a), the structure and preparation method of which are as follows:

[0059] Method 1:

[0060]

[0061] The specific steps are as follows: weigh 2-(2-iodophenyl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 70mg) and cesium carbonate (0.2mmol, 65.2mg) in a 25mL Shrek tube, add a magnetic bar, add DMF (2mL) and plug the stopper, move it into a sand bath pot at 120°C and stir, react overnight, and track the reaction by TLC detection. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel and purified by column chromatography using an eluent with a volume ratio of petroleum ether: ethyl acetate = 5:1 to obtain pure 2-phenylquinazolin-4(3H)-one as a white solid with an isolation yield of 69%.

[0062] Method 2:

[0063]

[0064] The specific steps are as follows: weigh 2-(2-iodophenyl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 70mg), potassium tert-butoxide (0.4mmol, 44.8mg) in a 25mL quartz tube, add a magnet, add DMF (2mL) and plug the rubber stopper, stir the mixture for 12 hours under the irradiation of a 10W white LED at room temperature, and track the reaction by TLC detection. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel, and the eluent is a volume ratio of petroleum ether: ethyl acetate = 5:1 for column chromatography purification to obtain pure 2-(5-methylphenyl)quinazolin-4(3H)-one as a white solid with an isolation yield of 76%.

[0065] Structural identification of compound 2a:

[0066] NMR data:

[0067] 1 H NMR (500MHz, DMSO-d6) δ12.52(s,1H),8.20(d,J=7.4Hz,2H),8.17(d,J=7.8Hz,1H),7.84(t,J=7.6Hz,1H),7.75(d,J=8.1Hz,1H),7.60–7.51(m,4H).

[0068] 13 C NMR (126MHz, DMSO-d6) δ162.86,152.95,149.19,135.00,133.32,131.81,129.05,128.24,127.87,126.98,126.33,121.47.

[0069] Compound 2ab 1 H NMR, 13 C NMR data analysis results showed that the target product was obtained correctly.

[0070] Example 3

[0071] A method for preparing a quinazolinone derivative (Compound 2e), the structure and preparation method of which are as follows:

[0072] Method 1:

[0073]

[0074] The specific steps are as follows: weigh 2-(2-bromo-4-methylphenyl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 63.2mg) and cesium carbonate (0.2mmol, 65.2mg) in a 25mL Shrek tube, add DMF (2mL) and plug the tube, move it into a sand bath at 120°C and stir, react overnight, and track the reaction by TLC detection. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel and purified by column chromatography using an eluent with a volume ratio of petroleum ether: ethyl acetate = 5:1 to obtain pure 2-(p-tolyl)quinazolin-4(3H)-one as a white solid with an isolation yield of 72%.

[0075] Method 2:

[0076]

[0077] The specific steps are as follows: weigh 2-(2-bromo-4-methylphenyl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 63.2mg), potassium tert-butoxide (0.4mmol, 44.8mg) in a 25mL quartz tube, add DMF (2mL) and plug the rubber stopper, and stir the mixture for 12 hours under the irradiation of a 10W white LED at room temperature. Use TLC to track the reaction. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel, and the eluent is a volume ratio of petroleum ether: ethyl acetate = 5:1 for column chromatography purification to obtain pure 2-(p-tolyl)quinazolin-4(3H)-one, a white solid, with an isolation yield of 81%.

[0078] Structural identification of compound 2e:

[0079] NMR data:

[0080] 1 H NMR (500 MHz, DMSO-d 6 )δ12.46(s,1H),8.14(dd,J=8.0,J=1.5Hz,1H),8.11(d,J=8.0Hz,2H),7.85–7.80(m, 1H),7.73(d,J=8.1Hz,1H),7.50(t,J=7.4Hz,1H),7.36(d,J=8.0Hz,2H),2.39(s,3H)

[0081] 13C NMR (126 MHz, DMSO-d 6 )δ163.04,152.99,149.30,141.83,134.92,130.58,129.63,128.16,127.74,126.74,126.31,121.37,21.45.

[0082] Compound 3b 1 H NMR, 13 C NMR data analysis results showed that the target product was obtained correctly.

[0083] Example 4

[0084] A method for preparing a quinazolinone derivative (Compound 2f), the structure and preparation method of which are as follows:

[0085]

[0086] The specific steps are as follows: weigh 2-(2-bromo-4-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 66.6mg) and cesium carbonate (0.2mmol, 65.2mg) in a 25mL Shrek tube, add DMF (2mL) and plug the tube, move it into a sand bath at 120°C and stir, react overnight, and track the reaction by TLC detection. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel and purified by column chromatography using an eluent with a volume ratio of petroleum ether: ethyl acetate = 5:1 to obtain pure 2-(p-tolyl)quinazolin-4(3H)-one as a white solid with an isolation yield of 57%.

[0087] Method 2:

[0088]

[0089] The specific steps are as follows: weigh 2-(2-bromo-4-methylphenyl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 66.2mg), potassium tert-butoxide (0.4mmol, 44.8mg) in a 25mL quartz tube, add a magnetic bar, add DMF (2mL) and plug the rubber stopper, stir the mixture for 12 hours under the irradiation of a 10W white LED at room temperature, and track the reaction by TLC detection. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel, and the eluent is a volume ratio of petroleum ether: ethyl acetate = 5:1 for column chromatography purification to obtain pure 2-phenylquinazolin-4(3H)-one as a white solid with a separation yield of 66%.

[0090] Structural identification of compound 2f:

[0091] NMR data:

[0092] 1 H NMR (500 MHz, DMSO-d 6 )δ12.39(s,1H),8.23–8.17(m,2H),8.13(dd,J=8.0,1.5Hz,1H),7.83–7.78(m, 1H),7.71(d,J=8.1Hz,1H),7.51–7.44(m,1H),7.11–7.07(m,2H),3.85(s,3H).

[0093] 13 C NMR (126MHz, DMSO) δ162.34,134.96,129.95,126.55,126.29,125.37,121. 12,114.47,55.95,40.90,40.49,40.33,40.16,39.99,39.83,39.66,39.49.

[0094] Compound 2c 1 H NMR, 13 C NMR data analysis results showed that the target product was obtained correctly.

[0095] Example 5

[0096] A method for preparing a quinazolinone derivative (Compound 2h), the structure and preparation method of which are as follows:

[0097] Method 1:

[0098]

[0099] The specific steps are as follows: weigh 2-(3-bromothiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 61.8mg) and cesium carbonate (0.2mmol, 65.2mg) in a 25mL Shrek tube, add a magnetic bar, add DMF (2mL) and plug the stopper, move it into a sand bath pot at 120°C and stir, react overnight, and track the reaction by TLC detection. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel and purified by column chromatography using a volume ratio of petroleum ether: ethyl acetate = 5:1 as the eluent to obtain pure 2-(thiophen-2-yl)quinazolin-4(3H)-one as a white solid with an isolation yield of 42%.

[0100] Method 2:

[0101]

[0102] The specific steps are as follows: weigh 2-(3-bromothiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one (0.2mmol, 61.8mg) and potassium tert-butoxide (0.4mmol, 44.8mg) in a 25mL quartz tube, add DMF (2mL) and plug the rubber stopper, stir the mixture for 12 hours under the irradiation of a 10W white LED at room temperature, and track the reaction by TLC detection. After the reaction is completed, cool the reaction tube to room temperature, add 10mL of saturated brine to the system, and stir; extract with ethyl acetate (10mL×3), combine the organic phases, and remove the solvent with a rotary evaporator to obtain a crude product; the crude product is loaded with silica gel and purified by column chromatography using an eluent with a volume ratio of petroleum ether: ethyl acetate = 5:1 to obtain pure 2-(thiophen-2-yl)quinazolin-4(3H)-one as a white solid with a separation yield of 39%.

[0103] Structural identification of compound 2n:

[0104] NMR data:

[0105] 1 H NMR (500MHz, DMSO-d6) δ12.56(s,1H),8.20(d,J=4Hz,1H),8.12(dd,J=8.0,1.5Hz,1H),7.85(d ,J=5.0Hz,1H),7.81–7.75(m,1H),7.64(d,J=8.5Hz,1H),7.50–7.43(m,1H),7.26–7.21(m,1H).

[0106] 13C NMR (126MHz, DMSO-d6) δ163.12,149.34,134.83,132.26,129.61,129.07,128.89,127.23,126.45,121.44.

[0107] Compound 2h 1 H NMR, 13 C NMR data analysis results showed that the target product was obtained correctly.

[0108] The applicant also synthesized other quinazolinone derivatives by a method similar to that of Example 1 above, the difference being that the reaction raw materials, products and product yields were different, see Table 1.

[0109]

[0110] Table 1 Synthesis of Quinazolinone Derivatives

[0111]

[0112]

[0113]

[0114]

[0115] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit it. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for preparing a quinazolinone derivative, characterized in that: The method comprises the following steps: under the action of a base, 2-(2-halophenyl)-2,3-dihydroquinazolin-4(1H)-one undergoes a dehalogenation and hydrogenation reaction to obtain a quinazolinone derivative, and the reaction formula is as follows: The X group is one of fluorine, chlorine, bromine and iodine, and the L group is oxygen or sulfur; The R1, R2, R3, R4, R5, R6, R7 and R8 groups are each independently selected from hydrogen, halogen, substituted or unsubstituted C 1～10 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted C 1～10 One of an alkoxy group, a substituted or unsubstituted amino group, a carboxyl group, an ester group, an acyl group, a cyano group, a nitro group, a hydroxyl group, and an azido group.

2. The method for preparing the quinazolinone derivative according to claim 1, characterized in that: The molar ratio of the base to 2-(2-bromophenyl)-2,3-dihydroquinazolin-4(1H)-one is 1-2:

1.

3. The method for preparing the quinazolinone derivative according to claim 1, characterized in that: The reaction is carried out in the presence of a solvent, and the solvent is one or more of water, methanol, ethanol, acetonitrile, benzene, toluene, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide, ethylene glycol, and polyethylene glycol; The base is one or more of sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium formate, potassium formate, sodium acetate, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, potassium phosphate, and DBU.

4. The method for preparing the quinazolinone derivative according to claim 1, characterized in that: The temperature of the thermal reaction process is 60-140°C.

5. The method for preparing the quinazolinone derivative according to claim 1, characterized in that: The photoreaction process temperature is room temperature.

6. The method for preparing the quinazolinone derivative according to claim 5, characterized in that: The reaction light source is a white LED 6000-6500k, and the power of the light source is 1-20W.

7. The method for preparing the quinazolinone derivative according to claim 1, characterized in that: The reaction is carried out in air or an inert atmosphere, and the inert atmosphere is a nitrogen atmosphere or an argon atmosphere.

8. The method for preparing a quinazolinone derivative according to claim 1, characterized in that: After the reaction is completed, the reaction solution is extracted with ethyl acetate, the organic phase is washed with water for multiple times and dried over anhydrous magnesium sulfate, and finally the organic phase is concentrated and subjected to flash chromatography and C18 silica gel column to obtain a quinazolinone derivative.

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