Method for preparing quinazoline-2,4(1H,3H)-dione compound by converting carbon dioxide under mild conditions

Abstract

The present invention belongs to the technical field of synthesis of quinazoline-2.4 (1H, 3H)-diketone compounds, and specifically relates to a method for preparing quinazoline-2,4 (1H, 3H)-diketone compounds by converting carbon dioxide under mild conditions and the compound prepared by the method. The present invention uses carbon dioxide and 2-aminobenzoyl compounds as raw materials, under the action of readily available and cheap DBN and triphenyl phosphite, at room temperature and normal pressure, in acetonitrile as a solvent, and reacts for 1-24 hours to obtain a high yield of quinazoline-2,4 (1H, 3H)-diketone compounds. The method has the advantages of mild reaction conditions, high yield, and a wide range of substrate applications, especially being able to directly synthesize N3-substituted quinazoline-2,4 (1H, 3H)-diketone compounds using carbon dioxide as a raw material.

Description

Technical Field

[0001] The present invention belongs to the technical field of synthesis of quinazoline-2,4(1H,3H)-dione compounds, and specifically relates to a method for preparing quinazoline-2,4(1H,3H)-dione compounds by converting carbon dioxide under mild conditions, and compounds prepared by the method. Background Art

[0002] Quinazoline-2,4(1H,3H)-dione is an important component of various biologically active compounds and commercial drugs, such as linagliptin, sotrastaurin, tioperidone, nitraquazone, and ketanserin. Traditional synthesis methods usually use phosgene or its derivative reagents, but these methods have disadvantages such as the use of toxic reagents or the need for multi-step synthesis. Recently, studies have reported the synthesis of 2,4-quinazolinediones using metal catalysis, such as iridium and copper catalyzed CH amidation / cyclization of benzamide to form quinazolinediones (J. Org. Chem. 2016, 81, 4898; Eur. J. Org. Chem. 2020, 2020, 708); nickel or copper catalysts catalyze the insertion of isocyanate or 2-aminopyridine to prepare quinazolinediones (Org. Lett. 2017, 19, 1052; Adv. Syn. Catal. 2018, 360, 3009). And Zhang Guisheng's group reported the use of CO as a C1 resource through palladium-catalyzed [4+1+1] modular preparation of 2.4 quinazolinediones (Green Chem. 2021, 23, 526). However, these methods are affected by specific and expensive metal catalysts, toxic reagents, limited substrate range, and harsh conditions (such as high temperature).

[0003] In recent decades, the synthesis of quinazoline-2,4(1H,3H)-diones under metal-free catalysis using CO2, which is abundant, cheap, green and renewable, as a raw material has attracted extensive attention. However, this method requires o-aminobenzonitrile compounds as raw materials, which is limited to the synthesis of unsubstituted quinazoline-2,4(1H,3H)-diones. Further derivatization of unsubstituted quinazoline-2,4(1H,3H)-diones will counteract the regioselectivity between the two nitrogens, resulting in low efficiency and low atom economy. In order to directly synthesize N-substituted quinazoline-2,4(1H,3H)-diones, Xu first reported the Pd-catalyzed insertion and cycloaddition of CO2 and isocyanide in 2-iodoaniline at atmospheric pressure to obtain N3-substituted quinazoline-2,4(1H,3H)-diones (Org.Lett.2017,19,4484). In addition, Zhang and Mampuys reported the palladium-catalyzed cyclization reaction of 2-bromoaniline, CO2 (1.0-2.0Mpa) and isocyanate to prepare N3-substituted quinazoline-2,4 (1H, 3H)-dione, etc. (Chinese J. Chem. 2018, 36, 112; ACS Catal. 2017, 7, 5549). However, these methods have some disadvantages, such as: environmental problems caused by metal catalysis, high reaction temperature, high carbon dioxide pressure required for some methods, and narrow substrate application range. Therefore, it is of great significance to develop a method for preparing unsubstituted and N3-substituted quinazoline-2,4 (1H, 3H)-dione by metal-free catalysis or promoting the conversion of CO2 under mild conditions to solve the problems of the prior art that it is limited to the synthesis of unsubstituted quinazoline-2,4 (1H, 3H)-dione compounds, requires metal catalysis, requires high temperature, requires high carbon dioxide pressure, and has a narrow substrate application range. Summary of the invention

[0004] In order to solve the deficiencies of the prior art, the present invention provides a method for preparing quinazoline-2,4(1H,3H)-dione compounds by converting carbon dioxide under mild conditions. The preparation method is to use carbon dioxide and 2-aminobenzoyl compounds as raw materials, react in acetonitrile as a solvent at room temperature and atmospheric pressure for 1-24 hours under the action of readily available and inexpensive DBN and triphenyl phosphite, and obtain a high-yield quinazoline-2,4(1H,3H)-dione compound. The method has the advantages of mild reaction conditions, high yield, and a wide range of substrate applications, especially being able to directly synthesize N3-substituted quinazoline-2,4(1H,3H)-dione compounds using carbon dioxide as a raw material.

[0005] The technical solution provided by the present invention is as follows:

[0006] A method for preparing a quinazoline-2,4(1H,3H)-dione compound, the reaction equation of which is shown below:

[0007]

[0008] The method comprises the following steps: taking 2-aminobenzamide compounds and carbon dioxide as raw materials, reacting in an organic solvent under the action of an organic base and a phosphite.

[0009] R1 is selected from hydrogen, alkyl, methoxy, halogen.

[0010] R2 is selected from hydrogen, alkyl, functionalized alkyl, aryl, ethynyl, benzyl, heterocycle.

[0011] The organic base is selected from DBU (I), DBN (II), and MTBD (III) and has the chemical structural formula shown below:

[0012] DBN(II) is preferred.

[0013] The phosphite has the chemical structure shown below:

[0014]

[0015] Wherein, R3 is selected from alkyl and aryl, and is preferably phenyl.

[0016] The organic solvent is selected from one of acetonitrile, dichloromethane, 1,2-dichloroethane and tetrahydrofuran, preferably acetonitrile.

[0017] The ratio of o-aminobenzamide to DBN and triphenyl phosphite is 1:(0.2-2):(0.2-2), preferably 1:1:1.

[0018] The reaction temperature is room temperature, specifically, 20-30°C, preferably, 25°C;

[0019] The reaction pressure is normal pressure, specifically, 0.09-0.11 MPa, preferably, 0.1 MPa.

[0020] The reaction time is 1-24h.

[0021] By means of the present invention, quinazoline-2,4(1H,3H)-dione compounds can be prepared in high yield, and the reaction substrates include but are not limited to the following compounds:

[0022]

[0023] The present invention also provides compounds prepared by the above preparation method. These compounds can be used to prepare biologically active compounds or commercial drugs.

[0024] The mechanism of the preparation method provided by the present invention is as follows:

[0025]

[0026] Compared with the prior art, the present invention has the following advantages:

[0027] The preparation method of quinazoline-2,4(1H,3H)-dione compound of the present invention uses 2-aminobenzamide and carbon dioxide as raw materials, preferably under the promotion of DBN and triphenyl phosphite, reacts in acetonitrile as a solvent at room temperature and normal pressure for 1-24 hours, and can obtain N-unsubstituted or N3-substituted quinazoline-2,4(1H,3H)-dione compound with a high yield of 81-99%. The method not only has mild reaction conditions, but also avoids the use of transition metals, is extremely environmentally friendly, and has a wide range of substrate applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is the NMR characterization spectrum of compound 2a provided by the present invention.

[0029] Figure 2 It is the nuclear magnetic resonance characterization spectrum of compound 2g provided by the present invention.

[0030] Figure 3 It is the NMR characterization spectrum of compound 2j provided by the present invention.

[0031] Figure 4 It is the nuclear magnetic resonance characterization spectrum of compound 2k provided by the present invention.

[0032] Figure 5 It is the nuclear magnetic resonance characterization spectrum of compound 2m provided by the present invention.

[0033] Figure 6 It is the nuclear magnetic resonance characterization spectrum of compound 2n provided by the present invention.

[0034] Figure 7 This is the NMR characterization spectrum of compound 2o provided by the present invention.

[0035] Figure 8 It is the nuclear magnetic resonance characterization spectrum of compound 2p provided by the present invention.

[0036] Fig. 9 It is the nuclear magnetic resonance characterization spectrum of compound 2q provided by the present invention.

[0037] Fig.10 It is the NMR characterization spectrum of compound 2u provided by the present invention.

[0038] Fig.11 It is the nuclear magnetic resonance characterization spectrum of compound 2v provided by the present invention.

[0039] Fig.12This is the NMR characterization spectrum of compound 2w provided by the present invention.

[0040] Fig.13 It is the nuclear magnetic resonance characterization spectrum of compound 2x provided by the present invention.

[0041] Fig.14 It is a flow chart of the preparation method provided by the present invention. DETAILED DESCRIPTION

[0042] The principles and features of the present invention are described below. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0043] The reaction products are as follows:

[0044]

[0045] Example 1

[0046] Synthesis of 2a: Weigh 0.5 mmol of 1a, 0.5 mmol of DBN and 0.5 mmol of triphenyl phosphite into a 10 mL reaction tube, and add 0.5 mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 1 hour to precipitate a white solid. After the reaction is completed, filter directly and wash with glacial ethyl acetate to obtain the target product 2a (77 mg, yield 95%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.20 (s, 2H), 7.89 (d, J = 3.0Hz, 1H), 7.63-7.65 (m, 1H), 7.16-7.19 (m, 2H). 13 CNMR(DMSO-d6,150MHz): δ163.30,150.77,141.34,135.41,127.41,122.78,115.78,114.80.

[0047] Example 2

[0048] Synthesis of 2b: Weigh 0.5 mmol of 1b, 0.5 mmol of DBN and 0.5 mmol of triphenyl phosphite into a 10 mL reaction tube, and add 0.5 mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 1 hour to precipitate a white solid. After the reaction is completed, filter directly and wash with glacial ethyl acetate to obtain the target product 2b (88 mg, yield 99%). White solid, 1H NMR (DMSO-d6, 600MHz): δ11.15 (s, 2H), 7.77 (d, J = 3.0Hz, 1H), 7.00 (d, J = 6.0Hz, 1H), 6.95 (s, 1H), 2.36 (s, 3H). 13 C NMR (DMSO-d6, 150MHz): δ163.16,150.92,146.05,141.41,127.37,124.11,115.52,112.51,21.89.

[0049] Example 3

[0050] Synthesis of 2c: Weigh 0.5 mmol of 1c, 0.5 mmol of DBN and 0.5 mmol of triphenyl phosphite into a 10 mL reaction tube, and add 0.5 mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 1 hour to precipitate a white solid. After the reaction is completed, filter directly and wash with glacial ethyl acetate to obtain the target product 2c (79 mg, yield 82%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.28(s,1H),11.03(s,1H),7.33(d,J=1.5Hz,1H),7.27-7.29(m,1H),7.12(d,J=3.0Hz,1H),3.79(s,3H). 13 C NMR (DMSO-d6, 150MHz): δ163.17,155.05,150.52,135.42,124.25,117.38,115.28,108.47,55.98.

[0051] Example 4

[0052] Synthesis of 2d: Weigh 0.5 mmol of 1d, 0.5 mmol of DBN and 0.5 mmol of triphenyl phosphite into a 10 mL reaction tube, and add 0.5 mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 1 hour to precipitate a white solid. After the reaction is completed, filter directly and wash with glacial ethyl acetate to obtain the target product 2d (73 mg, yield 81%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.29 (s, 2H), 7.58 (d, J = 3.0Hz, 1H), 7.53-7.56 (m, 1H), 7.19-7.21 (m, 1H). 13CNMR(DMSO-d6,150MHz): δ162.58(d,J=1.5Hz),157.73(d,J=237.0Hz),150.55,138.07, 123.35(d,J=24.0Hz), 118.04(d,J=7.5Hz), 115.85(d,J=7.5Hz), 112.41(d,J=24.0Hz).

[0053] Example 5

[0054] Synthesis of 2e: Weigh 0.5 mmol of 1e, 0.5 mmol of DBN and 0.5 mmol of triphenyl phosphite into a 10 mL reaction tube, and add 0.5 mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 1 hour to precipitate a white solid. After the reaction is completed, filter directly and wash with glacial ethyl acetate to obtain the target product 2e (83 mg, yield 84%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.32 (s, 2H), 7.81 (s, 1H), 7.67 (d, J = 3.0Hz, 1H), 7.18 (d, J = 6.0Hz, 1H). 13 CNMR(DMSO-d6,150MHz): δ162.33,150.60,140.34,135.23,126.67,126.36,118.06,116.26.

[0055] Example 6

[0056] Synthesis of 2f: Weigh 0.5 mmol of 1f, 0.5 mmol of DBN and 0.5 mmol of triphenyl phosphite into a 10 mL reaction tube, and add 0.5 mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 1 hour to precipitate a white solid. After the reaction is completed, filter directly and wash with glacial ethyl acetate to obtain the target product 2f (102 mg, yield 85%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.35 (s, 2H), 7.94 (s, 1H), 7.79 (d, J = 3.0Hz, 1H), 7.12 (d, J = 3.0Hz, 1H). 13 CNMR(DMSO-d6,150MHz): δ162.20,150.53,140.59,137.95,129.37,118.26,116.68,114.26.

[0057] Example 7

[0058] Synthesis of 2g: Weigh 0.5mmol of 1g, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, and add 0.5mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 2 hours to precipitate a white solid. After the reaction, column chromatography was used to separate and obtain the target product 2g (104mg, yield 95%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.43 (s, 1H), 7.93 (d, J = 6.0Hz, 1H), 7.64-7.67 (m, 1H), 7.17-7 .22(m,2H),3.88-3.90(m,2H),1.53-1.58(m,2H),1.28-1.34(m,2H),0.90-0.92(m,3H). 13 C NMR(DMSO-d6,150MHz): δ162.34,150.58,139.84,135.36,127.80,122.91,115.52,114.20,40.15,29.95,20.13,14.15.HRMS(ESI):[M+H] + Calculate for C 12 H 15 N2O2 219.1134, found 219.1129.

[0059] Example 8

[0060] Synthesis of 2h: Weigh 0.5mmol of 1h, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, and add 0.5mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 24 hours to precipitate a white solid. After the reaction, column chromatography was used to separate the target product 2h (102mg, yield 93%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.02(s,1H),7.83(d,J=6.0Hz,1H),7.57-7.59(m,1H),7.12-7.14(m,1H),7.08(d,J=6.0Hz,1H),1.67(s,9H). 13C NMR (DMSO-d6, 150MHz): δ164.34,151.47,139.18,134.79,127.64,122.44,116.58,114.70,60.67,29.94.

[0061] Example 9

[0062] Synthesis of 2i: Weigh 0.5 mmol of 1i, 0.5 mmol of DBN and 0.5 mmol of triphenyl phosphite into a 10 mL reaction tube, add 0.5 mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 2 hours under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2i (126 mg, yield 85%) was obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.02 (s, 1H), 7.80 (d, J = 6.0Hz, 1H), 7.56-7.58 (m, 1H), 7.11-7.13 (m, 1H), 7 .06(d,J=6.0Hz,1H),2.52(d,J=3.0Hz,6H),2.10(s,3H),1.70(d,J=6.0Hz,3H),1.64(d,J=6.0Hz,3H). 13 CNMR(DMSO-d6,150MHz): δ164.51,151.45,139.13,134.71,127.58,122.42,116.99,114.64,63.70,39.95,36.45,30.33.

[0063] Example 10

[0064] Synthesis of 2j: Weigh 0.5 mmol of 1j, 0.5 mmol of DBN and 0.5 mmol of triphenyl phosphite into a 10 mL reaction tube, add 0.5 mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 24 hours under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2j (143 mg, yield 87%) was obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.56 (s, 1H), 7.95 (d, J = 3.0Hz, 1H), 7.70-7.73 (m, 1H), 7.36-7.39 (m, 9H), 7.31-7.34 (m, 2H), 7.24-7.27 (m, 2H), 13C NMR(DMSO-d6,150MHz): δ162.44,150.57,139.98,139.00,135.75,128.84,128.52,128.12,127.51,123.15,115.61,114.40,58.67.HRMS(ESI):[M+Na] + Calculate for C 21 H 16 N2O2Na 351.1109,found351.1107.

[0065] Embodiment 11

[0066] Synthesis of 2k: Weigh 0.5mmol of 1k, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, add 0.5mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 1 hour under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2k (135mg, yield 89%) was obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.40 (s, 1H), 7.90 (d, J = 3.0Hz, 1H), 7.63-7.66 (m, 1H), 7.39-7.41 (m, 1H) ),7.29-7.31(m,1H),7.23-7.27(m,2H),7.17-7.21(m,2H),4.16-4.18(m,2H),3.03-3.05(m,2H). 13 C NMR(DMSO-d6,150MHz): δ162.27,150.46,139.85,136.83,135.41,133.73,131.59, 129.66,128.81,127.82,127.76,122.92,115.54,114.18,31.55.HRMS(ESI):[M+Na] + Calculate for C 16 H 13 ClN2NaO2 323.0558, found 323.0559.

[0067] Example 12

[0068] Synthesis of 2l: Weigh 0.5mmol of 1l, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, and add 0.5mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 1 hour to precipitate a white solid. After the reaction, column chromatography was used to separate the target product 2l (150mg, yield 92%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.52 (s, 1H), 8.03 (d, J = 3.0Hz, 1H), 7.74-7.77 (m, 1H), 7.27-7.32 (m, 2H), 6.96 (d,J=6.0Hz,1H),6.89(s,1H),6.83(d,J=3.0Hz,1H),4.18-4.21(m,2H),3.81(s,6H),2.90-2.93(m,2H). 13 C NMR(DMSO-d6,150MHz): δ162.27,150.48,149.07,147.83,139.83,135.44,131.47,1 27.81,122.97,120.98,115.54,114.22,112.83,112.36,55.93,55.76,41.81,33.29.

[0069] Embodiment 13

[0070] Synthesis of 2m: Weigh 0.5mmol of 1m, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, and add 0.5mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 2 hours to precipitate a white solid. After the reaction, column chromatography was used to separate the target product 2m (124mg, yield 90%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.44 (s, 1H), 7.93 (d, J = 6.0Hz, 1H), 7.64-7.67 (m, 1H), 7.17- 7.22(m,2H),4.02-4.04(m,2H),3.53-3.54(m,4H),2.50(d,J=3.0Hz,2H),2.44(s,4H). 13C NMR(DMSO-d6,150MHz): δ162.35,150.58,139.85,135.43,127.83,122.96,115.55,114.17,66.68,55.93,53.84,37.54.HRMS(ESI):[M+H] + Calculate for C 14 H 18 N3O3 276.1348, found 276.1352.

[0071] Embodiment 14

[0072] Synthesis of 2n: Weigh 0.5mmol of 1n, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, add 0.5mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 1 hour under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2n (132mg, yield 96%) is obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ10.86(s,1H),7.97(d,J=3.0Hz,1H),7.91(d,J=3.0Hz,1H),7.65-7.68(m,1H),7.35(d ,J=3.0Hz,1H),7.20-7.23(m,3H),7.01-7.10(m,1H),7.00-7.02(m,1H),4.15-4.18(m,2H),2.97-3.00(m,2H). 13 C NMR(DMSO-d6,150MHz): δ162.41,150.65,140.04,136.77,135.39,127.84,127.70,12 3.29,122.90,121.49,118.83,118.80,115.65,114.34,111.90,111.52,41.19,24.00.

[0073] Embodiment 15

[0074] Synthesis of 2o: Weigh 0.5mmol of 1o, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, and add 0.5mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 2 hours to precipitate a white solid. After the reaction, column chromatography was used to separate the target product 2o (124mg, yield 98%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.55(s,1H),8.43(d,J=1.5Hz,1H),7.94(d,J=6.0Hz ,1H),7.69-7.75(m,2H),7.30(d,J=3.0Hz,1H),7.22-7.25(m,3H),5.22(s,2H). 13 C NMR(DMSO-d6,150MHz): δ162.44,156.49,150.70,149.33,140.03,137.14,135. 63,127.96,123.08,122.57,121.21,115.70,114.20,44.95.HRMS(ESI):[M+Na] + Calculate for C 14 H 11 N3O2Na 276.0749, found 276.0750.

[0075] Example 16

[0076] Synthesis of 2p: Weigh 0.5mmol of 1p, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, and add 0.5mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 2 hours to precipitate a white solid. After the reaction, column chromatography was used to separate the target product 2p (88mg, yield 94%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.54 (s, 1H), 7.95 (d, J = 3.0 Hz, 1H), 7.68-7.70 (m, 1H), 7.20-7.25 (m, 2H), 4.63 (d, J = 3.0 Hz, 2H), 3.12-3.13 (m, 1H). 13C NMR (DMSO-d6, 150MHz): δ161.66,149.86,139.81,135.84,127.88,123.26,115.78,113.96,79.79,73.38,29.95.

[0077] Embodiment 17

[0078] Synthesis of 2q: Weigh 0.5mmol of 1q, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, add 0.5mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 22 hours under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction is completed, the target product 2q (164mg, yield 86%) is obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.52 (s, 1H), 7.86 (d, J = 6.0Hz, 1H), 7.64-7.67 (m, 1H), 7.28-7.33 (m, 5H), 7.1 3-7.21(m,6H),7.09-7.12(m,1H),5.86-5.89(m,1H),5.17(s,2H),3.52-3.56(m,1H),3.35-3.39(m,1H). 13 C NMR(DMSO-d6,150MHz): δ169.58,161.97,150.06,139.64,137.75,136.35,136.00,129.53,128.81,128 .58,128.43,128.04,128.01,126.90,123.37,115.69,113.51,66.69,54.39,34.39.HRMS(ESI):[M+Na] + Calculate for C 24 H 20 N2O4Na 423.1321, found 423.1324.

[0079] Embodiment 18

[0080] Synthesis of 2r: Weigh 0.5mmol of 1r, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, and add 0.5mL of acetonitrile as solvent. Connect the tube mouth to a balloon filled with carbon dioxide. In a carbon dioxide atmosphere (the pressure during the reaction is normal pressure), react at room temperature (25°C) for 5 hours to precipitate a white solid. After the reaction, column chromatography was used to separate the target product 2r (119mg, yield 94%). White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.52 (s, 1H), 7.93 (d, J = 6.0Hz, 1H), 7.68-7.71 (m, 1H ),7.27(d,J=3.0Hz,2H),7.21-7.23(m,2H),7.18(d,J=6.0Hz,2H),2.37(s,3H). 13 C NMR (DMSO-d6, 150MHz): δ162.72,150.72,140.27,137.90,135.62,133.56,129.75,129.23,128.05,122.94,115.66,114.79,21.21.

[0081] Embodiment 19

[0082] Synthesis of 2s: Weigh 0.5mmol of 1s, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, add 0.5mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 2 hours under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2s (119mg, yield 93%) is obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.56 (s, 1H), 7.93 (d, J = 3.0Hz, 1H), 7.69-7.71 (m, 1H), 7.38-7.40 (m, 2H), 7.30-7.33 (m, 2H), 7.22-7.24 (m, 2H). 13 C NMR(DMSO-d6,150MHz): δ162.74,162.02(d,J=241.5Hz),150.67,140.28,135.69,132.38( d,J=3.0Hz),131.66(d,J=9.0Hz),128.05,122.98,116.15,115.85(d,J=45.0Hz),114.78.

[0083] Embodiment 20

[0084] Synthesis of 2t: Weigh 0.5mmol of 1t, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, add 0.5mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 2 hours under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2t (130mg, yield 97%) is obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.50 (s, 1H), 7.93 (d, J = 3.0 Hz, 1H), 7.68-7.70 (m, 1H), 7.21-7.23 (m, 4H), 7.01 (d, J = 3.0 Hz, 2H), 3.81 (s, 3H). 13 C NMR (DMSO-d6, 150MHz): δ162.85,159.28,150.85,140.24,135.59,130.49,128.69,128.06,122.91,115.63,114.79,114.47,55.80.

[0085] Embodiment 21

[0086] Synthesis of 2u: Weigh 0.5mmol of 1u, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, add 0.5mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 2 hours under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2u (107mg, yield 90%) is obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.79(s,1H),8.71(d,J=3.0Hz,1H),8.66(d,J=1.5Hz,1H),8.06(d ,J=6.0Hz,1H),7.93-7.95(m,1H),7.81-7.84(m,1H),7.65-7.67(m,1H),7.34-7.37(m,2H). 13 C NMR(DMSO-d6,150MHz): δ162.72,150.56,150.33,149.42,140.32,137.47, 135.88,132.97,128.07,124.32,123.13,115.83,114.68.HRMS(ESI):[M+H] +Calculate for C 13 H 10 N3O2 240.0773, found 240.0775.

[0087] Embodiment 22

[0088] Synthesis of 2v: Weigh 0.5mmol of 1v, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, add 0.5mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 2 hours under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2v (136mg, yield 95%) is obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.65(s,1H),7.94(d,J=6.0Hz,1H),7.29-7.32(m,4H),7.23-7.26(m,2H),7.21(d,J=3.0Hz,1H),5.07(s,2H). 13 C NMR(DMSO-d6,150MHz): δ161.75,150.56,141.00,139.95,137.61,130.05,128.80,127.98,127.60,123.28,115.06,113.14,43.72.HRMS(ESI):[M+Na] + calcdfor C 15 H 11 N2O2NaCl 309.0407,found309.0408.

[0089] Embodiment 23

[0090] Synthesis of 2w: Weigh 0.5mmol of 1w, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, add 0.5mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 2 hours under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2w (128mg, yield 91%) is obtained by column chromatography. White solid, 1H NMR (DMSO-d6, 600MHz): δ11.41 (s, 1H), 7.86 (d, J = 6.0Hz, 1H), 7.29-7.31 (m, 4H), 7. 23-7.25(m,1H),6.80-6.82(m,1H),6.65(d,J=3.0Hz,1H),5.07(s,2H),3.83(s,3H). 13 C NMR(DMSO-d6,150MHz): δ164.96,161.91,150.92,141.86,138.00,129.88,128 .78,127.92,127.50,111.42,107.53,98.54,56.13,43.41.HRMS(ESI):[M+Na] + Calculate for C 16 H 14 N2O3Na 305.0902, found 305.0901.

[0091] Embodiment 24

[0092] Synthesis of 2x: Weigh 0.5mmol of 1x, 0.5mmol of DBN and 0.5mmol of triphenyl phosphite into a 10mL reaction tube, add 0.5mL of acetonitrile as solvent, connect the tube mouth to a balloon filled with carbon dioxide, react at room temperature (25°C) for 4 hours under a carbon dioxide atmosphere (pressure during the reaction is normal pressure), and a white solid precipitates. After the reaction, the target product 2x (185mg, yield 94%) is obtained by column chromatography. White solid, 1 H NMR (DMSO-d6, 600MHz): δ11.40 (s, 1H), 8.04-8.06 (m, 2H), 7.93 (d, J = 3.0Hz, 1H), 7.64-7.67 (m, 1H), 7.33-7.36 (m, 2H), 7.18-7.22 (m, 2H), 4 .02-4.05(m,2H),3.34-3.38(m,1H),2.98(d,J=6.0Hz,2H),2.53-2.55(m,2H),2.14-2.18(m,2H),1.73(d,J=6.0Hz,2H),1.50-1.55(m,2H). 13C NMR (DMSO-d6, 150MHz): δ201.64, 165.39 (d, J = 250.5Hz), 162.35, 150.61, 139.92, 135.40, 132.85, 131.62 (d, J = 9. 0Hz),127.82,122.91,116.26(d,J=22.5Hz),115.58,114.19,55.67,53.16,43.08,37.98,28.94.HRMS(ESI):[M+H] + Calculate for C 22 H 23 N3O3F 396.1723, found 396.1728.

[0093] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a quinazoline-2,4(1H,3H)-dione compound by converting carbon dioxide under mild conditions, characterized in that: The reaction is as follows: in: The reaction pressure is 0.09-0.11MPa; The reaction time is 1-24h; The R1 and R2 groups correspond to the corresponding groups in the following formulas: The organic base is DBN, and its structural formula is The phosphite is triphenyl phosphite; The organic solvent is acetonitrile.

2. The method for preparing quinazoline-2,4(1H,3H)-dione compound by converting carbon dioxide under mild conditions according to claim 1, characterized in that: The molar ratio of DBN to triphenyl phosphite is 1:(0.2-2):(0.2-2).

3. The method for preparing quinazoline-2,4(1H,3H)-dione compound by converting carbon dioxide under mild conditions according to claim 2, characterized in that: The molar ratio of DBN and triphenyl phosphite was 1:1:

1.

4. The method for preparing quinazoline-2,4(1H,3H)-dione compound by converting carbon dioxide under mild conditions according to claim 1, characterized in that: The room temperature is 20-30°C.

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