Method for synthesizing quinazoline diketone compound

Abstract

The invention discloses a method for synthesizing a quinazoline diketone compound, which comprises the following steps: firstly synthesizing a metallized porous organic polymer catalyst Pd (at) POL-TBZP, and successfully catalytically synthesizing the quinazoline diketone compound by taking the metallized porous organic polymer catalyst Pd (at) POL-TBZP as a basis and taking o-bromoaniline, isonitrile and carbon dioxide under normal pressure as raw materials. The method is low in cost and high in catalytic efficiency, the activity of the catalyst is still kept stable after the catalyst is recycled for 6 times, and good industrial application potential is shown.

Description

Technical Field

[0001] The invention relates to a chemical synthesis technology, in particular to a method for synthesizing quinazolinedione compounds. Background Art

[0002] In 1987, cardiovascular disease research scientists from the medical research department of Cyanogen Motion Corporation in the United States discovered that compounds with a quinazolinedione structure can produce anti-hypertensive effects in the body (J. Med. Chem., 1987, 30, 2277-2283.), and conducted preliminary research on a series of compounds with substituted groups. It was found that compounds substituted at the 6-, 7-, 8-positions of the benzene ring or the R1 position of the heterocycle showed more extensive and outstanding pharmaceutical activity. For example, Nitraquazone is a good phosphodiesterase inhibitor (Med.Chem.Res., 2012, 21, 3327-3335); Ketanserin can selectively block the action of 5-hydroxytryptamine (5-HT2A) receptors and can be used as an antihypertensive drug (Drugs, 1990, 40, 930-949; J.Phsrmacol.Exp.Ther., 2011, 339, 99-105). Figure 1 shown.

[0003] Quinazolinedione compounds are widely present in natural products and drug molecules, and have good anti-inflammatory, antibacterial, antiviral and other biological activities. Their synthesis methods have always been a hot topic in organic synthesis research. Commonly used clinical drugs such as praquinone, chloroquine and methaqualone sold on the market contain quinazolinone structures. The synthesis strategy with high atom economy in the prior art usually uses o-bromoaniline and isonitrile as reaction substrates to achieve the synthesis of quinazolinedione compounds under a carbon dioxide atmosphere. However, this type of reaction often requires harsh conditions such as high pressure and high temperature. Therefore, how to achieve the synthesis of quinazolinone compounds under mild conditions is a very challenging task. Summary of the invention

[0004] The object of the present invention is to provide a method for synthesizing quinazoline dione compounds in view of the deficiencies in the prior art. The method is not only low in cost and high in catalytic efficiency, but also the activity of the catalyst remains stable after being recycled for 6 times, showing good potential for industrial application.

[0005] The technical solution for achieving the purpose of the present invention is:

[0006] A method for synthesizing quinazolinedione compounds, wherein the general synthesis formula for synthesizing quinazolinedione compounds is:

[0007]

[0008] Among them, Pd@POL-TBZP is a metallized porous organic polymer catalyst Pd@POL-TBZP.

[0009] The synthesis method of the metallized porous organic polymer catalyst Pd@POL-TBZP is:

[0010]

[0011] The synthesis process of the metallized porous organic polymer catalyst Pd@POL-TBZP is as follows:

[0012] 1) 3 equiv. of magnesium powder is added to a round-bottom flask under a nitrogen atmosphere, 1,4-dioxane is added, and iodine particles are used to initiate the reaction. Subsequently, 3 equiv. of 4-bromomethylstyrene is slowly added dropwise to the flask, and the mixture is stirred at 80°C overnight. Then, 1 equiv. of phosphorus trichloride is slowly added to the 1,4-dioxane solution at 0°C, and the mixture is stirred at room temperature for 10 hours. The mixture is quenched with a saturated aqueous ammonium chloride solution, and then extracted with ethyl acetate. The organic layer is washed three times with water, dried over anhydrous magnesium sulfate, filtered and dried under reduced pressure, and then purified by silica gel column chromatography. During purification, silica gel and ethyl acetate / petroleum ether are used as eluents to obtain vinylated white solid tribenzylphosphine TBZP.

[0013] 2) Under argon protection, 100 mg of tribenzylphosphine TBZP and 10 mg of azobisisobutyronitrile were added to tetrahydrofuran, and copolymerization was carried out at 100°C for 24 hours. The mixture was filtered, washed with ethyl acetate three times, and dried in vacuo to obtain a porous polymer POL-TBZP. Then, 10 mg of tetrakistriphenylphosphine palladium was loaded into the polymer through the "metal-ligand" exchange method to obtain a metallized porous organic polymer catalyst Pd@POL-TBZP.

[0014] The method for synthesizing quinazoline dione compounds comprises the following steps:

[0015] A 10 mL reaction tube with a branch is selected, and a mixture of 0.2 mmol bromoaniline, 0.24 mmol tert-butyl isonitrile, 5 mg Pd@POL-TBZP, 0.45 mmol 1,8-diazabicycloundec-7-ene and 2 mL acetonitrile is stirred at 50° C. to 90° C. for 8 to 14 hours under a carbon dioxide atmosphere. After the reaction is completed, the mixture is cooled to room temperature, the solvent is removed under reduced pressure, and the residue is purified by silica gel column chromatography to obtain quinazolinedione compounds, wherein the metallized porous organic polymer catalyst Pd@POL-TBZP is the metallized porous organic polymer catalyst Pd@POL-TBZP synthesized by the above method.

[0016] This technical solution uses the metallized porous organic polymer catalyst Pd@POL-TBZP to successfully convert carbon dioxide gas into quinazoline dione compounds under normal pressure. This method is not only low-cost and high-catalytic efficiency, but also the activity of the catalyst remains stable after 6 cycles, showing good potential for industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 Schematic diagram of a representative drug containing a quinazolinone skeleton in the prior art;

[0018] Figure 2 Schematic diagram of the synthesis process of the catalyst in the embodiment;

[0019] Figure 3 Schematic diagram of the cycle experiment results in the embodiment. DETAILED DESCRIPTION

[0020] The content of the present invention is further described below in conjunction with the drawings and embodiments, but the present invention is not limited thereto.

[0021] Embodiment 1:

[0022] 1. Synthesis and product characterization of metallized porous organic polymer catalyst Pd@POL-TBZP, such as Figure 2 As shown, the synthesis of catalyst Pd@POL-TBZP includes the following steps:

[0023] 3 equiv. of magnesium powder is added to a round-bottom flask under a nitrogen environment, 1,4-dioxane is added, and iodine particles are used to initiate the process, then 3 equiv. of 4-bromomethylstyrene is slowly added dropwise to the flask, and the mixture is stirred at 80°C overnight, and then 1 equiv. of phosphorus trichloride is slowly added to the 1,4-dioxane solution at 0°C, and stirred at room temperature for 10 hours; the mixture is quenched with a saturated aqueous ammonium chloride solution, and then extracted with ethyl acetate, and the organic layer is washed three times with water, dried over anhydrous magnesium sulfate, filtered and dried under reduced pressure, and then purified by silica gel column chromatography, and silica gel, ethyl acetate / petroleum ether are used for elution to obtain vinylated white solid tribenzylphosphine TBZP;

[0024] Under argon protection, 100 mg of triphenylphosphine TBZP and 10 mg of azobisisobutyronitrile were added to tetrahydrofuran and copolymerized at 100°C for 24 hours. The mixture was filtered, washed with ethyl acetate three times, and dried in vacuo to obtain a porous polymer POL-TBZP. Then, 10 mg of tetrakistriphenylphosphine palladium was loaded into the polymer through the "metal-ligand" exchange method to obtain a metallized porous organic polymer catalyst Pd@POL-TBZP.

[0025] The product is characterized as: vinylated white solid tribenzylphosphine TBZP, with a yield of 98%, 1 H NMR (400MHz, CDCl3): δ7.36-7.34(m,6H),7.16-7.14(m,6H),6.75-6.68(m,3H),5.75-5.71(m,3H),5.23-5.20(m,3H),2.92(s,6H). 13 C NMR (101MHz, CDCl3): δ141.5,136.8,135.5,128.8,126.3,113.2,37.7. 31 P NMR (243MHz, CDCl3) δ=-6.84.Mp=187.2-200.3℃.

[0026] Embodiment 2:

[0027] 2. Preparation and characterization of quinazoline dione compounds:

[0028] 1-2): Preparation and characterization of 3-(tert-butyl)quinazoline-2,4(1H,3H)-dione (3a):

[0029]

[0030] A 10 mL reaction tube with a branch was used. Under a carbon dioxide atmosphere, a mixture of 2-bromoaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 50°C for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3a. The product 3a was characterized as: Colorless liquid (41.5 mg, 95%). 1 H NMR (400MHz, CDCl3): δ10.34(s,1H),8.01(d,J=7.4Hz,1H),7.56-7.52(m,1H),7.17-7.14(m,1H),7.02(d,J=8.1Hz,1H),1.81(s,9H). 13 C NMR (101MHz, CDCl3): δ164.5,153.5,138.3,134.5 128.2,122.9,117.1,114.2,62.2,30.1.

[0031] Embodiment 3:

[0032] 2-2): Preparation and characterization of 3-(tert-butyl)-6-methoxyquinazoline-2,4(1H,3H)-dione (3b):

[0033]

[0034] A 10 mL reaction tube with a branch was used. A mixture of 2-bromo-4-methoxyaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 65°C for 12 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3b. The product 3b was characterized as: Brown liquid (46.2 mg, 93%). 1 H NMR (400MHz, CDCl3): δ10.36 (s, 1H), 7.46 (s, 1H), 7.17-7.14 (m, 1H), 6.96 (d, J = 8.7Hz, 1H), 3.84 (s, 3H), 1.80 (s, 9H). 13 C NMR (101MHz, CDCl3): δ164.5,155.6,153.3,132.5,124.1,117.6,115.8,108.8,62.3,55.9,30.2.

[0035] Embodiment 4:

[0036] 3-2): Preparation and characterization of 3-(tert-butyl)-8-methoxyquinazoline-2,4(1H,3H)-dione (3c):

[0037]

[0038] A 10 mL reaction tube with a branch was used. A mixture of 2-bromo-6-methoxyaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 65°C for 12 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3c. The product 3c was characterized as: Yellow liquid (45.7 mg, 92%). 1H NMR (400MHz, CDCl3): δ8.43 (s, 1H), 7.56 (d, J = 7.9Hz, 1H), 7.08-6.99 (m, 2H), 3.92 (s, 3H), 1.76 (s, 9H). 13 C NMR (101MHz, CDCl3): δ164.4,151.6,145.2,128.6,122.3,119.2,117.4,113.8,61.9,56.2,30.0.

[0039] Embodiment 5:

[0040] 4-2): Preparation and characterization of 3-(tert-butyl)-7-methoxyquinazoline-2,4(1H,3H)-dione (3d):

[0041]

[0042] A 10 mL reaction tube with a branch was used. Under a carbon dioxide atmosphere, a mixture of 2-bromo-5-methoxyaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 65°C for 12 hours. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3d. The product 3d was characterized as: Colorless liquid (44.7 mg, 90%). 1 H NMR (400MHz, CDCl3): δ10.36(s,1H),7.91(d,J=8.8Hz,1H),6.71-6.69(m,1H),6.43(d,J=2.4Hz,1H),3.85(s,3H),1.79(s,9H). 13 C NMR (101MHz, CDCl3): δ164.7,164.1,153.9,140.1,130.0,111.2,110.4,97.2,62.0,55.7,30.2.

[0043] Embodiment 6:

[0044] 5-2): Preparation and characterization of 3-(tert-butyl)-6-methylquinazoline-2,4(1H,3H)-dione (3e):

[0045]

[0046] A 10 mL reaction tube with a branch was used. A mixture of 2-bromo-4-methylaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 12 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3e. The product 3e was characterized as: Colorless liquid (43.7 mg, 94%). 1 H NMR (400MHz, CDCl3): δ10.52(d,J=51.8Hz,1H),7.79(s,1H),7.35-7.33(m,1H),6.92(d,J=8.2Hz,1H),2.36(s,3H),1.79(s,9H). 13 C NMR (101MHz, CDCl3): δ164.6,153.6,136.1,135.5,132.5,127.7,116.9,114.1,62.0,30.1,20.9.

[0047] Embodiment 7:

[0048] 6-2): Preparation and characterization of 3-(tert-butyl)-7-methylquinazoline-2,4(1H,3H)-dione (3f):

[0049]

[0050] A 10 mL reaction tube with a branch was used. A mixture of 2-bromo-5-methylaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 12 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3f. The characterization of 3f was: Colorless liquid (45.1 mg, 97%). 1 H NMR (400MHz, CDCl3): δ10.02(s,1H),7.88(d,J=8.1Hz,1H),6.96(d,J=8.1Hz,1H),6.80(s,1H),2.40(s,3H),1.80(s,9H). 13C NMR (101MHz, CDCl3): δ164.5,153.5,145.7,138.3,128.1,124.3,114.8,114.1,62.0,30.1,22.0.

[0051] Embodiment 8:

[0052] 7-2): Preparation and characterization of 3-(tert-butyl)-6-fluoroquinazoline-2,4(1H,3H)-dione (3g):

[0053]

[0054] A 10 mL reaction tube with a branch was used. Under a carbon dioxide atmosphere, a mixture of 2-bromo-4-fluoroaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 3 g of the target product. The product 3 g was characterized as: Colorless liquid (42.5 mg, 90%). 1 H NMR (400MHz, CDCl3): δ10.88(s,1H),7.66(d,J=8.2Hz,1H),7.65-7.28(m,1H),7.02-6.99(m,1H),1.79(s,9H). 13 C NMR (101MHz, CDCl3): δ163.6 (J=2.6Hz), 158.5 (J=241.4Hz), 153.6, 134.7, 122. 5(J=24.3Hz), 118.1(J=8.1Hz), 116.0(J=7.5Hz), 113.7(J=25.7Hz), 62.6, 30.0.

[0055] Embodiment 9:

[0056] 8-2): Preparation and characterization of 3-(tert-butyl)-7-fluoroquinazoline-2,4(1H,3H)-dione (3h):

[0057]

[0058] A 10 mL reaction tube with a branch was used. Under a carbon dioxide atmosphere, a mixture of 2-bromo-5-fluoroaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3h. The product 3h was characterized as: Colorless liquid (43.0 mg, 91%). 1 H NMR (400MHz, CDCl3): δ10.73(s,1H),8.03-7.99(m,1H),6.87-6.82(m,1H),6.70-6.68(m,1H),1.79(s,9H). 13 C NMR (101MHz, CDCl3): δ166.5 (J=252.9Hz), 163.5, 153.7, 140.0 (J=12.6Hz), 131. 2(J=10.9Hz), 113.6(J=2.1Hz), 111.2(J=22.9Hz), 100.8(J=25.7Hz), 62.5, 30.1.

[0059] Embodiment 10:

[0060] 9-2): Preparation and characterization of 6-bromo-3-(tert-butyl)quinazoline-2,4(1H,3H)-dione (3i):

[0061]

[0062] A 10 mL reaction tube with a branch was used. A mixture of 2,4-dibromoaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 10 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3i. The product 3i was characterized as: Colorless liquid (52.9 mg, 89%). 1 H NMR (400MHz, CDCl3): δ10.16 (s, 1H), 8.14 (d, J = 2.2Hz, 1H), 7.64-7.61 (m, 1H), 6.89 (d, J = 8.5Hz, 1H), 1.78 (s, 9H). 13C NMR (101MHz, CDCl3): δ163.1,153.1,137.4,137.0,130.8,118.6,115.9,115.5,62.7,30.0.

[0063] Embodiment 11:

[0064] 10-2): Preparation and characterization of 7-bromo-3-(tert-butyl)quinazoline-2,4(1H,3H)-dione (3j):

[0065]

[0066] A 10 mL reaction tube with a branch was used. A mixture of 2,5-dibromoaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 10 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3j. The product 3j was characterized as: Colorless liquid (50.5 mg, 85%). 1 H NMR (400MHz, CDCl3): δ10.44(s,1H),7.86(d,J=8.4Hz,1H),7.27-7.24(m,1H),7.17(d,J=1.5Hz,1H),1.78(s,9H). 13 C NMR (101MHz, CDCl3): δ163.8,153.3,139.1,129.7,129.0,126.4,117.1,115.9,62.6,30.0.

[0067] Embodiment 12:

[0068] 11-2): Preparation and characterization of 3-(tert-butyl)-6-chloroquinazoline-2,4(1H,3H)-dione (3k):

[0069]

[0070] A 10 mL reaction tube with a branch was used. A mixture of 2-bromo-4-chloroaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 12 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3k. The product 3k was characterized as: Colorless liquid (44.0 mg, 87%). 1 H NMR (400MHz, CDCl3): δ9.88 (s, 1H), 7.98 (d, J = 2.3Hz, 1H), 7.50-7.47 (m, 1H), 6.94 (d, J = 8.5Hz, 1H), 1.77 (s, 9H). 13 C NMR (101MHz, CDCl3): δ163.3,152.9,136.6,134.6,128.5,127.9,118.3,115.6,62.6,30.0.

[0071] Embodiment 13:

[0072] 12-2): Preparation and characterization of 3-(tert-butyl)-7-chloroquinazoline-2,4(1H,3H)-dione (3l):

[0073]

[0074] A 10 mL reaction tube with a branch was used. A mixture of 2-bromo-5-chloroaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 12 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3l. The characterization of 3l was: Colorless liquid (41.4 mg, 82%). 1 H NMR (400MHz, CDCl3): δ10.54 (s, 1H), 7.93 (d, J = 8.5Hz, 1H), 7.12-7.10 (m, 1H), 7.00 (s, 1H), 1.79 (s, 9H). 13 C NMR (101 MHz, CDCl3): δ 163.6, 153.4, 140.6, 139.0, 129.7, 123.5, 115.5, 114. Example 4:

[0075] Embodiment 14:

[0076] 13-2): Preparation and characterization of 3-(tert-butyl)-6,8-dichloroquinazoline-2,4(1H,3H)-dione (3m):

[0077]

[0078] A 10 mL reaction tube with a branch was used. A mixture of 2-bromo-4,6-dichloroaniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 14 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3m. The product 3m was characterized as: Colorless liquid (43.1 mg, 75%). 1 H NMR (400MHz, CDCl3): δ8.52 (s, 1H), 7.92 (d, J = 2.2Hz, 1H), 7.57 (d, J = 2.3Hz, 1H), 1.74 (s, 9H). 13 C NMR (101MHz, CDCl3): δ162.4,150.3,133.6,128.2,126.9,119.1,119.0,62.9,29.7.

[0079] Embodiment 15:

[0080] 14-2): Preparation and characterization of 3-(tert-butyl)-6-trifluoromethylquinazoline-2,4(1H,3H)-dione (3n):

[0081]

[0082] A 10 mL reaction tube with a branch was used. A mixture of 2-bromo-4-(trifluoromethyl)aniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 14 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3n. The product 3n was characterized as: Colorless liquid (40.1 mg, 70%). 1H NMR (400MHz, CDCl3): δ10.55(s,1H),8.31(s,1H),7.78(d,J=2.1Hz,1H),7.11(d,J=8.5Hz,1H),1.80(s,9H). 13 C NMR (101MHz, CDCl3): δ163.3,153.3,140.5,131.1(q,J C-F =3.2Hz),126.3(q,J C-F =4.0Hz),125.5(d,J C-F =33.7Hz),123.8(d,J C-F =271.7Hz),117.0,114.9,63.0,30.0.

[0083] Embodiment 16:

[0084] 15-2): Preparation and characterization of 3-(tert-butyl)-7-trifluoromethylquinazoline-2,4(1H,3H)-dione (3o):

[0085]

[0086] A 10 mL reaction tube with a branch was used. A mixture of 2-bromo-5-(trifluoromethyl)aniline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 80°C for 14 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3o. The product 3o was characterized as: Colorless liquid (41.8 mg, 73%). 1 H NMR (400MHz, CDCl3): δ10.53(s,1H),8.12(d,J=8.1Hz,1H),7.37(d,J=8.4Hz,1H),7.24(s,1H),1.78(s,9H). 13 C NMR (101MHz, CDCl3): δ163.4,153.3,138.3,136.1(d,J C-F =33.0Hz),129.4,123.3(d,J C-F =273.3Hz),119.6,119.4(d,J C-F =6.9Hz),111.6(d,J C-F =4.0Hz),62.9,29.9.

[0087] Embodiment 17:

[0088] 16-2): Preparation and characterization of 3-(tert-butyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-carboxylic acid methyl ester (3p):

[0089]

[0090] A 10 mL reaction tube with a branch was used. Under a carbon dioxide atmosphere, a mixture of methyl 4-amino-3-bromobenzoate (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 90°C for 14 hours. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3p. The product 3p was characterized as: Colorless liquid (44.8 mg, 81%). 1 H NMR (400MHz, CDCl3): δ10.14(s,1H),8.71(d,J=2.0Hz,1H),8.22-8.19(m,1H),7.04(d,J=8.6Hz,1H),3.92(s,3H),1.79(s,9H). 13 C NMR (101MHz, CDCl3): δ166.0,163.6,153.0,141.4,135.5,130.8,125.1,116.8,114.2,62.7,52.4,30.0.

[0091] Embodiment 18:

[0092] 17-2): Preparation and characterization of 9-(tert-butyl)pyrazino[2,3-f]quinazoline-8,10(7H,9H)-dione (3q):

[0093]

[0094] A 10 mL reaction tube with a branch was used. A mixture of 6-amino-5-bromoquinoxaline (0.2 mmol), tert-butyl isonitrile (0.24 mmol), Pd@POL-TBZP (5 mg), 1,8-diazabicycloundec-7-ene (0.45 mmol) and acetonitrile (2 mL) was stirred at 90°C for 10 hours under a carbon dioxide atmosphere. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target product 3q. The product 3q was characterized as: Yellow liquid (41.0 mg, 76%). 1H NMR (400MHz, CDCl3): δ11.12(s,1H),8.61(d,J=2.0Hz,1H),8.53(d,J=2.0Hz,1H),7.83(d,J=9.2Hz,1H),7.13(d,J=9.2Hz,1H),1.53(s,9H). 13 C NMR (101MHz, CDCl3): δ168.8,154.4,141.9,138.6,132.7,126.3,114.2,103.0,51.1,29.3.

[0095] 3. Catalyst recycling experiment:

[0096] This example takes the reactant 2-bromoaniline as an example. Figure 3 As shown in Figure 2, after 6 cycles of Pd@POL-TBZP, the yield remained basically unchanged. Figure 3 As shown, it is proved that Pd@POL-TBZP can be recycled, and the metal will not agglomerate or fall off during the reaction process, and the pore structure remains stable without collapse.

Claims

1. A method for synthesizing quinazoline dione compounds, characterized in that: The general synthesis formula of the synthetic quinazoline dione compound is: Among them, Pd@POL-TBZP is a metallized porous organic polymer catalyst Pd@POL-TBZP.

2. The method for synthesizing quinazoline dione compounds according to claim 1, characterized in that: The synthesis method of the metallized porous organic polymer catalyst Pd@POL-TBZP is:

3. The method for synthesizing quinazoline dione compounds according to claim 2, characterized in that: The synthesis process of the metallized porous organic polymer catalyst Pd@POL-TBZP is as follows: 1) 3 equiv. of magnesium powder is added to a round-bottom flask under a nitrogen atmosphere, 1,4-dioxane is added, and iodine particles are used to initiate the reaction. Subsequently, 3 equiv. of 4-bromomethylstyrene is slowly added dropwise to the flask, and the mixture is stirred at 80°C overnight. Then, 1 equiv. of phosphorus trichloride is slowly added to the 1,4-dioxane solution at 0°C, and the mixture is stirred at room temperature for 10 hours. The mixture is quenched with a saturated aqueous ammonium chloride solution, and then extracted with ethyl acetate. The organic layer is washed three times with water, dried over anhydrous magnesium sulfate, filtered and dried under reduced pressure, and then purified by silica gel column chromatography. During purification, silica gel and ethyl acetate / petroleum ether are used as eluents to obtain vinylated white solid tribenzylphosphine TBZP. 2) Under argon protection, 100 mg of tribenzylphosphine TBZP and 10 mg of azobisisobutyronitrile were added to tetrahydrofuran, and copolymerization was carried out at 100°C for 24 hours. The mixture was filtered, washed with ethyl acetate three times, and vacuum dried to obtain a porous polymer POL-TBZP. Then, 10 mg of tetrakistriphenylphosphine palladium was loaded into the polymer through the "metal-ligand" exchange method to obtain a metallized porous organic polymer catalyst Pd@POL-TBZP.

4. The method for synthesizing quinazoline dione compounds according to claim 1, characterized in that: The method comprises the following steps: A 10 mL reaction tube with a branch is selected, and a mixture of 0.2 mmol bromoaniline, 0.24 mmol tert-butyl isonitrile, 5 mg metallized porous organic polymer catalyst Pd@POL-TBZP, 0.45 mmol 1,8-diazabicycloundec-7-ene and 2 mL acetonitrile is stirred at 50° C. to 90° C. for 8 to 14 hours under a carbon dioxide atmosphere. After the reaction is completed, the mixture is cooled to room temperature, the solvent is removed under reduced pressure, and the residue is purified by silica gel column chromatography to obtain a quinazoline dione compound, wherein the metallized porous organic polymer catalyst Pd@POL-TBZP is a metallized porous organic polymer catalyst Pd@POL-TBZP synthesized by the method described in claim 3.

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