6-BROMO-2,4(1H,3H)-QUINAZOLINEDIONE

A mixture of 2-amino-5-bromo-benzonitrile (10 g, 52 mmol) and 1, 8-diazobicyclo [5.4. 0] -undec-7-ene (DBU) (30 mL, 200 mmol) in dimethylformamide (DMF) (50 mL) was warmed (100 °C bath) with stirring under an atmosphere of carbon dioxide from an attached latex balloon for 48 hours. The solution was removed from the heat, added to cooled (ice bath) 1 N HC1 (500 mL) and the solids were collected, washed with H20 and dried to provide 6-BROMO-LH-QUINAZOLINE-2, 4-dione as a yellow solid (12 g, quantitative): Rf 0.27 (5percent methanol in dichloromethane) 1H NMR (DMSO-D6, 300 MHz) 8 11.41 (s, 1 H), 11.27 (s, 1 H), 7.91 (d, J = 2.3 Hz, 1 H), 7. 77 (dd, IL = 8.8 Hz, J2 = 2.3 Hz, 1 H), 7.11 (d, J = 8.8 Hz, 1 H). ESI-LCMS M/Z calcd for C8H5BRN202 : 240. 0 ; found 241.0 (M + 1).General procedure: Table 5: To a DMSO‑d6 solution (1 mL) of 2-aminobenzonitrile 4a (1 mmol) in a stainless steel autoclave was added a catalyst (0.01 mmol) under an argon atmosphere. The autoclave was sealed, heated at 110°C and then pressurized with CO2 of 2 MPa. The cyclization reaction of 4a proceeded by the magnetic stirring of the resulting mixture at 110°C for 3 h. After the reaction the autoclave was cooled in an ice bath and depressurized. The chemical yield of quinazoline-2, 4(1H, 3H)-dione 5a was determined by integrating 1HNMR with reference to an internal standard (3, 5-dimethoxybenzylalcohol), which was added to the reaction mixture. Table 6: DMSO solution (6 mL) of 4 (6 mmol) was treated for the carboxylative cyclization of 4 with CO2 according to the procedure of Table 5. After the reaction, the autoclave was cooled in an ice bath and depressurized, and the reaction mixture was added to water (60 mL). The precipitation was collected by filtration, washed with water and diethyl ether, and then dried in vacuo at 35°C for 15 h to give the pure product 5.General procedure: 2-aminobenzonitrile (1 mmol) and KCC-1/STPP NPs (0.7 mg) were mixed together. The autoclave was closed, purged twice with CO2 gas, pressurized to 1.5 MPa of CO2, and heated at 70°C for 50 min. Then, the reactor was cooled to ambient temperature and the resulting mixture was transferred to a 50 mL round-bottom flask. During completion, the reaction progress was monitored by TLC. Following its completion, EtOH was added to the reaction mixture and the catalyst was separated by filtration. Afterwards, the solvent was removed from the solution under reduced pressure and the resulting product was purified by recrystallization using n-hexane/ethyl acetate. The products are known and their sample characterization data is presented in the Supplemental Materials.General procedure: 2-aminobenzonitrile (1mmol), and KCC-1/IL NPs (0.0007g) were added. The autoclave was closed, purged twice with COWeigh 0.985 g (5 mmol) of 2-amino-5-bromobenzonitrile was placed in a Teflon liner of a stainless steel reactor, 3 mL of a 1 mol / L aqueous solution of diethanolamine was added and the mixture was stirred for 2 minutes. The carbon dioxide was heated to100 ° C and the carbon dioxide pressure was adjusted to 1 MPa. The reaction was carried out for 12 hours under stable conditions.The reactionAfter completion of the reaction system was cooled to room temperature slowly released unreacted carbon dioxide, was added 10mL of deionized water and stirred pointsdispersion product, resulting precipitate was filtered and washed with a small amount of distilled water, and then 15mL / wash three times with methyl tert-butyl ether Andthe product was dried at a temperature of100° C to give the product 6-bromoquinazoline-2, 4 (1H, 3H) -dione in a yield of 88percent.Example 1566 Compound 1566A(200mg, 1.02 mmol) and 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU, 459 ml, 3.06 mmol) were dissolved in DMF (2 ml) in a two-neck flask. The mixture was subjected to vacuum and the atmosphere refilled with COIn anhydrous, anaerobic, argon protection, 0.0999 g (7.5 x 10-5 mol) of {L2Eu [N (SiMe3) 2] THF} 2 was added to the reaction flask, An additional 11.2 μL (7.5 × 10 -5 mol) DBU was added, under the protection of carbon dioxide bag, Add 2 mL of dimethyl sulfoxide, add 0.3616 g (1.5 x 10-3 mol) of 2-amino-5-bromobenzonitrile, The reaction was stirred in a constant temperature bath at 100 ° C.After 24h, add 5mL 2mol / L hydrochloric acid to quench the reaction, and then suction filtered, The solid was washed with 3 × 5 mL of hydrochloric acid, then with toluene and then with diethyl ether. The residual solvent was removed and the solid was dried to give the product in 64percent yield.Example 1N-(5-{3-benzyl-2-[(2-methanesulfonylethyl)amino]-4-oxo-3, 4-dihydro methoxypyridin-3-yl)-2, 4-difluorobenzene-1-sulfonamideStep A6-bromo-2, 4( 1 H, 3H)-quinazolinedione [00123] A mixture of methyl 2-amino-5-bromobenzoate (50 g, 217 mmol) and urea (65.3 g, 1087 mmol) were ground together and heated to 200 °C for 2 hours with stirring and while under nitrogen. The mixture went fully into solution after 10 minutes, and then solidified after 40 minutes. The reaction was cooled and the resulting solid was washed with water (1 L). The solid was then filtered and the remaining solids rinsed with more water and broken up into fine particles. The residue was triturated with EtOAc (ca 300 mL) and dried to yield 6-bromo- 2, 4(1 H, 3H)-quinazolinedione (42g, 80percent). ES-LCMS: 241.0, 243.1 (M+1 ).

Molecular Weight:241.04
XLogP3:1.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:239.95344
Monoisotopic Mass:239.95344
Topological Polar Surface Area:58.2
Heavy Atom Count:13
Complexity:257
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes