2,4-Dichloro-6-methoxyquinazoline

Method F1: 2, 4-Dichloro-6-methoxyquinazoline (x-a) To a mixture of 6-methoxyquinazoline-2, 4 (1H, 3H) -dione (9.63 g, 50.2 mmol) in POCl 3 (150 mL)N, N-dimethylaniline (0.5 mL) was added.The resulting mixture was stirred at 120 ° C. for 2 hours.After the reaction was complete, the POCl 3 was removed in vacuo and the residue was slowly added to ice water.When the pH was adjusted to about 7 by the slow addition of saturated NaHCO 3 at 0 ° C., a precipitate formed.The solid was collected and dried under vacuum to afford 11.2 g of 2, 4-dichloro-6-methoxyquinazoline as a brown solid (98percent yield).A suspension of 6-methoxy-1H-quinazoline-2, 4-dione (0.85 g, 4.42 mmol) and N, N-dimethylaniline (1.66 mL, 2.6 mmol) in phosphoryl chloride (6 mL, 65.5 mmol) was heated under reflux for 5 h. General procedure: A mixture of quinazoline-2, 4(1H, 3H)-dione 4a (0.48 g, 2.96 mmol) in POCl3 (3.31 mL, 35.52 mmol) was stirred at room temperature for 30 min. AfterN, N-diethylaniline (0.167 mL, 0.86 mmol) was added drop-wise, the reaction mixture was heated to reflux for 14 h. After cooling to rt, remained POCl3 was removed under reduced pressure. Thereaction residue was extracted three times with CH2Cl2 (30 mL), dried over MgSO4, concentrated under reduced pressure, and purifiedby column chromatography (EtOAc/n-Hex = 1:9) on silica gelto get the title product 5a in 87percent yield (513 mg).A solution of 6-methoxyquinazoline- 2, 4(lH, 3H)-dione (5 g, 26.0 mmol) in trichloro phosphorus oxide (30 mL) was refluxed for 16 hours. After cooling down to ambient temperature, the resulting solution was concentrated under reduced pressure and the residue was purified by silica gel column chromatography, eluted with 1-2percent methanol in dichloromethane to afford 2, 4-dichloro-6-methoxyquinazoline as a yellow solid: MS (ESI, m/z): 229 A [M + 1]To a solution of 6-methoxyquinazoline-2, 4(lH, 3H)-dione (5.10 g, 26.6 mmol) in POCI 2, 4-dichloro-6-methoxyquinazoline