反应详情

To a solution of 5-chloro-2-thiophene-methanol (0.10 g, 0.67 mmol, prepared by NaBH4 reduction of 5-chloro-2-thiophene-carboxaldehyde) in 6 mL of CH2Cl2 is added 1,1′-carbonyldiimidazole (0.11 g, 0.67 mmol). The mixture is stirred at room temperature for 3 hours. Then 1-(4-aminoquinazoline-7-ylmethyl)piperazine-2-one (0.17 g, 0.67 mmol, EXAMPLE 72) and a catalytic amount of DMAP is added to the solution and the resulting mixture is heated at 35° C. for 18 hours. The mixture is dissolved in water/MeOH and the crude product is purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN. The appropriate fractions are combined and lyoppholized to provide the title compound as a white solid. ESI MS, [M+H]+=432,434 (Cl pattern).

1. temperaturethe resulting mixture is heated at 35° C. for 18 hours
2. customthe crude product is purified by RP-HPLC
3. washeluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN