反应详情

2-(2-Ethoxyphenyl)-8-methoxyquinazolin-4(3H)-one (Preparation 4; 2.1 g, 0.0071 mol) was added portionwise to stirred chlorosulphonic acid (15 ml) under a nitrogen atmosphere at 0° C. After 18 hours, the mixture was cautiously added dropwise to stirred ice/water (100 g) and the resulting mixture extracted with dichloromethane-methanol (9:1, 10×100 ml). The organic extracts were combined, dried (MgSO4) and evaporated under vacuum. A quantity (1.0 g) of the crude sulphonyl chloride was then added portionwise to a stirred solution of piperazine (2.1 g, 0.0244 mol) in ethanol (30 ml) at room temperature under a nitrogen atmosphere. After 18 hours the mixture was poured into stirred saturated aqueous sodium carbonate solution (100 ml) and the resulting mixture extracted with dichloromethane-methanol (9:1, 10×100 ml). The organic extracts were combined, dried (MgSO4) and evaporated under vacuum to give the title compound, which crystallized from ethanol as a colorless solid (0.8 g, 71%), m.p. 163-165° C.

1. additionthe mixture was cautiously added dropwise
2. extractionthe resulting mixture extracted with dichloromethane-methanol (9:1, 10×100 ml)
3. dry with materialdried (MgSO4)
4. customevaporated under vacuum
5. additionAfter 18 hours the mixture was poured
6. extractionthe resulting mixture extracted with dichloromethane-methanol (9:1, 10×100 ml)
7. dry with materialdried (MgSO4)
8. customevaporated under vacuum