反应详情

Sodium hydride (60%, 612 mg, 15.3 mmol) was added to a solution of 4-bromo-2,6-difluoroaniline (2.77 g, 6.65 mmol) in DMF (80 ml). After stiffing for 30 minutes at ambient temperature, 7-benzyloxy-4-chloro-6-methoxyquinazoline (2 g, 6.65 mmol), (prepared, for example, as described in WO 97/22596, Example 1, but the free base was generated prior to use), was added and stirring was maintained for 4 hours. The mixture was partitioned between ethyl acetate and water (200 ml). The organic layer was separated, washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was triturated with isopropanol, collected by filtration, washed with ether and dried under vacuum to give 7-benzyloxy-4-(4-bromo-2,6-difluoroanilino)-6-methoxyquinazoline (1.95 g, 62%).

1. additionwas added
2. temperaturewas maintained for 4 hours
3. customThe mixture was partitioned between ethyl acetate and water (200 ml)
4. customThe organic layer was separated
5. washwashed with water, brine
6. dry with materialdried (MgSO4)
7. customthe volatiles were removed by evaporation
8. customThe residue was triturated with isopropanol
9. filtrationcollected by filtration
10. washwashed with ether
11. customdried under vacuum