反应详情

A solution of oxindole (200 mg, 1.5 mmol) in THF (3 ml) was added dropwise under nitrogen to sodium hydride (60 mg, 1.5 mmol, prewashed with hexane) in THF (3 ml). After stirring for 20 minutes at ambient temperature, a solution of 4-chloro-6(3-morpholinopropoxy)-7-methoxyquinazoline (169 mg, 0.5 mmol) in DMF (3 ml) was added. The mixture was heated at 75° C. for 1 hour, allowed to cool and the volatiles removed by evaporation. The mixture was partitioned between water and ether. The aqueous layer was adjusted to pH8 with 2M hydrochloric acid. The resulting precipitate was collected by filtration, washed with water, and dried under vacuum. The solid was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml) was added. The mixture was diluted with ether, the solid was collected by filtration and dried under vacuum to give 7-methoxy-6-(3-morpholinopropoxy)-4-(oxindol-3-yl)quinazoline hydrochloride (175 mg, 69%).

1. temperatureThe mixture was heated at 75° C. for 1 hour
2. temperatureto cool
3. customthe volatiles removed by evaporation
4. customThe mixture was partitioned between water and ether
5. filtrationThe resulting precipitate was collected by filtration
6. washwashed with water
7. customdried under vacuum
8. dissolutionThe solid was dissolved in methylene chloride/methanol
9. addition3M ethereal hydrogen chloride (0.5 ml) was added
10. additionThe mixture was diluted with ether
11. filtrationthe solid was collected by filtration
12. customdried under vacuum