反应详情

A solution of oxindole (259 mg, 1.95 mmol) in THF (3 ml) was added dropwise to a suspension of sodium hydride (78 mg, 1.95 mmol, prewashed with hexane) in THF (3 ml). The mixture was stirred for 30 minutes at ambient temperature and a solution of 4-chloro-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline (200 mg, 0.65 mmol) in DMF (3 ml) was added dropwise. The mixture was heated at 60° C. for 30 minutes, the THF was removed by evaporation and the residue was partitioned between methylene chloride and water. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The solid residue was purified by chromatography on neutral aluminium oxide eluting with methylene chloride/methanol (80/20). The purified solid was dissolved in methylene chloride containing methanol and 3M ethereal hydrogen chloride was added. The volatiles were removed by evaporation and the residue was suspended in ether. The solid was collected by filtration, washed with ether and dried under vacuum to give 6-methoxy-4-(oxindol-3-yl)-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochloride (55 mg, 18%).

1. temperatureThe mixture was heated at 60° C. for 30 minutes
2. customthe THF was removed by evaporation
3. customthe residue was partitioned between methylene chloride and water
4. customThe organic layer was separated
5. washwashed with brine
6. dry with materialdried (MgSO4)
7. customthe solvent removed by evaporation
8. customThe solid residue was purified by chromatography on neutral aluminium oxide eluting with methylene chloride/methanol (80/20)
9. dissolutionThe purified solid was dissolved in methylene chloride
10. additioncontaining methanol and 3M ethereal hydrogen chloride
11. additionwas added
12. customThe volatiles were removed by evaporation
13. filtrationThe solid was collected by filtration
14. washwashed with ether
15. customdried under vacuum