反应详情

温度

100 °C

A mixture of 7-(2-(2-bromoethoxy)ethoxy)4-(chloro-2-fluoroanilino)4 methoxyquinazoline (150 mg, 0.32 mmol) in 1-methylpiperazine (2 ml) was heated at 100° C. for 1 hour. The mixture was allowed to cool and was partitioned between ethyl acetate and water. The organic layer was separated and washed with water and then brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography on silica eluting with methylene chloride/methanol (85/15 followed by 80/20). The purified solid product was dissolved in methylene chloride/methanol (III) and 2.9M ethereal hydrogen chloride was added. The volatiles were removed by evaporation and the solid was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)+methoxy-722-[4-methylpiperazin-1-yl]ethoxy)ethoxy)quinazoline hydrochloride (54 mg, 28%).

1. temperatureto cool
2. customwas partitioned between ethyl acetate and water
3. customThe organic layer was separated
4. washwashed with water
5. dry with materialbrine, dried (MgSO4)
6. customthe solvent removed by evaporation
7. customThe residue was purified by column chromatography on silica eluting with methylene chloride/methanol (85/15 followed by 80/20)
8. dissolutionThe purified solid product was dissolved in methylene chloride/methanol (III)
9. addition2.9M ethereal hydrogen chloride was added
10. customThe volatiles were removed by evaporation
11. customthe solid was triturated with ether
12. filtrationcollected by filtration
13. washwashed with ether
14. customdried under vacuum