反应详情

Under argon, sodium hydride (60%, 372 mg, 9.3 mmol) was added to a solution of 4-bromo-2,6-difluoroaniline (1.67 g, 8.08 mmol) in DMF. After stirring for 30 minutes at ambient temperature, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (1.3 g, 4.04 mmol) was added and stirring was continued for a further 20 hours. The mixture was poured onto water (130 ml) and extracted with ethyl acetate. The organic layers were washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography on silica, eluting with methylene chloride/methanol (95/5) followed by methylene chloride/methanol containing ammonia (1%) (90/10). The fractions containing the expected product were combined and evaporated. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum at 50° C. to give 4-(4-bromo-2,6-difluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (1.4 g, 70%).

1. stirringstirring
2. waitwas continued for a further 20 hours
3. additionThe mixture was poured onto water (130 ml)
4. extractionextracted with ethyl acetate
5. washThe organic layers were washed with water, brine
6. dry with materialdried (MgSO4)
7. customthe volatiles were removed by evaporation
8. customThe residue was purified by column chromatography on silica
9. washeluting with methylene chloride/methanol (95/5)
10. additioncontaining ammonia (1%) (90/10)
11. additionThe fractions containing the expected product
12. customevaporated
13. customThe residue was triturated with ether
14. filtrationcollected by filtration
15. washwashed with ether
16. customdried under vacuum at 50° C.