反应详情

4-Chloro-2-fluoroaniline (77 mg, 0.53 mmol) was added to a solution of 4-chloro-6-methoxy-7-(2-(N-methyl-N-(6-methylpyrimidin-4-yl)amino)ethoxy)quinazoline hydrochloride (140 mg, 0.35 mmol) in isopropanol (5 ml) and the mixture heated at reflux for 1 hour. The solvent was removed by evaporation and the residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography eluting with methylene chloride/methanol (95/5). The purified solid was dissolved in methylene chloride/methanol and ethereal hydrogen chloride (1 ml of a 5M solution) was added. The volatiles were removed by evaporation, the residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(6-methylpyrimidin-4-yl)amino)ethoxy)quinazoline hydrochloride (75 mg, 39%).

1. temperaturethe mixture heated
2. temperatureat reflux for 1 hour
3. customThe solvent was removed by evaporation
4. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution
5. customThe organic layer was separated
6. washwashed with brine
7. dry with materialdried (MgSO4)
8. customthe solvent removed by evaporation
9. customThe residue was purified by flash chromatography
10. washeluting with methylene chloride/methanol (95/5)
11. dissolutionThe purified solid was dissolved in methylene chloride/methanol
12. additionethereal hydrogen chloride (1 ml of a 5M solution) was added
13. customThe volatiles were removed by evaporation
14. customthe residue was triturated with ether
15. filtrationcollected by filtration
16. washwashed with ether
17. customdried under vacuum