反应详情

A mixture of 4-chloro-7-(3-morpholinopropoxy)quinazoline hydrochloride (238 mg, 0.69 mmol) and 4-chloro-2-fluoroaniline (145 mg, 1 mmol) in isopropanol (5 ml) was heated at reflux for 1 hour. The solvent was removed by evaporation and the residue partitioned between water and ethyl acetate and the aqueous layer adjusted to pH8 with sodium hydrogen carbonate. 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/acetonitrile/methanol (60/30/10 followed by 60/20/20). The resulting semi-purified solid was repurified by chromatography on neutral alumina eluting with methylene chloridelmetlhanol (95/5). The resulting white solid was dissolved in methylene chloride and 4 M ethereal hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation, and the residue triturated by the addition of methylene chloride followed by methanol and ether. The precipitated solid was collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-7-(3-morpholinopropoxy)quinazoline hydrochloride (35 mg, 10%).

1. temperaturewas heated
2. temperatureat reflux for 1 hour
3. customThe solvent was removed by evaporation
4. customthe residue partitioned between water and ethyl acetate
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/acetonitrile/methanol (60/30/10 followed by 60/20/20)
11. customThe resulting semi-purified solid was repurified by chromatography on neutral alumina eluting with methylene chloridelmetlhanol (95/5)
12. dissolutionThe resulting white solid was dissolved in methylene chloride
13. addition4 M ethereal hydrogen chloride (0.5 ml) was added
14. customThe volatiles were removed by evaporation
15. customthe residue triturated by the addition of methylene chloride
16. filtrationThe precipitated solid was collected by filtration
17. customdried under vacuum