反应详情

Methanesulphonyl chloride (35 μl, 0.46 mmol) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-methylaminopropoxy)quinazoline (170 mg, 0.43 mmol) and triethylamine (67 μl, 0.48 mmol) in methylene chloride (3 ml). The mixture was stirred for 5 hours at ambient temperature the volatiles was removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic layer was separated, 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/acetonitrile/methanol (70/28/2). The purified product was dissolved in a mixture of methylene chloride/methanol (1/1) and 2M ethereal hydrogen chloride (1 ml) was added. The volatiles were removed by evaporation and 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-(E-methyl-N-methylsulphonyl]amino)propoxy)quinazoline hydrochloride (133 mg, 61%).

1. customwas removed by evaporation
2. customthe residue was 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/acetonitrile/methanol (70/28/2)
8. dissolutionThe purified product was dissolved in a mixture of methylene chloride/methanol (1/1) and 2M ethereal hydrogen chloride (1 ml)
9. additionwas added
10. customThe volatiles were removed by evaporation
11. customthe residue was triturated with ether
12. filtrationcollected by filtration
13. washwashed with ether
14. customdried under vacuum