反应详情

To a suspension of [4-(4-dimethylamino-quinazolin-2-ylamino)-phenyl]-carbamic acid tert-butyl ester (380 mg, 1.00 mmol) in EtOAc (4 mL) and CH2Cl2 (4 mL) was added 4 M hydrogen chloride in EtOAc (4 mL). The mixture was stirred at ambient temperature for 4 hr and concentrated to give a white solid. The solid was alkalized with saturated aqueous NaHCO3 filtered, washed with H2O and hexane, and dried at 50° C. under reduced pressure. To a solution of 4-bromo-2-trifluoromethoxy-benzenesulfonyl chloride (680 mg, 2.00 mmol) in CH2Cl2 (30 mL) was added PVP (8 mL). To the resulting suspension was added a solution of the above solid in CH2Cl2 (5 mL). The mixture was stirred at ambient temperature for 10.5 hr and filtered. The filtrate was washed with saturated aqueous NaHCO3, dried over MgSO4, filtered, concentrated, and purified by medium-pressure liquid chromatography (NH-silica gel, EtOAc) to give a solid. The solid was washed with Et2O and dried at 50° C. under reduced pressure to give 4-bromo-N-[4-(4-dimethylamino-quinazolin-2-ylamino)-phenyl]-2-trifluoromethoxy-benzenesulfonamide (202 mg, 35%) as a pale yellow solid.

1. concentrationconcentrated
2. customto give a white solid
3. filtrationfiltered
4. washwashed with H2O and hexane
5. customdried at 50° C. under reduced pressure
6. stirringThe mixture was stirred at ambient temperature for 10.5 hr
7. filtrationfiltered
8. washThe filtrate was washed with saturated aqueous NaHCO3
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. custompurified by medium-pressure liquid chromatography (NH-silica gel, EtOAc)
13. customto give a solid
14. washThe solid was washed with Et2O
15. customdried at 50° C. under reduced pressure