4-Bromo-2-(Trifluoromethoxy)Benzene-1-Sulfonyl Chloride → 4-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-phenyl}-2-trifluoromethoxy-benzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a solution of {4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-phenyl}-carbamic acid benzyl ester (318 mg, 0.744 mmol) in MeOH (3 mL) was added 5% Pd/C (30 mg). The mixture was stirred at 50° C. under hydrogen atmosphere for 41.5 hr, filtered through a pad of celite, and concentrated. To a solution of 4-bromo-2-trifluoromethoxy-benzenesulfonyl chloride (505 mg, 1.49 mmol) in CH2Cl2 (12 mL) was added PVP (6 mL). To the resulting suspension was added a solution of the above residue in CH2Cl2 (10 mL). The mixture was stirred at ambient temperature for 1.5 days, filtered, poured into saturated aqueous NaHCO3. The aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by medium-pressure liquid chromatography (NH-silica gel, 33% EtOAc in hexane) to give 4-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-phenyl}-2-trifluoromethoxy-benzenesulfonamide (330 mg, 74%) as a pale brown solid.

Provenance & Evidence