Diisopropylethylamine → HCID 178483074, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of trans-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexyl}-carbamic acid benzyl ester (500 mg, 1.15 mmol) in MeOH (5 mL) was added 5% Pd/C (50 mg). The mixture was stirred at ambient temperature under hydrogen atmosphere for 2 hr, at 50° C. for 8 hr, and at ambient temperature for 10.5 hr, filtered, and concentrated to give a colorless oil. To a solution of the above oil in CH2Cl2 (5 mL) was added diisopropylethylamine (420 μL, 2.41 mmol). The mixture was cooled to 4° C. and a solution of 4-bromo-2-trifluoromethoxy-benzenesulfonyl chloride (431 mg, 1.27 mmol) in CH2Cl2 (2 mL) was added below 5° C. The reaction mixture was stirred at 4° C. for 1.5 hr. The reaction was quenched with 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 flash chromatography (NH-silica gel, 33% to 50% EtOAc in hexane) to give trans-4-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexyl}-2-trifluoromethoxy-benzenesulfonamide (560 mg, 81%) as a pale yellow solid.

Provenance & Evidence