Hydrochloric Acid → HCID 178483064, compound

Participants

Reaction Steps

To a suspension of trans-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]cyclohexylmethyl}-carbamic acid tert-butyl ester obtained in step G of example 1 (800 mg, 1.93 mmol) in EtOAc (10 mL) was added 4 M hydrogen chloride in EtOAc (10 mL). The mixture was stirred at ambient temperature for 60 min and concentrated to give a white solid. To a suspension of the solid in CH2Cl2 (10 mL) was added diisopropylethylamine (706 μL, 4.05 mmol). The mixture was cooled at 4° C. and a solution of 2-(trifluoromethoxy)benzoyl chloride (455 mg, 2.03 mmol) in CH2Cl2 (4 mL) was added below 5° C. The reaction mixture was stirred at 4° C. for 90 min. 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% EtOAc in hexane) to give trans-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl}-2-trifluoromethoxy-benzamide (772 mg, 80%) as a pale yellow solid.

Provenance & Evidence