反应详情

To a solution of trans-N2-{4-[(4-bromo-2-trifluoromethoxy-benzylamino)-methyl]-cyclohexylmethyl}-N4,N4-dimethyl-quinazoline-2,4-diamine obtained in step B of example 15 (290 mg, 0.52 mmol) in CH2Cl2 (3 mL) were added 37% aqueous formaldehyde (42 mg, 0.52 mmol), acetic acid (31 mg, 0.52 mmol), and NaBH(OAc)3 (165 mg, 0.78 mmol). The reaction mixture was stirred at ambient temperature for 19 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, 25% EtOAc in hexane) to give trans-N2-(4-{[(4-bromo-2-trifluoromethoxy-benzyl)-methyl-amino]-methyl}-cyclohexylmethyl)-N4,N4-dimethyl-quinazoline-2,4-diamine (153 mg, 51%) as a pale yellow solid.

1. customThe reaction was quenched with saturated aqueous NaHCO3 The aqueous layer
2. extractionwas extracted with CHCl3 (three times)
3. dry with materialThe combined organic layer was dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. custompurified by flash chromatography (NH-silica gel, 25% EtOAc in hexane)