反应详情

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 (500 mg, 1.21 mmol) in EtOAc (8 mL) was added 4 M hydrogen chloride in EtOAc (7 mL). The mixture was stirred at ambient temperature for 40 min and concentrated to give a white solid. To a suspension of the solid in CH2Cl2 (7 mL) was added pyridine (215 μL, 2.66 mmol). The mixture was cooled at 4° C. and a solution of 2-trifluoromethoxy-benzenesulfonyl chloride (331 mg, 1.27 mmol) in CH2Cl2 (2 mL) was added below 5° C. The reaction mixture was stirred at 4° C. for 2 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, 20% EtOAc in hexane) to give trans-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl}-2-trifluoromethoxy-benzenesulfonamide (231 mg, 36%) as a pale yellow solid.

1. concentrationconcentrated
2. customto give a white solid
3. temperatureThe mixture was cooled at 4° C.
4. stirringThe reaction mixture was stirred at 4° C. for 2 hr
5. customThe reaction was quenched with saturated aqueous NaHCO3 The aqueous layer
6. extractionwas extracted with CHCl3 (three times)
7. dry with materialThe combined organic layer was dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. custompurified by flash chromatography (NH-silica gel, 20% EtOAc in hexane)