反应详情

温度

50 °C

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.

1. waitat ambient temperature for 10.5 hr
2. filtrationfiltered
3. concentrationconcentrated
4. customto give a colorless oil
5. temperatureThe mixture was cooled to 4° C.
6. stirringThe reaction mixture was stirred at 4° C. for 1.5 hr
7. customThe reaction was quenched with saturated aqueous NaHCO3 The aqueous layer
8. extractionwas extracted with CHCl3 (three times)
9. dry with materialThe combined organic layer was dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. custompurified by flash chromatography (NH-silica gel, 33% to 50% EtOAc in hexane)