反应详情

To a solution of 2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-(6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-ylamino)bicyclo[3.1.0]hexan-3-ylcarbamate (200 mg, 340 mmol) in dioxane (10 mL) was added 12 M conc. HCl (1 mL) at room temperature. The resulting mixture was stirred overnight, then quenched with water (50 mL), and the pH of the solution was brought to pH=8-9 with saturated solution of sodium carbonate. The solution mixture was extracted with ethyl acetate (3×50 mL), and the combined layers were washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by thin layer chromatography (Prep-TLC) (dichloromethane:methanol=15:1), and then further purified by silica gel column chromatography (dichloromethane:methanol=20:1) to afford the title compound (70 mg, 46%) as a white solid. MS (ES+) C22H22Cl2N4O2 requires: 444, 446, found: 445, 447 [M+H]+.

1. customquenched with water (50 mL)
2. extractionThe solution mixture was extracted with ethyl acetate (3×50 mL)
3. washthe combined layers were washed with brine (50 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by thin layer chromatography (Prep-TLC) (dichloromethane:methanol=15:1)
8. customfurther purified by silica gel column chromatography (dichloromethane:methanol=20:1)