反应详情

温度

25 °C

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide (prepared as in Example 45, 121.9 mg, 0.29 mmol) and hydroxylamine hydrochloride (30.4 mg, 0.43 mmol) in methanol (0.85 mL) and pyridine (0.85 mL) was heated under reflux for 5 h. The reaction mixture was allowed to cool to 25° C. and was then concentrated in vacuo. The resulting residue was diluted with water (50 mL) and extracted with ethyl acetate (50 mL). The organic layer was washed with a 1N aqueous hydrochloric acid solution (2×50 mL) and a saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 80–100% ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxyimino-cyclopentyl)-N-pyrazin-2-yl-propionamide (68.8 mg, 55%) as a white solid: mp 205–207° C.; (ES)+-HRMS m/e calcd for C19H21ClN4O4S (M+H)+ 437.1045 found 437.1048.

1. temperatureunder reflux for 5 h
2. concentrationwas then concentrated in vacuo
3. additionThe resulting residue was diluted with water (50 mL)
4. extractionextracted with ethyl acetate (50 mL)
5. washThe organic layer was washed with a 1N aqueous hydrochloric acid solution (2×50 mL)
6. dry with materiala saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo