反应详情

温度

50 °C

Isopropylamine (372 μL, 4.37 mmol) was added to a solution of tert-butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate obtained in Example (201c) (162 mg, 0.437 mmol) in tetrahydrofuran (4 mL), and the mixture was heated under reflux at 50° C. for four hours. The reaction solution was concentrated under reduced pressure, and then tetrahydrofuran (3 mL) and methanol (3 mL) were added. Isopropylamine (37.2 μL, 0.437 mmol), sodium cyanoborohydride (82.4 mg, 1.31 mmol) and acetic acid (150 μL, 2.62 mmol) were added, and the mixture was stirred at room temperature for 15 hours. The reaction solution was concentrated under reduced pressure, and saturated aqueous sodium bicarbonate solution was added to the residue, followed by extraction with chloroform. The resulting organic layer was dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography and preparative TLC (eluent: chloroform:methanol=10:1 v/v) to obtain 24 mg of the cis isomer of the title compound (15%) as a pale yellow oily substance and 20 mg of the trans isomer of the title compound (12%) as a pale yellow oily substance.

1. temperaturethe mixture was heated
2. concentrationThe reaction solution was concentrated under reduced pressure
3. additiontetrahydrofuran (3 mL) and methanol (3 mL) were added
4. concentrationThe reaction solution was concentrated under reduced pressure, and saturated aqueous sodium bicarbonate solution
5. additionwas added to the residue
6. extractionfollowed by extraction with chloroform
7. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
8. customthe insoluble matter was separated by filtration
9. concentrationThe filtrate was concentrated under reduced pressure
10. customthe resulting residue was purified by silica gel column chromatography and preparative TLC (eluent: chloroform:methanol=10:1 v/v)