Acetic Acid → cis(+/-)-4-Chloro-5-ethyl-N-[3-(propylamino)piperidin-4-yl]-1H-imidazole-2-carboxamide trans(+/-)-4-Chloro-5-ethyl-N-[3-(propylamino)piperidin-4-yl]-1H-imidazole-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

Propylamine (226 μL, 2.75 mmol) was added to a mixed solution of tert-butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate obtained in Example (201c) (102 mg, 0.275 mmol) in tetrahydrofuran (5 mL) and methanol (5 mL) under ice-cooling, and the mixture was heated under reflux at 70° C. for three hours. The reaction solution was concentrated under reduced pressure, and then the residue was dissolved in tetrahydrofuran (5 mL) and methanol (5 mL). Acetic acid (315 μL, 5.50 mmol) and sodium cyanoborohydride (69 mg, 1.10 mmol) were added, and the mixture was stirred at room temperature for 12 hours. The reaction solution was concentrated under reduced pressure, and a 1 N aqueous hydrochloric acid solution was added. The aqueous layer was washed with diethyl ether. The aqueous layer was concentrated under reduced pressure with heating, and then 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 NH-silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v) to obtain 17 mg of the cis isomer of the title compound (20%) as a colorless oily substance and 10.0 mg of the trans isomer of the title compound (12%) as a colorless oily substance.

Provenance & Evidence