Dimethylformamide → ethyl [6-({(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoyl}amino)pyridin-3-yl]acetate

Participants

Reaction Steps

To a solution of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propionic acid (110 mg) in dichloromethane (3 mL) were added sequentially oxalyl chloride (0.03 mL) and a catalytic amount of DMF under ice-cooling, followed by stirring for 1 hour, and then ethyl (6-aminopyridin-3-yl)acetate (58 mg) and pyridine (0.05 mL) were added thereto under ice-cooling, followed by stirring for 2 hours. To the reaction mixture were added water and ethyl acetate. The organic layer was sequentially washed with water, saturated aqueous sodium bicarbonate, and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain ethyl [6-({(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoyl}amino)pyridin-3-yl]acetate (57 mg) as a pale yellow amorphous substance. To a solution of the obtained ethyl [6-({(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoyl}amino)pyridin-3-yl]acetate (57 mg) in THF (3 mL) was added 1 M aqueous sodium hydroxide solution (0.22 mL), and further added a drop of ethanol, followed by stirring at room temperature overnight. To the reaction solution was added 1 M hydrochloric acid (0.22 mL) to adjust the pH to 4, followed by dilution with saturated brine and dichloromethane for liquid separation. The organic layer was dried over anhydrous magnesium sulfate and the solvent was then evaporated under reduced pressure. To a solution of the residue in ethyl acetate (3 mL) was added a 4 M hydrogen chloride/ethyl acetate solution (0.07 mL) under ice-cooling, followed by stirring for 10 minutes under ice-cooling, and the solvent was then evaporated under reduced pressure. To the residue was added ethyl acetate (3 mL), and the precipitate was collected by filtration and dried under reduced pressure to obtain [6-({(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoyl}amino)pyridin-3-yl]acetic acid hydrochloride (30 mg) as a colorless solid.

Provenance & Evidence