To a solution of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propionic acid (120 mg) in dichloromethane (5 mL) was sequentially added a solution of 0.5 M oxalyl chloride in dichloromethane (0.77 mL) and DMF (10 μL) under ice-cooling, followed by stirring under ice-cooling for 1 hour. Thereafter, 5-[2-(benzyloxy)ethoxy]pyrazin-2-amine (86 mg) and pyridine (0.05 mL) were added thereto under ice-cooling, followed by stirring for 2 hours under ice-cooling. To the reaction mixture was added water under ice-cooling, followed by extraction with ethyl acetate. The organic layer was sequentially washed with 1 M hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine, and then dried over anhydrous magnesium sulfate. The oily substance obtained by concentration was purified by silica gel column chromatography (hexane:ethyl acetate=5:1-1:1) to obtain (2R)—N-{5-[2-(benzyloxy)ethoxy]pyrazin-2-yl}-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanamide (175 mg) as a pale yellow amorphous substance. To a solution of the obtained (2R)—N-{5-[2-(benzyloxy)ethoxy]pyrazin-2-yl}-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanamide (175 mg) in methanol (10 mL) was added 10% palladium carbon (50 mg). Under a hydrogen atmosphere, it was stirred at room temperature at 4 atm for 7 hours. The reaction mixture was filtered through Celite and concentrated. To a solution of the obtained oily substance in THF (10 mL) was added 1 M hydrochloric acid (10 mL) at room temperature, followed by stirring at room temperature for 30 minutes. The reaction mixture was extracted with ethyl acetate. The organic layer was sequentially washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The oily substance obtained by concentration was purified by silica gel column chromatography (wetting with hexane:ethyl acetate=1:1, chloroform:methanol=1:0-10:1) to obtain (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(2-hydroxyethoxy)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide (103 mg) as a pale yellow amorphous substance.
