To a solution of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propionic acid (200 mg) in dichloromethane (10 mL) were sequentially added a solution of oxalyl chloride in 0.5 M dichloromethane (1.3 mL) and DMF (16 μL) under ice-cooling, followed by stirring for 30 minutes under ice-cooling. Thereafter, 1-(5-aminopyrazin-2-yl)ethanol (81 mg) and pyridine (0.09 mL) were added thereto under ice-cooling, followed by stirring for 3 hours. 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 dried over anhydrous magnesium sulfate. To a solution of the oily substance obtained by concentration in methanol (4 mL) was added 1 M aqueous sodium hydroxide solution (1 mL) at room temperature, followed by stirring at room temperature for 1 hour. To the reaction mixture was added 1 M hydrochloric acid to adjust the pH to 3, followed by extraction with ethyl acetate. The organic layer was sequentially washed with 1 M aqueous sodium hydroxide solution and saturated brine, and dried over anhydrous magnesium sulfate. The crude product 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-(1-hydroxyethyl)pyrazin-2-yl]-3-(tetrahydro-2H-pyran-4-yl)propanamide (170 mg) as a white amorphous substance.
