反应详情

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.

1. temperaturecooling
2. temperaturecooling
3. temperatureunder ice-cooling
4. stirringby stirring for 3 hours
5. temperaturecooling
6. extractionfollowed by extraction with ethyl acetate
7. washThe organic layer was sequentially washed with 1 M hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. customTo a solution of the oily substance obtained by concentration in methanol (4 mL)
10. stirringby stirring at room temperature for 1 hour
11. extractionfollowed by extraction with ethyl acetate
12. washThe organic layer was sequentially washed with 1 M aqueous sodium hydroxide solution and saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. customThe crude product obtained by concentration
15. customwas purified by silica gel column chromatography (wetting with hexane:ethyl acetate=1:1, chloroform:methanol=1:0-10:1)