反应详情

To a solution of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoic acid (252 mg) in dichloromethane (2.5 mL) were added oxalyl chloride (68 μL) and DMF (104 μL) under ice-cooling, followed by stirring for 20 minutes. Thereafter, pyridine (65 μL) and 5-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrazin-2-amine (240 mg) were added thereto under ice-cooling, followed by stirring for 20 minutes under ice-cooling. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (ethyl acetate:chloroform=20:80). Further, it was purified by preparative TLC using the same solvent system to obtain a white amorphous substance (200 mg). A mixture of the obtained amorphous substance, 2 M hydrochloric acid (1 mL), and THF (1 mL) was stirred at room temperature for 2 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50) to obtain (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(hydroxymethyl)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide (136 mg) as a white amorphous substance.

1. temperaturecooling
2. temperatureunder ice-cooling
3. stirringby stirring for 20 minutes under ice-
4. temperaturecooling
5. extractionfollowed by extraction with ethyl acetate
6. washThe organic layer was washed with saturated brine
7. dry with materialdried over anhydrous sodium sulfate
8. customThe solvent was evaporated
9. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate:chloroform=20:80)
10. customFurther, it was purified by preparative TLC
11. customto obtain a white amorphous substance (200 mg)
12. stirringwas stirred at room temperature for 2 hours
13. extractionfollowed by extraction with ethyl acetate
14. washThe organic layer was washed with saturated brine
15. dry with materialdried over anhydrous sodium sulfate
16. customThe solvent was evaporated
17. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50)