反应详情

To a solution of N-{2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxoethyl}-3-(trifluoromethyl)benzamide hydrochloride (22.10 g, 47.1 mmol) and 4-hydroxy-4-(5-pyrimidin-2-ylpyridin-2-yl)cyclohexanone (12.7 g, 47.1 mmol) in isobutyl alcohol (80.0 mL) was added triethylamine (19.7 mL, 141 mmol). The reaction mixture was cooled in an ice bath and stirred for 30 minutes. To it was added sodium triacetoxyborohydride (11.0 g, 51.8 mmol) in portion. After being stirred at room temperature for 4 hours, the solvent was removed by evaporation under reduced pressure. Saturated aqueous NaHCO3 solution was added and the solution was extracted with ethyl acetate (150×3). The combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was columned on silica gel, eluting with ethyl acetate (1% NH4OH aqueous solution)/methanol (95/5 to 80/20). The appropriate fractions were combined and concentrated to give the title compound as a white powder (17.77 g). MS (M+H) 569.

1. temperatureThe reaction mixture was cooled in an ice bath
2. stirringAfter being stirred at room temperature for 4 hours
3. customthe solvent was removed by evaporation under reduced pressure
4. additionSaturated aqueous NaHCO3 solution was added
5. extractionthe solution was extracted with ethyl acetate (150×3)
6. washThe combined extracts were washed with brine
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. washeluting with ethyl acetate (1% NH4OH aqueous solution)/methanol (95/5 to 80/20)
11. concentrationconcentrated