反应详情

To a 50 round-bottomed flask equipped with stirring was added tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperidyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl)carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Example 20) (462 mg, 0.75 mmol) followed by 1,2-dichloroethane (20 mL) and cyclopropyl-carboxaldehyde (Aldrich) (58 mg, 0.83 mmol). The reaction mixture was stirred for 6 h, then treated with sodium triacetoxyborohydride (Aldrich) (176 mg, 0.83 mmol) at 0° C. After stirring for 12 h at RT, the reaction mixture was quenched with satd NaHCO3 (20 mL). The organic layer was separated and the aqueous layer extracted with CH2Cl2 (2×20 mL). The organic fractions were combined, washed with satd NaCl (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (1:10 MeOH:EtOAc) provided the title compound as a white foam (431 mg). MS (ESI, pos. ion) m/z: 671 (M+1); MS (ESI, neg. ion) m/z: 669 (M−1). Calcd for C39H47ClN4O4: 670.33.

1. customTo a 50 round-bottomed flask equipped
2. stirringThe reaction mixture was stirred for 6 h
3. stirringAfter stirring for 12 h at RT
4. customthe reaction mixture was quenched with satd NaHCO3 (20 mL)
5. customThe organic layer was separated
6. extractionthe aqueous layer extracted with CH2Cl2 (2×20 mL)
7. washwashed with satd NaCl (50 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customPurification by silica gel chromatography (1:10 MeOH:EtOAc)