反应详情

To a 50 mL 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) and CH2Cl2 (15 mL) followed by DIEA (0.16 mL, 0.9 mmol). The reaction mixture was stirred for 5 min at RT then treated with methyl chloroformate (Aldrich) (84.6 mg, 0.9 mmol) at 0° C. The reaction mixture was stirred at RT for 12 h then quenched with satd NaHCO3 (15 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (2×15 mL). The organic fractions were combined, washed with satd NaCl (15 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (100% EtOAc) provided the title compound as a white foam (412 mg). MS (ESI, pos. ion) m/z: 675 (M+1); MS (ESI, neg. ion) m/z: 673 (M−1). Calc'd for C11H13ClN4O6: 674.29.

1. customTo a 50 mL round-bottomed flask equipped
2. stirringThe reaction mixture was stirred for 5 min at RT
3. stirringThe reaction mixture was stirred at RT for 12 h
4. customthen quenched with satd NaHCO3 (15 mL)
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with CH2Cl2 (2×15 mL)
7. washwashed with satd NaCl (15 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customPurification by silica gel chromatography (100% EtOAc)