反应详情

To a solution of 2-(5-{6-[4-(2-{1-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.25 g, 0.36 mmol) in EtOH (3.5 mL) was added Palladium on carbon (10%, 0.42 g, 0.39 mmol) and Potassium Carbonate (0.10 g, 0.70 mmol). The slurry was stirred at room temperature under an atmosphere of H2 for 72 h. The slurry was filtered through celite and washed with EtOH. The filtrate was concentrated to an oil and diluted with CH2Cl2 (3 mL). Methoxycarbonylamino-phenyl-acetic acid (0.11 g, 0.54 mmol) and Potassium Phosphate (0.08 g, 0.35 mmol) were added and the resulting slurry was cooled to 0° C. (external, ice). COMU (0.19 g, 0.44 mmol) was added and the reaction was stirred at 0° C. for 2 h. The slurry was diluted with CH2Cl2 and filtered through celite. The filtrate was concentrated and purified by column chromatography (SiO2, 30→100% EtOAc (10% MeOH) in Hexanes to 60% MeOH in EtOAc) to provide 2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.20 g, 74%). LCMS-ESI+: calc'd for C45H47N7O5: 765.36 (M+); Found: 766.64 (M+H+).

1. filtrationThe slurry was filtered through celite
2. washwashed with EtOH
3. concentrationThe filtrate was concentrated to an oil
4. additiondiluted with CH2Cl2 (3 mL)
5. temperaturethe resulting slurry was cooled to 0° C. (external, ice)
6. stirringthe reaction was stirred at 0° C. for 2 h
7. filtrationfiltered through celite
8. concentrationThe filtrate was concentrated
9. custompurified by column chromatography (SiO2, 30→100% EtOAc (10% MeOH) in Hexanes to 60% MeOH in EtOAc)