Potassium Carbonate → 4,4-Difluoro-2-(5-{4-[6-(2-{1-[2-methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-naphthalen-2-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a solution of 2-[5-(4-{6-[2-(1-Benzyloxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-naphthalen-2-yl}-phenyl)-1H-imidazol-2-yl]-4,4-difluoro-pyrrolidine-1-carboxylic acid tert-butyl ester (0.25 g, 0.34 mmol) in EtOH (3.5 mL) was added Palladium on carbon (10%, 0.18 g, 0.02 mmol) and Potassium Carbonate (0.14 g, 1.0 mmol). The slurry was stirred at room temperature under an atmosphere of H2 for 5 h. The slurry was filtered through celite and washed with EtOH. The filtrate was concentrated to an oil and diluted with CH2Cl2 (3 mL) and DMF (2 mL). Methoxycarbonylamino-(tetrahydro-pyran-4-yl)-acetic acid (0.11 g, 0.50 mmol), HATU (0.15 g, 0.40 mmol), and DIPEA (0.3 mL, 1.7 mmol) were added. The resulting solution was stirred at room temperature for 5 h. The solution was diluted with CH2Cl2 and washed with saturated sodium bicarbonate. The organic layer was dried over Na2SO4 and concentrated. The crude oil was concentrated and purified by preparative HPLC (Gemini, 15→50% MeCN in H2O (0.1% TFA)) to provide to provide 4,4-Difluoro-2-(5-{4-[6-(2-{1-[2-methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-naphthalen-2-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.04 g, 14%). LCMS-ESI+: calc'd for C44H49F2N7O6: 809.37 (M+); Found: 810.79 (M+H+).

Provenance & Evidence