Potassium Carbonate → HCID 69675309, compound

Participants

Reaction Steps

To a solution of (S)-benzyl 2-(5-(4′-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)biphenyl-4-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (0.65 g, 0.92 mmol), potassium carbonate (200 mg, 1.4 mmol) and water (2 drops) in ethanol (11.6 mL) was added 10% palladium on carbon (260 mg). The reaction flask was flushed with argon for 2 minutes. Hydrogen gas was bubbled through the reaction mixture for 10 minutes. The reaction was stirred under hydrogen gas for 18 hours, and then flushed with argon. The mixture was diluted with methanol and filtered through Celite. The filtrate was concentrated and used without purification in the next step. The crude material was dissolved in dimethylformamide (7.4 mL). To this solution was added (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (156 mg, 0.9 mmol), HATU (340 mg, 0.9 mmol) and diisopropylethylamine (0.39 mL, 2.2 mmol). The reaction was stirred at room temperature for one hour, and then diluted with acetonitrile (2 mL) and methanol (2 mL). To this solution was added ten drops of 5M aqueous NaOH solution and stirring was continued for 30 minutes. The reaction was diluted with ethyl acetate and the organic layer was washed with water and brine. The combined aqueous washings were extracted three times with ethyl acetate, and the combined organic layers were dried (MgSO4) and concentrated. The crude material was purified by flash column chromatography to yield (S)-tert-butyl 2-(6-(4′-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)biphenyl-4-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate (368 mg, 68%). LCMS-ESI+: calculated for C42H49N7O5: 731.88; observed [M+1]+: 732.75.

Provenance & Evidence