Water → HCID 49868881, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of methyl ((S)-1-((S)-2-(4-(4′-bromo-[1,1′-biphenyl]-4-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate (99.6 mg, 0.1896 mmol), methyl ((S)-3-methyl-1-oxo-1-((S)-2-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)butan-2-yl)carbamate and Pd(DPPF)(Cl)2. CH2Cl2 (15.48 mg, 0.01896 mmol) in acetonitrile (2 mL) is added aqueous 1M NaHCO3 (0.284 mL, 0.569 mmol). The reaction mixture is heated in a microwave oven at 130° C. for 10 minutes, cooled to rt, and diluted with water (10 mL). The reaction mixture is extracted by CH2Cl2 (5×10 mL), and the combined organic layers are dried over Na2SO4, filtered, and concentrated to dryness. The residue is purified by flash column chromatography on silica gel (2 to 20% methanol in CH2Cl2) and is further purified by reverse phase preparative HPLC to give ((S)-1-[(S)-2-[5-(4′-{2-[(S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-benzoimidazol-5-yl]-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (30 mg, 19%).

Provenance & Evidence