Diisopropylethylamine → HCID 178502431, compound

Participants

Reaction Steps

To a solution of methyl {(S)-2-methyl-1-[(2S,4S)-4-methyl-2-(5-{4′-[2-((2S,4S)-4-methyl-pyrrolidin-2-yl)-1H-imidazol-4-yl]-biphenyl-4-yl}-1H-benzoimidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester hydrochloride (68.7 mg, 0.0987 mmol) and (2S)-2-[methoxycarbonyl(methyl)amino]-3-methyl-butanoic acid (18.67 mg, 0.09867 mmol) in DMF (2 mL), cooled in an ice bath is sequentially added HATU (41.25 mg, 0.1085 mmol) and DIPEA (38.26 mg, 51.56 μL, 0.2960 mmol) under nitrogen atmosphere. The reaction mixture is stirred at room temperature for 5 hours, and diluted with water (6 mL). The mixture is extracted with EtOAc (5×6 mL), and the combined organic layers are washed with H2O (3×3 mL), dried over Na2SO4, filtered, and concentrated to dryness. The residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2) and is further purified by reverse phase preparative HPLC to give methyl ((S)-1-((2S,4S)-2-(4-(4′-(2-((2S,4S)-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-4-methylpyrrolidin-2-yl)-3H-benzo[d]imidazol-6-yl)-[1,1′-biphenyl]-4-yl)-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)(methyl)carbamate (36 mg, 41%).

Provenance & Evidence