Hydrochloric Acid → Methyl (S)-1-((S)-2-(6-(7-bromo-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

Participants

Reaction Steps

A solution of (S)-tert-butyl 2-(6-(7-bromo-9,10-dihydro-phenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)-pyrrolidine-1-carboxylate (582 mg, 1.1 mmol), 4M HCl solution in dioxanes (5 mL, 20 mmol) and methanol (3 mL) was stirred at room temperature for twenty minutes. The reaction was concentrated, suspended in dichloromethane, and thoroughly concentrated. This crude amine was dissolved in dimethylformamide (5 mL). To this solution were added (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (281 mg, 1.6 mmol), HATU (691 mg, 1.8 mmol) and diisopropylethylamine (0.65 mL, 3.7 mmol). The reaction was stirred at room temperature for fifteen minutes, and then diluted ethyl acetate. The organic layer was washed with saturated aqueous NaHCO3 solution and brine, dried (Na2SO4) and concentrated. The crude material was purified by flash column chromatography to yield Methyl (S)-1-((S)-2-(6-(7-bromo-9,10-dihydrophenanthren-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (376 mg, 58%).

Provenance & Evidence