Hydrochloric Acid → methyl 3-methyl-1-oxo-1-((S)-2-(5-(8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6H-benzo[c]chromen-3-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate

Participants

Reaction Steps

A solution of (S)-tert-butyl 2-(5-(8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6H-benzo[c]chromen-3-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (670 mg, 1.23 mmol), ethanol (6 mL) and concentrated HCl (2 mL) was heated to 60° C. for 1.5 hours. The reaction was concentrated and the crude material dissolved in DCM (10 mL). This solution was concentrated and to this material was added a solution of 2-methoxycarbonylamino-3-methylbutyric acid (268 mg, 1.6 mmol) and HATU (537 mg, 1.41 mmol) in DMF (6 mL). To the resulting solution was added diisopropylethylamine (640 μL, 3.68 mmol). After stirring for 18 hours at room temperature, the reaction was diluted with ethyl acetate, washed with water and brine, dried (Na2SO4), concentrated. The crude residue was purified by flash chromatography to yield methyl 3-methyl-1-oxo-1-((S)-2-(5-(8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6H-benzo[c]chromen-3-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (205 mg, 28%). LCMS-ESI+: calculated for C33H41BN4O6: 600.53; observed [M+1]+: 601.39.

Provenance & Evidence