Potassium Carbonate → (1S,3R)-tert-butyl 3-(6-(8-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methyl-butanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-6H-benzo[c]chromen-3-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of (1S,3R)-tert-butyl 3-(6-(8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6H-benzo[c]chromen-3-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (275 mg, 0.44 mmol), methyl (S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (221 mg, 0.55 mmol), tetrakis(triphenylphosphine) palladium(0) (20 mg, 0.02 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (26 mg, 0.04 mmol) in a mixture of 1,2-dimethoxyethane (5.0 mL) and dimethylformamide (1 mL) was added a solution of potassium carbonate (2M in water, 0.7 mL, 1.3 mmol). The resulting mixture was degassed and then heated to 85° C. under argon for 18 hours. After cooling to room temperature, the reaction was diluted with ethyl acetate. The organics were washed with water and brine, dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography to yield (1S,3R)-tert-butyl 3-(6-(8-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methyl-butanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-6H-benzo[c]chromen-3-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (70 mg, 20%). LCMS-ESI+: calculated for C45H51N7O6: 785.95; observed [M+1]+: 786.85.

Provenance & Evidence