反应详情

温度

85 °C

To a solution of methyl (S)-3-methyl-1-oxo-1-((1R,3S,4S)-3-(5-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,10-dihydrophenanthren-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)butan-2-ylcarbamate (˜0.67 mmol), (S)-tert-butyl 2-(4-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (266 mg, 0.84 mmol), tetrakis(triphenylphosphine) palladium(0) (23 mg, 0.02 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (30 mg, 0.04 mmol) in a mixture of 1,2-dimethoxyethane (10.0 mL) and dimethylformamide (2 mL) was added a solution of potassium carbonate (2M in water, 1.0 mL, 2.0 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 S)-tert-butyl 2-(5-(7-(2-((1R,3S,4S)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[2.2.1]heptan-3-yl)-1H-imidazol-5-yl)-9,10-dihydrophenanthren-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (182 mg, 56%)

1. customThe resulting mixture was degassed
2. temperatureAfter cooling to room temperature
3. additionthe reaction was diluted with ethyl acetate
4. washThe organics were washed with water and brine
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated
7. customThe crude residue was purified by flash chromatography