反应详情

温度

85 °C

A mixture of methyl (R)-2-oxo-1-phenyl-2-((S)-2-(5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)ethylcarbamate (261 mg, 0.39 mmol), (S)-tert-butyl 2-(4-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (125 mg, 0.39 mmol), and tetrakis(triphenylphosphine) palladium (0) (45 mg, 0.039 mmol), 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (29 mg, 0.039 mmol), potassium carbonate (109 mg, 0.78 mmol), dimethoxyethane (5 mL), and water (1 mL) was heated at 85° C. for 16 hours. The solvent was removed under reduced pressure and the residue was take up in dichloromethane (15 mL) and washed with water (5 mL) and brine (5 mL). The organic phase was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was subjected to flash chromatography with eluant of (10% methanol in ethyl acetate) and hexane. The product containing fractions were combined and the solvent was removed under reduced pressure to provide (S)-tert-Butyl 2-(4-(2-(4-(2-((S)-1-((R)-2-(methoxycarbonylamino)-2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)benzo[b]thiophen-6-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (88 mg, 0.011 mmol, 28%).

1. customThe solvent was removed under reduced pressure
2. washwashed with water (5 mL) and brine (5 mL)
3. dry with materialThe organic phase was dried over sodium sulfate
4. filtrationfiltered
5. customThe solvent was removed under reduced pressure
6. additionThe product containing fractions
7. customthe solvent was removed under reduced pressure