反应详情

温度

90 °C

From Intermediate 4G. To a solution of 6-Amino-1-{4-[(5-chloropentyl)oxy]-2,6-difluorophenyl}-5-(2,4-difluorobenzoyl)pyridin-2(1H)-one (96 mg, 0.20 mmol) in anhydrous DMF (3 ml) under an atmosphere of nitrogen was added tert-butyl L-leucinate hydrochloride (198 mg, 0.99 mmol, 5 eq), sodium iodide (60 mg, 0.40 mmol, 2 eq) and N,N-diisopropylethylamine (0.072 ml, 0.40 mmol, 2 eq). The mixture was heated at 90° C. for 20 hours, before being allowed to cool to room temperature and diluted with EtOAc (20 ml). The solution was washed with water (2×20 ml) and brine (20 ml). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography (1-3% MeOH in DCM) followed by preparative HPLC afforded the title compound as a white solid (23 mg, 18% yield).

1. temperatureto cool to room temperature
2. washThe solution was washed with water (2×20 ml) and brine (20 ml)
3. dry with materialThe organic layer was dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customPurification by column chromatography (1-3% MeOH in DCM)