反应详情

温度

90 °C

From Intermediate 4H. To a solution of 6-amino-1-{4-[(5-chloropentyl)oxy]-2,6-difluorophenyl}-5-(4-fluorobenzoyl)pyridin-2(1H)-one (99 mg, 0.21 mmol) in anhydrous DMF (3 ml) under an atmosphere of nitrogen was added cyclopentyl L-leucinate (Intermediate 8) (212 mg, 1.06 mmol, 5 eq), sodium iodide (64 mg, 0.43 mmol, 2 eq) and N,N-diisopropylethylamine (0.039 ml, 0.21 mmol, 1 eq). The mixture was heated at 90° C. for 20 hours, before being allowed to cool to room temperature and diluted with EtOAc (25 ml). The solution was washed with water (2×25 ml) and brine (25 ml). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography (2% MeOH in DCM) followed by preparative HPLC afforded the title compound as a yellow solid (64 mg, 48% yield).

1. temperatureto cool to room temperature
2. washThe solution was washed with water (2×25 ml) and brine (25 ml)
3. dry with materialThe organic layer was dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customPurification by column chromatography (2% MeOH in DCM)