反应详情

温度

120 °C

A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (136 mg, 0.4 mmol), 1-fluoro-4-methylsulfonyl-benzene (105 mg, 0.6 mmol) and potassium carbonate (111 mg, 0.8 mmol) in DMA (5 mL) was stirred at 120° C. for 2 hours. The solution was evaporated under reduced pressure, the residue dissolved in ethyl acetate (40 mL), washed with water (2×20 mL), brine (20 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica, eluting with a gradient of 0-4% methanol in DCM to afford product (135 mg, 68%). 1H NMR δ (300 MHz, CDCl3) 2.15-2.30 (m, 1H), 2.53-2.69 (m, 4H), 2.94 (s, 3H), 3.08 (s, 3H), 3.36-3.58 (m, 2H), 4.96 (t, 1H), 7.02 (s, 1H), 7.15 (d, 2H), 7.25 (s, 1H), 7.50 (s, 1H), 7.93 (d, 2H), 8.15 (s, 1H), 8.55 (s, 1H), 9.53 (s, 1H); m/z 497 (M+H)+.

1. customThe solution was evaporated under reduced pressure
2. dissolutionthe residue dissolved in ethyl acetate (40 mL)
3. washwashed with water (2×20 mL), brine (20 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customthe solvent removed under reduced pressure
7. customThe residue was purified by flash chromatography on silica
8. washeluting with a gradient of 0-4% methanol in DCM