反应详情

温度

135 °C

N-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamide (705 mg, 1.94 mmol) was added to 3-hydroxy-5-[(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (512 mg, 1.86 mmol) and potassium carbonate (536 mg, 3.88 mmol) in DMA (25 mL) and the mixture was heated at 135° C. for 5 hours. Water (100 mL) was added and the reaction mixture extracted with ethyl acetate (3×30 mL). The combined organic phases were washed with water (2×30 mL), brine (2×30 mL), dried (MgSO4), filtered and evaporated. Purification by column chromatography on silica, eluting with 40-100% ethyl acetate in hexanes, afforded the desired compound as a pale yellow oil (300 mg). 1H NMR δ (CDCl3): 1.28 (d, 6H), 3.17 (s, 3H), 3.53 (t, 2H), 3.73 (s, 3H), 4.48 (t, 2H), 4.48-4.55 (m, 1H), 6.63 (t, 1H), 6.71 (d, 1H), 6.73 (d, 1H), 6.95 (t, 1H), 7.12 (t, 1H), 7.22 (d, 1H), 7.61 (d, 1H), 8.52 (s, 1H), m/z 485 (M+H)+ 483 (M−H)−

1. extractionthe reaction mixture extracted with ethyl acetate (3×30 mL)
2. washThe combined organic phases were washed with water (2×30 mL), brine (2×30 mL)
3. dry with materialdried (MgSO4)
4. filtrationfiltered
5. customevaporated
6. customPurification by column chromatography on silica
7. washeluting with 40-100% ethyl acetate in hexanes