反应详情

温度

85 °C

To a solution of N-(4-(4-hydroxy-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (5-3, 1.92 g, 5.91 mmol) in DMF (15 mL) were added cesium carbonate (2.41 g, 7.39 mmol) and Cu (116 mg, 1.78 mmol, 0.30 equiv). The mixture was stirred at 80-90° C. for 60 min. 5-Bromo-2-methoxy-pyridine (9-1, 1.67 g, 8.87 mmol) was added to the solution and the reaction mixture was stirred at 100° C. for additional 24 hr. The solution was quenched with water (40 mL) and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (NH silica gel, hexane/ethyl acetate=3/1-1/3) to give 5 (0.97 g) in 38% yield: 1H NMR (CDCl3, 500 MHz) δ 8.89 (d, J=5.0 Hz, 2H), 8.23 (d, J=5.0 Hz, 2 H), 8.02 (s, 1 H), 7.37 (d, J=3.0 Hz, 1 H), 6.89 (s, 1 H), 6.80 (d, J=9.0 Hz, 1 H), 6.69 (s, 2 H), 3.94 (s, 3H), 2.17 (s, 6 H), ESI-MS=m/z 433.2 (M+H)+.

1. stirringthe reaction mixture was stirred at 100° C. for additional 24 hr
2. customThe solution was quenched with water (40 mL)
3. extractionextracted with ethyl acetate
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by column chromatography (NH silica gel, hexane/ethyl acetate=3/1-1/3)