反应详情

To a solution of 5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carboxamide (1.65 g, 5.14 mmol) in toluene (20 ml) was added bis(4-methoxyphenyl)methanol (1.32 g, 5.39 mmol) and p-toluenesulfonic acid monohydrate (0.098 g, 0.51 mmol). The reaction mixture was heated to reflux with a Dean-Stark apparatus attached. After 2 hours, the reaction mixture was cooled to ambient temperature and diluted with ethyl acetate (600 mL). This mixture was washed with saturated aqueous sodium bicarbonate (2×100 mL) and brine (50 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-60% ethyl acetate/hexanes). The isolated product was dissolved in 25 mL hot ethyl acetate (˜50° C.). The mixture was allowed to cool to ambient temperature, and then it was diluted dropwise with hexanes (100 mL). After 4 hours, the mixture was filtered, and the collected solids were dried under reduced pressure to afford N-[bis(4-methoxyphenyl)methyl]-5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carboxamide. MS ESI calc'd. For C28H28BrN4O3 [M+H]+ 547 and 549. found 547 and 549. 1H NMR (500 MHz, DMSO-d6) δ 11.47 (s, 1H), 9.68 (d, J=2.0 Hz, 1H), 9.26 (d, J=8.5 Hz, 1H), 8.18 (d, J=2.0 Hz, 1H), 7.27 (d, J=8.5 Hz, 4H), 6.88 (d, J=8.5 Hz, 4H), 6.66 (s, 1H), 6.55 (s, 1H), 6.19 (d, J=9.0 Hz, 1H), 3.71 (s, 6H), 2.36 (s, 3H), 2.19 (s, 3H).

1. temperatureThe reaction mixture was heated
2. temperatureto reflux with a Dean-Stark apparatus
3. washThis mixture was washed with saturated aqueous sodium bicarbonate (2×100 mL) and brine (50 mL)
4. dry with materialThe organic layer was dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by chromatography on silica gel (0-60% ethyl acetate/hexanes)
8. dissolutionThe isolated product was dissolved in 25 mL hot ethyl acetate (˜50° C.)
9. temperatureto cool to ambient temperature
10. additionit was diluted dropwise with hexanes (100 mL)
11. waitAfter 4 hours
12. filtrationthe mixture was filtered
13. customthe collected solids were dried under reduced pressure