反应详情

A dry round bottomed flask was charged with 2-amino-4-cyclopropylpyridine (5.00 g, 31.7 mmol) and 2,6-dibromo-4-methylpyridine (7.95 g, 31.7 mmol). The reaction vessel was placed under an atmosphere of nitrogen (3× vacuum/N2 cycle), then 1,4-dioxane (100 mL) was added and the mixture was degassed with a steady stream of nitrogen for 30 minutes. Sodium tert-butoxide (3.35 g, 34.8 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (0.49 g, 0.75 mmol) were added to the reaction flask, then the reaction was stirred at room temperature for 15 minutes then heated to 50° C. for five hours. After cooling to room temperature for 14 hours, the resulting reaction mixture was poured into water (200 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were further washed with water and brine (200 mL portions). The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure to yield an oil. The crude product was purified by silica gel chromatography (0-30% ethyl acetate/hexanes) to give the title compound as a brown solid. 1H NMR (600 MHz, DMSO-d6) δ 9.80 (s, 1H), 8.06 (d, J=5.3 Hz, 1H), 7.70 (s, 1H), 7.23 (s, 1H), 6.92 (s, 1H), 6.61 (dd, J=1.4, 5.3 Hz, 1H), 2.25 (s, 3H), 1.91-1.78 (m, 1H), 1.09-0.98 (m, 2H), 0.82-0.66 (m, 2H).

1. customthe mixture was degassed with a steady stream of nitrogen for 30 minutes
2. temperaturethen heated to 50° C. for five hours
3. temperatureAfter cooling to room temperature for 14 hours
4. customthe resulting reaction mixture
5. extractionextracted with ethyl acetate (2×100 mL)
6. washThe combined organic layers were further washed with water and brine (200 mL portions)
7. dry with materialThe organic phase was dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto yield an oil
11. customThe crude product was purified by silica gel chromatography (0-30% ethyl acetate/hexanes)