反应详情

温度

25 °C

Sodium tert-butoxide (5.87 g, 61.1 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (0.905 g, 1.4 mmol) were added to a solution of 2,6-dibromo-4-methyl pyridine (13.9 g, 55.5 mmol) and 2-amino-4-trifluoromethyl pyridine (9.0 g, 55.5 mmol) in nitrogen sparged dioxane (180 mL). The slurry was evacuated and refilled with nitrogen. The mixture was stirred at 25° C. for 15 minutes and then heated to 75° C. for 12 hours. The reaction mixture was cooled to 25° C., water (20 mL) was added, and the mixture was extracted with ethyl acetate (2×200 mL). The combined extracts were dried over sodium sulfate, filtered, concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to afford 6-bromo-4-methyl-N-[4-(trifluoromethyl)pyridine-2-yl]pyridine-2-amine as a white solid. MS ESI calc'd. for C12H10BrF3N3[M+H]+ 332 and 334. found 332 and 334. 1H NMR (600 MHz, DMSO-d6) δ 10.40 (s, 1H), 8.46 (d, J=6.0 Hz, 1H), 7.90 (s, 1H), 7.60 (s, 1H), 7.18 (d, J=6.0 Hz, 1H), 7.00 (s, 1H), 2.25 (s, 3H).

1. customsparged dioxane (180 mL)
2. customThe slurry was evacuated
3. additionrefilled with nitrogen
4. temperatureheated to 75° C. for 12 hours
5. temperatureThe reaction mixture was cooled to 25° C.
6. additionwater (20 mL) was added
7. extractionthe mixture was extracted with ethyl acetate (2×200 mL)
8. dry with materialThe combined extracts were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by column chromatography on silica gel