Nitrogen → 6-bromo-4-methyl-N-[4-(trifluoromethyl)pyridine-2-yl]pyridine-2-amine

Participants

Reaction Conditions

Reaction Steps

N2 was bubbled through a solution of 4-(trifluoromethyl)pyridin-2-amine (12.0 g, 74.0 mmol) and 2,6-dibromo-4-methylpyridine (18.57 g, 74.0 mmol) in 1,4-dioxane (240 mL) for five minutes. Sodium tert-butoxide (7.83 g, 81 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (1.204 g, 1.851 mmol) were added and the solution was heated to 75° C.; the mixture was stirred using a magnetic stirrer. Upon completion, the reaction mixture was cooled and then partitioned between EtOAc (200 mL) and 5% aqueous ammonium chloride solution (200 mL). The layers were separated and the aqueous layer was extracted with EtOAc (200 mL). The combined organic layers were washed with water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel (gradient of 0-40% EtOAc/hexane) to provide 6-bromo-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine (22.5 g, 67.7 mmol, 92%). MS ESI calcd for C12H9BrF3N3 [M+H]+ 332, found 332. 1H NMR (600 MHz, CDCl3) δ 8.39 (s, 1H), 7.73 (s, 1H), 7.54 (s, 1H), 7.33 (s, 1H), 7.05 (s, 1H), 6.92 (d, J=2.7 Hz, 1H), 2.31 (d, J=3.6 Hz, 3H) ppm.

Provenance & Evidence