Dichloromethane → 5-(4-Bromo-2-fluorophenyl)pyrazin-2-amine

Participants

Reaction Steps

To a solution of 5-bromopyrazin-2-amine (1.74 g, 10.0 mmol) in 1,4-dioxane (40 mL) were added 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.65 g, 10.5 mmol) and KOAc (1.96 g, 20.0 mmol). The mixture was sparged with N2 several times before adding Pd(dppf)Cl2.CH2Cl2 (0.41 g, 0.5 mmol). The resultant mixture was stirred at 90° Celsius for 60 hours under N2. After cooling to rt, 4-bromo-2-fluoro-1-iodobenzene (4.5 g, 15.0 mmol), K2CO3 (2.76 g, 20.0 mmol) and another portion of Pd(dppf)Cl2.CH2Cl2 (0.41 g, 0.5 mmol) were added. The resultant mixture was sparged with N2 again, and stirred at 80° Celsius for 48 hours under N2. The mixture was then cooled to rt, diluted with THF (30 mL) and filtered. The filtrate was concentrated to dryness and the residue purified by FCC to give 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine (0.4 g, 15%). 1H NMR (300 MHz, DMSO-d6) δ 8.33 (s, 1H), 8.01 (s, 1H), 7.82 (m, 1H), 7.63 (dd, J=11.1, 2.1, 1H), 7.50 (dd, J=8.4, 2.1, 1H), 6.75 (s, 2H).

Provenance & Evidence