Sodium Carbonate → 5-[2-Fluoro-4-(methylthio)phenyl]-2-pyrazinamine

Participants

Reaction Conditions

Reaction Steps

A mixture of [2-fluoro-4-(methylthio)phenyl]boronic acid (5 g, 26.9 mmol), 5-bromo-2-pyrazinamine (4.7 g, 26.9 mmol), Pd(PPh3)4 (0.62 g, 0.54 mmol), 2M Na2CO3 (25 mL), 1,4-dioxane (50 mL), and methanol (25 mL) was stirred and heated at 100° C. for 5 h, then at 25° C. overnight. The reaction was charged with water (300 mL) and extracted with EtOAc (100 mL). The organic extracts were dried over MgSO4, filtered, and concentrated to dryness to give a tan solid. The solid was triturated with CH2Cl2, filtered, and the solid air-dried to afford 5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinamine (3.43 g, 54% yield) as a tan solid. The filtrate was concentrated to dryness to give additional solid (2.5 g) that was purified by SiO2 chromatography (0-25% EtOAc/hexanes, 20 min. gradient; then 25% EtOAc/hexanes, 60 min.; 100 g column) to afford additional product (940 mg, 15% yield) as a tan solid. 1H NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 8.10 (d, 1H, J=1.4 Hz), 7.83 (t, 1H, J=8.3 Hz), 7.10 (dd, 1H, Ja=8.3 Hz, Jb=1.9 Hz), 7.00 (dd, 1H, Ja=12.1 Hz, Jb=1.9 Hz), 4.80 (bs, 2H), 2.50 (s, 3H).

Provenance & Evidence