Bromine → 3-Bromo-8-chloroimidazo[1,2-a]pyrazine

Participants

Reaction Steps

A cooled (0° C.) suspension of 8-chloroimidazo[1,2-a]pyrazine (18.6 g, 0.12 mol) and sodium acetate (29.8 g, 0.36 mol) in methanol (125 ml, pre-saturated with solid potassium bromide) was treated with bromine (6.5 ml, 0.13 mol) added dropwise over 5 min. After stirring for 10 min thin-layer chromatography indicated no starting material. Solid sodium sulphite (15.3 g, 0.12 mol) was then added to the slurry and stirring continued for 10 min. The mixture was then treated with saturated aqueous sodium hydrogencarbonate (650 ml) added in portions. This mixture was extracted with dichloromethane (2×350 ml). The organics were combined, dried over anhydrous magnesium sulphate, filtered and concentrated to afford 3-bromo-8-chloroimidazo[1,2-a]pyrazine as a cream-coloured solid: δH (400 MHz, CDCl3) 7.82 (1H, d, J 4.5), 7.83 (1H, s), 8.05 (1H, d, J 4.6). This solid was suspended in 1:1 dichloromethane/methanol (160 ml) and treated with solid sodium methoxide (9.8 g, 0.18 mol). The resulting mixture was then stirred at 40° C. for 2 h. The reaction was cooled, diluted with water (750 ml) then extracted with dichloromethane (600 ml). The organics were dried over anhydrous magnesium sulphate, filtered and concentrated to give 3-bromo-8-methoxyimidazo[1,2-a]pyrazine as a white solid (24.5 g, 89% over 2 steps): δH (360 MHz, DMSO) 4.06 (3H, s), 7.57 (1H, d, J 4.5), 7.81 (1H, s), 8.03 (1H, d, J 4.5).

Provenance & Evidence