Aminopyrazine → 2-(Trifluoromethyl)imidazo[1,2-a]pyrazine

Participants

Reaction Steps

2-Pyrazinamine (11.89 g, 125 mmol, commercially available from e.g. Sigma-Aldrich, Fluka or Acros) was dissolved in isopropanol (IPA) (200 mL) and 3-bromo-1,1,1-trifluoro-2-propanone (12.98 mL, 125 mmol) was added. The solution was stirred at room temperature for 2 hours and the heated at reflux for 18 h. The solution was concentrated in vacuo and the residue partitioned between saturated sodium bicarbonate solution (200 ml) and 20% IPA/DCM (300 ml). The aqueous phase was extracted with 20% IPA/DCM (5×200 ml) and the combined extracts were concentrated in vacuo. The residue was dissolved in ethyl acetate (500 ml) and washed with brine (2×100 ml), dried over anhydrous sodium sulfate and concentrated in vacuo to afford a crude solid (17.69 g). The solid was dissolved in dichloromethane and initially purified by filtration through a plug of silica to afford product in 15.14 g. The solid was purified by flash chromatography (Biotage flash 65+, 0-100% [10% 2M NH3 in MeOH/DCM]/DCM) to afford the desired product in 5.61 g. LC/MS=408/410 (M+H)+, retention time=2.05 minutes (5 minute).

Provenance & Evidence