1206825-03-7

1206825-06-0

1206825-03-7

The general procedure for the synthesis of 4-chloroimidazo[2,1-f][1,2,4]triazin-4(3H)-ones from imidazo[2,1-f][1,2,4]triazines was as follows: imidazo[2,1-f][1,2,4]triazin-4(3H)-ones (400 mg, 2.94 mmol, 1.0 eq.) were dissolved in phosphorus oxychloride (POCl3, 10 mL , 109.2 mmol, 37.1 eq.), the resulting mixture was stirred and refluxed for 2 hours. Upon completion of the reaction, the mixture was concentrated under vacuum to remove excess POCl3. The residue was carefully poured into ice water (30 mL) and neutralized with saturated aqueous sodium bicarbonate (NaHCO3) to adjust the pH to 6-7 while controlling the temperature below 5 °C. The mixture was then purified with ethyl acetate (10 mL, 109 mmol, 37.1 eq.). Subsequently, the mixture was extracted with ethyl acetate (30 mL x 4). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate (Na2SO4) and filtered. The filtrate was concentrated under vacuum and the residue was purified by rapid column chromatography on silica gel (eluent: 16% petroleum ether solution of ethyl acetate) to afford 4-chloroimidazo[2,1-f][1,2,4]triazine (300 mg, 66.0% yield).