Chloroacetic Acid → 2-Chloro-6-isopropylimidazo[1,2-B]pyridazine

Chloroacetic acid (0.32 g, 3.3 mmol), triethylamine (0.33 g, 3.3 mmol), ethanol (5.0 ml) and water (5.0 ml) were mixed and 3-amino-6-isopropylpyridazine (0.45 g, 3.28 mmol) was added thereto with stirring at room temperature, and after the mixture was heated at 80 to 90° C. for 5 hours under stirring, the reaction solution was concentrated to dryness. The resulting solids and phosphorus oxychloride (5.0 ml) were stirred at 150° C. for 12 hours in a sealed tube reactor. The reaction solution was left and cooled to room temperature and poured into water (50.0 ml) of 40 to 50° C., to decompose an excess of phosphorus oxychloride. The reaction solution was adjusted to pH 7 with 20% aqueous sodium hydroxide solution and extracted 3 times with ethyl acetate, and the extracts were combined, dried over anhydrous magnesium sulfate and concentrated. The residues were purified by silica gel column chromatography (ethyl acetate:chloroform=1:2), to give the title compound as pale yellow crystals. The yield was 0.15 g (23.4%).