2-Aminothiazole → 1-(6-Methylimidazo[2,1-b][1,3]thiazol-5-yl)ethanone

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Reaction Steps

2-Aminothiazole was recrystallized from anhydrous ethanol, filtered and dried before use. A solution of 2-aminothiazole (16) (20.9 g, 202.4 mmoL) and 3-Chloro-2,5-pentanedione (2) (33.7 g, 97%, 242.9 mmol, 1.2 eq) in 180 mL of anhydrous ethanol was refluxed for 72 h in an oil bath. The black reaction mixture was cooled and concentrated under reduced pressure. The residue was treated with saturated sodium bicarbonate solution in portions, and then extracted with dichloromethane. The organic phase was dried and concentrated. The residue was purified by flash chromatography on a silica gel column using dichloromethane-methanol (80:1). The product fractions were collected (TLC, Rf 0.60 neutral form; Rf=0.5 salt form, dichloromethane-methanol 40:1) and concentrated providing white solid product 17 in 11.7% yield, 1.6 g neutral form and 3.2 g salt form. 1H NMR (CDCl3) δ 2.55 (s, 3H, 5-COCH3), 2.70 (s, 3H, 6-CH3), 6.78 (d, 1H, J=4.8 Hz), 8.39 (d, 1H, J=4.8 Hz).

Provenance & Evidence