Thionyl Chloride → HCID 178478567, compound

Participants

Reaction Steps

1.0 g 2-Hydroxymethyl-5-chloro-3H-imidazo[4,5-b]pyridine (5.45 mmol) was suspended in chloroform (10.0 ml) and treated with 3.3 ml thionyl chloride (45 mmol) for 4 h at reflux. The mixture was evaporated and the residue triturated with methanol. After concentration the residue was stirred over night in ether and the suspension was then filtered. The residue on the filter was dried to yield 0.67 g 5-chloro-2-chloromethyl-3H-imidazo[4,5-b]pyridine hydrochloride as a brown solid; M.p.: 218–220° C., (dec.). 14.5 ml Triethyl amine (104.0 mmol), 1.67 g sulfur (52.0 mmol) and 0.65 g 5-chloro-2-chloromethyl-3H-imidazo[4,5-b]pyridine hydrochloride (26.0 mmol) were dissolved in DMF (15 ml) and stirred at ambient temperature for 2 h. After cooling to 0° C., 1.6 ml MeI (26.0 mmol) were added and stirring at ambient temperature was continued for 1 h. Then water (100 ml) was added and the mixture extracted 3 times with ethyl acetate (150 ml). The combined organic phase were filtered over dicalit® and concentrated. The residue was dissolved in ethanol (100 ml) and treated with 5.4 g 2-methoxy-5-morpholin-4-yl-phenylamine (26 mmol) for 16 h at reflux. Upon cooling to ambient temperature a precipitate formed, which was isolated and dried in vacuo. 2 g 5-chloro-3H-imidazo[4,5-b]pyridine-2-carbothioic acid (2-methoxy-5-morpholin-4-yl-phenyl)-amide (19%) was obtained as a red solid; MS (ISP): m/e=404 (M+H+).

Provenance & Evidence