Dimethylformamide → HCID 18537716, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 3,5-dimethylbenzenethiol (41.3 g), 6-chloro-2-methylamino-3-nitropyridine (56.1 g), potassium carbonate (207 g) and anhydrous N,N-dimethylformamide (300 ml) was stirred at 80° C. for 1.5 hours. The reaction mixture was concentrated and partitioned between ethyl acetate and water. The extract was dried over anhydrous sodium sulfate and concentrated. To a solution of the residue in a mixture of ethanol and toluene (1:1, 600 ml) was added 10% palladium on carbon (41.1 g) and the mixture was vigorously stirred under a hydrogen atmosphere at room temperature for 4 hours. The catalyst was removed by filtration and the filtrate was concentrated. To the residue was added glycolic acid (68.4 g) and the mixture was heated at 150° C. for 1.5 hours, 3N hydrochloric acid (200 ml) was added, and the mixture was then heated at reflux for 1 hour. The reaction mixture was neutralized with aqueous sodium bicarbonate solution (10%). The precipitate was isolated by filtration, washed with water and ethyl acetate and then dried under reduced pressure to give 5-(3,5-dimethylphenylthio)-2-hydroxymethyl-3-methyl-3H-imidazo[4,5-b]pyridine. A solution of the product in thionyl chloride (150 ml) was stirred in a bath at 80° C. for 30 minutes. The reaction mixture was concentrated, diluted with water, neutralized with sodium bicarbonate and then extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on a silica gel column using ethyl acetate:n-hexane=1:1 as the eluant to afford the desired compound (54.3 g, mp 87-90° C.).

Provenance & Evidence