N-bromobutanimide → HCID 178455730, compound

Participants

Reaction Steps

N-bromosuccinimide (4.07 g, 22.9 mmol) was added to a room temperature solution of racemic 4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (4.14 g, 7.63 mmol) stirring in degassed chloroform (38 mL). The reaction was heated to reflux for 1.5 hours. The mixture was cooled to room temperature, diluted with dichloromethane, and washed with saturated aqueous sodium thiosulfate (2×) and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-80% ethyl acetate/hexanes, linear gradient) to afford racemic 2-bromo-4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. The racemic material was then purified by chiral supercritical fluid chromatography (Chiralpak IB, 21×250 mm, 25% methanol in CO2) to afford 2-bromo-4-(5-chloropyridin-3-yl)-3-[(1S)-1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile and 2-bromo-4-(5-chloropyridin-3-yl)-3-[(1R)-1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. Faster eluting enantiomer 1: MS ESI calc'd. for C21H21BrClN5 [M+H]+ 458. found 458. Slower eluting enantiomer 2: MS ESI calc'd. for C21H21BrClN5 [M+H]+ 458. found 458.

Provenance & Evidence