Methyl iodide → HCID 178459020, compound

Participants

Reaction Steps

Steps 5 & 6: A stirred solution of 2-(3-{[tert-butyl(dimethyl)silyl]oxy}prop-1-en-2-yl)-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (1.2 g, 2.24 mmol) in THF (20 mL) was cooled to 0° C. Tetrabutylammonium fluoride (3.36 mL, 3.36 mmol, 1M solution in THF) was added dropwise over a period of 5 minutes, and the reaction mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (15 mL). The organic phase was separated, washed with brine solution (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The crude 4-(5-chloropyridin-3-yl)-2-(3-hydroxyprop-1-en-2-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (0.9 g, 2.14 mmol) was dissolved in dry THF (10 mL) and cooled to 0° C. NaH (0.123 g, 3.12 mmol, 60% in mineral oil) was added in several portions and stirred for 15 minutes. Methyl iodide (0.16 mL, 2.57 mmol) was added dropwise over a period of 5 minutes, and the reaction mixture was slowly warmed to room temperature and stirred for 1 h. The reaction mixture was quenched with ice and extracted with ethyl acetate (100 mL). The organic layer was separated, washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 15% ethyl acetate/petroleum ether as eluent to yield 4-(5-chloropyridin-3-yl)-2-(3-methoxyprop-1-en-2-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCI calcd. for C24H26ClN5O [M+H]+ 436. found 436

Provenance & Evidence