Chloroacetyl chloride → 1-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethyl)-4-chloro-2-(chloromethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridine

Participants

Reaction Conditions

Reaction Steps

N4-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethyl)-2-chloro-5,6-dimethylpyridine-3,4-diamine (2.85 g, 8.29 mmol) was dissolved in 100 mL of dry 1,2-dichloroethane and the solution was cooled to 0° C. as it stirred under an atmosphere of N2. Triethylamine (2.3 mL, 16.58 mmol) and chloroacetyl chloride (0.92 mL, 11.60 mmol) were added sequentially. After 30 minutes, the reaction mixture was allowed to warm to ambient temperature and stirred for 3 days followed by heating to 70° C. for 2 days. The reaction mixture was allowed to cool to ambient temperature and was washed with saturated NaHCO3 solution (2×100 mL) and brine (100 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product as a brown solid. Chromatography (SiO2, 20-50% ethyl acetate/hexanes) gave 1-((1S)-2{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-4-chloro-2-(chloromethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridine (0.44 g) as a yellow oil.

Provenance & Evidence