2-(Dimethylamino)ethanol → (+/-)-2-(dimethylamino)ethyl ((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate

Participants

Reaction Steps

A solution of (+/−)-2-((3-((3R,4R)-4-amino-3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (32 mg, 0.055 mmol) in THF (1 mL) was added to CDI (35.8 mg, 0.221 mmol) in THF (1 mL) at 0° C. and the reaction mixture was stirred at room temperature overnight. In a 1-dram vial charged with 2-(dimethylamino)ethanol (44.6 mg, 0.500 mmol) in THF (1 mL) was added lithium bis(trimethylsilyl)amide (1M in THF, 0.884 mL, 0.884 mmol) at 0° C. and the resulting reaction solution was stirred at room temperature for 10 min before added to the above intermediate. The reaction mixture was stirred at room temperature for 1 h Solvent was evaporated and the residue was partitioned between dichloromethane and saturated sodium bicarbonate. The layers were separated and the organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 1-8% methanol/dichloromethane). (+/−)-2-(dimethylamino)ethyl ((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate (34 mg) was obtained as a white solid.

Provenance & Evidence