4-Morpholineacetic acid → (+/-)-N-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)-2-morpholinoacetamide

Participants

Reaction Steps

A mixture of (+/−)-2-((3-((3R,4R)-4-amino-3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 171E, 40 mg, 0.057 mmol), 2-morpholinoacetic acid (9.96 mg, 0.069 mmol) and HATU (26.1 mg, 0.069 mmol) in DMF (1 mL) was stirred at room temperature for 6 h. The reaction mixture was diluted with dichloromethane and was filtered. The filtrate was concentrated in vacuo and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 5-50% ethyl acetate/hexanes). (+/−)-N-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)-2-morpholinoacetamide (46 mg) was obtained as a white solid.

Provenance & Evidence