Acetic Acid → (+/-)-2-((3-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-(oxetan-3-ylamino)piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino) imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Participants

Reaction Steps

(+/−)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 (Example 171C)(60 mg, 0.104 mmol) was taken up in MeOH (1 mL) and THF (1 mL) and trimethyl orthoformate (0.859 mL, 7.77 mmol), AcOH (0.024 mL, 0.414 mmol), and oxetan-3-one (0.066 mL, 1.036 mmol) were added. The reaction was stirred at room temperature for 2 h, then NaCNBH3 (65.1 mg, 1.036 mmol) was added and the reaction was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc and washed with sat'd NaHCO3, then brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography, eluting with 0-3% MeOH/DCM. (+/−)-2-((3-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-(oxetan-3-ylamino)piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino) imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (30 mg) was obtained as a white foam.

Provenance & Evidence