Cesium carbonate → (+/-)-tert-butyl ((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)carbamate

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(cyclopropyl(4-methoxybenzyl)amino)-2-(methylsulfonyl) imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 2, 185 mg, 0.464 mmol), (+/−)-tert-butyl ((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((tert-butyldimethyl silyl)oxy)piperidin-4-yl)carbamate (223 mg, 0.464 mmol) and cesium carbonate (302 mg, 0.927 mmol) in DMF (5 mL) was heated at 50° C. for 4 h. LCMS showed completion of reaction. The reaction mixture was diluted with ethyl acetate and the solid was filtered off. The filtrate was concentrated in vacuo and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10-35% ethyl acetate/hexanes). (+/−)-tert-butyl ((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)carbamate (270 mg) was obtained as a white solid.

Provenance & Evidence