Cesium carbonate → 2-((3-(4-((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

Participants

Reaction Conditions

Reaction Steps

(I13C): 2-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 1) (0.646 g, 1.820 mmol), 3-amino-5-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-4-chlorobenzonitrile (I13B) (0.666 g, 1.820 mmol), Pd(OAc)2 (0.123 g, 0.546 mmol), DPPF (0.101 g, 0.182 mmol), Xantphos (0.105 g, 0.182 mmol), and cesium carbonate (1.186 g, 3.64 mmol) were combined in a round bottom flask and dioxane (12.13 ml) was added. The flask was evacuated and backfilled with nitrogen (3×), then heated at 100° C. 10 h. The reaction mixture was diluted with ethyl acetate and vacuum filtered through a pad of Celite. The filtrate was concentrated in vacuo and the crude material purified by column chromatography on the ISCO system (40 g, 0-100% EtOAc/Hex). 2-((3-(4-((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 (0.9309 g) was isolated as a dark yellow solid.

Provenance & Evidence