Cesium carbonate → Tert-butyl 4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-2-(dimethylcarbamoyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (197 mg, 0.555 mmol), tert-butyl 4-(3-amino-2-chloro-5-cyanophenyl)-2-(dimethylcarbamoyl)piperazine-1-carboxylate (227 mg, 0.557 mmol), palladium (II) acetate (37.4 mg, 0.167 mmol), DPPF (30.8 mg, 0.056 mmol), Xantphos (32.1 mg, 0.056 mmol), and cesium carbonate (271 mg, 0.833 mmol) were combined in a 100 ml round bottom flask and dioxane (5 mL) was added. The flask was evacuated and backfilled with N2 3×, then heated at 100° C. for 1 h. Some SM remaining by LCMS. The reaction was cooled to room temperature and an additional 0.15 eq. catalyst and 0.05 eq of each ligand was added. The flask was purged with N2 and heated for an additional 30 min. The reaction was cooled to room temperature and filtered through celite, rinsing with EtOAc. The solvent was removed in vacuo to leave a brown solid. The crude material was purified by flash column chromatography (0-40% EtOAc/DCM; 40 g column). Tert-butyl 4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-2-(dimethylcarbamoyl)piperazine-1-carboxylate (321 mg) was obtained as a yellow solid.

Provenance & Evidence