Trifluoroacetic acid → 4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-1-(2,2-difluoroethyl)-N,N-dimethylpiperazine-2-carboxamide

Participants

Reaction Steps

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)-1-(2,2-difluoroethyl)-N,N-dimethylpiperazine-2-carboxamide (37 mg, 0.054 mmol) was taken up in DCE (0.5 mL) and anisole (0.029 mL, 0.268 mmol) was added, followed by TFA (0.124 mL, 1.608 mmol). The reaction was stirred at room temperature overnight. LCMS indicates mostly SM is present. An additional 30 eq. of TFA was added and the reaction was heated at 50° C. After 4 h, an additional 30 eq. of TFA was added, and the reaction heated for 1.5 h. The solvent was removed in vacuo and the material azeotroped 2× with toluene, then triturated with Et2O to remove anisole. The material was purified by preparative HPLC to provide 4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-1-(2,2-difluoroethyl)-N,N-dimethylpiperazine-2-carboxamide (20.1 mg) as a yellow solid.

Provenance & Evidence