Trifluoroacetic acid → 2-((2-Chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Participants

Reaction Conditions

Reaction Steps

2-((2-Chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (69 mg, 0.108 mmol) was dissolved in DCE (1 mL) at room temperature. Anisole (59.2 μl, 0.542 mmol) followed by 200 μL of TFA were added and the reaction was stirred at 40° C. overnight and concentrated. The residue was dissolved in MeOH and loaded onto a 1 g/6 mL Strata SCX ion exchange column, washing with CH3OH. The desired product was eluted with 7 N NH3—CH3OH, concentrated under a stream of N2. Column chromatography (12 g SiO2, 0 to 20% CH3OH—CH2Cl2 gradient elution) followed by trituration with ACN afforded 2-((2-chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (14.6 mg).

Provenance & Evidence