Trifluoroacetic acid → 2-((3-(4-(1-Acetylazetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-((3-(4-(1-acetylazetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (110 mg, 0.169 mmol) in DCE (1.1 mL) and anisole (0.108 mL, 0.985 mmol) was added TFA (0.296 mL, 3.84 mmol) slowly drop wise at room temperature and the reaction mixture was heated at 50° C. for overnight. The reaction mixture was concentrated to remove solvent completely; the resultant residue was washed with hexane to remove anisole. The residue was diluted with Ethyl acetate, washed with aq. ammonia solution, brine, dried over Na2SO4 and concentrated. The crude material was purified by reverse phase HPLC, the fractions were concentrated and the resultant solid was dissolved in HPLC grade Chloroform (20 ml), washed with 10% NaHCO3 solution, brine, dried over Na2SO4 and concentrated. The solid was dissolved in Acetonitrile/water (1:3). Froze the mixture using a dry-ice acetone bath and then dried under lyophilization for 2 days. Lyophlization afforded 2-((3-(4-(1-acetylazetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (50 mg) as a off white solid.

Provenance & Evidence