Trifluoroacetic acid → HCID 89922735, compound

Participants

Reaction Steps

To a round bottom flask charged with 2-((2-chloro-5-cyano-3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (30 mg, 0.052 mmol) in dichloromethane (345 μl) was added anisole (22.64 μl, 0.207 mmol), followed by trifluoroacetic acid (200 μl, 2.59 mmol). The reaction mixture was stirred at room temperature 2 d. Excess TFA was removed by concentration in vacuo. The crude residue was taken up in methanol and free based using a Phenomenex Strata SCX 1 g column. The column was flushed with 3 column volumes MeOH and 1 column volume 7 N NH3/MeOH. The ammonia containing fraction was concentrated in vacuo. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 10-mM ammonium acetate; Gradient: 20-100% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. 2-((2-Chloro-5-cyano-3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (8 mg) was isolated.

Provenance & Evidence