Trifluoroacetic acid → HCID 89923291, compound

Participants

Reaction Steps

To a round bottom flask charged with (+/−)-2-((2-chloro-5-cyano-3-(2-(hydroxymethyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (35.2 mg, 0.06 mmol) in dichloromethane (200 μl) was added anisole (32.8 μl, 0.300 mmol), followed by trifluoroacetic acid (185 μl, 2.400 mmol). The reaction mixture was stirred at room temperature ON. LCMS indicated primarily the trifluoroacetate product was present. Excess TFA was removed in vacuo. The residue was treated with toluene and concentrated in vacuo (2×). The crude solid was treated with 2 N NH3/MeOH (˜1.5 mL)—a solid immediately precipitated out. After 20 min, the solid was isolated by vacuum filtration. LCMS indicated the solid was the desired alcohol product. 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: 15-100% 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-(2-(hydroxymethyl)morpholino)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (3.5 mg) was isolated.

Provenance & Evidence