Dichloromethane → HCID 89919477, compound

Participants

Reaction Steps

To a solution of 2-((3-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 375B) (50 mg, 0.110 mmol) and DIPEA (0.031 mL, 0.221 mmol) in MeOH (0.5 mL)/DCM (0.5 ml) was added (S)-2-methyloxirane (64.1 mg, 1.104 mmol). The reaction was stirred for 16 hours. The solvents were removed and the crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 20-mM ammonium acetate; Gradient: 10-55% B over 25 minutes, then a 8-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford 2-((2-chloro-5-cyano-3-((3R,4R)-3-hydroxy-4-(((S)-2-hydroxypropyl)amino)piperidin-1-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (14.5 mg).

Provenance & Evidence