Acetic Acid → HCID 86708667, compound

Participants

Reaction Steps

A suspension of 2-((2-chloro-5-cyano-4-(piperidin-4-ylamino)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 410) (36 mg, 0.080 mmol), oxetan-3-one (116 mg, 1.604 mmol), trimethylorthoformate (0.443 mL, 4.01 mmol), and acetic acid (0.046 mL, 0.802 mmol) in a mixture of MeOH (0.5 mL) and DCM (0.5 mL) was stirred at room temperature for 15 min. Sodium cyanoborohydride (1M in THF, 0.802 mL, 0.802 mmol) was added and the reaction was left stirring for 9 hrs. It was partitioned between EtOAc and sat. aq. NaHCO3 solution. After stirring for 15 min, the aqueous phase was separated and washed with EtOAc (3×) and then a mixture of 10% MeOH in DCM (4×). The combined organic phases were dried with sodium sulfate and the solvent removed. Preparative HPLC (Column: Waters XBridge C18, 19×200 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: 10-100% B over 30 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min) afforded the title compound (13 mg).

Provenance & Evidence