Acetic Acid → HCID 86708603, compound

Participants

Reaction Steps

2-((3-(4-aminopiperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 329) (48 mg, 0.110 mmol) was taken up in THF (2 mL) and Methanol (2 mL) and trimethyl orthoformate (0.5 mL, 4.52 mmol), AcOH (0.05 mL, 0.873 mmol) in a round bottom flask. Oxetan-3-one (0.1 mL, 1.560 mmol) was added. The reaction mixture was stirred at room temperature for 15 mins. Sodium cyanoborohydride (50 mg, 0.796 mmol) was added and the reaction was stirred at room temperature for 2 hrs. LC/MS showed about 40% conversion to the desired product. Another batch of oxetan-3-one (0.1 mL, 1.560 mmol), trimethyl orthoformate (0.5 mL, 4.52 mmol), AcOH (0.05 mL, 0.873 mmol) and sodium cyanoborohydride (50 mg, 0.796 mmol) were added to the reaction mixture and let stirred for another 30 mins. LC/MS showed completed conversion to the product. The mixture was concentrated to almost dryness, diluted with EtOAc and washed with NaHCO3, then brine, dried over MgSO4 and concentrated. The crude was then purified by PREP-HPLC to give 21.3 mg of desired product

Provenance & Evidence