Oxalyl chloride → (E)-N-[2-[(4-Ethoxy-2-pyridyl)amino]ethyl]-4,4-difluoro-pent-2-enamide

(E)-4,4-Difluoropent-2-enoic acid (31 mg, 0.23 mmol) was dissolved in dichloromethane (0.5 ml containing one drop of dimethyl formamide), oxalyl chloride was added (20 μl, 0.23 mmol) and the solution was stirred at room temperature for 15 minutes. This solution was added to a solution of N-(4-ethoxy-2-pyridyl)ethane-1,2-diamine (27 mg, 0.15 mmol) and diisopropylethylamine (88 μl, 0.5 mmol) dissolved in DCM (2 ml) and the resulting mixture was stirred at room temperature for three hours. The volatiles were removed under reduced pressure and the residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and 10% to 100% acetonitrile) to yield 18.7 mg of a residue that was purified again by preparative HPLC (gradient of water containing 0.1% trifluoroacetic acid and 10% to 100% acetonitrile). The product obtained was converted to the free base by dissolving in DCM, washing with 1N NaOH solution, water and evaporation to dryness under reduced pressure to yield 13.2 mg of a solid (0.044 mmol, 29%).

1. stirringthe resulting mixture was stirred at room temperature for three hours
2. customThe volatiles were removed under reduced pressure
3. customthe residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and 10% to 100% acetonitrile)

ORD record

ord-e572b33baf8849f095fc1faea1226258

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321724B2