Cyanoacetic acid → HCID 90427540, compound

Participants

Reaction Steps

A RT solution of cyanoacetic acid (0.500 g, 5.88 mmol) in DCM (20 mL) and DMF (0.1 mL) was treated drop-wise with oxalyl chloride (1.1 mL, 12.52 mmol), stirred at RT for 2.5 h, then concentrated to dryness. The residue was dissolved in DCM (5 mL), added drop-wise to a 0° C. solution of N-(4-((2-aminopyridin-4-yl)oxy)-5-chloro-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (0.210 g, 0.467 mmol) in pyridine (10 mL), stirred for 0.5 h, then concentrated to dryness. The residue was dissolved in DCM, washed with satd. NaHCO3 and the aqueous layer extracted with EtOAc (3×). The combined organics were dried over Na2SO4, concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM, then MeOH/EtOAc). The material was further purified via silica gel chromatography (MeOH/DCM) to afford N-(5-chloro-4-((2-(2-cyanoacetamido)pyridin-4-yl)oxy)-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (120 mg, 49%). MS (ESI) m/z: (M+H+): 516.8.

Provenance & Evidence