Propylphosphonic anhydride → N-(3-((1R,5S,6R)-3-amino-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-5-chloro-3-methoxypicolinamide

Participants

Reaction Steps

A solution of 1-propanephosphonic acid cyclic anhydride (50 wt % in EtOAc, 0.352 ml, 0.553 mmol) was added to a solution of (1R,5S,6R)-5-(5-amino-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine (16g-B, 0.075 g, 0.277 mmol) and 5-chloro-3-methoxypicolinic acid (0.062 g, 0.332 mmol) in EtOAC (2 mL) at room temperature. The reaction mixture was stirred at rt for 12 h, diluted with aqueous saturated NaHCO3 solution and extracted with EtOAC. The organic phase dried over MgSO4 and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography using (0-100% EtOAc/heptane) to give the title compound (0.082 g, 0.186 mmol, 67.3% yield). MS m/z=441.1 [M+H]+

Provenance & Evidence