HOBt (60 mg, 0.43 mmol), DIPEA (141 mg, 1.09 mmol), EDCI.HCl (84 mg, 0.43 mmol), 3-cyano-phenyl)-piperazin-1-yl-methanone hydrochloride (110 mg, 0.439 mmol) were added to a stirred solution of N-biphenyl-4-yl-2-fluoro-malonamic acid (100 mg, 0.36 mmol) in DMF (2.0 mL) and the resulting mixture was stirred at the ambient temperature overnight. The mixture was then diluted with water and the product was extracted with ethyl acetate. The organics were washed with brine and concentrated to afford 51 mg (29.65%) of N-Biphenyl-4-yl-3-[4-(3-cyano-benzoyl)-piperazin-1-yl]-2-fluoro-3-oxo-propionamide. LCMS: 471.18 (M+1)+, 95.1%, 1H NMR (DMSO-d6): δ 8.3 (s, 1H), 7.8-7.3 (m, 13H), 4.3-3.7 (m, 3H), 3.7-3.3 (m, 5H).
