To a solution of 1-benzyl-4-(benzyloxy)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylic acid (0.15 g, 0.39 mmol) in DMF (4 mL) was added HOAT (0.26 g, 1.94 mmol) and EDC (0.07 g, 0.47 mmol). The solution was stirred for 10 minutes at which time EDC (0.036 g, 0.23 mmol), {4-fluoro-2-[(methylamino)carbonyl]phenyl}methanaminium chloride (0.108 g, 0.47 mmol), and DIEA (0.10 g, 0.78 mmol) were added. The reaction was then stirred at room temperature overnight at which time the solution was purified by preparative reverse phase HPLC eluting with a gradient of 5-95% acetonitrile/water (0.1% TFA). The fractions that contained the desired product were concentrated. Note that during the prep des-O-benzyl product was also obtained. The mixture was taken on to the next step.
