To a mixture of methy 4-amino-3-bromo-5-[(2-hydroxy-2-methylpropyl)amino]benzoate (513 mg, 1.617 mmol), palladium(II) acetate (7.26 mg, 0.032 mmol), (4-fluorophenyl)boronic acid (453 mg, 3.23 mmol) and 4,4′,4″-phosphinetriyltribenzenesulfonic acid-sodium salt (48.8 mg, 0.097 mmol) were added DMF (2.43 mL) and water (0.809 mL) followed by diisopropylamine (0.461 mL, 3.23 mmol). The reaction was capped and heated at 80° C. for 2 h. The reaction was cooled, quenched with saturated sodium bicarbonate and diluted with EtOAc. The aqueous layers were washed with EtOAc (2×) and the combined organics were washed with water (3×) and brine (1×). Organics were dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% TFA) gave the title compound (377 mg): LC-MS [M+1]=333.3.
