To a solution of ethyl 6-bromo-1-cyclohexyl-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate (Intermediate 47, 208 mg, 0.5 mmol, 1 equiv.) and 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazole-2-yl)pyridine-3-ylboronic acid (180 mg, 0.5 mmol, 1 equiv., WO2009106885) in 1,4-dioxane (3 mL) was added tetrakis(triphenylphosphino)palladium(0) (58 mg, 0.05 mmol, 0.1 equiv.) followed by a solution of cesium carbonate (326 mg, 1.0 mmol, 2 equiv.) in water (1 mL). This reaction mixture was stirred at 100° C. for 2 h. 2 M lithium hydroxide (0.5 mL) was added. The reaction mixture was stirred at 100° C. for 9 h, cooled to room temperature, and diluted with water. To this was added 1 N HCl was added until pH 3-4 was reached. The precipitate was collected by filtration, washed with water and hexanes and dried under high pressure. The compound was purified (HPLC) and concentrated to provide 1-cyclohexyl-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylic acid as a solid (46.4 mg, 15%). Calcd for C27H25F3N6O4S [M+H]+: 587.09.
