Hydrochloric Acid → HCID 131730928, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-ethyl 6-bromo-1-(1-(2-(diethylamino)ethyl)piperidin-3-yl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate (Intermediate 63, 461 mg, 0.96 mmol, 1 equiv.) and 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazole-2-yl)pyridine-3-ylboronic acid (WO2009106885, 519 mg, 1.44 mmol, 1.5 equiv.) in 1,4-dioxane (4 mL) was added tetrakis(triphenylphosphino)palladium(0) (111 mg, 0.1 mmol, 0.1 equiv.) followed by a solution of cesium carbonate (627 mg, 1.92 mmol, 2.0 equiv.) in water (1.3 mL). This reaction mixture was stirred at 100° C. for 2 h. 2 M Lithium hydroxide (0.96 mL) was added. The reaction mixture was stirred at 100° C. for 9 h, cooled to room temperature, and diluted with water. 1 N HCl was added until pH 3-4 was reached. The precipitate was washed with water and hexanes and dried. The compound was purified (C18 silica gel chromatography) and concentrated to provide (5)-1-(1-(2-(diethylamino)ethyl)piperidin-3-yl)-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 (193 mg, 30%). Calcd for C32H37F3N8O4S [M+H]+: 687.23.

Provenance & Evidence