Hydrochloric Acid → (R)-1-(1-(2-(diethylamino)ethyl)piperidin-3-yl)-6-(6-(3-ethylureido)-4-(4-phenylthiazol-2-yl)pyridin-3-yl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-(3-ethylureido)-4-(4-phenylthiazol-2-yl)pyridine-3-ylboronic acid (WO2009106885) (624 mg, 1.69, 1 equiv.) and (R)-ethyl 6-bromo-1-(1-(2-(diethylamino)ethyl)piperidin-3-yl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylate Intermediate 65 (765 mg, 1.69 mmol, 1 equiv.) in 1,4-dioxane (7 mL) was added tetrakis(triphenylphosphino)palladium(0) (196 mg, 0.17 mmol, 0.1 equiv.) followed by a solution of cesium carbonate (828 mg, 2.54 mmol, 2.0 equiv.) in water (1.7 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, and the reaction was concentrated. The compound was purified (C18 silica gel chromatography) and concentrated to provide (R)-1-(1-(2-(diethylamino)ethyl)piperidin-3-yl)-6-(6-(3-ethylureido)-4-(4-phenylthiazol-2-yl)pyridin-3-yl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylic acid (422.1 mg, 36%). Calcd for C37H42N8O4S [M+H]+: 695.3.

Provenance & Evidence