Lithium Hydroxide → 6-(6-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-((1-methylpiperidin-4-yl)methyl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl 6-iodo-1-((1-methylpiperidin-4-yl)methyl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 1, 952 mg, 2.32 mmol) and 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 834 mg, 2.32 mmol) in 1,4-dioxane (7.5 mL) was added tetrakis(triphenylphosphine)palladium(0) (268 mg, 0.23 mmol) followed by a solution of cesium carbonate (1.51 g, 4.63 mmol) in water (2 mL). The reaction mixture was stirred at 100° C. for 2 h. 2 M lithium hydroxide (2.32 mL, 4.63 mmol) was then added and the mixture was stirred at 100° C. for 12 h. The reaction mixture was diluted with water, and the precipitate was washed with water and hexanes and then dried. The compound was purified via reverse phase HPLC (C18, 0-95% acetonitrile/water, gradient) and concentrated under reduced pressure to give 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-((1-methylpiperidin-4-yl)methyl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid as a light yellow solid (106.1 mg, 7%).

Provenance & Evidence