Lithium Hydroxide → HCID 59415945, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-ethyl 6-iodo-4-oxo-1-(piperidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylate (Intermediate 108, 200 mg, 0.42 mmol, 1 equiv.) and 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 17, 151 mg, 0.42 mmol, 1 equiv.) in 1,4-dioxane (4.5 mL) was added tetrakis(triphenylphosphine)palladium(0) (48.5 mg, 0.04 mmol, 0.1 equiv.) followed by a solution of cesium carbonate (205 mg, 0.63 mmol, 1.5 equiv.) in water (1.5 mL). This was stirred at 100° C. for 2 h. 2 M lithium hydroxide (0.629 mL, 1.26 mmol, 3 equiv.) was then added and the mixture was stirred at 100° C. for 12 h. The reaction mixture was diluted with water, and the precipitate that formed was collected by filtration, washed with water and hexanes and dried under vacuum. Purification via reverse phase HPLC (C18, 0-95% acteonitirile/water gradient) gave (R)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-4-oxo-1-(piperidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylic acid as a light yellow solid (92.5 mg, 36%).

Provenance & Evidence