Water → HCID 53311109, compound

Participants

Reaction Steps

To a solution of 0.16 g (0.25 mmol) 2-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-4-methyl-thiazole-5-carboxylic acid ethyl ester (Example 45) in 2 mL dioxane were added 2 mL water and 0.013 g (0.31 mmol) lithiumhydroxide monohydrate. The resulting suspension was stirred at room temperature for 2 hours and then stirred at reflux temperature for 5.5 hours. Another 0.013 g (0.31 mmol) lithiumhydroxide monohydrate were added and heating was continued for another 8 hours. The oil bath was removed and the reaction mixture was stirred at room temperature overnight. After evaporation of the organic solvent the pH of the resulting solution was adjusted to 2 to 3 using 1M aqueous hydrochloric acid and the solution was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The product was purified by preparative HPLC (Phenomenex Gemini Column) with a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2) to give 0.058 g (37%) of the title compound as a light brown solid. MS (ESI): m/z=624.1 [M+H]+.

Provenance & Evidence