Sulfuric Acid → HCID 178433995, compound

Participants

Reaction Conditions

Reaction Steps

6-Hydroxy-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carbonitrile (0.911 g) was dissolved in concentrated H2SO4 (3.0 mL) and stirred at 40° C. for 24 hrs. The solution was poured into ice-water and the precipitated solid was filtered, washed with water, and dried under high vacuum to give 6-hydroxy-1,3-dimethylpyrazolo[5,4-b]pyridin-5-carboxamide as a white solid. A portion of this material (0.122 g) was dissolved in DMF (2.0 mL). 2-Chlorotriethylamine hydrochloride (0.192 g) and potassium carbonate (0.304 g) were added to the solution. The reaction mixture was stirred at 60° C. for 18 h. The reaction mixture was poured into water, extracted with ethyl acetate. The extract was washed with saturated NaHCO3 solution and the brine, and dried over Na2SO4. The extract was evaporated under reduced pressure to give 6-[2-(diethylamino)ethoxy]-1,3-dimethylpyrazolo[5,4-b]pyridine-5-carboxamide as a white solid. A portion of this material (0.059 g) was dissolved in hot toluene (10 mL) and azeotroped for 2 hrs. The solution was cooled to room temperature. 4-Fluoro-3-(trifluoromethyl)phenylisocyanate (0.098 g) was added to the solution. The mixture was heated at reflux for 23 hrs, and then, cooled to room temperature. The solvent was evaporated under reduced pressure, and the residue was purified with the column chromatography (ethyl acetate). A portion of this material (20mg) was dissolved in tetrahydrofuran (1.0 mL) and treated with 1N hydrochloric acid solution (1.0 mL). The mixture was lyophilized to give {6-[2-(diethylamino)ethoxy]-1,3-dimethylpyrazolo[5,4-b]pyridin-5-yl}-N-({[4-fluoro-3-trifluoromethyl)phenyl]amino}carbonyl)carboxamide hydrochloride as a white solid.

Provenance & Evidence