Formic Acid → ethyl (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylate

Participants

Reaction Steps

A mixed solution prepared from acetic anhydride (6.29 mL) and formic acid (9.42 mL) was added dropwise to a solution of ethyl (E)-3-(5-amino-6-methoxypyridin-2-yl)acrylate (1.85 g) in THF (30 mL) at 0° C. The reaction solution was stirred at room temperature for one hour and then added dropwise to ice water. Ethyl acetate was added and the organic layer was separated. The resulting organic layer was washed with saturated sodium bicarbonate water and brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. Subsequently, cesium carbonate (4.87 g), potassium iodide (124 mg) and chloroacetone (1.23 mL) were added to a solution of the residue in DMF (20 mL), and the reaction solution was stirred at room temperature for 12 hours. Ice water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain a crude product. Subsequently, ammonium acetate (2.88 g) was added to a solution of the resulting compound in acetic acid (4.28 mL), and the reaction solution was stirred at 130° C. for one hour. The reaction solution was left to cool to room temperature. Ice water and ethyl acetate were added and the organic layer was separated. The resulting organic layer was washed with saturated sodium bicarbonate water and brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 1.50 g of the title compound. The property values of the compound are as follows.

Provenance & Evidence