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

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.

1. customthe organic layer was separated
2. washThe resulting organic layer was washed with saturated sodium bicarbonate water and brine
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. additionSubsequently, 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)
6. stirringthe reaction solution was stirred at room temperature for 12 hours
7. additionIce water and ethyl acetate were added to the reaction solution
8. customthe organic layer was separated
9. washThe resulting organic layer was washed with water and brine
10. dry with materialdried over anhydrous magnesium sulfate
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)
13. customto obtain a crude product
14. stirringthe reaction solution was stirred at 130° C. for one hour
15. waitThe reaction solution was left
16. temperatureto cool to room temperature
17. customthe organic layer was separated
18. washThe resulting organic layer was washed with saturated sodium bicarbonate water and brine
19. dry with materialdried over anhydrous magnesium sulfate
20. concentrationconcentrated under reduced pressure
21. customThe residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)

ORD 기록

ord-0843a8feec5f4b18a8dfa3f530c42072

출처 데이터셋

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07935815B2