反应详情

Under nitrogen atmosphere, triethylamine (6.97 mL) was added under ice-cooling to a mixture of acetic acid (601 mg), TFFH (2.64 g), and dichloromethane (50 mL), and the resulting mixture was stirred for 1 hour. To the resulting mixture, a mixture of N-[1-amino-1-(4-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide (Example 1a, 3 g), DMAP (5 mg), and DMF (50 mL) was added dropwise. After stirring the resulting mixture overnight at room temperature, the solvent in the mixture was distilled off under reduced pressure. The residue obtained was dissolved in a small amount of THF, and ethyl acetate (300 mL) and water (100 mL) were added to the resulting mixture. After a buffer (prepared by adding 37 mL of 0.1 M citric acid to 63 mL of 0.2 M disodium hydrogen phosphate) was added to the resulting mixture to adjust the pH to 6, the mixture was shaken, and the organic layer was collected. The organic layer was sequentially washed twice with water (100 mL) and with saturated aqueous sodium chloride solution (100 mL), and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain the captioned compound (2.16 g).

1. additionwas added dropwise
2. stirringAfter stirring the resulting mixture overnight at room temperature
3. distillationthe solvent in the mixture was distilled off under reduced pressure
4. customThe residue obtained
5. additionwere added to the resulting mixture
6. additionwas added to the resulting mixture
7. stirringthe mixture was shaken
8. customthe organic layer was collected
9. washThe organic layer was sequentially washed twice with water (100 mL) and with saturated aqueous sodium chloride solution (100 mL)
10. dry with materialdried over anhydrous magnesium sulfate
11. filtrationThe resulting mixture was filtered
12. customthe filtrate obtained
13. concentrationwas concentrated under reduced pressure
14. customThe residue obtained
15. customwas purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate)