反应详情

温度

-10 °C

To a mixture of dichloromethane (20 mL), THF (20 mL), and water (20 mL), 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, 901 mg), sodium hydrogen carbonate (632 mg), and tetrabutylammonium hydrogen sulfate (102 mg) were sequentially added. After cooling the resulting mixture to −10° C., a mixture of chloromethyl chlorosulfate (373 mg) and dichloromethane (5 mL) was added dropwise thereto with stirring, and the resulting mixture was stirred overnight at room temperature. Dichloromethane (10 mL), THF (10 mL), and water (10 mL) were added to the mixture, and the resulting mixture was cooled again to −10° C., after which a mixture of chloromethyl chlorosulfate (373 mg) and dichloromethane (5 mL) was added dropwise thereto with stirring, and the resulting mixture was stirred overnight at room temperature. Ethyl acetate (300 mL) and water (100 mL) were added to the mixture, and the resulting mixture was shaken, after which the organic layer was collected. Ethyl acetate (80 mL) and THF (20 mL) were added to the aqueous layer, and the resulting mixture was shaken again, after which the organic layer was collected. The combined organic layers were dried over anhydrous magnesium sulfate. The 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 heptane-ethyl acetate) to obtain the captioned compound (340 mg).

1. additionwere sequentially added
2. additionwas added dropwise
3. stirringthe resulting mixture was stirred overnight at room temperature
4. temperaturethe resulting mixture was cooled again to −10° C.
5. additionwas added dropwise
6. stirringwith stirring
7. stirringthe resulting mixture was stirred overnight at room temperature
8. stirringthe resulting mixture was shaken
9. customafter which the organic layer was collected
10. additionEthyl acetate (80 mL) and THF (20 mL) were added to the aqueous layer
11. stirringthe resulting mixture was shaken again
12. customafter which the organic layer was collected
13. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
14. filtrationThe mixture was filtered
15. customthe filtrate obtained
16. concentrationwas concentrated under reduced pressure
17. customThe residue obtained
18. customwas purified by NAM silica gel column chromatography (mixed solvent of heptane-ethyl acetate)