反应详情

温度

85 °C

Under nitrogen atmosphere, a mixture of acetic acid 2-{3-[(R)-{4-[amino(2-methylallyloxycarbonylimino)methyl]phenylamino}-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy}ethyl ester (Example 45, 508 mg), carbonic acid chloromethyl ester 2-fluoro-1,1,dimethylethyl ester (Example 56a, 295 mg), rubidium carbonate (166 mg) and N,N-dimethylacetamide (15 mL) was stirred at 85° C. for 60 minutes. After cooling the mixture to room temperature, the reaction solution was concentrated under reduced pressure. The obtained residue was purified by reverse phase silica gel column chromatography (mixed solvent of methanol-water containing 0.1% of acetic acid), and then the obtained compound was further purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate-methanol) to obtain the captioned compound (104 mg).

1. temperatureAfter cooling the mixture to room temperature
2. concentrationthe reaction solution was concentrated under reduced pressure
3. customThe obtained residue was purified by reverse phase silica gel column chromatography (mixed solvent of methanol-water containing 0.1% of acetic acid)
4. customthe obtained compound was further purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate-methanol)