Dimethylformamide → Acetic acid 2-(3-{(R)-(4-{amino[2-methylallyloxycarbonylimino]methyl}phenylamino)-[5-(1-ethylpropoxycarbonyloxymethoxy)-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl]methyl}-2-fluoro-5-methoxyphenoxy)ethyl ester

Beteiligte Stoffe

Reaktionsschritte

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-methoxyphenoxyl}ethyl ester (Example 45, 300 mg), carbonic acid chloromethyl ester 1-ethylpropyl ester [CAS No. 176310-42-2] (177 mg), potassium carbonate (80 mg) and N,N-dimethylformamide (5 mL) was stirred at 85° C. for 60 minutes. After cooling the mixture to room temperature, ethyl acetate and water were added thereto. The organic layer was collected, the aqueous layer was reextracted with ethyl acetate, and all the organic layers were combined. The organic layer was sequentially washed with water and with saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The desiccant was filtered off, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate-methanol) to obtain the captioned compound (130 mg) as a solid.

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