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DOI: 10.1055/s-0029-1216978
Prompt Lithiation of 1-Dimethylsulfamoylthymine Used for the Synthesis of 1-Allyloxymethyl-6-(α,2,6-trifluorobenzyl)thymine
Publikationsverlauf
Publikationsdatum:
28. August 2009 (online)
Abstract
The 6-position of the uracil ring was activated for a lithiation reaction by condensing thymine with dimethylsulfamoyl chloride. X-ray crystallography was used to confirm the structure of the intermediate product 1-dimethylsulfamoylthymine, which was lithiated and subsequently treated with 2,6-difluorobenzaldehyde. The dimethylsulfamoyl group was removed by treatment with aq HCl and the alcohol was fluorinated with DAST. The fluoro-derivative was silylated and alkylated at the N1-position with bis(allyloxy)methane to give 1-allyloxymethyl-6-[(2,6-difluorophenyl)fluo-romethyl]-5-methylpyrimidine-2,4(1H,3H)-dione, which showed moderate activity against HIV-1. An attempt was also made to activate 5-methyl-2-(methylthio)pyrimidin-4(3H)-one with dimethylsulfamoyl chloride for a lithiation reaction. However, X-ray crystallography and subsequent reactions showed that the sulfamoylation had taken place on the oxygen at the 4-position.
Key words
antiviral agents - heterocycles - HIV - medicinal chemistry - sulfonamides
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