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Issue 39, 2016
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A one-pot synthesis of tetrazolones from acid chlorides: understanding functional group compatibility, and application to the late-stage functionalization of marketed drugs

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Abstract

A one-pot and scalable synthesis of tetrazolones (tetrazol-5-ones) from acid chlorides using azidotrimethylsilane is presented. The reaction tolerates many functional groups and can furnish aryl-, heteroaryl-, alkenyl-, or alkyl-substituted tetrazolone products in moderate to excellent yield (14–94%). No reduction in yield was observed when the reaction was undertaken on a larger-scale (20–36 g). The method could be used for the late-stage functionalization of pharmaceuticals, to provide tetrazolone congeners of the marketed drugs aspirin, indomethacin, probenecid, telmisartan, bexarotene, niacin (vitamin B3), and the active metabolite of the recently-launched immuno-modulatory agent, BG-12 (Tecfidera®). The ability of a tetrazolone group to serve as a bioisostere of a carboxylic acid, and to improve drug pharmacokinetic profiles is also highlighted.

Graphical abstract: A one-pot synthesis of tetrazolones from acid chlorides: understanding functional group compatibility, and application to the late-stage functionalization of marketed drugs

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Article information


Submitted
01 Aug 2016
Accepted
31 Aug 2016
First published
15 Sep 2016

Org. Biomol. Chem., 2016,14, 9338-9342
Article type
Paper

A one-pot synthesis of tetrazolones from acid chlorides: understanding functional group compatibility, and application to the late-stage functionalization of marketed drugs

M. A. J. Duncton and R. Singh, Org. Biomol. Chem., 2016, 14, 9338
DOI: 10.1039/C6OB01644H

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