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Synthesis 2013; 45(8): 1083-1093
DOI: 10.1055/s-0032-1316877
paper
© Georg Thieme Verlag Stuttgart · New York

A Safe Synthesis of 1,5-Disubstituted 3-Amino-1H-1,2,4-triazoles from 1,3,4-Oxadiazolium Hexafluorophosphates

Brian Wong
a   Small Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA   Fax: +1(650)2256238   Email: zhang.haiming@gene.com
,
Andreas Stumpf
a   Small Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA   Fax: +1(650)2256238   Email: zhang.haiming@gene.com
,
Diane Carrera
a   Small Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA   Fax: +1(650)2256238   Email: zhang.haiming@gene.com
,
Chunang Gu
b   Small Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
,
Haiming Zhang*
a   Small Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA   Fax: +1(650)2256238   Email: zhang.haiming@gene.com
› Author Affiliations
Further Information

Publication History

Received: 04 February 2013

Accepted after revision: 05 March 2013

Publication Date:
19 March 2013 (online)

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Abstract

Hexafluorophosphoric acid promotes 1,3,4-oxadiazolium hexafluorophosphate formation from N′-acyl-N-aroyl-N-arylhydrazides or N′-acyl-N-acyl-N-arylhydrazides under mild conditions. These 1,3,4-oxadiazolium hexafluorophosphates can be treated with cyanamide in propan-2-ol in the presence of triethylamine to generate 1,5-disubstituted 3-amino-1H-1,2,4-triazoles in good yields. This safe and scalable protocol displays a broad scope with respect to N-substitutions and N′-acyl protecting groups.

Key words

heterocycles - substituent effects - rearrangement - hydrazide - aminotriazole

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
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