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

Brian Wong; Andreas Stumpf; Diane Carrera; Chunang Gu; Haiming Zhang

doi:10.1055/s-0032-1316877

Synthesis, Table of Contents

Synthesis 2013; 45(8): 1083-1093
DOI: 10.1055/s-0032-1316877

paper

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

Authors

Brian Wong

^aSmall 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

^aSmall 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

^aSmall 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

^bSmall Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA
Haiming Zhang*

^aSmall Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA Fax: +1(650)2256238 Email: zhang.haiming@gene.com

Abstract

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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

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References

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Supplementary Material

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