1,2,4-Triazoles and 1,3,4-oxadiazoles are prevalent moieties in pharmaceutical agents, yet fused [1,2,4]triazolo[3,4-b][1,3,4]oxadiazoles are surprisingly under-represented for both synthesis and biological application. We report a rapid, two-step synthesis of [1,2,4]triazolo[3,4-b][1,3,4]oxadiazoles from commercial 4-amino-1,2,4-triazoles that is highlighted by a microwave accelerated intramolecular cyclization to generate the fused ring system. Our efforts to optimize reaction conditions and elucidate reaction mechanism are also described.
Bibliographical noteFunding Information:
We gratefully acknowledge funding by the National Institutes of Health ( R01-GM110129 ) and the University of Minnesota , Office of the Vice President for Research (Equipment Grant-in-Aid to purchase the CEM Discover SP Microwave Synthesizer). S.L.B. thanks the University of Minnesota, Undergraduate Research Opportunities Program (UROP) and the Department of Chemistry Heisig/Gleysteen Summer Undergraduate Research Fellowship Program for financial support. M.E.O. acknowledges the National Institutes of Health for a Ruth L. Kirschstein NRSA Predoctoral Fellowship (F31-CA183246). Mass spectrometry was performed at the Analytical Biochemistry Core Facility of the Masonic Cancer Center (University of Minnesota), which is supported in part by the National Institutes of Health (P30-CA77598).
© 2016 Elsevier Ltd
- Intramolecular cyclization
- Microwave chemistry