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Synthesis 2021; 53(11): 1980-1988
DOI: 10.1055/s-0040-1706642
paper

An Ugi Reaction/Intramolecular Cyclization/Oxidation Cascade towards Tetrazole-Linked Dibenzoxazepines

Qiang Zheng
,
André Boltjes
,
Alexander Dömling  ∗
This research has been supported (A.D.) by the Center for Scientific Review, National Institute of Health (NIH) (2R01GM097082-05), the European Lead Factory (IMI) (Grant No. 115489), the Qatar National Research Foundation (NPRP6-065-3-012). Funding was also received through the Horizon 2020 Framework Programme, AEGIS (Accelerated Early stage drug dIScovery) Innovative Training Network (ITN) (Grant No. 675555) and COFUND ALERT (Grant No. 665250), and the KWF Kankerbestrijding (Dutch Cancer Society) (Grant No. 10504). Q.Z. acknowledges the China Scholarship Council for support.
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In memoriam Albert van Leusen

Abstract

A series of tetrazole-linked dibenzo[b,f][1,4]oxazepines is synthesized through a short sequence involving an Ugi tetrazole reaction. The intermediate tetrazole undergoes a potassium carbonate mediated SNAr cyclization, followed by oxidation to afford the target tricyclic heterocyclic scaffold. The optimization, scope and limitations of this two-step and efficient methodology are investigated. A 1000-member library of tetrazole-linked dibenzo[b,f][1,4]oxazepines is generated and the physicochemical properties are analyzed. great

Key words

dibenzo[b,f][1,4]oxazepines - Ugi tetrazole - cyclization - library - drug-like properties

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1706642.
  • Supporting Information


Publication History

Received: 16 October 2020

Accepted after revision: 19 November 2020

Article published online:
15 January 2021

© 2021. Thieme. All rights reserved

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