Elsevier

Tetrahedron Letters

Volume 64, 2 February 2021, 152684
Tetrahedron Letters

Facile Construction of an Amino-1,3-Oxazine Scaffold using Burgess Reagent Under Mild Conditions

https://doi.org/10.1016/j.tetlet.2020.152684Get rights and content

Highlights

  • •

    Use of Burgess reagent enabled cyclization of amino-1,3-oxazine scaffolds under a mild condition.

  • •

    Dehydrative cyclization reaction tolerated fragile functional groups.

  • •

    The method serves as development of 1,3-oxazine-based BACE1 inhibitors.

Abstract

The development of a cyclization reaction to access amino-1,3-oxazines under mild conditions is described. The synthesis was achieved using dehydrating reagents, such as phosphorus pentoxide and Burgess reagent. In particular, the cyclization with Burgess reagent proceeded under mild conditions and tolerated potentially labile functional groups, such as the acetoxy group, and therefore can be used to synthesize β-secretase (BACE1) inhibitors with a variety of amino-1,3-oxazine warheads.

Section snippets

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

We gratefully thank Harrie Gijsen and Takuya Oguma for their insightful comments and Masayoshi Ogawa for the NMR experiments.

References (9)

  • R. Yan et al.

    Lancet Neurol.

    (2014)
  • T.J. Woltering et al.

    Bioorg. Med. Chem. Lett.

    (2013)
    D. Oehlrich et al.

    Bioorg. Med. Chem. Lett.

    (2014)
  • K. Fuchino et al.

    J. Med. Chem.

    (2018)
  • E.M. Burgess et al.

    J. Am. Chem. Soc.

    (1970)
    M.M. Heravi et al.

    Curr. Org. Chem.

    (2015)
There are more references available in the full text version of this article.
View full text
© 2020 Elsevier Ltd. All rights reserved.