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

• Published in: Tetrahedron letters Vol. 64; p. 152684
• Main Authors: Fuchino, Kouki, Masui, Moriyasu, Yoshida, Shuhei, Kusakabe, Ken-ichi
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 02-02-2021
• Subjects: Amino-1,3-oxazine; BACE1 inhibitor; Burgess reagent; Cyclization; BACE1 inhibitor; Cyclization; Burgess reagent; Amino-1,3-oxazine
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2020.152684

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•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.
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.