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Updated: Jun 19, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Access to N2-Substituted (Aza)Indazoles
Flora Fan1,2, Xiangfeng Niu3, Wanqi Su1
1Discovery Process Chemistry, Small Molecule Process Research & Development, Merck & Co., Inc., South San Francisco, California 94080, United States.
None:
N2-Substituted (aza)indazoles are versatile heterocycles that commonly feature in bioactive, drug-like molecules. We report a practical one-pot method developed as part of medicinal chemistry efforts to access these from amino (aza)benzaldehydes and a wide array of amines. The key oxidative N-N bond cyclization is mediated by PhI(OAc)2, enabling rapid access to a breadth of N2-functionalized (aza)indazoles. This protocol can also be scaled up in batch for multigram, chromatography-free synthesis.
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