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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
General Method for the Preparation of Electron-Deficient Imidazo[1,2-a]pyridines and Related Heterocycles
Ivar M McDonald1, Kevin M Peese1
1Bristol-Myers Squibb Research & Development , Department of Discovery Chemistry, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Abstract:
A new annulation method for the preparation of the imidazo[1,2-a]pyridine ring system under mild conditions is presented. Treatment of a 2-aminopyridine with a dimethylketal tosylate in acetonitrile at elevated temperature (80-140 °C) in the presence of catalytic Sc(OTf)3 provides the imidazo[1,2-a]pyridine product in good yield. The annulation method is broadly applicable to electron-poor 2-aminopyridines and displays a complementary profile to the classic preparation of the imidazo[1,2-a]pyridine ring system by reaction of a bromoketone with electron-rich and -neutral substrates. The scope of the process and mechanistic considerations are discussed.
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