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Library-to-Library Synthesis of Highly Substituted ?-Aminomethyl Tetrazoles via Ugi Reaction.

ABSTRACT: ?-Aminomethyl tetrazoles, recently made accessible by an Ugi multicomponent reaction (MCR), were shown to be excellent starting materials for a further Ugi MCR, yielding substituted N-methyl-2-(((1-methyl-1H-tetrazol-5-yl)methyl)amino)acetamides having four points of diversity in a library-to-library approach. The scope and limitations of the two-step sequence was explored by conducting more than 50 reactions. Irrespective of electron-rich and electron-deficient oxo-components and the nature of the isocyanide component, the reactions give excellent yields. Sterically less hindered ?-aminomethyl tetrazoles give better yields of in further Ugi MCR. The target scaffold has four points of diversity and is finding applications to fill screening decks for high-throughput screening (HTS) in the European Lead Factory and in structure-based drug design.

SUBMITTER: Patil P

PROVIDER: S-EPMC5813278 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Library-to-Library Synthesis of Highly Substituted α-Aminomethyl Tetrazoles via Ugi Reaction.

Patil Pravin P Mishra Bhupendra B Sheombarsing Gitanjali G Kurpiewska Katarzyna K Kalinowska-Tłuścik Justyna J Dömling Alexander A

ACS combinatorial science 20180104 2

α-Aminomethyl tetrazoles, recently made accessible by an Ugi multicomponent reaction (MCR), were shown to be excellent starting materials for a further Ugi MCR, yielding substituted N-methyl-2-(((1-methyl-1H-tetrazol-5-yl)methyl)amino)acetamides having four points of diversity in a library-to-library approach. The scope and limitations of the two-step sequence was explored by conducting more than 50 reactions. Irrespective of electron-rich and electron-deficient oxo-components and the nature of ...[more]

PMID: 29215263

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