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The use of the Ugi four-component condensation

Nature Protocols volume 2, pages 632–639 (2007)Cite this article

Abstract

This protocol describes a procedure for the Ugi four-component condensation. It describes the general mechanism as well as the effects of the nature of the components on the Ugi reaction. It also describes the effects of the reaction conditions on the reaction, along with special procedures and workup. The experimental procedure is exemplified by a description of the preparation of N-cyclohexyl 2-[N-(2-chloroacetyl)-N-(4-chlorobenzyl)]amino-2-(4-chlorophenyl)acetamide, a typical Ugi product, that is subsequently used for the synthesis of a 2,5-diketopiperazine, an example of an important type of pharmaceutical compound. The experimental procedure is then extended to the synthesis of a 1,5-disubstituted tetrazole via Ugi four-component condensation. The protocol describes the preparation and characterization of the new 1-cyclohexyl-5-(1-phenylamino-2-methyl)propyltetrazole. The total time for the synthesis and isolation of the two example reactions in parallel is 3 d.

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Acknowledgements

The authors want to thank Dr. J. Delgado and M. Sañudo for help with NMR recording. This work was supported by the Dirección General de Investigación of Spain (project refs. CTQ2005-07562-C04-02/BQU and CTQ2006-15456-C04-04/BQU) and Junta de Castilla y León, Consejería de Educación y Cultura, y Fondo Social Europeo (project ref. BU013A06).

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Authors and Affiliations

  1. Dipartimento di Chimica Organica “Ugo Schiff”, Università di Firenze, Via della Lastruccia, 13, Sesto Fiorentino, I-50019, Italy

    Stefano Marcaccini

  2. Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Burgos, 09001, Spain

    Tomás Torroba

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  1. Stefano Marcaccini
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Correspondence to Tomás Torroba.

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Marcaccini, S., Torroba, T. The use of the Ugi four-component condensation. Nat Protoc 2, 632–639 (2007). https://doi.org/10.1038/nprot.2007.71

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