An Expeditious Library Synthesis of N-Monoalkylated Aminopiperidines and -pyrrolidines

✍ Scribed by Susana Ayesa; Dimitris Argyropoulos; Tatiana Maltseva; Christian Sund; Bertil Samuelsson

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 238 KB
• Volume: 2004
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200300760

✦ Synopsis

Abstract

N‐Monosubstituted aminopiperidines and ‐pyrrolidines are important building blocks for the synthesis of small‐molecule compound libraries. We have developed a practical solid‐phase route to N‐monosubstituted aminopiperidines and ‐pyrrolidines utilizing a selective reductive alkylation of primary or secondary amines attached to a Merrifield or Wang resin. Purification is achieved by simple filtration after each reaction step. The synthetic route developed can be readily applied to an extensive pool of commercially available aromatic and aliphatic aldehydes for conversion into the corresponding N‐monoalkylated diamino templates. Solid‐phase NMR spectroscopy was used to monitor the reactions. The new pulse sequences described in this report have further extended the usefulness of this nondestructive analytical methodology. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)