Solid-Phase Synthesis of Lidocaine and Procainamide Analogues Using Backbone Amide Linker (BAL) Anchoring

Simon K. Shannon, Mandy J. Peacock, Steven A. Kates, George Barany

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

New solid-phase strategies have been developed for the synthesis of lidocaine (1) and procainamide (2) analogues, using backbone amide linker (BAL) anchoring. Both sets were prepared starting from a common resin-bound intermediate, followed by four general steps: (i) attachment of a primary aliphatic or aromatic amine to the solid support via reductive amination (as monitored by a novel test involving reaction of 2,4-dinitrophenylhydrazine with residual aldehyde groups); (ii) acylation of the resultant secondary amine; (iii) displacement of halide with an amine; and (iv) trifluoroacetic acid-mediated release from the support. A manual parallel strategy was followed to provide 60 novel compounds, of which two dozen have not been previously described. In most cases, initial crude purities were >80%, and overall isolated yields were in the 40-88% range.

Original languageEnglish (US)
Pages (from-to)860-868
Number of pages9
JournalJournal of Combinatorial Chemistry
Volume5
Issue number6
DOIs
StatePublished - Nov 2003

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