Synthesis and differential functionalisation of pyrrolidine and piperidine based spirodiamine scaffolds

Kamil Weinberg, Axel Stoit, Chris G. Kruse, Mairi F. Haddow, Timothy Gallagher*, Tim C Gallagher

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)

Abstract

The synthesis and differential substitution/protection of a series of spirodiamine scaffolds are described. Methods for selective access to the two mono-N-methyl isomers based on 2,7-diazaspiro[4,5]decane are also described. Key precursors associated with this chemistry are prone to rearrangement and methods for circumventing this issue are reported. While direct motto-carbamoylation (Boc) was not efficient, selective deprotection of doubly Boc-protected derivatives derived from symmetrical diamines provided mono-Boc variants. N-Arylation, exemplified by a series of monosubstituted spirodiamines incorporating the 2-chloro-5-pyridyl moiety, which is a privileged nicotinic agonist substructure, has also been carried out to provide monoarylated secondary and tertiary spirodiamines variants. (C) 2013 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)4694-4707
Number of pages14
JournalTetrahedron
Volume69
Issue number23
DOIs
Publication statusPublished - 10 Jun 2013

Keywords

  • NICOTINIC ACETYLCHOLINE-RECEPTORS
  • POLY(ADP-RIBOSE) POLYMERASE-1 PARP-1
  • GAMMA-SECRETASE INHIBITORS
  • CATION-PI INTERACTION
  • IIB-IIIA ANTAGONISTS
  • ONE-POT SYNTHESIS
  • CONFORMATIONAL-ANALYSIS
  • ASYMMETRIC-SYNTHESIS
  • BUILDING-BLOCKS
  • IN-VIVO

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