Diastereoselective intramolecular Ritter reaction: generation of a cis-fused hexahydro-4aH-indeno[1,2-b]pyridine ring system with 4a,9b-diangular substituents.
Indanol intermediates 5, prepared via Michael addition of 1-indanone beta-ketoester and acrylonitrile followed by reduction or Grignard reaction of the ketone group, were submitted to intramolecular Ritter reaction using various acid reaction conditions to produce tricyclic lactams 4. This cis-fused hexahydro-4aH-indeno[1,2-b]pyridine ring system, substituted at both angular positions 4a and 9b, provides access to constrained analogues of non-peptide NK(1)-antagonists with monocyclic piperidine structure.
Van Emelen
K
K
Department of Chemistry, University of Leuven, Celestijnenlaan 200F, 3001 Heverlee, Belgium.
De Wit
T
T
Hoornaert
G J
GJ
Compernolle
F
F
D001713:Biphenyl Compounds / Q000737:chemistry*; D002855:Chromatography, Thin Layer; D018360:Crystallography, X-Ray; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D018040:Receptors, Neurokinin-1 / Q000737:chemistry; D013237:Stereoisomerism; D013373:Substance P / Q000037:antagonists & inhibitors*
D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011725:Pyridines; D018040:Receptors, Neurokinin-1; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; C066892:CP 96345