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Synthesis 2007(17): 2667-2673  
DOI: 10.1055/s-2007-983852
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Substituted Imidazo[1,5-a]pyridines Starting from N-2-Pyridylmethylamides Using Lawesson’s Reagent and Mercury(II) Acetate

Aline Moulin, Sandra Garcia, Jean Martinez, Jean-Alain Fehrentz*
Institut des Biomolécules Max Mousseron, UMR 5247 Faculté de Pharmacie, CNRS - Universités Montpellier I et II, 15 avenue Charles Flahault, BP 1441, 34093 Montpellier Cedex 5, France
Fax: +33(4)67548654; e-Mail: jean-alain.fehrentz@univ-montp1.fr;
Further Information

Publication History

Received 28 February 2007
Publication Date:
08 August 2007 (online)

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Abstract

A new method for the synthesis of substituted imidazo[1,5-a]pyridines (2-azaindolizines) starting from carboxylic acid and 2-methylaminopyridine is described. The reaction of the obtained N-2-pyridylmethylamides with Lawesson’s reagent gene­rated the target imidazopyridines, along with the corresponding thioamide intermediates. After a simple filtration on alumina, addition of mercury(II) acetate allowed for total conversion of the thioamides into the imidazopyridines. The reaction conditions, as well as the influence of the substituent in position 3 of the imidazopyridine ring were explored. We also demonstrated that this heterocyclization was racemization free in the presence of a chiral carbon in position α to the heterocycle.

Key words

heterocycles - imidazo[1,5-a]pyridines - 2-azaindolizines - Lawesson’s reagent - mercury(II) acetate

    References

  • 1 El hadem HS. Kawai J. Swartz DL. Carbohydr. Res.  1989,  189:  149 
    CrossrefSearch in Google Scholar
  • 2 Kim D. Wang L. Hale JJ. Lynch CL. Budhu RJ. MacCoss M. Mills SG. Malkowitz L. Gould SL. DeMartino JA. Springer MS. Hazuda D. Miller M. Kessler J. Hrin RC. Carver G. Carella A. Henry K. Lineberger J. Schleif WA. Emini EA. Bioorg. Med. Chem. Lett.  2005,  15:  2129 
    CrossrefSearch in Google Scholar
  • 3 Degoey DA, Flentge CA, Flosi WJ, Grampovnik DJ, Kempf DJ, Klein LL, Yeung MC, Randolph JT, Wang XC, and Yu S. inventors; US Patent  2005148623.  ; Chem. Abstr. 2005, 143, 133693
  • 4 Nakatsuka M, and Shimamura T. inventors; Jpn. Kokai Tokkyo Koho JP  2001035664.  ; Chem. Abstr. 2001, 134, 170632
  • 5 Tominaga T, Kohama T, and Takano A. inventors; Jpn. Kokai Tokkyo Koho JP  2001006877.  ; Chem. Abstr. 2001, 134, 93136
  • 6 Kitasawa D. inventors; Tominaga, T.; Takano, A. Jpn. Kokai Tokkyo Koho JP  2001057292.  ; Chem. Abstr. 2001, 134, 200276
  • 7 Nakamura H, and Yamamoto H. inventors; PCT Int. Appl. WO  2005043630.  ; Chem. Abstr. 2005, 142, 440277
  • 8 Alcarazo M. Roseblade SJ. Cowley AR. Fernandez R. Brown JM. Lassaletta JM. J. Am. Chem. Soc.  2005,  127:  3290 
    CrossrefPubMedSearch in Google Scholar
  • 9 Burstein C. Lehmann CW. Glorius F. Tetrahedron  2005,  61:  6207 
    CrossrefSearch in Google Scholar
  • 10 Bower JD. Ramage GR. J. Chem. Soc.  1955,  2834 
  • 11 Wang J. Mason R. VanDerveer D. Feng K. Bu XR. J. Org. Chem.  2003,  68:  5415 
    CrossrefPubMedSearch in Google Scholar
  • 12 Wang J. Dyers L. Mason R. Amoyaw P. Bu XR. J. Org. Chem.  2005,  70:  2353 
    CrossrefSearch in Google Scholar
  • 13 Shibahara F. Kitagawa A. Yamaguchi E. Murai T. Org. Lett.  2006,  8:  5621 
    CrossrefSearch in Google Scholar
  • 14 Bluhm ME. Ciesielski M. Gorls H. Doering M. Angew. Chem. Int. Ed.  2002,  41:  2962 
    CrossrefSearch in Google Scholar
  • 15 Bluhm ME. Folli C. Pufky D. Kroeger M. Walter O. Doering M. Organometallics  2005,  24:  4139 
    CrossrefSearch in Google Scholar
  • 16 Castro B. Dormoy JR. Evin G. Selve C. Tetrahedron Lett.  1975,  1219 
    Crossref
  • 17 Pedersen BS. Scheibye S. Nilsson NH. Lawesson SO. Bull. Soc. Chim. Belg.  1978,  87:  223 
    Search in Google Scholar
  • 18 Moulin A. Martinez J. Fehrentz J.-A. Tetrahedron Lett.  2006,  47:  7591 
    CrossrefSearch in Google Scholar