PDF icon Download PDF
Synthesis 2010(20): 3429-3432  
DOI: 10.1055/s-0030-1258212
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Facile and Green Synthesis of a Naphthyridine Derivative: A Novel Hedgehog Pathway Modulator

Wen-Chung Shieh*, Song Xue, Joe McKenna, Kapa Prasad, Mahavir Prashad
Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA
Fax: +1(973)7817566; e-Mail: wen.shieh@novartis.com;
Further Information

Publication History

Received 6 May 2010
Publication Date:
13 August 2010 (online)

   Permissions and Reprints All articles of this category
Preview

Abstract

A green and highly efficient synthesis of a naphthyridine derivative, a novel hedgehog pathway modulator, in high yield and purity from inexpensive starting materials is described. The key step involves an acid-promoted aryl amination reaction of aniline with naphthyridine halides.

Key words

aryl amination - acid-promoted coupling - green chemistry - naphthyridine - pyridine cyclization

    References

  • 1a Xie J. Curr. Oncol. Rep.  2008,  10:  107 
    Search in Google Scholar
  • 1b Xie J. Future Oncol.  2005,  1:  331 
    Search in Google Scholar
  • 2a Kumar SK. Roy I. Anchoori RK. Fazli S. Maitra A. Beachy PA. Khan SR. Bioorg. Med. Chem.  2008,  16:  2764 
    Search in Google Scholar
  • 2b Levitt RJ. Zhao Y. Blouin M.-J. Pollak M. Cancer Lett.  2007,  255:  300 
    Search in Google Scholar
  • 2c Chen JK. Taipale J. Young KE. Maiti T. Beachy PA. Proc. Natl. Acad. Sci. U.S.A.  2002,  99:  14071 
    Search in Google Scholar
  • 3 Cheng D, Han D, Gao W, Jiang J, Pan S, and Wan Y. inventors; Patent WO  2008014291.  ; Chem. Abstr. 2008, 148, 191938
  • 4 Singh B. Lesher GY. Brundage RP. Synthesis  1991,  894 
    Thieme Connect
  • 5 Bredereck H. Effenberger F. Botsch H. Chem. Ber.  1964,  97:  3397 
    CrossrefSearch in Google Scholar
  • For recent reviews on Buchwald-Hartwig aryl amination reactions, see:
  • 6a Mauger CC. Mignani GA. Aldrichimica Acta  2006,  39:  17 
    Search in Google Scholar
  • 6b Schlummer B. Scholz U. Adv. Synth. Catal.  2004,  346:  1599 
    Search in Google Scholar
  • 6c Frost C. G., Mendonça P.; J. Chem. Soc., Perkin Trans. 1; 1998, 2615
  • For articles on palladium-catalyzed aryl amination of heteroaromatic compounds with morpholine or aniline, see:
  • 7a Navarro O. Marion N. Mei J. Nolan SP. Chem. Eur. J.  2006,  12:  5142 
    Search in Google Scholar
  • 7b Tewari A. Hein M. Zapf A. Beller M. Tetrahedron  2005,  61:  9705 
    Search in Google Scholar