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Synlett 2010(3): 467-469  
DOI: 10.1055/s-0029-1219177
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Scalable Synthesis of (±)-2-Oxoclopidogrel

Janna Veldera, Christoph Hirschhäusera, Christopher Waldmanna, Dirk Taubertb, Heleen J. Boumanc, Hans-Günther Schmalz*a
a Department für Chemie, Universität zu Köln, Greinstr. 4, 50939 Köln, Germany
Fax: +49(221)4703064; e-Mail: schmalz@uni-koeln.de;
b Institut für Pharmakologie, Universitätsklinikum Köln, Gleveler Str. 24, 50931 Köln, Germany
c St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands
Further Information

Publication History

Received 29 October 2009
Publication Date:
07 January 2010 (online)

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Abstract

As a precondition for detailed pharmacological investigations, an efficient chemical method for the conversion of the antiplatelet drug clopidogrel into its first metabolite 2-oxoclopidogrel was developed. The one-pot procedure, which can easily be performed on a gram scale, exploits the selective borylation of a di-­anionic intermediate derived from clopidogrel with subsequent oxidative workup.

Key words

clopidogrel - drugs - lithiation - oxidation - thiophenes

    References

  • 1a Yusuf S. Zhao F. Mehta SR. Chrolavicius S. Tognoni G. Fox KK. New Engl. J. Med.  2001,  345:  494 
    Google Scholar
  • 1b Mehta SR. Yusuf S. Peters RJ. Bertrand ME. Lewis BS. Natarajan MK. Malmberg K. Rupprecht H. Zhao F. Chrolavicius S. Copland I. Fox KA. Lancet  2001,  358:  527 
    Google Scholar
  • 2a Wang TH. Bhatt DL. Topol EJ. Eur. Heart J.  2006,  27:  647 
    Google Scholar
  • 2b Gurbel PA. Bliden KP. Hiatt BL. O’Connor CM. Circulation  2003,  107:  2908 
    Google Scholar
  • 3a Matetzky S. Shenkman B. Guetta V. Shechter M. Bienart R. Goldenberg I. Novikov I. Pres H. Savion N. Varon D. Hod H. Circulation  2004,  109:  3171 
    Google Scholar
  • 3b Gurbel PA. Bliden KP. Samara W. Yoho JA. Hayes K. Fissha MZ. Tantry US. J. Am. Coll. Cardiol.  2005,  46:  1827 
    Google Scholar
  • 3c Hochholzer W. Trenk D. Bestehorn HP. Fischer B. Valina CM. Ferenc M. Gick M. Caputo A. Buttner HJ. Neumann FJ. J. Am. Coll. Cardiol.  2006,  48:  1742 
    Google Scholar
  • 4a Savi P. Pereillo JM. Uzabiaga MF. Combalbert J. Picard C. Maffrand JP. Pascal M. Herbert JM. Thromb. Haemost.  2000,  84:  891 
    Google Scholar
  • 4b Pereillo JM. Maftouh M. Andrieu A. Uzabiaga MF. Fedeli O. Savi P. Pascal M. Herbert JM. Maffrand JP. Picard C. Drug Metab. Dispos.  2002,  30:  1288 
    Google Scholar
  • 4c Clarke T. Waskell LA. Drug Metab. Dispos.  2003,  31:  53 
    Google Scholar
  • 5a Von Beckerath N. Taubert D. Pogatsa-Murray G. Schomig E. Kastrati A. Schomig A. Circulation  2005,  112:  2946 
    Google Scholar
  • 5b Wallentin L. Varenhorst C. James S. Erlinge D. Braun OO. Jakubowski JA. Sugidachi A. Winters KJ. Siegbahn A. Eur. Heart J.  2008,  29:  21 
    Google Scholar
  • 6a Angiolillo DJ. Fernandez-Ortiz A. Bernardo E. Ramirez C. Cavallari U. Trabetti E. Sabate M. Hernandez R. Moreno R. Escaned J. Alfonso F. Banuelos C. Costa MA. Bass TA. Pignattim PF. Macaya C. Arterioscler., Thromb., Vasc. Biol.  2006,  26:  1895 
    Google Scholar
  • 6b Brandt JT. Close SL. Iturria SJ. Payne CD. Farid NA. Ernest CS. Lachno DR. Salazar D. Winters KJ. J. Thromb. Haemost.  2007,  5:  2429 
    Google Scholar
  • 6c Mega JL. Close SL. Wiviott SD. Shen L. Hockett RD. Brandt JT. Walker JR. Antman EM. Macias W. Braunwald E. Sabatine MS. New Engl. J. Med.  2009,  360:  354 
    Google Scholar
  • 7 Boigegrain R, Maffrand J.-P, Suzuki N, Matsubayashi K, and Ashida S. inventors; US  4,515,951. 
  • 8a Prakash C. Saleh S. Blair IA. Tetrahedron Lett.  1989,  30:  19 
    Google Scholar
  • 8b Ikawa T. Hattori K. Sajiki H. Hirota K. Tetrahedron  2004,  60:  6901 
    Google Scholar
  • 8c Paquette LA. Collado I. Purdie M. J. Am. Chem. Soc.  1998,  120:  2553 
    Google Scholar
  • 8d Fürstner A. Weintritt H. J. Am. Chem. Soc.  1998,  120:  2817 
    Google Scholar
  • 8e Batten RJ. Dixon AJ. Taylor RK. Synthesis  1980,  234 
    Google Scholar
  • 9 Dess DB. Martin JC. J Am. Chem. Soc.  1991,  113:  7277 
    CrossrefGoogle Scholar
  • 10 Bowden K. Heilbron IM. Jones ERH. Weedon BCL. J. Chem. Soc.  1946,  39 
    CrossrefGoogle Scholar