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Synthesis 2009(5): 731-740  
DOI: 10.1055/s-0028-1083365
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Convenient Synthesis of Fluorinated Pyrazolo[3,4-b]pyridine and ­Pyrazolo[3,4-d]pyrimidine Nucleosides

Viktor O. Iaroshenko*a,b, Dmitri V. Sevenarde, Anton Kotljarovd, Dmitriy M. Volochnyukb,c, Andrei O. Tolmacheva,b, Vyacheslav Ya. Sosnovskikhf
a National Taras Shevchenko University, 62 Volodymyrska st., Kyiv-33, 01033, Ukraine
b Enamine Ltd., 23 A. Matrosova st., 01103 Kyiv, Ukraine
Fax: +380(44)5373253; e-Mail: yaroshenko@enamine.net;
c Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, Kyiv-94, 02094, Ukraine
d Institute of Organic and Bioorganic Chemistry, University of Tartu, Jakobi 2, 51014 Tartu, Estonia
e Hansa Fine Chemicals GmbH, BITZ, Fahrenheitstr. 1, 28359 Bremen, Germany
f Department of Chemistry, Ural State University, 51 Lenina Ave., 620083 Ekaterinburg, Russian Federation
Further Information

Publication History

Received 26 September 2008
Publication Date:
11 February 2009 (online)

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Abstract

Starting from 5-amino-1-(2,3-O-isopropylidene-β-d-ribofuranosyl)-1H-pyrazole, fluorine-containing 1,3-CCC-, 1,3-CNC-dielectrophiles and 2,4,6-tris(trifluoromethyl)-1,3,5-triazine, a set of fluorinated pyrazolo[3,4-b]pyridine and pyrazolo[3,4-d]pyrimidine nucleosides was obtained. Synthetic access to stable 4-(polyfluoroalkyl)-4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-ole was elaborated, which can be considered to be mimetics of the putative transition state involved in adenosine deaminase activity.

Key words

pyrazole - pyridine - pyrimidine - fluorine - annulation - electrophilic aromatic substitution

    References

  • 1a Cristalli G. Costanzi S. Lambertucci C. Lupidi G. Vittori S. Volpini R. Camaioni E. Med. Res. Rev.  2001,  21:  105 
    Google Scholar
  • 1b Maydanovych O. Beal PA. Chem. Rev.  2006,  106:  3397 
    Google Scholar
  • 1c Nair V. IMPDH inhibitors: Discovery of antiviral agents against emerging diseases, In Antiviral Drug Discovery for Emerging Diseases and Bioterrorism Threats   Chap. 8:  Torrence PF. John Wiley & Sons; Hoboken: 2005.  p.179-202  
    Google Scholar
  • 1d Shu Q. Nair V. Med. Res. Rev.  2008,  28:  219 
    Google Scholar
  • 2a Agarwal RP. Pharmacol. Ther.  1982,  17:  399 
    Google Scholar
  • 2b Weber G. Cancer Res.  1983,  43:  3466 
    Google Scholar
  • 3 Pankiewicz KW. Goldstein BM. Inosine mono phosphate dehydrogenase, ACS Symposium Series 839   American Chemical Society; Washington DC: 2003. 
    Google Scholar
  • 4a Burns CM. Chu H. Rueter SM. Hutchinson LK. Canton H. Sanders-Bush E. Emeson RB. Nature  1997,  387:  303 
    Google Scholar
  • 4b Higuchi M. Single FN. Kohler M. Sommer B. Sprengel R. Seeburg PH. Cell  1993,  75:  1361 
    Google Scholar
  • 5a Giblett ER. Anderson JE. Cohen F. Pollara B. Meuwissen HJ. Lancet  1972,  2:  1067 
    Google Scholar
  • 5b Hirshhorn R. Clin. Immunol. Immunopathol.  1995,  76:  S219 
    Google Scholar
  • 6a Niedzwicki JG. Kouttab NM. Mayer KH. Carpenter CC. Parks RE. Abushanab E. Abernethy DR. J. Acquir. Immune Defic. Syndr.  1991,  4:  178 
    Google Scholar
  • 6b Salvatore D. Claudio MM. Anna PM. Clin. Chem.  1987,  33:  1675 
    Google Scholar
  • 6c Valenzuela A. Blanco J. Callebaut C. Jacotot E. Lluis C. Hovanessian AG. Franco R. J. Immunol.  1997,  158:  3721 
    Google Scholar
  • 7a Ungerer JPJ. Oosthuizen HM. Retief JH. Bissbort SH. Chest  1994,  106:  33 
    Google Scholar
  • 7b Banales JL. Rivera Martinez E. Perez Gonzalez L. Selman M. Raymond Y. Nava A. Arch. Med. Res.  1999,  30:  358 
    Google Scholar
  • 8a Chiba S. Matsumoto H. Saitoh M. Kasahara M. Matsuya M. Kashiwagi MA. J. Neurol. Sci.  1995,  132:  170 
    Google Scholar
  • 8b Gakis C. Eur. Respir. J.  1996,  9:  632 
    Google Scholar
  • 9a Demeocq F. Viallard JL. Boumsell L. Richard Y. Chassgne J. Plagne R. Lemerle J. Bernard A. Leuk. Res.  1982,  6:  211 
    Google Scholar
  • 9b Carlucci F. Rosi F. Di Pietro C. Marinello E. Biochim. Biophys. Acta  1997,  1360:  203 
    Google Scholar
  • 10 Erion MD. Reddy MR. J. Am. Chem. Soc.  1998,  120:  3295 
    CrossrefGoogle Scholar
  • 11a Begue J.-P. Bonnet-Delpon D. Chemie bioorganique et medicinale du fluor   EDP Sciences; France: 2005.  p.366 
    Google Scholar
  • 11b Silverman RB. The organic chemistry of drug design, and drug action   2nd ed.:  Elsevier Academic Press; London: 2004.  p.617 
    Google Scholar
  • 12a Cristalli G. Costanzi S. Lambertucci C. Lupidi G. Vittori S. Volpini R. Camaioni E. Med. Res. Rev.  2001,  21:  105 
    Google Scholar
  • 12b Adenosine Deaminase in Disorders of Purine Metabolism and in Immune Deficiency   Vol. 451:  Tritsch GL. New York Academy of Sciences; New York: 1985. 
    Google Scholar
  • For related inverse electron-demand Diels-Alder reactions, see:
  • 13a Dang Q. Brown BS. Erion MD. J. Org. Chem.  1996,  61:  5204 
    Google Scholar
  • 13b Dang Q. Gomez-Galeno JE. J. Org. Chem.  2002,  67:  8703 
    Google Scholar
  • 13c Dang Q. Liu Y. Erion MD. J. Am. Chem. Soc.  1999,  121:  5833 
    Google Scholar
  • 14a Volochnyuk DM. Pushechnikov AO. Krotko DG. Sibgatulin DA. Kovalyova SA. Tolmachev AA. Synthesis  2003,  1531 
    Google Scholar
  • 14b Iaroshenko VO. Volochnyuk DM. Wang Y. Vovk MV. Boiko VJ. Rusanov EB. Groth UM. Tolmachev AO. Synthesis  2007,  3309 
    Google Scholar
  • 15a Sosnovskikh VYa. Irgashev RA. Barabanov MA. Synthesis  2006,  2707 
    Google Scholar
  • 15b Sosnovskikh VYa. Irgashev RA. Heteroat. Chem.  2006,  17:  99 
    Google Scholar
  • 16 Marcoux J.-F. Corley EG. Rossen K. Pye P. Wu J. Robbins MA. Davies IW. Larsen RD. Reider PJ. Org. Lett.  2000,  2:  2339 
    CrossrefGoogle Scholar
  • 17 Cottam HB. Petrie CR. McKernan PA. Goebel RJ. Dalley NK. Davidson RB. Robins RK. Revankar GR. J. Med. Chem.  1984,  27:  1119 
    CrossrefGoogle Scholar
  • 18a Behforouz M. Ahmadian M. Tetrahedron  2001,  56:  5259 
    Google Scholar
  • 18b Buonora P. Olsen J.-C. Oh T. Tetrahedron  2001,  57:  6099 
    Google Scholar
  • 18c Jayakumar S. Ishar MPS. Mahajan PM. Tetrahedron  2002,  58:  379 
    Google Scholar
  • 19 Guranowski A. Montgomery JA. Cantoni GL. Chiang PK. Biochemistry  1981,  20:  110 
    CrossrefGoogle Scholar
20

Sheldrick G. M., SHELXTL PLUS. PC Version. A system of computer programs for the determination of crystal structure from X-ray diffraction data. Rev. 5.1., 1998.