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Synthesis 2010(10): 1692-1696  
DOI: 10.1055/s-0029-1218739
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Imidazo[1,2]hetarylglyoxylates: Synthesis and Reactivity toward Nucleophiles

Irina A. Zamkovaa, Oleksiy O. Chekotyloa, Oleksandr V. Geraschenkoa,b, Oleksandr O. Grygorenko*a,b, Pavel K. Mykhailiuk*a,b, Andrey A. Tolmacheva,b
a Enamine Ltd., Oleksandra Matrosova Street 23, Kyiv 01103, Ukraine
b Department of Chemistry, Kyiv National Taras Shevchenko University, Volodymyrska Street 64, Kyiv 01033, Ukraine
Fax: +380(44)2351273; e-Mail: gregor@univ.kiev.ua; e-Mail: pashamk@gmx.de;
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Publication History

Received 3 February 2010
Publication Date:
15 April 2010 (online)

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Abstract

A practical approach to imidazo[1,2]hetarylglyoxylates via Friedel-Crafts acylation of the parent fused imidazoles with ethyl oxalyl chloride is reported. The reaction is strongly influenced by the electron-donating properties of the starting heterocycle. The generated imidazo[1,2]hetarylglyoxylates undergo standard transformations typical of α-keto esters upon reaction with various nucleophiles. All the products contain an imidazoheterocyclic scaffold which is considered a privileged structure for drug discovery.

Key words

imidazoheterocycles - acylation - glyoxylates - privileged scaffolds

    References

  • 1 Evans BE. Rittle KE. Bock MG. DiPardo RM. Freidinger RM. Whitter WL. Lundell GF. Veber DF. Anderson PS. Chang RSL. Lotti VJ. Cerino DJ. Chen TB. Kling PJ. Kunkel KA. Springer JP. Hirshfield J. J. Med. Chem.  1988,  31:  2235 
    CrossrefPubMedGoogle Scholar
  • 2a Duarte CD. Barreiro EJ. Fraga CA. Mini-Rev. Med. Chem.  2007,  7:  1108 
    Google Scholar
  • 2b DeSimone RW. Currie KS. Mitchell SA. Darrow JW. Pippin DA. Comb. Chem. High Throughput Screening  2004,  7:  473 
    Google Scholar
  • 2c Costantino L. Barlocco D. Curr. Med. Chem.  2006,  13:  65 
    Google Scholar
  • 3a Langer SZ. Arbilla S. Benavides J. Scatton B. Adv. Biochem. Psychopharmacol.  1990,  46:  61 
    Google Scholar
  • 3b George P. Rossey G. Depoortere H. Mompon B. Allen J. Wick A. Farmaco  1991,  46:  277 
    Google Scholar
  • 4 Mizushige K. Ueda T. Yukiiri K. Suzuki H. Cardiovasc. Drug. Rev.  2002,  20:  163 
    CrossrefPubMedGoogle Scholar
  • 5 Carminati GM. Farmaco Prat.  1978,  33:  68 
    Google Scholar
  • For selected examples, see:
  • 6a Primofiore G. Da Settimo F. Taliani S. Marini AM. La Motta C. Novellino E. Greco G. Gesi M. Trincavelli L. Martini C. J. Med. Chem.  2000,  43:  96 
    Google Scholar
  • 6b Tse B. Jones AB. Tetrahedron Lett.  2001,  42:  6429 
    Google Scholar
  • 6c Zhu G. Conner S. Zhou X. Shih C. Brooks HB. Considine E. Dempsey JA. Ogg C. Patel B. Schultz RM. Spencer CD. Teicher B. Watkins SA. Bioorg. Med. Chem. Lett.  2003,  13:  1231 
    Google Scholar
  • 6d Willardsen JA. Dudley DA. Cody WL. Chi L. McClanahan TB. Mertz TE. Potoczak RE. Narasimhan LS. Holland DR. Rapundalo ST. Edmunds JJ. J. Med. Chem.  2004,  47:  4089 
    Google Scholar
  • 6e Kishorebabu N. Periasamy M. Tetrahedron Lett.  2006,  47:  2107 
    Google Scholar
  • 7 Clayton JR, Diefenbacher CG, Engler TA, Furness KW, Henry JR, Malhotra S, Marquart AL, McLean JA, Mendel D, Burkholder TP, Li Y, and Reel JK. inventors;  WO03076442.  ; Chem. Abstr. 2003, 139, 261331
  • 8 Recently, the Friedel-Crafts acylation of benzene derivatives with ethyl oxalyl chloride was applied to the synthesis of ethyl arylglyoxylates, see: Xiang JM. Li BL. Chin. Chem. Lett.  2009,  20:  55 
    CrossrefGoogle Scholar
  • 9a Anisimova VA. Simonov AM. Chem. Heterocycl. Compd.  1976,  12:  110 
    Google Scholar
  • 9b Anisimova VA. Korochina TB. Avdyunina NI. Simonov AM. Chem. Heterocycl. Compd.  1986,  22:  275 
    Google Scholar
  • 9c Anisimova VA. Avdyunina NI. Simonov AM. Kovalev GV. Gofman SM. Chem. Heterocycl. Compd.  1976,  12:  1365 
    Google Scholar
  • 9d Kawamoto T. Tomimatsu K. Ikemoto T. Abe H. Hamamura K. Takatani M. Tetrahedron Lett.  2000,  41:  3447 
    Google Scholar
  • 9e Daly M. Hopkinson C. J. Chem. Soc., Perkin Trans. 1  1991,  855 
    Google Scholar
  • 10a Montgomery JA. Sechrist JA. In Comprehensive Heterocyclic Chemistry   Vol. 5:  Katritzky AR. Rees CW. Pergamon Press; Oxford: 1984.  p.608-668  
    Google Scholar
  • 10b Anisimova VA. Avdyunina NI. Pozharskii AF. Simonov AM. Talanova LN. Chem. Heterocycl. Compd.  1980,  16:  409 
    Google Scholar
  • 11 Tschitschibabin AE. Chem. Ber.  1926,  59:  2048 
    Google Scholar
  • 12 Djerassi C. Pettit GR. J. Am. Chem. Soc.  1954,  76:  4470 
    CrossrefGoogle Scholar
  • 13 Meakins GD. Musk SRR. Robertson CA. Woodhouse LS. J. Chem. Soc., Perkin Trans. 1  1989,  643 
    CrossrefGoogle Scholar
  • 14 Palagiano F. Arenare L. Luraschi E. de Caprariis P. Abignente E. D’Amico M. Filippelli W. Rossi F. Eur. J. Med. Chem.  1995,  30:  901 
    CrossrefGoogle Scholar