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Synthesis 2011(6): 943-953  
DOI: 10.1055/s-0030-1258432
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis and Characterization of Substituted Pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidines and Related Molecules

Antonio Fernández-Mato, Carlos Peinador*, José M. Quintela*
Departamento de Química Fundamental, Facultad de Ciencias, Universidade da Coruña, Campus A Zapateira, A Coruña 15008, Spain
Fax: +34(981)167065; e-Mail: carlos.peinador@udc.es; e-Mail: jose.maria.quintela@udc.es;
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Publication History

Received 14 December 2010
Publication Date:
10 February 2011 (online)

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Abstract

An efficient access for the synthesis of substituted pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidines and pyrazino[2′,3′:4,5]thieno[3,2-d]-1,2,3-triazines, heteroaromatic nitrogen ligands, is reported. The title compounds were obtained by functionalization of the corresponding chloro precursors, synthesized by reaction between 7-aminothieno[2,3-b]pyrazine-6-carbonitrile and N,N-dimethyldichloromethyleniminium chloride (Viehe’s salt) or sodium nitrite/hydrochloric acid, respectively. Moreover, this procedure provided a convenient synthetic route to bis(pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidines), functionalized molecules that are not readily available by other synthetic methods.

Key words

heterocycles - ligands - ring closure - antitumor agents - fused-ring systems

    References

  • 1a Pitt RW. Parry DM. Perry BG. Groom CR.
    J. Med. Chem.  2009,  52:  2952 
    Google Scholar
  • 1b Carr RAE. Congreve M. Murray CW. Rees DC. Drug Discovery Today  2005,  10:  987 
    Google Scholar
  • For recent contributions, see:
  • 2a Haraguchi K. Kubota Y. Tanaka H. J. Org. Chem.  2004,  69:  1831 
    Google Scholar
  • 2b Depecker G. Patino N. Giorgio CD. Terreux R. Cabrol-Bass D. Bailly C. Aubertin A.-M. Condom R. Org. Biomol. Chem.  2004,  2:  74 
    Google Scholar
  • 3a Palacios F. Alonso C. Amezua P. Rubiales G. J. Org. Chem.  2002,  67:  1941 ; and references cited therein
    Google Scholar
  • 3b Renslo AR. Danheiser RL. J. Org. Chem.  1998,  63:  7840 
    Google Scholar
  • 3c Neuschütz K. Velker J. Neier R. Synthesis  1998,  227 
    Google Scholar
  • 3d Ihara M. Fukumoto K. Nat. Prod. Rep.  1997,  14:  413 
    Google Scholar
  • 3e Taylor EC. Dowling JE. J. Org. Chem.  1997,  62:  1599 ; and pertinent references cited therein
    Google Scholar
  • 3f Jones G. In Comprehensive Heterocyclic Chemistry II   Vol. 5:  Katritzky AR. Rees CW. Scriven EFV. McKillop A. Pergamon; Oxford: 1996. 
    Google Scholar
  • 3g Oikawa T. Kanomata N. Tada M. J. Org. Chem.  1993,  58:  2046 
    Google Scholar
  • For examples, see:
  • 4a Chambhare RV. Khadse BG. Bobde AS. Bahekar RH. Eur. J. Med. Chem.  2003,  38:  89 
    Google Scholar
  • 4b Sishoo CJ. Shirsath VS. Rathod IS. Yande VD. Eur. J. Med. Chem.  2000,  35:  351 
    Google Scholar
  • 4c Walter H. inventors; WO  9,914,202.  ; Chem. Abstr. 1999, 130, 252368k
    Google Scholar
  • 4d Varvounis G. Giannopoulos T. Adv. Heterocycl. Chem.  1996,  66:  193 
    Google Scholar
  • For recent reviews on the synthesis, properties and biological activity of thienopyridines, see:
  • 4e Backhite EA.-G. Phosphorus, Sulfur Silicon Relat. Elem.  2003,  178:  929 
    Google Scholar
  • 4f Litvinov VP. Dotsenko VV. Krivokolysko SG. Russ. Chem. Bull.  2005,  54:  864 
    Google Scholar
  • 5a Quintela JM. González L. Devesa I. Ferrándiz ML. Alcaraz MJ. Riguera R. Bioorg. Med. Chem.  2003,  11:  863 
    Google Scholar
  • 5b Quintela JM. Peinador C. Moreira MJ. Alfonso A. Botana LM. Riguera R. Eur. J. Med. Chem.  2001,  36:  321 
    Google Scholar
  • 5c Quintela JM. Peinador C. Veiga C. González L. Botana LM. Alfonso A. Riguera R. Bioorg. Med. Chem.  1998,  6:  1911 
    Google Scholar
  • 6a Martínez-Poveda B. Muñoz-Chápuli R. Rodríguez-Nieto S. Quintela JM. Fernndez A. Medina MA. Quesada AR. Mol. Cancer Ther.  2007,  6:  2675 
    Google Scholar
  • 6b Rioja I. Ubeda A. Terencio MC. Guillén I. Riguera R. Quintela JM. Peinador C. González L. Alcaraz MJ. Eur. J. Pharmacol.  2000,  397:  207 
    Google Scholar
  • 6c Quintela JM. Peinador C. González LM. Rioja I. Terencio MC. Ubeda A. Alcaraz MJ. Riguera R. J. Med. Chem.  1999,  42:  4720 
    Google Scholar
  • 7 Quintela JM. Peinador C. González L. Iglesias R. Paramá A. Alvarez F. Sanmartín M. Riguera R. Eur. J. Med. Chem.  2003,  38:  265 
    CrossrefGoogle Scholar
  • 8 Chill L. Aknin M. Kashman Y. Org. Lett.  2003,  5:  2433 
    CrossrefGoogle Scholar
  • 9a Pettit GR. Tan R. Xu J. Ichihara Y. Williams MD. Boyd MR. J. Nat. Prod.  1998,  61:  955 
    Google Scholar
  • 9b Immamura N. Nishijima M. Takadera T. Adachi K. Sakai M. Sano H. J. Antibiot.  1997,  50:  8 
    Google Scholar
  • 10a Baker DC. Hand ES. Plowman J. Rampal JB. Safavy A. Haugwitz RD. Narayanan VL. Anti-Cancer Drug Des.  1987,  2:  297 
    Google Scholar
  • 10b For a recent review, see: Pawar VG. De Borggraeve WH. Synthesis  2006,  2799 
    Google Scholar
  • 11 Burns CJ, Wil ks AF, and Bu X. inventors; WO  2005,054,230. For a recent example, see: ; Chem. Abstr. 2005, 143, 60004o
  • 12a Abboto A. Bradamante S. Facchetti A. Pagani GA. J. Org. Chem.  2002,  67:  5753 
    Google Scholar
  • 12b Wang S. Coord. Chem. Rev.  2001,  215:  79 
    Google Scholar
  • 12c Balzani V. Juris A. Venturi M. Campagna S. Serroni S. Chem. Rev.  1996,  96:  759 
    Google Scholar
  • 12d Di Bella S. Chem. Soc. Rev.  2001,  30:  355 
    Google Scholar
  • 13a Schubert US. Hofmeier H. Newkome GR. Modern Terpyridine Chemistry   Wiley-VCH; Weinheim: 2006. 
    Google Scholar
  • 13b Chelucci G. Thummel RP. Chem. Rev.  2002,  102:  3129 
    Google Scholar
  • 13c Fache F. Schulz E. Thommasino ML. Lemaire M. Chem. Rev.  2000,  100:  2159 
    Google Scholar
  • 14 Garas AMS. Vagg RS. J. Heterocycl. Chem.  2000,  37:  151 ; and references cited therein
    CrossrefGoogle Scholar
  • 15a Encyclopedia of Supramolecular Chemistry   Atwood JL. Steed JW. Marcel Dekker; New York: 2004. 
    Google Scholar
  • 15b Steed JW. Atwood JL. Supramolecular Chemistry   John Wiley & Sons; New York: 2000. 
    Google Scholar
  • 15c Lehn J.-M. Supramolecular Chemistry: Concepts and Prospectives   VCH; Weinheim: 1995. 
    Google Scholar
  • 15d Steel PJ. Acc. Chem. Res.  2005,  38:  243 
    Google Scholar
  • 16a Blanco G. Fernández-Mato A. Quintela JM. Peinador C. Synthesis  2009,  438 
    Google Scholar
  • 16b Blanco G. Fernández-Mato A. Quintela JM. Peinador C. Tetrahedron  2008,  64:  11136 
    Google Scholar
  • 16c Fernández-Mato A. Blanco G. Quintela JM. Peinador C. Tetrahedron  2008,  64:  3446 
    Google Scholar
  • 16d Blanco G. Quintela JM. Peinador C. Synthesis  2007,  1397 
    Google Scholar
  • 16e Blanco G. Quintela JM. Peinador C. Tetrahedron  2007,  63:  2034 
    Google Scholar
  • 16f Blanco G. Seguí N. Quintela JM. Peinador C. Chas M. Toba R. Tetrahedron  2006,  62:  11124 
    Google Scholar
  • 16g Blanco G. Quintela JM. Peinador C. J. Heterocycl. Chem.  2006,  43:  1051 
    Google Scholar
  • 17 Johnston DBR. inventors; US  4,442,095. 
  • 18 Schneller SW. Clough FW. J. Heterocycl. Chem.  1975,  12:  513 
    CrossrefGoogle Scholar
  • 19 For a review see: Janousek Z. Viehe HG. In Iminium Salts in Organic Chemistry, Advances in Organic Chemistry: Chemistry of Dichloromethyleniminium Salts (Phosgeniminium Salts)   Vol. 9:  Böhme H. Viehe HG. John Wiley & Sons; New York: 1976.  p.343 
    Google Scholar
  • 20a Peinador C. Quintela JM. Moreira MJ. Tetrahedron  1997,  53:  8269 
    Google Scholar
  • 20b Kokel B. Menichi G. Hobar-Habart M. Tetrahedron Lett.  1984,  25:  1557 
    Google Scholar
  • 21 Guillot N. Viehe HG. Tinault B. DeClerq JP. Tetrahedron  1990,  46:  3897 
    CrossrefGoogle Scholar
  • 22 Bemis GW. Murcko MA. J. Med. Chem.  1996,  39:  2887 
    CrossrefPubMedGoogle Scholar
  • 23a Quintela JM. Peinador C. Veiga MC. Botana LM. Alfonso A. Riguera R. Eur. J. Med. Chem.  1998,  33:  887 
    Google Scholar
  • 23b Beck JR. Yahner JA. J. Org. Chem.  1976,  41:  1733 
    Google Scholar
  • 24a Hotze ACG. Bacac M. Velders AH. Jansen BAJ. Kooijman H. Spek AL. Haasnoot JG. Reedijk J.
    J. Med. Chem.  2003,  46:  1743 
    Google Scholar
  • 24b Dimmock JR. Vashishtha SC. Quali JW. Pugazhenthi U. Zimple Z. Sudom AM. Allen TM. Kao GY. Balzarini J. DeClercq E. J. Med. Chem.  1999,  42:  4012 
    Google Scholar
  • 24c Buckley RG. Elsome AM. Fricker SP. Henderson GR. Theobald BRC. Parish RV. Howe BP. Kelland LR. J. Med. Chem.  1996,  39:  5208 
    Google Scholar