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Synthesis 2011(20): 3323-3331  
DOI: 10.1055/s-0030-1260217
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Convenient One-Pot Synthesis of Functionalized Thieno[3,2-d]pyrimidine and Thieno[2,3-d]pyrimidine Derivatives

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

Received 7 June 2011
Publication Date:
08 September 2011 (online)

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Abstract

A versatile one-pot method was developed for the preparation of a range of functionalized thieno[3,2-d]pyrimidine and thieno[2,3-d]pyrimidine derivatives. This protocol significantly reduces the cost and time for the synthesis of these compounds in comparison with previous routes, while facilitating scale up to multigram quantities in good yields (66-99%). The technique also permits the synthesis of bis(thienopyrimidine) derivatives not readily available by other methods.

Key words

heterocycles - domino reaction - Wittig reaction - bicyclic compounds - cyclization

    References

  • For reviews on the synthesis and biological activity of thienopyridines, see:
  • 1a Litvinov VP. Dotsenko VV. Krivokolysko SG. Russ. Chem. Bull.  2005,  54:  864 
    Search in Google Scholar
  • 1b Bakhite EA.-G. Phosphorus, Sulfur Silicon Relat. Elem.  2003,  178:  929 
    Search in Google Scholar
  • 2 Madding GD. Thompson MD. J. Heterocycl. Chem.  1987,  24:  581 
    Search in Google Scholar
  • 3a Chambhare RV. Khadse BG. Bobde AS. Bahekar RH. Eur. J. Med. Chem.  2003,  38:  89 
    Search in Google Scholar
  • 3b Vieweg H, Leitsner S, Wagner G, Boehm N, Krasset U, Grupe R, Lohmann D, and Loban G. inventors; DD  257830.  ; Chem. Abstr. 1988, 110, 95262
  • 3c Vieweg H, Leitsner S, Wagner G, Boehm N, Krasset U, Grupe R, Lohmann D, and Loban G. inventors; DD  258234.  ; Chem. Abstr. 1988, 110, 95263
  • 4a Alagarsamy V. Meena S. Ramseshu KV. Solomon VR. Thirumurugan K. Dhanabal K. Murugan M. Eur. J. Med. Chem.  2006,  41:  1293 
    Search in Google Scholar
  • 4b Leitsner S. Wagner G. Gnetscharo M. Glusa E. Pharmazie  1986,  41:  54 
    Search in Google Scholar
  • 4c Chaykovsky M. Lin M. Rosowsky A. Modest EJ. J. Med. Chem.  1973,  16:  188 
    Search in Google Scholar
  • 5a Dave CG. Shah PR. Dave KC. Patel VJ.
    J. Indian Chem. Soc.  1989,  66:  48 
    Search in Google Scholar
  • 5b Bousquet E. Romera G. Guerrera F. Caruso A. Roxas MA. Farmaco, Ed. Sci.  1985,  40:  869 
    Search in Google Scholar
  • 5c Bousquet E. Guerrera F. Siracusa NA. Caruso A. Roxas MA. Farmaco, Ed. Sci.  1984,  39:  110 
    Search in Google Scholar
  • 6a Lilienkampf A. Karkola S. Alho-Richmond S. Koskimies P. Johansson N. Huhtinen K. Vihko K. Wähälä K. J. Med. Chem.  2009,  52:  6660 
    Search in Google Scholar
  • 6b Cheng CC. Prog. Med. Chem.  1989,  35 
  • 7a Dai Y. Guo Y. Frey RR. Ji Z. Curtin ML. Ahmed AA. Albert DH. Arnold L. Arries SS. Barlozzari T. Bauch JL. Bouska JJ. Bousquet PF. Cunha GA. Glaser KB. Guo J. Li J. Marcotte PA. Marsh KC. Moskey MD. Pease LJ. Stewart KD. Stoll VS. Tapang P. Wishart N. Davidsen SK. Michaelides MR. J. Med. Chem.  2005,  48:  6066 
    Search in Google Scholar
  • 7b Munchhof MJ. Beebe JS. Casavant JM. Cooper BA. Doty JL. Higdon RC. Hillerman SM. Soderstron CI. Knauth EA. Marx MA. Rossi AMK. Sobolov SB. Sun J. Bioorg. Med. Chem. Lett.  2004,  14:  21 
    Search in Google Scholar
  • 7c Duval E. Case A. Stein RL. Cuny GD. Bioorg. Med. Chem. Lett.  2005,  15:  1885 
    Search in Google Scholar
  • 8 Horiuchi T. Chiba J. Uoto K. Soga T. Bioorg. Med. Chem. Lett.  2009,  19:  305 
    CrossrefSearch in Google Scholar
  • 9a Witty DR. Bateson J. Hervieu G. Al-Barazanji K. Jeffrey P. Hamprecht D. Haynes A. Jonson CN. Muir AI. O’Hanlon PJ. J. Heterocycl. Chem.  1992,  29:  1693 
    Search in Google Scholar
  • 9b Stemp G. Stevens AJ. Thewlis K. Winborn KY. Bioorg. Med. Chem. Lett.  2006,  16:  4872 
    Search in Google Scholar
  • 9c Zhang M. Tamiya J. Nguyen L. Rowbottom MW. Dyck B. Vickers TD. Grey J. Schwartz DA. Heise CH. Halewyn J. Mistry MS. Goodfellow VA. Bioorg. Med. Chem. Lett.  2007,  17:  2535 
    Search in Google Scholar
  • 9d Tavares FX. Al-Barazanji KA. Bigham EC. Bishop MJ. Britt CS. Carlton DL. Feldman PL. Goetz AS. Grizzle MK. Guo YC. Handlon AL. Hertzog DL. Ignar DM. Lang DG. Ott RJ. Peat AJ. Zhou H.-Q. J. Med. Chem.  2006,  49:  7095 
    Search in Google Scholar
  • 9e Deng Y. Zhou X. Desmoulin SK. Wu J. Cherian C. Hou Z. Matherly LH. Gangjee A. J. Med. Chem.  2009,  52:  2940 
    Search in Google Scholar
  • 10a Martínez-Poveda B. Muñoz-Chápuli R. Rodríguez-Nieto S. Quintela JM. Fernández A. Medina MA. Quesada AR. Mol. Cancer Ther.  2007,  6:  2675 
    Search in Google Scholar
  • 10b Quintela JM. González L. Devesa I. Ferrándiz ML. Alcaraz MJ. Riguera R. Bioorg. Med. Chem.  2003,  11:  863 
    Search in Google Scholar
  • 10c Rioja I. Ubeda A. Terencio MC. Guillén I. Riguera R. Quintela JM. Peinador C. González L. Alcaraz MJ. Eur. J. Pharmacol.  2000,  397:  207 
    Search in Google Scholar
  • 10d Quintela JM. Peinador C. González LM. Riguera R. Rioja I. Terencio MC. Ubeda A. Alcaraz MJ. J. Med. Chem.  1999,  42:  4720 
    Search in Google Scholar
  • 10e Quintela JM. Peinador C. Veiga MC. Botana LM. Alfonso A. Riguera R. Eur. J. Med. Chem.  1998,  33:  887 
    Search in Google Scholar
  • 11a Quintela JM. Peinador C. González L. Iglesias R. Paramá A. Alvarez F. Sanmartín M. Riguera R. Eur. J. Med. Chem.  2003,  38:  265 
    Search in Google Scholar
  • 11b Paramá A. Iglesias R. Álvarez F. Leiro JM. Quintela JM. Peinador C. González L. Riguera R. Sanmartín ML. Dis. Aquat. Org.  2004,  62:  97 
    Search in Google Scholar
  • For examples, see:
  • 12a Zhang Z. Zhang Q. Sun S. Xiong T. Liu Q. Angew. Chem. Int. Ed.  2007,  46:  1726 
    Search in Google Scholar
  • 12b Chapman CJ. Frost CG. Synthesis  2007,  1 ; and references cited therein
  • 12c Elliot GI. Velcicky J. Ishikawa H. Li Y. Boger DL. Angew. Chem. Int. Ed.  2006,  45:  620 
    Search in Google Scholar
  • For reviews on heterocyclic synthesis by the aza-Wittig methodology, see:
  • 13a Palacios F. Alonso C. Aparicio D. Rubiales G. de los Santos JM. Tetrahedron  2007,  63:  523 
    Search in Google Scholar
  • 13b Fresneda PM. Molina P. Synlett  2004,  1 
  • 13c Eguchi S. Okano T. Okawa T. Recent Res. Dev. Org. Chem.  1997,  337 
  • 13d Wamhoff H. Richardt G. Stöben G. Adv. Heterocycl. Chem.  1995,  64:  159 
    Search in Google Scholar
  • 13e Molina P. Vilaplana MJ. Synthesis  1994,  1197 
  • 13f Eguchi S. Matshushita Y. Yamashita K. Org. Prep. Proced. Int.  1992,  24:  209 
    Search in Google Scholar
  • 13g Gololobov YG. Kasukhin LF. Tetrahedron  1992,  48:  1353 
    Search in Google Scholar
  • 13h Gussar NI. Russ. Chem. Rev.  1991,  60:  146 
    Search in Google Scholar
  • 14a Blanco G. Fernández-Mato A. Quintela JM. Peinador C. Synthesis  2009,  438 
  • 14b Blanco G. Quintela JM. Peinador C. Synthesis  2008,  1397 
  • 14c Blanco G. Quintela JM. Peinador C. Tetrahedron  2007,  63:  2034 
    Search in Google Scholar
  • 14d Peinador C. Ojea V. Quintela JM. J. Heterocycl. Chem.  1992,  29:  1693 
    Search in Google Scholar
  • The iminophosphorane synthesis is known as the Appel method, i.e., the modified Kirsanov reaction; see:
  • 15a Appel R. Halstenberg M. In Organophosphorous Reagents in Organic Synthesis   Cadogan J. I. G. Academic Press; London: 1979.  p.378 
  • The synthesis has often been used in the literature as well, for example:
  • 15b Okawa T. Eguchi S. Tetrahedron  1998,  54:  5853 
    Search in Google Scholar
  • 15c Álvarez-Sarandés R. Peinador C. Quintela JM. Tetrahedron  2001,  57:  5413 
    Search in Google Scholar
  • 15d Peinador C. Moreira MJ. Quintela JM. Tetrahedron  1994,  50:  6705 
    Search in Google Scholar
  • 16a Ding M.-W. Xu Sh.-Zh. Zhao J.-F. J. Org. Chem.  2004,  69:  8366 
    Search in Google Scholar
  • 16b Vázquez D. Peinador C. Quintela JM. Tetrahedron  2004,  60:  275 
    Search in Google Scholar
  • 16c Quintela JM. Álvarez-Sarandés R. Peinador C. Tetrahedron  1998,  54:  8107 
    Search in Google Scholar
  • 17a Blanco G. Quintela JM. Peinador C. Tetrahedron  2008,  64:  1033 
    Search in Google Scholar
  • 17b Blanco G. Seguí N. Quintela JM. Peinador C. Chas M. Toba R. Tetrahedron  2006,  62:  11124 
    Search in Google Scholar
  • 18a Quintela JM. Peinador C. González L. Devesa I. Ferrándiz ML. Alcaraz MJ. Riguera R. Bioorg. Med. Chem.  2003,  11:  863 
    Search in Google Scholar
  • 18b Quintela JM. Peinador C. Veiga C. González L. Botana LM. Alfonso A. Riguera R. Bioorg. Med. Chem.  1998,  6:  1911 
    Search in Google Scholar
  • 18c Quintela JM. Peinador C. Botana LM. Estévez M. Riguera R. Bioorg. Med. Chem.  1997,  5:  1543 
    Search in Google Scholar
  • 18d Peinador C. Quintela JM. Moreira MJ. Tetrahedron  1997,  53:  8269 
    Search in Google Scholar
  • 18e Quintela JM. Peinador C. Moreira MJ. Tetrahedron  1995,  31:  5901 
    Search in Google Scholar