Synthesis of Pyrazinothienopyrimidine Derivatives by the Application of the Intramolecular and Intermolecular Aza-Wittig Reaction/Heterocyclization

 

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Abstract

Pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidine derivatives 6 were synthesized by the intermolecular aza-Wittig reaction of N-heteroaryl phosphazene derivatives with carboxylic acid chlorides. The heterocyclization occurs via imidoyl chloride intermediates derived from phosphazenes 4a,b, obtained in a one-step process from α-azidothieno[2,3-b]pyrazine carboxylic acid 3. Moreover, cyclic pyrazinothienopyrimidines were prepared, in a two-step procedure, from amides and azidothienopyrazine-α-carbonyl chloride using an intramolecular aza-Wittig heterocyclization reaction strategy.

References

• For recent contributions, see:
• 1a Cushman M. Sambaiah T. Jin G. Illarionov B. Fischer M. Bacher A. J. Org. Chem.  2004,  69:  601 
  CrossrefSearch in Google Scholar
• 1b Haraguchi K. Kubota Y. Tanaka H. J. Org. Chem.  2004,  69:  1831 
  CrossrefSearch in Google Scholar
• 1c Depecker G. Patino N. Giorgio CD. Terreux R. Cabrol-Bass D. Bailly C. Aubertin A.-M. Condom R. Org. Biomol. Chem.  2004,  2:  74 
  CrossrefSearch in Google Scholar
• For reviews on the synthesis and biological activity of thienopyridines, see:
• 2a Litvinov VP. Dotsenko VV. Krivokolysko SG. Russ. Chem. Bull. Int. Ed.  2005,  54:  864 
  CrossrefSearch in Google Scholar
• 2b Bakhite EA.-G. Phosphorus, Sulfur, Silicon Relat. Elem.  2003,  178:  929 
  CrossrefSearch in Google Scholar
• 3a Chambhare RV. Khadse BG. Bobde AS. Bahekar RH. Eur. J. Med. Chem.  2003,  38:  89 
  CrossrefPubMedSearch in Google Scholar
• 3b Walter H. inventors; WO Patent  9914202.  ; Chem. Abstr. 1999, 130, 252368
  CrossrefPubMed
• 4a Sishoo CJ. Shirsath VS. Rathod IS. Yande VD. Eur. J. Med. Chem.  2000,  35:  351 
  Search in Google Scholar
• 4b Santagati M. Modica M. Santagati A. Russo F. Spampinato S. Pharmazie  1996,  51:  7 
  Search in Google Scholar
• 5a Quintela JM. Peinador C. González L. Devesa I. Ferrándiz ML. Alcaraz MJ. Riguera R. Biorg. Med. Chem.  2003,  11:  863 
  CrossrefSearch in Google Scholar
• 5b Quintela JM. Peinador C. González L. Iglesias R. Paramá A. Alvarez F. Sanmartín M. Riguera R. Eur. J. Med. Chem.  2003,  38:  265 
  CrossrefSearch in Google Scholar
• 5c Rioja I. Ubeda A. Terencio MC. Guillén I. Riguera R. Quintela JM. Peinador C. González L. Alcaraz MJ. Eur. J. Pharmacol.  2000,  397:  207 
  CrossrefSearch in Google Scholar
• 5d Quintela JM. Peinador C. González LM. Rioja I. Terencio MC. Ubeda A. Alcaraz MJ. Riguera R. J. Med. Chem.  1999,  42:  4720 
  CrossrefSearch in Google Scholar
• 5e Quintela JM. Peinador C. Veiga C. González L. Botana LM. Alfonso A. Riguera R. Bioorg. Med. Chem.  1998,  6:  1911 
  CrossrefSearch in Google Scholar
• 5f Quintela JM. Peinador C. Veiga MC. Botana LM. Alfonso A. Riguera R. Eur. J. Med. Chem.  1998,  33:  887 
  CrossrefSearch in Google Scholar
• 5g Peinador C. Ojea V. Quintela JM. J. Heterocycl. Chem.  1992,  29:  1693 
  CrossrefSearch in Google Scholar
• 6a Chill L. Aknin M. Kashman Y. Org. Lett.  2003,  5:  2433 
  CrossrefSearch in Google Scholar
• 6b Pettit GR. Tan R. Xu J. Ichihara Y. Williams MD. Boyd MR. J. Nat. Prod.  1998,  61:  995 
  CrossrefSearch in Google Scholar
• 6c Immamura N. Nishijima M. Takadera T. Adachi K. Sakai M. Sano H. J. Antibiot.  1997,  50:  8 
  CrossrefSearch in Google Scholar
• 7a Baker DC. Hand ES. Plowman J. Rampal JB. Safavy A. Haugwitz RD. Narayanan VL. Anticancer Drug Des.  1987,  2:  297 
  Thieme ConnectSearch in Google Scholar
• 7b For a recent review, see: Pawar VG. De Borggraeve WH. Synthesis  2006,  2799 
  Thieme Connect
• 8 Burns CJ, Wilks AF, and Bu X. inventors; WO Patent  2005054230. For a recent example, see: ; Chem. Abstr. 2005, 143, 60004
• For reviews, see:
• 9a Palacios F. Alonso C. Aparicio D. Rubiales G. de los Santos JM. Tetrahedron  2007,  63:  523 
  Thieme ConnectSearch in Google Scholar
• 9b Palacios F. Aparicio D. Rubiales G. Alonso C. de los Santos JM. Curr. Org. Chem.  2006,  10:  2371 
  Thieme ConnectSearch in Google Scholar
• 9c Eguchi S. Top. Heterocycl. Chem.  2006,  6:  113 
  Thieme ConnectSearch in Google Scholar
• 9d Eguchi S. ARKIVOC  2005,  (ii):  98 
  Thieme ConnectSearch in Google Scholar
• 9e Arqués A. Molina P. Curr. Org. Chem.  2004,  8:  827 
  Thieme ConnectSearch in Google Scholar
• 9f Fresneda PM. Molina P. Synlett  2004,  1 
  Thieme Connect
• 10a Blanco G. Quintela JM. Peinador C. Tetrahedron  2007,  63:  2034 
  CrossrefSearch in Google Scholar
• 10b Blanco G. Seguí N. Quintela JM. Peinador C. Chas M. Toba R. Tetrahedron  2006,  62:  11124 
  CrossrefSearch in Google Scholar
• 10c Vázquez D. Peinador C. Quintela JM. Tetrahedron  2004,  60:  275 
  CrossrefSearch in Google Scholar
• 10d Álvarez-Sarandés R. Peinador C. Quintela JM. Tetrahedron  2001,  57:  5413 
  CrossrefSearch in Google Scholar
• 11 Okawa T. Toda M. Eguchi S. Kakehi A. Synthesis  1998,  1467 
  Thieme Connect
• 12 Molina P. Conesa C. Velasco MD. Liebigs Ann./Recl.  1997,  107 
• 13 Wamhoff H. Hermann S. Stölben S. Nieger M. Tetrahedron  1993,  49:  581 
  CrossrefSearch in Google Scholar
• 14 Ding M.-W. Huang N.-Y. He H.-W. Synthesis  2005,  1601 
  Thieme Connect
• 15 Zbiral E. Bauer E. Stroh J. Monatsh. Chem.  1971,  102:  168 
  CrossrefSearch in Google Scholar
• 16 Lowe-Ma CK. Nissan RA. Wilson WS. J. Org. Chem.  1990,  55:  3755 
  CrossrefSearch in Google Scholar
• 18 Sheldrick GM. SHELXL-97 Program   University of Göttingen; Germany: 1997. 

Crystallographic data (excluding structure factors) for 6b and 9a have been deposited with the Cambridge Crystallographic Data Center as supplementary publication numbers 6b: CCDC 668435, and 9a: CCDC 668436. Copies of the data may be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: +44 1223 33603 or e-mail: deposit@ccdc.cam.ac.uk).