Download PDF
Synthesis 2003(9): 1377-1382
DOI: 10.1055/s-2003-40209
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Novel Thieno- and Pyrrolo[2,3-d]pyrimidines peri-Fused with Pyrimidine­, 1,4-Diazepine and 1,4-Thiazepine Rings

Sigitas Tumkevicius*, Zivile Sarakauskaite, Viktoras Masevicius
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, 2006 Vilnius, Lithuania
Fax: +37(5)2330987; e-Mail: sigitas.tumkevicius@chf.vu.lt;
Further Information

Publication History

Received 25 February 2003
Publication Date:
24 June 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

An easy and efficient synthesis of the versatile, hitherto unreported alkyl 4-chloro- or 4-(alkoxycarbonylmethyl)amino(thio)-5-amino-2-methylthiothieno[2,3-d]- and pyrrolo[2,3-d]pyrimidine-6-carboxylates 3,5,6,8, from 6-chloro-4-(alkoxycarbonylmethylamino)-2-methylthiopyrimidine-5-carbonitriles 2a,b is described. Reaction of 5-amino-4-chloropyrrolo[2,3-d]pyrimidine 6 with sarcosine methyl ester gave the novel 2,3,5,6,9-pentaazabenz[cd]azulene 7. Heating 5-amino-4-(ethoxycarbonylmethylthio)pyrrolo[2,3-d]pyrimidine 5 in DMSO in the presence of potassium carbonate afforded the first representative of 6-thia-2,3,5,9-tetraazabenz[cd]azulene 9. Reaction of 5-amino-4-(alkoxycarbonylmethylamino)thieno- and pyrrolopyrimidines 3 and 8 with ethyl orthoformate or formalin in the presence of acids furnished the new 1-thia-3,5,6,8-tetraaza-, 1,3,5,6,8-pentaazaacenaphthylenes 10a,b and their 3,4-dihydro derivatives 11a,b. Acylation of 3 and 8 with chloroacetyl chloride gave the 5-chloroacetylamino intermediates 12a,b, which on heating in DMF in the presence of potassium carbonate cyclised to give the 2-thia-3,5,6,8-tetraaza- and 2,3,5,6,9-pentaazabenz[cd]azulene derivatives 13a,b.

Key words

cyclisations - heterocycles - amino acids - 2,3,5,6,9-pentaazabenz[cd]azulenes - 1-thia-3,5,6,9-tetraazabenz[cd]azulenes - 6-thia-1,3,5,9-tetraazabenz[cd]azulene - azaacenaphthylenes

    References

  • 1 Russel RK. Press JB. Rampulla RA. McNally JJ. Falotico R. Keiser JA. Bright DA. Tobia A. J. Med. Chem.  1988,  31:  1786 
    Google Scholar
  • 2 Russel RK. Rampulla RA. Van Nievelt CE. Klaubert DH. J. Heterocycl. Chem.  1990,  27:  1761 
    Google Scholar
  • 3 Modica M. Santagati M. Santagati A. Cutuli V. Mangano N. Caruso A. Pharmazie  2000,  55:  500 
    Google Scholar
  • 4 Panico A. Cardile V. Santagati A. Gentile B. Farmaco  2001,  56:  959 
    CrossrefGoogle Scholar
  • 5 Katada J. Iijima K. Muramatsu M. Takami M. Yasuda E. Hayashi M. Hattori M. Hayashi Y. Biorg. Med. Chem. Lett.  1999,  9:  797 
    Google Scholar
  • 6 Porcari AR. Ptak RG. Borysko KZ. Breitenbach JM. Vittori S. Wotring LL. Drach JC. Townsend LB. J. Med. Chem.  2000,  43:  2438 
    CrossrefGoogle Scholar
  • 7 El-Sherbenyl MA. El-Ashmawy MB. El-Emam HI. Badria FA. Eur. J. Med. Chem. Chim. Ther.  1995,  30:  445 
    Google Scholar
  • 8 Pauwels R. Andries K. Desmyter J. Schols D. Kukla MJ. Breslin HJ. Raeymaeckers A. Van Gelder J. Woestenborgs R. Haaykants J. Schellekens K. Janssen MAC. De Clercq E. Jannsen PAJ. Nature (London)  1990,  343:  470 
    CrossrefPubMedGoogle Scholar
  • 9 Bellarosa D. Antonelli G. Bambacioni F. Giannotti D. Viti G. Nannicini R. Giachetti A. Dianzani F. Witvrouw M. Pauwels R. Desmyter J. De Clercq E. Antiviral Res.  1996,  30:  109 
    CrossrefGoogle Scholar
  • 10 Taylor EC. Patel HH. Sabitha G. Chaudhari R. Heterocycles  1996,  43:  349 
    Google Scholar
  • 11 Rosowsky A. Papoulis T. Queener SF. J. Med. Chem.  1997,  40:  3694 
    CrossrefGoogle Scholar
  • 12 Tumkevicius S. Liebigs Ann. Chem.  1995,  1703 
    Google Scholar
  • 13 Tumkevicius S. Pupeikyte R. J. Chem. Res., Synop.  1995,  286 
    Google Scholar
  • 14 Tumkevicius S. Kaminskas A. Kulbokaite J. J. Chem. Res., Synop.  2000,  287 
    Google Scholar
  • 15 Tumkevicius S. Agrofoglio LA. Kaminskas A. Urbelis G. Zevaco TA. Walter O. Tetrahedron Lett.  2002,  43:  695 
    CrossrefGoogle Scholar
  • 16 Santilli AA. Kim DH. Wanser SV. J. Heterocycl. Chem.  1971,  8:  445 
    Google Scholar
  • 17 Wang Z. Neidlein R. Krieger C. Synthesis  2000,  255 
    Article in Thieme ConnectGoogle Scholar
  • 18 Clark J. Shahhet MS. Korakas D. Varvounis G. J. Heterocycl. Chem.  1993,  30:  1065 
    CrossrefGoogle Scholar
  • 19 Hirota K. Shirahashi M. Senda S. Yogo M. J. Heterocycl. Chem.  1990,  27:  717 
    Google Scholar
  • 20 Tumkevicius S. Masevicius V. Khim. Geterotsikl. Soedin.  1999,  35:  1577 ; Chem. Abstr. 2000, 133, 164037
    Google Scholar
  • 21 Schram KH. Townsend LB. Tetrahedron Lett.  1971,  49:  4757 
    Google Scholar