PDF herunterladen
Synthesis 2010(10): 1593-1598  
DOI: 10.1055/s-0029-1218746
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 2-(2-Dialkylamino-4H-3,1-benzothiazin-4-yl)acetic Acid Derivatives and 2-(2-Thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetic Acid Derivatives

Shuhei Fukamachi, Hisatoshi Konishi, Kazuhiro Kobayashi*
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Fax: +81(857)315263; e-Mail: kkoba@chem.tottori-u.ac.jp;
Weitere Informationen

Publikationsverlauf

Received 5 January 2010
Publikationsdatum:
15. April 2010 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

An efficient method for the preparation of 2-(4H-3,1-benzothiazin-4-yl)acetic acid derivatives and 2-(2-thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetic acid derivatives has been developed. The reaction of 3-(2-isothiocyanatophenyl)propenoic acid derivatives with secondary amines in methanol at room temperature gave the corresponding thiourea intermediates, which on heating at reflux temperature cyclized by an attack of the sulfur atom on the propenoic moiety in a 1,4-addition manner, to give 2-(2-dialkylamino-4H-3,1-benzothiazin-4-yl)acetic acid derivatives in one pot. A similar sequence using primary amines in place of secondary amines afforded 2-[3-alkyl(or aryl)-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-yl]acetic acid derivatives.

Key words

4H-3,1-benzothiazines - 2-thioxo-1,2,3,4-tetrahydroquinazolines - 3-(2-isothiocyanatophenyl)propenoic acids - thioureas - 1,4-addition

    References

  • 1a Schilling S, Cynis H, Hoffmann T, and Demuth H.-U. inventors; US Pat. Appl. US  068699.  ; Chem. Abstr. 2009, 150, 322579
  • 1b Anzini M, Giordani A, Makovec F, Cappelli A, Vomero S, Caselli G, Rovati G, and Lucio C. inventors; PCT Int. Pat. Appl.  040331.  ; Chem. Abstr. 2009, 150, 374522
  • 1c Reynisson J. Court W. O’Neill C. Day J. Patterson L. McDonald E. Workman P. Katan M. Eccles SA. Bioorg. Med. Chem.  2009,  17:  3169 
    Google Scholar
  • 1d Anthes JC, McCormick KD, Hey JA, Aslanian RG, Biju PJ, Berlin MY, Solomon DM, Wang DM, Wang H, Lim Y.-H, Lee YJ, and Bitar R. D. inventors; PCT Int. Pat. Appl. WO  085879.  ; Chem. Abstr. 2009, 151, 124232
  • 1e Nielsen M, Liljefors T, Nilsson J, and Sterner O. inventors; PCT Int. Pat.  Appl. WO 123536.  ; Chem. Abstr. 2009, 151, 425736
  • 2a Beilenson B. Hamer FM. J. Chem. Soc.  1942,  98 
    Google Scholar
  • 2b Besson T. Guillaumet G. Lamazzi C. Rees CW. Thiery V. J. Chem. Soc., Perkin Trans. 1  1998,  4057 
    Google Scholar
  • 2c El-Desoky SI. Kandeel EM. Abd-el-Rahman AH. Schmidt RR. J. Heterocycl. Chem.  1999,  36:  153 
    Google Scholar
  • 2d Hari A. Miller BL. Org. Lett.  2000,  2:  3667 
    Google Scholar
  • 2e Femandes MA. Reid DA. Synlett  2003,  2231 
    Google Scholar
  • 3 After completion of our work, we became aware of a report by Gimbert and Vallribera, which describe a synthesis of 2-[2-alkyl(or aryl)-4H-3,1-benzothiazin-4-yl]acetic acid derivatives by the reaction of 3-(2-acylamino­-phenyl)propenoic acid derivatives with Lawesson’s reagent in refluxing toluene: Gimbert C. Vallribera A. Org. Lett.  2009,  11:  269 
    CrossrefGoogle Scholar
  • 4a Hasegawa H. Muraoka M. Ohmori M. Matsui K. Kojima A. Bioorg. Med. Chem.  2005,  13:  3721 
    Google Scholar
  • 4b Sarli V. Huemmer S. Sunder-Plassmann N. Mayer TU. Giannis A. ChemBioChem  2005,   6:   2005 
    Google Scholar
  • 4c Peters J.-U. Luebbers T. Alanine A. Kolczewski S. Blasco F. Steward L. Bioorg. Med. Chem. Lett.  2008,   18:   256 
    Google Scholar
  • 4d Peters J.-U. Luebbers T. Alanine A. Kolczewski S. Blasco F. Steward L. Bioorg. Med. Chem. Lett.  2008,   18:   262 
    Google Scholar
  • 5a Pflegel P. Kuehmstedt C. Richter P. Pharmazie  1981,   36:  65 
    Google Scholar
  • 5b Richter P. Oertel F. Pharmazie  1990,  45:  721 
    Google Scholar
  • 5c Pfeiffer WD. Pazdera P. Hetzheim A. Muecke J. Pharmazie  1995,  50:  21 
    Google Scholar
  • 6 Fujiwara S. Shin-Ike T. Sonoda N. Aoki M. Okada K. Miyoshi N. Kambe N. Tetrahedron Lett.  1991,  32:  3503 
    CrossrefGoogle Scholar
  • 7 Xiao W.-J. Alper H. J. Org. Chem.  1999,  64:  9646 
    CrossrefGoogle Scholar
  • 8 Hays SJ. Caprathe BW. Gilmore JL. Amin N. Emmerling MR. Michael W. Nadimpalli R. Nath R. Raser KJ. Stafford D. Watson D. Wang K. Jaen JC. J. Med. Chem.  1998,  41:  1060 
    CrossrefPubMedGoogle Scholar
  • 9 Kobayashi K. Yoneda K. Miyamoto K. Morikawa O. Konishi H. Tetrahedron  2004,  60:  11639 
    CrossrefGoogle Scholar
  • 10 Ziegler CB. Heck RF. J. Org. Chem.  1978,  43:  2941 
    CrossrefGoogle Scholar
  • 11 Tokuyama H. Kaburagi Y. Chen X. Fukuyama T. Synthesis  2000,  429 
    Artikel in Thieme ConnectGoogle Scholar
  • 12 Ito Y. Kobayashi K. Seko N. Saegusa T. Bull. Chem. Soc. Jpn.  1984,  54:  73 
    Google Scholar