PDF herunterladen
Synthesis 2013; 45(24): 3399-3403
DOI: 10.1055/s-0033-1340008
paper
© Georg Thieme Verlag Stuttgart · New York

A Simple Synthesis of the Novel Antihistaminic Drug Olopatadine Hydrochloride­

Subhash P. Chavan*
Division of Organic Chemistry, CSIR-NCL (National Chemical Laboratory), Pune 411008, India   Fax: +91(20)5892629   eMail: sp.chavan@ncl.res.in
,
Pradeep B. Lasonkar
Division of Organic Chemistry, CSIR-NCL (National Chemical Laboratory), Pune 411008, India   Fax: +91(20)5892629   eMail: sp.chavan@ncl.res.in
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 04. Juli 2013

Accepted after revision: 18. September 2013

Publikationsdatum:
23. Oktober 2013 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik


Abstract

A new alternative route for the synthesis of olopatadine is described. The present strategy involves a Lewis acid mediated ring opening of a cyclic ether to introduce 3-(dimethylamino)propylidene group as the side chain.

Key words

antihistaminic drugs - chelates - zinc - spiro compounds - Lewis acids

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis. Included are copies of 1H and 13C NMR spectra for all new compounds and the HPLC chromatogram of 2.
  • Supporting Information
 

  • References

  • 1 McGrath NA, Njardarson JT. J. Chem. Educ. 2010; 87: 1348
    Crossref
    • 2a Ohshima E, Otaki S, Sato H, Kumazawa T, Obase H, Ishii A, Ishii H, Ohmori K, Hirayama N. J. Med. Chem. 1992; 35: 2074
      Crossref
    • 2b Sano T, Sugaya T, Kasai M. Org. Process Res. Dev. 1998; 2: 169
      Crossref
  • 3 Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han G, Kobayashi T, Stevens R, Iwata S. Nature 2011; 475: 65
    Crossref

      • For synthetic processes, see:
    • 4a Oshima E, Kumazawa T, Otaki S, Obase H, Ohmori K, Ishii H, Manabe H, Tamura T, Shuto K. US Patent US005116863, 1992 ; Chem Abstr. 1988, 108, 167330.
    • 4b Lever W, Leighton H. European Patent EP0214779, 1990 ; Chem Abstr. 1987, 107, 58673.
    • 4c Bosch C, Bachs R, Gomez A, Alonso M, Bessa A. Patent WO2006/010459, 2006; Chem Abstr. 2006, 144, 192128.
    • 4d Tarur V, Bhise N, Sathe D, Naidu A, Aher U, Patil S, Verma S, Sawant K, Naik T, Amre R. WO2007/105234 A2, 2007 ; Chem Abstr. 2007, 147, 371628.
    • 4e Castellin A, Ferrari C, Galvagni M. U.S. Patent US 2011/0065936 A1, 2011 ; Chem Abstr. 2010, 153, 554939.
  • 5 Bosch J, Bachs J, Gómez AM, Griera R, Écija M, Amat M. J. Org. Chem. 2012; 77: 6340
    Crossref
  • 6 Nishimura K, Kinugawa M. Org. Process Res. Dev. 2012; 16: 225
    Crossref
  • 7 Ueno K, Kubo S, Tagawa H, Yoshioka T, Tsukada W, Tsubokawa M, Kojima H, Kasahara A. J. Med. Chem. 1976; 19: 941
    Crossref
  • 8 Barbier P.  C. R. Acad. Sci. 1898; 128: 110
    • 9a Brown HC, Subba Rao BC. J. Am. Chem. Soc. 1956;  78: 5694
    • 9b Brown HC, Zweifel G. J. Am. Chem. Soc. 1959;  81: 247
  • 10 Recrystallization details: after two recrystallization using PE–EtOAc (9:1) system, compound 2 with E/Z = 2:3 ratio could be improved to E/Z = 1:9 ratio.