Premium
Methodes de Syntheses de l'idazoxan ‐ RX: 781094 [( Imidazolinyl‐2 ) ‐2‐Benzodioxanne‐1,4]Marque au Tritium a Haute Activite Specifique: Un Ligand Radioactif Antagoniste Selectif des α 2 ‐Adrenorecepteurs Presynaptiques
Author(s) -
Guillaumet G.,
Coudert G.,
Clement R.,
Ponchant P.,
Pichat L.
Publication year - 1986
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580230805
Subject(s) - chemistry , tritium , toluene , trifluoroacetic acid , nuclear chemistry , medicinal chemistry , ethylenediamine , organic chemistry , nuclear physics , physics
Four methods of syntheses of IDAZOXAN (RX 781094): |2‐(2‐imidazolinyl)‐1,4‐benzodioxane| labelled with tritium: 1 at high specific activity, a selective radioligand presynaptic α 2 ‐ adrenoreceptor antagonist are described. 2‐carbethoxy‐1,4‐benzodioxine 5 was treated with tritium in benzene in presence of Wilkinson's catalyst leading to 2‐carbethoxy [2,3‐ 3 H]‐1,4‐benzodioxane: 6 spec. act. 60 Ci/m which was then condensed in toluene with a reagent made from trimethylaluminium and ethylenediamine giving rise to 1 specific activity 44 Ci/mMole. 2‐(carbamido N‐cyanomethyl)1,4‐benzodioxine: 2 was prepared from 2‐chlorocarbonyl‐1,4‐benzodioxine: 10 and 2‐aminoacetonitrile. 2 was reduced with tritium in trifluoroacetic acid in presence of Pd/C giving 8 which, without purification was ring closed into 2 by trimethylaminium treatment. Spec. act. 35.5 Ci/mMole. When reduced with tritium in presence of Wilkinson's catalyst, 7 gave 9 spect. act. 55 Ci/mMole. After purification 9 was again reduced with tritium in trifluoroacetic acid in presence of Pd/C, or PtO 2 , or Rh/Al 2 O 3 giving 8 which was cyclised into 1 by trimethylaluminium treatment in toluene. spec. act. of 1 was 41.5 ‐ 39 Curies/mMole. 1 was purified by successive preparative thin layer chromatography. The radiochemical purity checked by TLC and PLC was better than 99%. Some observations on the rate of self radiolysis of 1 are reported.