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Synthese de L'Acide [Pyridinyl‐2‐( 14 C‐2,6) Dithio]‐3 Propanoique Reactif de Couplage Covalent
Author(s) -
Noel J. P.,
Pichat L.
Publication year - 1983
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.2580201105
Subject(s) - chemistry , pyridine , medicinal chemistry , acetic anhydride , nuclear chemistry , propanoic acid , hydrolysis , organic chemistry , catalysis
3‐([2,6‐ 14 C]2‐pyridinyldithio) propanoic acid, a disulphide covalent coupling reagent was synthesized in 12 steps from sodium [ 14 C] cyanide. Condensation of sodium [ 14 C] cyanide with 1,3‐dibromopropane gave, after hydrolysis [1,5‐ 14 C] glutaric acid: 4 which was converted into [1,5‐ 14 C] glutarimide : 5 by heating at 280°C with anhydrous ammonia. The imide : 5 was then converted into [2, 6‐ 14 C] 2, 6‐dichloropyridine: by 6 by treatment with phosphorous penta and trichlorides. Chlorine removal from 6 by hydrogen (Roney Nickel) gave [2, 6‐ 14 C] pyridine: 7 which was isolated as the hydrochloride. The latter was tranformed into [2, 6‐ 14 C] pyridine‐N‐oxide : 11 by hydrogen peroxide treatment. 11 treated by acetic anhydride (15 hours ‐ 130°C) rearranged into 2‐acetyloxy [2, 6‐ 14 C] pyridine: 12 which was hydrolysed into [2, 6‐ 14 C] 2‐pyridone: 13 . Thiation of the latter by P 2 S 5 in xylene gave 2‐mercapto [2, 6‐ 14 C] pyridine: 10 which was then oxidized into [2, 6‐ 14 C] 2‐dipyridinyldisuplphide: 14 the chlorination of which lead to [2, 6‐ 14 C] 2‐pyridinylsulfenyl chloride: 15 which was not isolated. It was condensed with 3‐mercapto propanoic acid to give 1 with an overall yield of 4% based on sodium cyanide ‐ Specific activity was 55 mCi/mMol. The radiochemical purity checked by TLC and HPLC was 98.7%.