Premium
Synthesis of 7‐chloro‐1,3,‐dihydro‐3‐hydroxy‐1‐methyl‐5‐phenyl‐2h‐1,4‐benzodiazepin‐2‐one‐2‐ 14 c (2‐ 14 C‐temazepam)
Author(s) -
Dain Jeremy G.
Publication year - 1987
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.2580240504
Subject(s) - chemistry , thionyl chloride , acetic acid , acetic anhydride , amide , hydrolysis , benzophenone , chloride , temazepam , sulfuric acid , yield (engineering) , hydroxylamine , chloroacetic acid , medicinal chemistry , organic chemistry , benzodiazepine , receptor , metallurgy , biochemistry , materials science , catalysis
Temazepam‐2‐ 14 C, 7‐Chloro‐1,3,‐dihydro‐3‐hydroxy‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐one‐2‐ 14 C, was prepared in a five‐step synthesis. Chloroacetic‐1‐ 14 C acid was converted to the acid chloride with thionyl chloride. The acid chloride was allowed to react with 2‐methylamino‐5‐chloro‐benzophenone to form the amide. The amide was reacted with hydroxylamine and directly cyclized to the benzodiazepine N‐oxide which was converted to the acetate with acetic anhydride. The acetate was hydrolyzed with concentrated sulfuric acid to give the final product (3.8% radiochemical yield at 52. mCi/mmol). This procedure provides temazepam with the radiolabel in a metabolically stable position.