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The synthesis of 7‐chloro‐5‐pentadeuteriophenyl‐1‐methyl‐1 h ‐1,5‐benzodiazepine‐2,4(3 H , 5 H )dione ([ 2 H 5 ]clobazam)
Author(s) -
Borel Anthony G.,
Abbott Frank S.
Publication year - 1990
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.2580280706
Subject(s) - chemistry , aniline , clobazam , nucleophilic substitution , deuterium , medicinal chemistry , d 1 , ring (chemistry) , nucleophile , nuclear magnetic resonance spectroscopy , stereochemistry , organic chemistry , catalysis , physics , quantum mechanics , neuroscience , epilepsy , biology , biochemistry , receptor
Pentadeuteriophenyl clobazam 5 was synthesized in essentially quantitative isotopic purity, and characterized by 1 H‐NMR and mass spectroscopy. The title compound was found to be ≥98% pure by HPLC, and its retention time (t R 6.17 min) was less than that of an authentic clobazam standard (t R 6.32 min). Of the five steps in the synthesis of 5 , the most susceptible to deuterium exchange was the nucleophilic substitution of 2,4‐dichloronitrobenzene by aniline‐d 7 to form N‐(5‐chloro‐2‐nitrophenyl)pentadeuteriophenylamine 2 . In this step, the isotopic impurity aniline‐2,3,4,5,‐d 5 introduced protons from nitrogen into the ortho and para positions of the deuteriophenyl ring of 2 .