Premium
Synthesis of 7‐chloro‐1,3‐dihydro‐5‐(2‐fluorophenyl)‐1‐methyl‐2H‐1,4‐benzodiazepin‐2‐one‐5‐ 14 C (fludiazepam‐ 14 C)
Author(s) -
Nakatsuka Iwao,
Kawahara Kazuo,
Kamada Takeshi,
Shono Fumiaki,
Yoshitake Akira
Publication year - 1977
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.2580130401
Subject(s) - chemistry , phosphorus pentoxide , yield (engineering) , medicinal chemistry , amide , carbonation , aqueous solution , carbonic acid , phosphorus , bicarbonate , nuclear chemistry , carbon dioxide , organic chemistry , metallurgy , materials science
7‐Chloro‐1,3‐dihydro‐5‐(2‐fluorophenyl)‐1‐methyl‐2H‐1,4‐benzodiazepin‐2‐one (Fludiazepam) (I), an anti‐anxiety agent, was labelled with carbon‐14 at C‐5 position for metabolic studies. The reaction sequence for the synthesis is shown in Fig. 2. o‐Fluorobenzoic‐ 14 C acid (IV) was prepared in 65% yield by carbonation of o‐fluorophenyllithium with carbon‐ 14 C dioxide. The acid (IV) was condensed with N‐(4‐chlorophenyl)‐N‐ methylethylenediamine, followed by Bischler‐Napieralski cyclization of the resulting amide with phosphorus pentoxide and phosphorus oxychloride to afford 7‐chloro‐2,3‐dihydro‐5‐(2‐fluorophenyl)‐1‐methyl‐1H‐1,4‐benzodiazepine‐5‐ 14 C (VII) in good yield. Oxidation of VII by N‐bromosuccinimide in aqueous solution of sodium bicarbonate gave Fludiazepam‐ 14 C (I). The overall yield of I was 24% from barium carbonate‐ 14 C.