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14 C‐labeling of a tetrahydroacridine, a novel CNS‐selective cholinesterase inhibitor
Author(s) -
Nishioka Kazuhiko,
Kamada Takeshi,
Kanamaru Hiroshi
Publication year - 1992
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.2580310707
Subject(s) - chemistry , thionyl chloride , citric acid , ammonia , chloride , nuclear chemistry , medicinal chemistry , organic chemistry
9‐Amino‐8‐fluoro‐2, 4‐methano‐1,2,3,4‐tetrahydroacridine citrate (SM‐10888), a novel cholinesterase inhibitor, was labeled with carbon‐14 at C9 of the tetrahydroacridine ring for use in metabolic studies. Carbonation of 2,6‐difluorophenyllithium ( 3 ) with [ 14 C]carbon dioxide gave the acid ( 4 ). Chlorination of 4 followed by treatment of the resulting acid chloride with ammonia afforded the amide ( 5 ). Dehydration of 5 with thionyl chloride and subsequent displacement reaction with ammonia gave the aminobenzonitrile ( 7 ). Condensation of 7 with the ketone ( 8 ) in the presence of anhydrous zinc chloride yielded the aminoacridine ( 9 ), which was treated with citric acid to afford [9‐ 14 C]SM‐10888 ( 1 ). The overall yield of 1 was 37% from 2 , and the specific activity was 1.35 GBq/mmol.