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Preparation of pyridostigmine bromide labeled with carbon‐14 and tritium 1
Author(s) -
Kepler J. A.,
Twine C. E.,
Austin R. D.
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.2580310808
Subject(s) - chemistry , bromide , pyridostigmine , yield (engineering) , medicinal chemistry , bromine , tritium , carbamate , radiochemistry , organic chemistry , nuclear chemistry , medicine , myasthenia gravis , materials science , metallurgy , physics , nuclear physics
Abstract [2‐ 14 C]Pyridostigmine bromide was prepared in 17.6% radiochemical yield with specific activity of 18 mCi/mmol. The reaction sequence involved preparation of 2‐furan[ 14 C]carboxylic acid by carbonation of 2‐lithiofuran, followed by conversion to 2‐amino[ 14 C]methyl furan by lithium aluminum hydride reduction of its carboxamide. Oxidative rearrangement of 2‐amino[ 14 C]methylfuran gave 3‐hydroxy[2‐ 14 C]pyridine which was converted to [2‐ 14 C]pyridostigmine bromide by reaction with dimethylcarbamyl chloride and quarternization with bromomethane. Pyridostigmine bromide labeled in the methyl group of the carbamate function was prepared in 73% yield with specific activity of 37.6 mCi/mmol by reaction of bis‐3‐pyridyl carbonate with [ 14 C]dimethylamine followed by quarternization with bromomethane. [6‐ 3 H]‐Pyridostigmine bromide with specific activity of 22.5 mCi/mmol was prepared by catalytic halogen‐tritium replacement of 2,6‐dibromo‐3‐dimethylcarbamyloxypyridine followed by quarternization with bromomethane and back‐exchanging the labile 2‐tritium.