Preparation of pyridostigmine bromide labeled with carbon-14 and tritium

Abstract

[2‐14C]Pyridostigmine bromide was prepared in 17.6% radiochemical yield with specific activity of 18 mCi/mmol. The reaction sequence involved preparation of 2‐furan[14C]carboxylic acid by carbonation of 2‐lithiofuran, followed by conversion to 2‐amino[14C]methyl furan by lithium aluminum hydride reduction of its carboxamide. Oxidative rearrangement of 2‐amino[14C]methylfuran gave 3‐hydroxy[2‐14C]pyridine which was converted to [2‐14C]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 [14C]dimethylamine followed by quarternization with bromomethane. [6‐3H]‐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.