A nine‐step synthesis of [ 14 C]flupirtine maleate labeled in the pyridine ring

A nine‐step procedure for microscale synthesis of ethyl 2‐amino‐6‐{[(4‐fluorophenyl)methyl]amino}‐3‐pyridinyl‐2,6‐ 14 C carbamate maleate [ 10 ], [ 14 C]flupirtine maleate, was developed. The synthesis started with the readily avaiable and economical reagents, potassium cyanide‐ 14 C and 1,3‐dibromopropane making the following intermediates: glutaronitrile‐ 14 C [ 2 ], glutarimide‐ 14 C [ 3 ], 2,6‐dichloropyridine‐2,6‐ 14 C [ 4 ], 2,6‐dichloro‐3‐nitro‐pyridine‐2,6‐ 14 C [ 5 ], 2‐amino‐3‐nitro‐6‐chloropyridine‐2,6‐ 14 C [ 6 ], 2‐amino‐3‐nitro‐6‐( p ‐fluorobenzylamino)pyridine‐2,6‐ 14 C [ 7 ], 2,3‐diamino‐6‐( p ‐fluoro‐benzylamino)pyridine‐2,6‐ 14 C [ 8 ], and ethyl 2‐amino‐6‐{[4‐fluoropheny(l)‐methyl]amino}‐3‐pyridinyl‐2,6‐ 14 C carbamic acid ester hydrochloride [ 9 ]. The overall yield was 6.3% (5.4 mCi), and the radioactivity was 99.8% as determined by high performance liquid chromatogrphy and liquid scintillation counting.