Radiolabelling of NNC 05‐1869, a compound for treatment of diabetic neuropathy

Synthesis of ³H‐, ¹⁴C‐ and ¹²⁵I‐labelled NNC 05‐1869 is described. The ³H‐label was obtained by catalytic hydrogenation of a carbon–carbon double bond with tritium gas, which after purification yielded 470 µCi ³H]NNC 05‐1869 with a specific radioactivity of 36 Ci/mmol. ¹⁴C‐labelling was accomplished in three steps, including a chiral HPLC separation, starting from ethyl 3‐carboxyl‐¹⁴C]piperidinecarboxylate (1 ). The overall radiochemical yield was 1.5 mCi of carboxyl‐¹⁴C]NNC 05‐1869 (14%) with a specific radioactivity of 55 mCi/mmol. Electrophilic aromatic iododestannylation of the tin‐precursor NNC 47‐4310 with Na¹²⁵ I resulted in a cis/trans mixture, which was separated on RP‐HPLC to give the two isomers in 20% and 22%, yield, respectively. Copyright © 2002 John Wiley & Sons, Ltd.