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 Na125I 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.