Synthesis of tritiated N1′-alkyl derivatives of the delta opioid receptor ligand naltrindole

Tritiated N1′-methyl and N1′-ethyl analogues of naltrindole (NTI) have been synthesized for evaluation as radioligands for studies of delta opioid receptors. The two N1′-alkyl-5′,7′-dibromoNTI precursors for radiolabeling were prepared by base-promoted alkylation of 2,4-dibromophenylhydrazine with either iodomethane or iodoethane followed by condensation with naltrexone using the Fischer indole synthesis. Catalytic debromotritiation followed by HPLC purification afforded [3H]MeNTI (17.3 Ci/mmol) and [3H]EtNTI (22.5 Ci/mmol) with high chemical and radiochemical purities (≥ 99.8%).