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%).