N-Arylation of indoles with 4-[¹⁸F]fluoroiodobenzene: synthesis of 18F-labelled σ₂ receptor ligands for positron emission tomography (PET)

Summary: The palladium-mediated N-arylation of indoles with 4-[¹⁸F]fluoroiodobenzene as a novel radiolabelling method has been developed. Optimized reaction conditions were elaborated by variation of different catalyst systems (CuI/1,2-diamines and Pd₂(dba)₃/phosphine ligands), based and solvents in the reaction of indole with 4-[¹⁸F]fluoroiodobenzene. Optimized reaction conditions (Pd₂(dba)₃/(2-(dicyclohexyl-phosphino)-2´-(N,N-dimethylamino)-biphenyl, NaOBu^t, toluene, 100 °C for 20 min) were applied for the synthesis of ¹⁸F-labelled σ₂ receptor ligands [¹⁸F]-11 and [¹⁸F]-13 which were obtained in 91 and 84 % radiochemical yields, respectively.