Novel 2,4,5-Trisubstituted Pyridines as Key Intermediates for the Preparation of the TSPO Ligand 6-F-PBR28: Synthesis and Full ~1H and ~(13)C NMR Characterization

摘要

As part of our ongoing research for molecular structures binding to the translocator protein (TSPO 18 kDa), we investigated the preparation of a number of new 2,4,5-trisubstituted pyridines as novel building blocks. In particular, 5-amino-2-halo-4-phenoxypyridines (11–13) were designed as key intermediates for the synthesis of the recently developed TSPO ligand 6-F-PBR28 and its fluorine-18-labeled version for positron emission tomography, 6-[~(18)F]F-PBR28. We hereby report the chemical preparation as well as the ~1H and ~(13)C NMR spectroscopic data of polysubstituted pyridines 2–14. The latter demonstrates dramatic changes in electron density repartition of the aromatic ring upon substitution.