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Multiple Site Hydrogen Isotope Labelling of Pharmaceuticals
Author(s) -
DanielBertrand Marion,
GarciaArgote Sébastien,
Palazzolo Alberto,
Mustieles Marin Irene,
Fazzini PierFrancesco,
Tricard Simon,
Chaudret Bruno,
Derdau Volker,
Feuillastre Sophie,
Pieters Grégory
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202008519
Subject(s) - chemistry , iridium , labelling , aniline , combinatorial chemistry , carbazole , nitrile , pyridine , indole test , deuterium , tryptamine , organic chemistry , catalysis , biochemistry , physics , quantum mechanics
Radiolabelling is fundamental in drug discovery and development as it is mandatory for preclinical ADME studies and late‐stage human clinical trials. Herein, a general, effective, and easy to implement method for the multiple site incorporation of deuterium and tritium atoms using the commercially available and air‐stable iridium precatalyst [Ir(COD)(OMe)] 2 is described. A large scope of pharmaceutically relevant substructures can be labelled using this method including pyridine, pyrazine, indole, carbazole, aniline, oxa‐/thia‐zoles, thiophene, but also electron‐rich phenyl groups. The high functional group tolerance of the reaction is highlighted by the labelling of a wide range of complex pharmaceuticals, containing notably halogen or sulfur atoms and nitrile groups. The multiple site hydrogen isotope incorporation has been explained by the in situ formation of complementary catalytically active species: monometallic iridium complexes and iridium nanoparticles.