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Identification of unexpected unlabeled N,N ‐dimethylamide formation in the synthesis of deuterated fragment of ribociclib by a HATU‐mediated coupling reaction
Author(s) -
Gai Kuo,
Liu Baomin,
Zhang Yinsheng
Publication year - 2019
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3690
Subject(s) - chemistry , dimethylamine , reagent , deuterium , hexafluorophosphate , combinatorial chemistry , stereochemistry , organic chemistry , ionic liquid , physics , quantum mechanics , catalysis
Starting from N,N ‐dimethylamine and D 2 O, deuterated fragment of ribociclib was synthesized for use as a mass spectroscopy internal standard. Furthermore, systematic studies on D 0 (unlabeled material) formation during the amidation reaction were performed, leading to the identification of a coupling reagent, HATU ( O ‐(7‐azabenzotriazol‐1‐yl)‐ N,N,N′,N ′‐tetramethyluronium hexafluorophosphate), as main cause. Finally, an alternative route was designed using EDCI/HOBT as coupling reagents to produce the desired deuterated compound without D 0 residue.