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Synthesis of stable‐isotope‐labeled N ‐(3‐dimethylaminopropyl)‐ N ′‐ethylcarbodiimide and N ‐(3‐dimethylaminopropyl)‐ N ′‐ethylurea
Author(s) -
Cao Kai,
Brailsford John A.,
Bonacorsi Samuel J.
Publication year - 2020
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.3877
Subject(s) - chemistry , carbodiimide , reagent , mass spectrometry , chromatography , radiochemistry , isotope , medicinal chemistry , nuclear chemistry , organic chemistry , physics , quantum mechanics
Summary N ‐(3‐Dimethylaminopropyl)‐ N ′‐ethylcarbodiimide (EDC) is a carbodiimide coupling reagent commonly used for the preparation of amides from carboxylic acids and amines. Because of initial concerns regarding the genotoxicity of EDC and its use in GMP syntheses at Bristol Myers Squibb, the quantitation of residual EDC and its by‐product N ‐(3‐dimethylaminopropyl)‐ N ′‐ethylurea (EDU) by liquid chromatography–mass spectrometry (LCMS) impurity analysis was required. These analyses required the use of stable‐isotope‐labeled EDC and EDU to serve as internal standards. To meet this need, stable‐isotope‐labeled EDC 9 and EDU 10 were prepared from [1,2‐ 13 C 2 ] ethylene glycol and [ 13 C, 15 N] potassium cyanide in overall yields of 6% and 8%, respectively.