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Synthesis of a deuterium labeled variant of the rat hepatocarcinogen, methapyrilene
Author(s) -
Kammerer R. Craig,
Kloc Kenneth
Publication year - 1987
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.2580241209
Subject(s) - chemistry , thiophene , methylene , yield (engineering) , medicinal chemistry , dimethylformamide , deuterium , derivative (finance) , acetyl chloride , methylamine , aldehyde , imine , organic chemistry , physics , quantum mechanics , solvent , economics , financial economics , metallurgy , catalysis , materials science
Methapyrilene, I, once a commonly found antihistamimic drug, has been synthesized with four deuterium labels, three of which are on the thiophene ring. Initially, thiophene was deuterated by solvolysis of the tetramercuric acetate‐derivative with deuterium chloride. Carbonylation of the thiophene ring at the 2‐position, by the addition of dimethylformamide to the 2‐lithio‐derivative, gave [3,4,5‐d 3 ] thiophene‐2‐carboxaldehyde. Condensation of this aldehyde with 2‐aminopyridine was followed by reduction of the resulting imine with sodium borodeuteride to yield the N‐([3,4,5‐d 3 ]‐2‐thienyl[d]‐methylene)‐2‐aminopyridine, VIII. Alkylation of the lithium salt of VIII with dimethylaminoethylchloride gave N, N‐dimethyl‐N'‐[2‐pyridyl]‐N'‐([3,4,5‐d 3 ]‐2‐thienyl‐[d]methylene)‐1,2‐ethane diamine, I, in good yield. Combustion analysis, 500 mHz NMR, and mass spectrometry confirmed the identity of the product which will be useful for metabolic studies.