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Synthesis of 14 C‐labeled piperidines and application to synthesis of [ 14 C]SCH 351125, a CCR5 receptor antagonist
Author(s) -
Ren Sumei,
McNamara Paul,
Royster Pernilla,
Lee Jae,
Saluja Surinderjit S.,
Koharski David,
Hendershot Sharon,
Truong Van
Publication year - 2007
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.1306
Subject(s) - chemistry , iminium , piperidine , intramolecular force , stereochemistry , atropisomer , cationic polymerization , chemical synthesis , antagonist , yield (engineering) , medicinal chemistry , ion , receptor , organic chemistry , in vitro , biochemistry , materials science , metallurgy
1‐Benzyl‐4‐hydroxy[2‐ 14 C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [ 14 C]formaldehyde in high yield. The distribution pattern of 14 C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza‐Cope rearrangement. These steps precede the rate‐determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [ 14 C]SCH 351125, required for metabolism studies, was prepared from 1‐benzyl‐4‐hydroxy[2‐ 14 C]piperidine in six steps. [ 14 C]SCH 351125 is a mixture of four atropisomers. Preparation of [ 14 C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd.