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Facile synthesis of stable isotope‐labeled antibacterial agent RWJ‐416457 and its metabolite
Author(s) -
Lin Ronghui,
Weaner Larry E.
Publication year - 2012
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.2936
Subject(s) - chemistry , metabolite , amide , dimethyl sulfate , sodium methoxide , acetamide , stereochemistry , pyridine , amine gas treating , chemical synthesis , ring (chemistry) , medicinal chemistry , organic chemistry , catalysis , biochemistry , in vitro
Synthesis of multiple stable isotope‐labeled antibacterial agent RWJ‐416457, ( N ‐{3‐[3‐fluoro‐4‐(2‐methyl‐2,6‐dihydro‐4 H ‐pyrrolo[3,4‐c]pyrazol‐5‐yl)‐phenyl]‐2‐oxo‐oxazolidin‐5‐ylmethyl}‐acetamide), and its major metabolite, N ‐{3‐[4‐(2,6‐dihydro‐4 H ‐pyrrolo[3,4‐c]pyrazol‐5‐yl)‐3‐fluoro‐phenyl]‐2‐oxo‐oxazolidin‐5‐ylmethyl}‐acetamide, is described. The stable isotope‐labeled [ 13 CD 3 ]RWJ‐416457 was prepared readily by acetylation of the precursor amine, 5‐aminomethyl‐3‐[3‐fluoro‐4‐(2‐methyl‐2,6‐dihydro‐4H‐pyrrolo[3,4‐c]pyrazol‐5‐yl)‐phenyl]‐oxazolidin‐2‐one with CD 3 13 COCl in pyridine. Synthesis of the stable isotope‐labeled metabolite involved a construction of multiple isotope‐labeled pyrazole ring. N , N ‐dimethyl(formyl‐ 13 C,D)amide dimethyl acetal was first prepared by treating N , N ‐dimethyl(formyl‐ 13 C,D)amide with dimethyl sulfate, followed by sodium methoxide. Then, N ‐{3‐[3‐fluoro‐4‐(3‐oxo‐pyrrolidin‐1‐yl)‐phenyl]‐2‐oxo‐oxazolidin‐5‐ylmethyl}‐acetamide was condensed with N , N ‐dimethyl(formyl‐ 13 C,D)amide dimethyl acetal, and the resultant β ‐ketoenamine intermediate underwent pyrazole ring formation with hydrazine‐ 15 N 2 , to give the [ 13 C 15 N 2 D]‐labeled metabolite. Copyright © 2012 John Wiley & Sons, Ltd.