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DOI: 10.1055/s-2007-966037
A New Approach to the Synthesis of the Nonpeptide NOP Receptor Antagonist J-113397
Publication History
Publication Date:
02 May 2007 (online)
Abstract
A new synthesis that eliminates the need for chromatographic separation in order to obtain multigram quantities of J-113397, a competitive antagonist of the N/OFQ-NOP receptor system, is reported. N-Benzyl protected 4-oxopiperidinecarboxylate was used as the starting material to obtain an N-benzyl intermediate that could be resolved at a relatively early stage in the synthesis. The crucial step in the synthesis was reduction of the double bond of the β-enaminoester functionality of 1-benzyl-4-(3-ethyl-2-oxo-2,3-dihydrobenzoimidazol-1-yl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester, since Pd/C reduction gave inseparable mixtures. It could be reduced and epimerized to the desired trans diastereoisomer in a one-pot reaction by treatment with magnesium metal in methanol.
Key words
NOP antagonist - receptor - synthesis - enantiomeric resolution - β-enaminoester reduction
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