863249-47-2Relevant academic research and scientific papers
Practical Kilogram Synthesis of (S)-1-Benzyl-4-Bromo-3-Methyl-1,2,3,6-Tetrahydropyridine
Lombardo, Vincent M.,Bernier, Louise,Chen, Ming Z.,Farrell, William,Flick, Andrew,Nuhant, Philippe,Sach, Neal W.,Tao, Yong,Trujillo, John I.
, p. 2315 - 2322 (2021/10/21)
Despite chiral piperidines being a commonly found motif in approved drugs and drug candidates, the synthesis of these compounds occasionally suffers from challenges of scalability and stereochemical control. As part of a medicinal chemistry program, we sought access to a series of stereochemically pure 3,4-disubstituted piperidines. A classical ammonium salt resolution was investigated to furnish chiral (S)-1-benzyl-4-bromo-3-methyl-1,2,3,6-tetrahydropyridine as a valuable chiral precursor to C-3,4 di-substituted piperidines, which may have broader utility for other pharmaceutical intermediates. Specifically, in this work, in support of scale-up efforts for toxicology studies, we describe a practical synthesis to access kilogram quantities of enantiopure (S)-1-benzyl-4-bromo-3-methyl-1,2,3,6-tetrahydropyridine, utilizing a Shapiro reaction, followed by a classical salt resolution with an inexpensive chiral acid in high yield and enantioselectivity.
CHEMOKINE RECEPTOR ANTAGONISTS
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Page/Page column 28; 43, (2010/02/13)
A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof, wherein the variants R, R9, Z, X, Q and Y are defined in the specification.
