170937-36-7Relevant articles and documents
Tritiation of SR141716 by metallation-iodination-reduction: Tritium-proton nOe study
Seltzman, Herbert H.,Carroll, F. Ivy,Burgess, Jason P.,Wyrick, Christopher D.,Burch, David F.
, p. 59 - 70 (2007/10/03)
The central cannabinoid receptor antagonist SR141716, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1 H-pyrazole-3-carboxamide, was synthesized from commercially available starting materials. Condensation of an aryl hydrazine with a diketone followed by base promoted isomerization/cyclization of the intermediate anti-imine gave the pyrazole acid which was converted to the title hydrazide via its acid chloride. Facile iodination via metallation followed by in situ trapping with an iodine source gave a modest yield of the iodinated SR 141716. The iodine was selectively reduced with tritium gas and catalyst while retaining the three aryl chlorine atoms in the structure. The tritiated SR 141716 exhibited a tritium-proton nOe both definitively identifying the position of the tritium as well as the sought isomer of the diarylpyrazole. This work provides a direct method for the preparation of preferred iodinated aryl substrates that offer advantages where selectivity and high incorporation in catalytic reduction is sought. Copyright
