Synthesis and Characterization of the Biologically Active 2-[1-(4-Chlorobenzyl)-1H-indol-3-yl]-2-oxo-N-pyridin-4-yl Acetamide

Abstract

The spectroscopic characterization of the new potent tubulin inhibitor 2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxo-N-pyridin-4-yl acetamide (D-24851) (7), which is under preclinical development, is described. The synthesis was optimized and follows a straightforward route from the unsubstituted indole via the 1-(4-chlorobenzyl)-indole (3) and the indol-3-yl-2-oxo-acetyl chloride (5) to the indol-3-yl-2-oxo acetamide product. The structure was assigned by sophisticated NMR experiments, for example a 1,1-ADEQUATE experiment, and X-ray crystallography.