A General Approach to Indoles: Practical Applications for the Synthesis of Highly Functionalized Pharmacophores
DOI:
https://doi.org/10.2533/chimia.2006.543Keywords:
Dihydrobenzofuran, Indole, Nitrostyrene, Reductive cyclizationAbstract
The development of a long-term manufacturing route to a potent and selective KDR kinase inhibitor has led to the discovery of several novel methodologies for the general synthesis of indoles. The key transformations involved addition of a trimethylsilylnitro benzene to an aromatic aldehyde which afforded the key nitroalcohol intermediate. Oxidation of the nitroalcohol intermediate led to a nitroketone; whereas, elimination afforded exclusively a trans-nitrostyrene. Reductive cyclization gave the target compounds in excellent overall yield from readily available bulk chemicals. Application of this methodology has led to the synthesis of highly functionalized pharmacophores including other KDR kinase inhibitors, biindoles and tjipanazole natural products, indolo[2,3-a]pyrrolo [3,4-c]carbazoles, indole-4-carboxylic amides, N-hydroxyindoles, and 2,3-dihydrobenzofurans.Downloads
Published
2006-09-01
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Scientific Articles
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Copyright (c) 2006 Swiss Chemical Society
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How to Cite
[1]
J. T. Kuethe, Chimia 2006, 60, 543, DOI: 10.2533/chimia.2006.543.