Synthesis of the 6-Azaindole Containing HIV-1 Attachment Inhibitor Pro-Drug, BMS-663068
The Journal of Organic Chemistry2014Vol. 79(18), pp. 8757–8767
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Ke Chen, Christina A. Risatti, Michael Bultman, Maxime Soumeillant, James H. Simpson, Bin Zheng, Dayne Fanfair, Michelle Mahoney, Boguslaw Mudryk, Richard J. Fox, Yi Hsaio, Saravanababu Murugesan, David A. Conlon, Frédéric G. Buono, Martin D. Eastgate
Abstract
The development of a short and efficient synthesis of a complex 6-azaindole, BMS-663068, is described. Construction of the 6-azaindole core is quickly accomplished starting from a simple pyrrole, via a regioselective Friedel-Crafts acylation, Pictet-Spengler cyclization, and a radical-mediated aromatization. The synthesis leverages an unusual heterocyclic N-oxide α-bromination to functionalize a critical C-H bond, enabling a highly regioselective copper-mediated Ullmann-Goldberg-Buchwald coupling to install a challenging triazole substituent. This strategy resulted in an efficient 11 step linear synthesis of this complex clinical candidate.
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