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Synfacts 2014; 10(12): 1239
DOI: 10.1055/s-0034-1379407
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of BMS-663068

Contributor(s):
Philip Kocienski
Eastgate MD * Bristol-Myers Squibb, New Brunswick, USA
Synthesis of the 6-Azaindole Containing HIV-1 Attachment Inhibitor Pro-Drug, BMS-663068.

J. Org. Chem. 2014;
79: 8757-8767
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Further Information

Publication History

Publication Date:
18 November 2014 (online)

 
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Key words

BMS-663068 - HIV attachment inhibitors - 6-azaindoles - Ullmann–Goldberg–Buchwald coupling - bromination

Significance

Attachment inhibitor BMS-663068 is currently in clinical development for the treatment of HIV infection. Key steps in the synthesis depicted are (1) a radical-mediated redox-aromatization to generate the 6-azaindole (B → C) and (2) the regioselective bromination of an N-oxide using PyBroP (D → E).


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Comment

High regioselectivity was observed in the copper(I)-mediated Ullmann–Goldberg–Buchwald coupling (H → K) using the diamine ligand J (N1/N2 = 22:1), whereas a thermal SNAr reaction gave N1/N2 = 1:1. Alternative conditions for the bromination of the N-oxide D led mainly to deoxygenation.


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