Development of an Effective Scalable Enantioselective Synthesis of the HIV‑1 Entry Inhibitor BNM-III-170 as the Bis-trifluoroacetate Salt

We report here the development and optimization of a process synthesis for the human immunodeficiency virus-1 entry inhibitor BNM-III-170 bis-trifluoroacetate salt (1). The synthesis features a dynamic-kinetic resolution to establish the initial stereogenicity. By taking advantage of significant seq...

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Bibliographic Details
Published in:	Organic process research & development Vol. 23; no. 11; pp. 2464 - 2469
Main Authors:	Chen, Junhua, Park, Jun, Kirk, Sharon M, Chen, Hung-Ching, Li, Xiangqin, Lippincott, Daniel J, Melillo, Bruno, Smith, Amos B
Format:	Journal Article
Language:	English
Published:	American Chemical Society 15-11-2019
Subjects:	dynamic-kinetic resolution guanidine formation Gabriel amine synthesis CD4-mimetic HIV-1 entry inhibitor aminolysis
Online Access:	Get full text
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Summary:	We report here the development and optimization of a process synthesis for the human immunodeficiency virus-1 entry inhibitor BNM-III-170 bis-trifluoroacetate salt (1). The synthesis features a dynamic-kinetic resolution to establish the initial stereogenicity. By taking advantage of significant sequence modifications of our first-generation synthesis, in conjunction with the low solubility of late-stage intermediates, the overall efficiency of the synthesis has been significantly improved, now to proceed in an overall yield of 9.64% for the 16 steps, requiring only a single chromatographic separation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Junhua Chen and Jun Park contributed equally to this work.
ISSN:	1083-6160 1520-586X
DOI:	10.1021/acs.oprd.9b00353