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

作者：Junhua Chen, Jun Park, Sharon Kirk, Hung-Ching Chen, Xiangqin Li, Daniel J. Lippincott, Bruno Melillo, Amos B. Smith · 发表于：Organic Process Research & Development · 年份：2019 · DOI：10.1021/acs.oprd.9b00353 · 被引用次数：26 · 研究领域：Chemical Synthesis and Analysis、HIV/AIDS drug development and treatment、Asymmetric Hydrogenation and Catalysis

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.