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 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.