Related Experiment Videos
Stereoselective Synthesis of HIV-1 Protease Inhibitor, DMP 323
Michael E. Pierce1, Gregory D. Harris, Qamrul Islam
1Chemical Proces R&D Department, Process Research Facility, The DuPont Merck Pharmaceutical Company, Deepwater, New Jersey 08023-0999, and Chemical & Physical Sciences Department, The DuPont Merck Pharmaceutical Company, Experimental Station, Wilmington, Delaware 19880-0500.
Abstract:
DMP 323, a potent HIV-1 protease inhibitor, has been synthesized by an efficient stereoselective process, amenable to large scale preparations. The core C(2) symmetric diol was synthesized by a stereoselective pinacol coupling of CBZ protected D-phenylalanine. Judicious selection of protecting groups allowed cyclic urea formation under mild conditions, enhanced the ease of bis-alkylation, and led to intermediates which were easily purified without chromatography. Additionally, a one-pot, high yield process was developed to prepare the alkylating agent, 4-[(triphenylmethoxy)methyl]benzyl chloride from 1,4-benzenedimethanol.