Fragment B of Lenacapavir

Synthesis of Fragment B of Lenacapavir

Medicines for All Institute (M4ALL) developed a 5-step route to make Fragment B (Frag B) that offers an overall raw material cost (RMC) reduction of 45-55%.

Key Assumptions

• Projected material cost reductions are significantly impacted by market dynamics for starting materials and reagents, and economies of scale related thereto. Please reach out to M4ALL for more information.
• The baseline route refers to the Gilead’s route described in the process development report below.

Scientific Highlights

• We report a 5-step synthesis of Frag B from inexpensive 2,6-dichlorobenzonitrile.
• Key steps include regioselective bromination, regioselective pyrazole formation and Grignard-mediated borylation.
• The process produces Frag B in approximately 12% overall yield without column purification, and has been demonstrated end-to-end on 100-gram scale.