Lenacapavir API | Medicines for All Institute

Synthesis of Sodium Salt Lenacapavir API

Medicines for All Institute (M4ALL) demonstrated a telescoped 3-step route to make sodium salt lenacapavir API that offers an overall raw material cost (RMC) reduction of 20-30%.

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.
Key advanced fragments A, B, and C are synthesized in accordance with the M4ALL Y1 Len PDRs. The raw material cost (RMC) for each fragment is derived from its respective synthesis route.
The baseline route corresponds to Gilead’s process, as outlined in the process development report provided below.

Scientific Highlights

We demonstrate a telescoped Heck-Suzuki sequence for the synthesis of lenacapavir sodium salt API.
The key transformations include a one-pot Pd-catalyzed Heck-Suzuki coupling, H2SO4-promoted Boc-deprotection, and T3P-mediated late-stage amidation.
Process development of this 3-step strategy enables the production of lenacapavir sodium salt API in 50-55% overall isolated yield, demonstrated at scales up to 50 grams.