Abstract

The Medicines for All Initiative: A Flow-based Synthesis of Nevirapine

Frank Gupton, Professor, Virginia Commonwealth University

The Medicines for All Initiative employs an interdisciplinary approach to chemical process development that holistically examines the chemical structure of drug targets and determines a set of low cost starting materials that can be used to assemble the molecule. The team then defines the best chemistry and technology to develop the lowest cost manufacturing route. Continuous automation and system monitoring capabilities are integrated with the new chemistry to further reduce direct costs, which provides an agnostic platform for active pharmaceutical ingredient (API) process development. These principals were applied towards the development of a low cost process for nevirapine, the active ingredient in a widely prescribed treatment for HIV-infected patients. The streamlined synthesis includes the preparation of the two pyridine precursors from very low cost raw materials. The condensation of the two pyridine fragments and subsequent cyclization into the drug substance is carried out in a single unit operation in high yield.