Emtricitabine (FTC), is a nucleoside reverse transcriptase inhibitor (NRTI) for the prevention and treatment of HIV. Access to this high volume WHO essential medicine is largely driven by the cost of the active pharmaceutical ingredient (API). 5-Fluorocytosine (5-FC) is a key starting material in the commercial synthesis of FTC and represents a major cost driver in the API process. A scalable route for 5-FC has been developed using inexpensive acyclic precursors, while avoiding the use of hazardous direct fluorination methods. In addition, this route takes advantage of a secure chemical supply chain, well known robust chemistry and high yielding reactions. Starting from chloroacetamide, proceeding through a key sodium (Z)-2-cyano-2-fluoroethen-1-olate, 5-fluorocytosine is isolated in 51% overall yield in 5 steps with 2 intermediate isolations and no column chromatography. The 40 – 60% reduction in cost of 5-FC will reduce the overall cost of FTC and improve global access to this life saving medication.

Synthesis of 5-fluorocytosine from acyclic precursors: Improving global access to emtricitibine

2019 Fall National Meeting

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