Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet¹
• Suzanne M. Opalka¹
• Brian S. Campbell¹
• B. Frank Gupton²
• Tyler McQuade¹

• ¹ Department of Chemistry and Biochemistry, Florida State University, United States
• ¹ Department of Chemistry, Virginia Commonwealth University, United States

2-Chloro-3-amino-4-picoline (CAPIC) is a strategic building block for the preparation of nevirapine, a widely-prescribed non-nucleosidic reverse transcriptase inhibitor for the treatment of HIV-infected patients. A continuous synthesis to the bromo derivative of a CAPIC intermediate, 2-bromo-4-methylnicotinonitrile, that terminates in a dead-end crystallization is described. The route uses inexpensive, acyclic commodity-based raw materials and has the potential to enable lower cost production of nevirapine as well as other value added structures that contain complex pyridines. The route terminates in a batch crystallization yielding high purity CAPIC. This outcome is expected to facilitate regulatory implementation of the overall process.

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