Beilstein Journal of Organic Chemistry (Nov 2013)

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

  • Ashley R. Longstreet,
  • Suzanne M. Opalka,
  • Brian S. Campbell,
  • B. Frank Gupton,
  • D. Tyler McQuade

DOI
https://doi.org/10.3762/bjoc.9.292
Journal volume & issue
Vol. 9, no. 1
pp. 2570 – 2578

Abstract

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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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