title: Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL 32306, United States.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Longstreet
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL 32306, United States.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Opalka
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL 32306, United States.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Campbell
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, P.O. Box 842006 Richmond, Virginia 23284, United States.
authors.forename: B Frank
authors.initials: BF
authors.lastname: Gupton
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL 32306, United States.
authors.forename: D Tyler
authors.initials: DT
authors.lastname: McQuade
keywords: HIV; Knoevenagel; continuous; flow chemistry; nevirapine; nicotinonitriles