An Efficient Undergraduate Synthesis of the Exorbitantly Priced Lambert–Eaton Myasthenic Syndrome Drug Amifampridine

• Augustine N. Vu ^[1] ; Santana P. Garcia ^[1] ; Jenny H. Tran ^[1] ; Adrian A. Godoy ^[1] ; Joaquin M. Mesa ^[1] ; Cassidy M. DiTirro ^[1] ; Kinsey L. Kotsch ^[1] ; Sarah E. Sullivan ^[1] ; Vincent J. Tavalez ^[1] ; Kateri A. Ahrendt ^[1]
  1. [1] Regis University

     Regis University

     Estados Unidos

     
• Localización: Journal of chemical education, ISSN 0021-9584, Vol. 100, Nº 2, 2023, págs. 914-920
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • An efficient synthesis of the exorbitantly priced Lambert–Eaton myasthenic syndrome drug amifampridine was developed and applied in the second-semester undergraduate organic chemistry laboratory. The two-step synthesis entails a nucleophilic aromatic substitution reaction of commercial 4-chloro-3-nitropyridine with methanolic ammonia to afford 4-amino-3-nitropyridine. Subsequent palladium-catalyzed nitro reduction provides amifampridine in high yield and purity. Amifampridine can alternatively be prepared by advanced undergraduate students in four linear steps beginning with 4-hydroxypyridine. Nitration of 4-hydroxypyridine to 4-hydroxy-3-nitropyridine and subsequent treatment with phosphoryl chloride provides the intermediate 4-chloro-3-nitropyridine, which is then subjected to the SNAr and reduction reactions to cleanly afford amifampridine without the need for column chromatography.