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Síntesis y funcionalización en etapa tardía de moléculas complejas a través de la fluoración C-H y la sustitución

Patrick S Fier¹, John F Hartwig

¹Department of Chemistry, University of California , Berkeley, California 94720, United States.

Journal of the American Chemical Society

|June 12, 2014

Resumen

Este estudio introduce un nuevo método para la funcionalización en etapa tardía de piridinas y diazinas. El proceso instala eficientemente diversos grupos químicos en importantes compuestos medicinales y productos farmacéuticos.

Área de la Ciencia:

Química orgánica es la química orgánica.
Química Medicinal La Química Medicinal es un campo de estudio de la química medicinal.
Química Heterocíclica La Química Heterocíclica es una de las más conocidas.

Sus antecedentes:

Las piridinas y diazinas multisubstituidas son estructuras centrales en muchos productos farmacéuticos.
La funcionalización en etapa tardía permite la modificación de moléculas complejas, mejorando el descubrimiento y desarrollo de fármacos.
Los métodos existentes para funcionalizar estos heterociclos a menudo carecen de eficiencia o amplia aplicabilidad.

Objetivo del estudio:

Desarrollar una nueva estrategia de funcionalización en etapa tardía para las piridinas y las diazinas.
Para permitir la instalación de diversos sustituyentes en la posición alfa al nitrógeno.
Proporcionar un método versátil aplicable a compuestos médicamente importantes y a la síntesis farmacéutica.

Principales métodos:

La estrategia combina la fluoración electrofílica con la sustitución aromática nucleofílica (S(N) Ar).
Los 2-fluoroheteroarenos se generan in situ y posteriormente reaccionan con varios nucleófilos.
Se optimizaron las condiciones de reacción leve para el paso S(N) Ar para garantizar un amplio alcance del sustrato.

Principales resultados:

Se logró una exitosa funcionalización en etapa tardía de piridinas y diazinas multisubstituidas.
Se instaló una amplia gama de grupos funcionales (N, O, S, C-bound) en la posición alfa.
El método demostró su aplicabilidad en la modificación de productos farmacéuticos existentes y la mejora de la eficiencia sintética.

Conclusiones:

La secuencia de fluoración-S(N) Ar desarrollada ofrece un enfoque poderoso y versátil para la funcionalización de heterociclos que contienen nitrógeno.
Este método facilita la síntesis de nuevos análogos de compuestos biológicamente activos.
Los hallazgos proporcionan un marco para la planificación estratégica de la funcionalización en etapa tardía en el desarrollo de fármacos.

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