perampanel 3/4 hydrate Chemische Eigenschaften,Einsatz,Produktion Methoden
Clinical Use
Perampanel is a selective, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
receptor (AMPAR) antagonist approved for partial-onset seizures in patients with epilepsy. Perampanel was discovered and developed by Eisai.
Synthese
A number of synthetic routes to perampanel have
been reported and the process scale route is described herein.Bromination of commercial 2-methoxypyridine (120) gave 5-bromo-2-methoxypridine 121 in 86%
yield (the scheme). Lithium halogen exchange was then accomplished by treating 121 with nbutyllithium
followed by reaction with 2-benzenesulfonylpyridine (122) to provide bi-aryl 123 which
was hydrolyzed under acidic conditions to give pyridine 124 in 60% overall yield. N-Arylation with
triphenylboroxine (125) in the presence of copper acetate afforded N-aryl pyridine 126 in 91% yield.
Pyridone 126 was reacted with N-bromosuccinimide to give bromopyridine 127 which was coupled
with 2-(1,3,2-dioxaborinan-2-yl)benzonitrile (128) under palladium catalyzed conditions to give
perampanel hydrate (XIX) in 86% yield after recrystallization from acetone/H2O.
perampanel 3/4 hydrate Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
