WO2010038167 Oxopiperidinyl and pyranyl sulfonamides as AMPA potentiators

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Scaffold: Tetrahydropyran

Biological target:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor: AMPA

Activity:

Positive allosteric modulators

Steps Conditions Reactions
a tBuOK, THF, -25oC, 1h Tetrahydropyran formation (trans cyclization)
b KOH, EtOH, H2O reflux, 16h Saponification (COOH formation)
c Diphenylphosphoryl azide, DIEA, Toluene, 85oC, 2h then 2N NaOH 2h Curtius rearrangement (Amine primaire formation)
d DBU, CH2Cl2, 16h N-Sulfonylation
e Chiral HPLC chromatography, chiralpak AD-H Ester reduction (OH formation)
f Pd(PPh3)4, Na2CO3, MeOH, 80oC, 16h Suzuki cross coupling reaction