Pictet-Spengler based synthesis of a bisarylmaleimide glycogen synthase kinase-3 inhibitor.
A practical synthesis of the glycogen synthase kinase-3 (GSK3) inhibitor bisarylmaleimide 1 has been accomplished employing Pictet-Spengler methodology to access the indole 7-position in preparing the benzodiazepine tricyclic fragment. A seven-step linear sequence that starts with commercially available 5-fluoroindole 7 affords the bisarylmaleimide 1 in 33% overall yield.
Magnus
Nicholas A
NA
Eli Lilly and Company, Chemical Product Research and Development Division, Indianapolis, Indiana 46285, USA. magnus_nicholas@lilly.com
Ley
Christopher P
CP
Pollock
Patrick M
PM
Wepsiec
James P
JP
D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000737:chemistry*; D008301:Maleimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure
D007211:Indoles; D008301:Maleimides; C553355:bisarylmaleimide; C095066:5-fluoroindole; D038362:Glycogen Synthase Kinase 3