Efficient synthesis of [6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]-acetic acid, a novel COX-2 inhibitor.
The synthesis of 6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-ylacetic acid (1), a selective cyclooxygenase 2 (COX-2) inhibitor, is described. The synthesis relied on a novel indole formation that involved an alkylation/1,4-addition/elimination/isomerization cascade. It was demonstrated that the entire sequence from sulfonamide 13 and bromoketone 14 to the desired indole (1) could be executed in a single pot.
Caron
Stéphane
S
Chemical R&D, Pfizer Global Research & Development, Groton, Connecticut 06340-8118, USA. stephane_caron@groton.pfizer.com
Vazquez
Enrique
E
Stevens
Rodney W
RW
Nakao
Kazunari
K
Koike
Hiroki
H
Murata
Yoshinori
Y
D000478:Alkylation; D002384:Catalysis; D002723:Chlorobenzoates / Q000138:chemical synthesis* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007202:Indicators and Reagents; D007210:Indoleacetic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases
C479620:(6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl)acetic acid; D002723:Chlorobenzoates; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007210:Indoleacetic Acids; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases