An efficient synthesis of a potent PPARpan agonist.
An efficient synthesis of 2-{4-[({4-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)thio]phenoxy}-2-methylpropanoic acid (1), a potent PPARpan agonist, is described. The seven-step synthesis, which afforded 1 in 30% overall yield, includes a highly regioselective carbon-sulfur bond formation via coupling of a bishydroxymethylthiazole (3) with 4-hydroxythiophenol, displacement of the remaining alcohol through a three-step telescoped sequence involving an efficient cleavage of an aryl mesylate, and an efficient and practical method of introducing an isobutyric acid fragment.
Guo
Jiasheng
J
Synthetic Chemistry, Chemical Development, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA. jiasheng.x.guo@gsk.com
Erickson
Greg A
GA
Fitzgerald
Russ N
RN
Matsuoka
Richard T
RT
Rafferty
Stephen W
SW
Sharp
Matthew J
MJ
Sickles
Barry R
BR
Wisowaty
James C
JC
D002087:Butyrates / Q000737:chemistry; D058610:Isobutyrates; D008698:Mesylates / Q000737:chemistry; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D011422:Propionates / Q000138:chemical synthesis*
D002087:Butyrates; D058610:Isobutyrates; D008698:Mesylates; D047492:Peroxisome Proliferator-Activated Receptors; D011422:Propionates; C020380:isobutyric acid; C029658:propionic acid