Synthesis of a unique dimethyl thiazoline containing intermediate of novel peroxisome proliferator-activated receptors(PPAR)δ agonists

Peroxisome proliferator-activated receptor delta (PPARδ) is considered as a promising biological target for the development of new drugs to treat metabolic syndrome including hyperlipidemia. In this study, a simple and efficient method for the preparation of a unique dimethyl thiazoline containing intermediate (13) of new PPARδ agonists as GW501516 analogue is described. The intermediate 13 was readily obtained by coupling reaction of 4-(chloromethyl)-5,5-dimethyl-2-(4-(trifluoromethyl)phenyl)-4,5-dihydrothiazole (11) with 4-mercapto-2-methylphenol (12) in the presence of tetrabutylammonium hydrogensulfate (TBAHS) and Cs₂CO₃ in DMF at 80 °C for 1 h. This unique intermediate could be useful for the synthesis of various novel PPARδ agonists to understand the structural and biological significance of PPARδ.