Synthesis of a unique dimethyl thiazoline containing intermediate of novel peroxisome proliferator-activated receptors(PPAR)δ agonists. Issue 50 (12th December 2018)

• Record Type: Journal Article
• Authors: Man Kadayat, Tara; Lee, Geumwoo; Jung, Kyungjin; Hwang, Hee-Jong; Joo, Jeongmin; Hahn, Dongyup; Hwang, Hayoung; Park, Keun-Gyu; Cho, Sung Jin; Kim, Kyung-Hee; Chin, Jungwook
• Is Part Of: Tetrahedron letters. Volume 59:Issue 50(2018)
• Page Start: 4384
• Page End: 4386
• Publication Date: 2018-12-12
• Subjects: GW501516 -- TBAHS catalyst -- d-Penicillamine -- 4-Mercapto-2-methylphenol -- PPAR agonists; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2018.10.051
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Method for unique dimethyl thiazoline containing intermediate of PPARδ agonists. TBAHS as catalyst for efficient coupling of11 with12 . Potential use of intermediate13 for synthesis of novel PPARδ-selective agonists. Abstract: 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 intermediate13 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 Cs2 CO3 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.