新产品编号:271031
Chemical Name: 2-[3-[4-(3-Phenyl-7-propyl-1,2-benzisoxazol-6-yloxy)butoxy]phenyl]acetic acid sodium salt
CAS No. 194980-75-1 (free acid), 477936-07-5 (labeled)
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:Claisen rearrangement of allyl ether (I) in refluxing o-dichlorobenzene affords (II).The allyl group of (II) is subsequently hydrogenated over Pd/C to provide the propyl derivative (III).Benzophenone (III) is converted into the corresponding oxime (IV) by means of hydroxylamine hydrochloride and NaOAc.Acetylation of oxime (IV),followed by refluxing in pyridine gives rise to the benzisoxazole (V).The phenolic hydroxyl group of (V) is then alkylated by 1,4-dibromobutane (VI) producing the bromobutyl ether (VII).3-Hydroxyphenylacetic acid (VIII) is esterified with MeOH/H2SO4 to give the methyl ester (IX).This is then condensed with bromide (VII) in the presence of K2CO3 to furnish diether (X).Finally,saponification of the methyl ester group of (X) employing LiOH yields the target carboxylic acid (1,2)
📌 参考资料/链接：
参考文献标题:Heterocyclic derivs.as antidiabetic and antiobesity agents
文献作者:Adams,A.D.; Berger,J.P.; Berger,G.D.; Fitch,K.J.; Graham,D.W.; Jones,A.B.; Von Langen,D.; Leibowitz,M.D.; Moller,D.E.; Patchett,A.A.; Santini,C.; Sahoo,S.P.; Tolman,R.L.; Toupence,R.B.; Walsh,T.F.(Merck & Co.,Inc.)
参考来源:EP 0882029; JP 2002503203; US 6090836; WO 9728137
📄 详细内容
合成路线:Claisen rearrangement of allyl ether (I) in refluxing o-dichlorobenzene affords (II).The allyl group of (II) is subsequently hydrogenated over Pd/C to provide the propyl derivative (III).Benzophenone (III) is converted into the corresponding oxime (IV) by means of hydroxylamine hydrochloride and NaOAc.Acetylation of oxime (IV),followed by refluxing in pyridine gives rise to the benzisoxazole (V).The phenolic hydroxyl group of (V) is then alkylated by 1,4-dibromobutane (VI) producing the bromobutyl ether (VII).3-Hydroxyphenylacetic acid (VIII) is esterified with MeOH/H2SO4 to give the methyl ester (IX).This is then condensed with bromide (VII) in the presence of K2CO3 to furnish diether (X).Finally,saponification of the methyl ester group of (X) employing LiOH yields the target carboxylic acid (1,2)
参考文献标题:Amphipathic 3-phenyl-7-propylbenzisoxazoles; human PPAR gamma,delta and alpha agonists
文献作者:Adams,A.D.; Yuen,W.; Hu,Z.; Santini,C.; Jones,A.B.; MacNaul,K.L.; Berger,J.P.; Doebber,T.W.; Moller,D.E.
参考来源:Bioorg Med Chem Lett 2003,13(5),931