Y-39677
Chemical Name: cis-2-[2-(Octahydro-2H-isoindol-2-yl)-2-oxoethyl]-3-[4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl]-2(E)-propenoic acid
CAS No. 312688-85-0
项目整合开发状态: Preclinical
项目研究机构: Mitsubishi Pharma (Originator)
合成路线:The title compound was synthesized by two related methods.Stobbe condensation between 4-hydroxybenzaldehyde (I) and diethyl succinate (II) in the presence of NaOEt afforded the benzylidenesuccinate monoester (III).Coupling of (III) with cis-hexahydroisoindoline (IV) gave the amidoester (V).The phenolic hydroxyl group of (V) was then alkylated with tosylate (VI) to provide the corresponding ether (IX).Alternatively,intermediate (IX) was obtained by initial alkylation of 4-hydroxybenzaldehyde (I) with tosylate (VI).The resultant alkyloxy benzaldehyde (VII) was then subjected to Stobbe condensation with diethyl succinate (II) to afford the benzylidenesuccinate (VIII),which was further coupled with the bicyclic amine (IV) to produce (IX).Finally,ester (IX) obtained by either synthetic method was hydrolyzed with NaOH to furnish the target carboxylic acid.
📌 参考资料/链接：
参考文献标题:Hybridization of non-sulfonylurea insulin secretagogue and thiazolidinedione-derived insulin sensitizer
文献作者:Kitajima,H.; Nakamura,M.; Tamakawa,H.; Goto,N.
参考来源:Bioorg Med Chem Lett 2000,10(21),2453
📄 详细内容
合成路线:The title compound was synthesized by two related methods.Stobbe condensation between 4-hydroxybenzaldehyde (I) and diethyl succinate (II) in the presence of NaOEt afforded the benzylidenesuccinate monoester (III).Coupling of (III) with cis-hexahydroisoindoline (IV) gave the amidoester (V).The phenolic hydroxyl group of (V) was then alkylated with tosylate (VI) to provide the corresponding ether (IX).Alternatively,intermediate (IX) was obtained by initial alkylation of 4-hydroxybenzaldehyde (I) with tosylate (VI).The resultant alkyloxy benzaldehyde (VII) was then subjected to Stobbe condensation with diethyl succinate (II) to afford the benzylidenesuccinate (VIII),which was further coupled with the bicyclic amine (IV) to produce (IX).Finally,ester (IX) obtained by either synthetic method was hydrolyzed with NaOH to furnish the target carboxylic acid.
参考文献标题:Hybridization of non-sulfonylurea insulin secretagogue and thiazolidinedione-derived insulin sensitizer
文献作者:Kitajima,H.; et al.
参考来源:222nd ACS Natl Meet (Aug 26 2001,Chicago) 2001,Abst MEDI 37