KCL-1998001079
Chemical Name: (?-2-[4-Methoxy-3-[N-[4-(trifluoromethyl)benzyl]carbamoyl]benzyl]butyric acid
项目整合开发状态: Preclinical
项目研究机构: Kyorin (Originator)
合成路线:5-Formyl-2-methoxybenzoic acid (I) is converted to the corresponding benzyl ester (II) upon treatment with benzyl bromide and potassium bicarbonate.Subsequent Wadsworth-Emmons condensation between aldehyde (II) and triethyl 2-phosphonobutyrate (III) gives the unsaturated ester (IV).Double bond hydrogenation in (IV) with concomitant hydrogenolysis of the benzyl ester affords acid (V),which is subsequently coupled with 4-(trifluoromethyl)benzyl amine (VI),via the mixed anhydride with ethyl chloroformate,to produce amide (VII).The ethyl ester group of (VII) is finally hydrolyzed to the title carboxylic acid employing NaOH in aqueous ethanol.
📌 参考资料/链接：
参考文献标题:Substd.phenylpropionic acid derivs.as agonists to human peroxisome proliferator-activated receptor (PPAR) alpha
文献作者:Murakami,K.; Takahashi,Y.; Nomura,M.; Miyachi,H.; Ide,T.; Tsunoda,M.; Tanase,T.(Kyorin Pharmaceutical Co.,Ltd.)
参考来源:EP 1184366; JP 2001055367; WO 0075103
📄 详细内容
合成路线:5-Formyl-2-methoxybenzoic acid (I) is converted to the corresponding benzyl ester (II) upon treatment with benzyl bromide and potassium bicarbonate.Subsequent Wadsworth-Emmons condensation between aldehyde (II) and triethyl 2-phosphonobutyrate (III) gives the unsaturated ester (IV).Double bond hydrogenation in (IV) with concomitant hydrogenolysis of the benzyl ester affords acid (V),which is subsequently coupled with 4-(trifluoromethyl)benzyl amine (VI),via the mixed anhydride with ethyl chloroformate,to produce amide (VII).The ethyl ester group of (VII) is finally hydrolyzed to the title carboxylic acid employing NaOH in aqueous ethanol.
参考文献标题:Design,synthesis and evaluation of substituted phenylpropanoic acid derivatives as peroxisome proliferator-activated receptor (PPAR) activators: Novel human PPARalpha-selective activators
文献作者:Miyachi,H.; Nomura,M.; Tanase,T.; Takahashi,Y.; Ide,T.; Tsunoda,M.; Murakami,K.; Awano,K.
参考来源:Bioorg Med Chem Lett 2002,12(1),77