LR-90
Chemical Name: 2,5,5-Tris(4-chlorophenyl)-1,3-dioxane-2-carboxylic acid
项目整合开发状态: Preclinical
项目研究机构: Lipha (Originator)
合成路线:Darzen�?condensation of 4,4'-dichlorobenzophenone (I) with ethyl chloroacetate (II) produced the glycidic ester (III),which was subsequently converted to aldehyde (IV) upon treatment with KOH.Diol (V) was then obtained by Tollens?reaction of aldehyde (IV) with formaldehyde.Ethyl 4-chlorophenylglyoxylate (VII) was prepared by addition of the Grignard reagent prepared from 1-bromo-4-chlorobenzene (VI) to diethyl oxalate.The condensation between diol (V) and keto ester (VII) in the presence of boron trifluoride furnished the cyclic ketal (VIII).Finally,saponification of the ethyl ester group gave rise to the target carboxylic acid.
📌 参考资料/链接：
参考文献标题:Cyclic cpds.useful in the treatment of dyslipidaemia,atherosclerosis and diabetes,pharmaceutical compsns.and preparation process
文献作者:Zeiller,J.-J.; Rasp? E.; Guerrier,D.; Berthelon,J.-J.(Merck Patent GmbH)
参考来源:EP 1098893; FR 2781222; WO 0004011
📄 详细内容
合成路线:Darzen�?condensation of 4,4'-dichlorobenzophenone (I) with ethyl chloroacetate (II) produced the glycidic ester (III),which was subsequently converted to aldehyde (IV) upon treatment with KOH.Diol (V) was then obtained by Tollens?reaction of aldehyde (IV) with formaldehyde.Ethyl 4-chlorophenylglyoxylate (VII) was prepared by addition of the Grignard reagent prepared from 1-bromo-4-chlorobenzene (VI) to diethyl oxalate.The condensation between diol (V) and keto ester (VII) in the presence of boron trifluoride furnished the cyclic ketal (VIII).Finally,saponification of the ethyl ester group gave rise to the target carboxylic acid.
参考文献标题:ZD1839 (Iressa(TM)),an EGFR-TKI,and cisplatin have an additive effect on programmed cell death in human head and neck squamous carcinoma cells in vitro
文献作者:Al Hazaa,A.; et al.
参考来源:Clin Cancer Res 2000,6(Suppl.),Poster N?308