新产品编号:1943205
Chemical Name: 4,4'-Bis[4-(methylsulfanyl)-3-(4-morpholinylsulfonyl)benzamido]stilbene-2,2'-disulfonic acid disodium salt
项目整合开发状态: Biological Testing
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:N-protection of 4,4'-diamnostilbene-2,2'-disulfonic acid (I) with 9-fluorenylmethyl chloroformate (Fmoc-Cl) by means of Na2CO3 in dioxane yields Fmoc-protected derivative (II),which reacts with triisopropylorthoformate in refluxing dioxane to provide bis(isopropyl) ester (III).Removal of the Fmoc-protecting groups of (III) by means of piperidine in DMF affords diamino compound (IV),which is then condensed with acid chloride (V) by means of K2CO3 in THF to provide compound (VI) [acid chloride (V) can be obtained by first treatment of p-(methylsulfanyl)benzoic acid (VII) with morpholine (VIII) in chlorosulfonic acid to give (IX),followed by reaction with oxalyl chloride in THF/DMF].Finally,the target compound is obtained by treatment of bis(isopropyl) ester (VI) with sodium iodide (NaI) in acetone.
📌 参考资料/链接：
参考文献标题:Aryl sulfonic acids and derivs.as FSH antagonists
文献作者:Rogers,J.F.; Jetter,J.W.; Wrobel,J.E.; Green,D.M.; Kao,W.(American Home Products Corp.)
参考来源:WO 0058277
📄 详细内容
合成路线:N-protection of 4,4'-diamnostilbene-2,2'-disulfonic acid (I) with 9-fluorenylmethyl chloroformate (Fmoc-Cl) by means of Na2CO3 in dioxane yields Fmoc-protected derivative (II),which reacts with triisopropylorthoformate in refluxing dioxane to provide bis(isopropyl) ester (III).Removal of the Fmoc-protecting groups of (III) by means of piperidine in DMF affords diamino compound (IV),which is then condensed with acid chloride (V) by means of K2CO3 in THF to provide compound (VI) [acid chloride (V) can be obtained by first treatment of p-(methylsulfanyl)benzoic acid (VII) with morpholine (VIII) in chlorosulfonic acid to give (IX),followed by reaction with oxalyl chloride in THF/DMF].Finally,the target compound is obtained by treatment of bis(isopropyl) ester (VI) with sodium iodide (NaI) in acetone.
参考文献标题:Synthesis of stilbene (bis)sulfonic acid,(bis)benzamides as FSH antagonists
文献作者:Wrobel,J.; Rogers,J.F.
参考来源:220th ACS Natl Meet (Aug 20 2000,Washington DC) 2000,Abst MEDI 314