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【结 构 式】 
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【药物名称】 【化学名称】4,4'-Bis[4-(methylsulfanyl)-3-(4-morpholinylsulfonyl)benzamido]stilbene-2,2'-disulfonic acid disodium salt 【CA登记号】 【 分 子 式 】C38H38N4Na2O14S6 【 分 子 量 】1013.10856 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】Contraceptives, Disorders of Sexual Function and Reproduction, Treatment of, ENDOCRINE DRUGS, FSH Antagonists |
合成路线1
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.
| 【1】 Wrobel, J.; Rogers, J.F.; Synthesis of stilbene (bis)sulfonic acid, (bis)benzamides as FSH antagonists. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 314. |
| 【2】 Rogers, J.F.; Jetter, J.W.; Wrobel, J.E.; Green, D.M.; Kao, W. (American Home Products Corp.); Aryl sulfonic acids and derivs. as FSH antagonists. WO 0058277 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 46706 | 5-amino-2-[(E)-2-(4-amino-2-sulfophenyl)ethenyl]benzenesulfonic acid | 81-11-8 | C14H14N2O6S2 | 详情 | 详情 |
| (II) | 46707 | 5-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-2-[(E)-2-(4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-2-sulfophenyl)ethenyl]benzenesulfonic acid | C44H34N2O10S2 | 详情 | 详情 | |
| (III) | 46708 | isopropyl 5-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-2-[(E)-2-[4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-2-(isopropoxysulfonyl)phenyl]ethenyl]benzenesulfonate | C50H46N2O10S2 | 详情 | 详情 | |
| (IV) | 46709 | isopropyl 5-amino-2-[(E)-2-[4-amino-2-(isopropoxysulfonyl)phenyl]ethenyl]benzenesulfonate | C20H26N2O6S2 | 详情 | 详情 | |
| (V) | 46712 | 4-(methylsulfanyl)-3-(4-morpholinylsulfonyl)benzoyl chloride | C12H14ClNO4S2 | 详情 | 详情 | |
| (VI) | 46711 | isopropyl 2-[(E)-2-(2-(isopropoxysulfonyl)-4-[[4-(methylsulfanyl)-3-(4-morpholinylsulfonyl)benzoyl]amino]phenyl)ethenyl]-5-[[4-(methylsulfanyl)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonate | C44H52N4O14S6 | 详情 | 详情 | |
| (VII) | 30683 | 4-(methylsulfanyl)benzoic acid | 13205-48-6 | C8H8O2S | 详情 | 详情 |
| (VIII) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (IX) | 46710 | 4-(methylsulfanyl)-3-(4-morpholinylsulfonyl)benzoic acid | C12H15NO5S2 | 详情 | 详情 |