【结 构 式】 |
【药物名称】Z-335 【化学名称】2-[2-(4-Chlorophenylsulfonamidomethyl)indan-5-yl]acetic acid sodium salt 【CA登记号】146731-14-8, 146737-36-2 (free acid) 【 分 子 式 】C18H17ClNNaO4S 【 分 子 量 】401.84729 |
【开发单位】Zeria (Originator) 【药理作用】Antiplatelet Therapy, Atherosclerosis Therapy, CARDIOVASCULAR DRUGS, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Prostanoid TP (Thromboxane A2) Antagonists |
合成路线1
Curtius rearrangement of indanylacetic acid (I) using diphenylphosphoryl azide (DPPA) in the presence of benzyl alcohol afforded benzyl carbamate (II). Hydrogenolytic deprotection of (II) in the presence of palladium catalyst then provided amine (III), which was condensed with 4-chlorobenzenesulfonyl chloride (IV) to give sulfonamide (V). Subsequent Friedel Crafts reaction of (V) with ethyl a-chloro-a-(methylsulfanyl)acetate (VI) and SnCl4 furnished sulfide (VII), from which the methylthio group was removed by reductive treatment with Zn dust in AcOH yielding (VIII). Finally, alkaline hydrolysis of the indanylacetic ester (VIII) provided the title carboxylic acid, isolated as the corresponding sodium salt.
【1】 Iwakuma, T.; Kurimoto, T.; Yoshida, K.; Shinozaki, K.; Sato, R.; Sato, H.; Synthesis and thromboxane A2 antagonistic activity of indane derivatives. Bioorg Med Chem Lett 1999, 9, 3, 401. |
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) | 21721 | 2-(2,3-dihydro-1H-inden-2-yl)acetic acid | 37868-26-1 | C11H12O2 | 详情 | 详情 |
(II) | 21722 | benzyl 2,3-dihydro-1H-inden-2-ylmethylcarbamate | C18H19NO2 | 详情 | 详情 | |
(III) | 21723 | 2,3-dihydro-1H-inden-2-ylmethylamine; 2,3-dihydro-1H-inden-2-ylmethanamine | C10H13N | 详情 | 详情 | |
(IV) | 15787 | 4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride | 98-60-2 | C6H4Cl2O2S | 详情 | 详情 |
(V) | 21725 | 4-chloro-N-(2,3-dihydro-1H-inden-2-ylmethyl)benzenesulfonamide | C16H16ClNO2S | 详情 | 详情 | |
(VI) | 21726 | ethyl 2-chloro-2-(methylsulfanyl)acetate | C5H9ClO2S | 详情 | 详情 | |
(VII) | 21727 | ethyl 2-[2-([[(4-chlorophenyl)sulfonyl]amino]methyl)-2,3-dihydro-1H-inden-5-yl]-2-(methylsulfanyl)acetate | C21H24ClNO4S2 | 详情 | 详情 | |
(VIII) | 21728 | ethyl 2-[2-([[(4-chlorophenyl)sulfonyl]amino]methyl)-2,3-dihydro-1H-inden-5-yl]acetate | C20H22ClNO4S | 详情 | 详情 |