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【结 构 式】 
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【药物名称】Linotroban, HN-11500, CL-871502 【化学名称】2-[5-[2-(Benzenesulfonamido)ethyl]thien-2-yloxy]acetic acid 【CA登记号】120824-08-0, 141443-73-4 (HN-11500) 【 分 子 式 】C14H15NO5S2 【 分 子 量 】341.40735 |
【开发单位】Amersham Health (Originator), Nycomed Pharma (Originator) 【药理作用】Antiplatelet Therapy, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Prostanoid TP (Thromboxane A2) Antagonists |
合成路线1
The reaction of 2-bromothiophene (I) with the monosodium salt of ethylene glycol (II) in the same solvent gives 2-(2-hydroxyethoxy)thiophene (III), which is condensed with 3,4-dihydro-2H-pyran (IV) by means of p-toluenesulfonic acid in THF yielding the corresponding tetrahydropyranyl ether (V). The reaction of (V) with N-(benzenesulfonyl)aziridine (VI) by means of BuLi in THF - hexane affords N-[2-[5-(2-hydroxyethoxy)thien-2-yl]ethyl]benzenesulfonamide (VII), which is finally oxidized with silver oxide in aqueous NaOH.
| 【1】 Binder, D.; Rovensky, F.; Ferber, H.P. (CL Pharma; Nycomed Pharma); Novel 2-thienyloxyacetic acid derivs., a process for their preparation and pharmaceutical preparations containing them. EP 0284892; US 4877809 . |
| 【2】 Castaner, J.; Prous, J.; Graul, A.; Linotroban. Drugs Fut 1994, 19, 10, 913. |
| 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) | 13681 | 2-Bromothiophene | 1003-09-4 | C4H3BrS | 详情 | 详情 |
| (II) | 13682 | sodium 2-hydroxy-1-ethanolate | C2H5NaO2 | 详情 | 详情 | |
| (III) | 13683 | 2-(2-Thienyloxy)-1-ethanol | C6H8O2S | 详情 | 详情 | |
| (IV) | 13684 | 3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran | 110-87-2 | C5H8O | 详情 | 详情 |
| (V) | 13685 | Tetrahydro-2H-pyran-2-yl 2-(2-thienyloxy)ethyl ether; 2-[2-(2-Thienyloxy)ethoxy]tetrahydro-2H-pyran | C11H16O3S | 详情 | 详情 | |
| (VI) | 13686 | 1-Benzenesulfonyl-aziridine; 1-(Phenylsulfonyl)aziridine | 10302-15-5 | C8H9NO2S | 详情 | 详情 |
| (VII) | 13687 | N-[2-[5-(2-Hydroxyethoxy)-2-thienyl]ethyl]benzenesulfonamide | C14H17NO4S2 | 详情 | 详情 |