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【结 构 式】 
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【药物名称】Dazoxiben hydrochloride, UK-37248-01 【化学名称】4-[2-(1H-Imidazol-1-yl)ethoxy]benzoic acid monohydrochloride 【CA登记号】74226-22-5, 78218-09-4 (free base) 【 分 子 式 】C12H13ClN2O3 【 分 子 量 】268.70201 |
【开发单位】Pfizer (Originator) 【药理作用】Antiplatelet Therapy, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Thromboxane Synthase Inhibitors |
合成路线1
A new synthesis of dazoxiben has been described: The condensation of methyl 4-hydroxybenzoate (I) with 1,2-dibromoethane (II) by means of NaOH gives methyl 4-(2-bromoethoxy)benzoate (III), which is hydrolyzed with H2SO4 to the corresponding free acid (IV). Finally, this compound is condensed with imidazole (V) in refluxing butanol.
| 【1】 Palei, R.M.; Kochergin, P.M.; Balandina, L.V.; Govorukhina, E.I.; Persanova, L.V.; Frolova, M.A.; Kravchenko, A.N.; Kharitonova, A.E.; A simplified synthesis of dazoxibene. Khim Farm Zh 1995, 29, 2, 56. |
| 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) | 10251 | methyl 4-hydroxybenzoate; Methyl p-hydroxybenzoate | 99-76-3 | C8H8O3 | 详情 | 详情 |
| (II) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
| (III) | 10253 | methyl 4-(2-bromoethoxy)benzoate | 56850-91-0 | C10H11BrO3 | 详情 | 详情 |
| (IV) | 10254 | 4-(2-bromoethoxy)benzoic acid | 51616-09-2 | C9H9BrO3 | 详情 | 详情 |
| (V) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
合成路线2
This compound can be obtained in several different ways: 1) The condensation of imidazole (I) with 4-(2-chloroethoxy)benzamide (II) by means of NaH in DMF gives 1-[2-(4-carbamoylphenoxy)ethyl]imidazole (III), which is hydrolyzed by refluxing with 5N aqueous HCl. 2) Esters of 4-(2-chloroethoxy)benzoic acid (IV) can also be used instead of (II) in the first step of the synthesis. 3) This compound can also be obtained by direct condensation of imidazole (I) with 4-(2-chloroethoxy)benzoic acid (IV) by means of NaH in THF.
| 【1】 DE 2950019 . |
| 【2】 Sneddon, J.; Castaner, J.; UK-37,248-01. Drugs Fut 1981, 6, 11, 693. |