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【结 构 式】 
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【药物名称】Strontium ranelate, Ranelic acid distrontium salt, FK-481, S-12911-2, S-12911, Protos 【化学名称】2-[2-Carboxy-4-cyano-5-[N,N-di(carboxymethyl)amino]thiophen-3-yl]acetic acid distrontium salt 【CA登记号】135459-87-9, 135459-90-4 (free acid) 【 分 子 式 】C12H6N2O8SSr2 【 分 子 量 】513.49422 |
【开发单位】Servier (Originator), Fujisawa (Licensee) 【药理作用】Bone Diseases, Treatment of, Bone Formation Stimulants, Bone Resorption Inhibitors, METABOLIC DRUGS, Prevention of Osteoporosis, Treatment of Osteoporosis |
合成路线1
Condensation of substituted aminothiophene (I) with ethyl bromoacetate (II) by means of K2CO3 in refluxing acetone furnishes the corresponding ethyl tetraester (III) (1), which can be converted into the desired strontium salt by treatment with NaOH in refluxing EtOH /H2O, followed by reaction with strontium hydroxide or strontium chloride in H2O. Alternatively, this transformation can also be achieved by direct treatment of (III) with strontium hydroxide in H2O/EtOH.
| 【1】 Wierzbicki, M.; et al.; Reactivity of 2-aminothiophenes. Application to the synthesis of some thieno[2,3-b]pyrroles. Bull Soc Chim France 1975, 7-8, Part 2, 1786. |
| 【2】 Wierzbicki, M.; Bonnet, J.; Brisset, M.; Tsouderos, Y. (ADIR et Cie.); Bivalent metal salts of 2-N,N-di(carboxymethyl)amino, 3-cyano,4-carboxymethyl,5-carboxy-thiophene-acid, process for their preparation and pharmaceutical compsns. containing them. AU 9162033; EP 0415850; FR 2651497; JP 1991169876; US 5128367 . |
| 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) | 50839 | ethyl 5-amino-4-cyano-3-(2-ethoxy-2-oxoethyl)-2-thiophenecarboxylate | C12H14N2O4S | 详情 | 详情 | |
| (II) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (III) | 50840 | ethyl 5-[bis(2-ethoxy-2-oxoethyl)amino]-4-cyano-3-(2-ethoxy-2-oxoethyl)-2-thiophenecarboxylate | C20H26N2O8S | 详情 | 详情 |