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【结 构 式】 
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【药物名称】Amosulalol hydrochloride, YM-09538, Lowgan 【化学名称】(±)-5-[1-Hydroxy-2-[[2-(o-methoxyphenoxy)ethyl]amino]ethyl]-o-toluenesulfonamide monohydrochloride 【CA登记号】70958-86-0, 85320-68-9 (free base) 【 分 子 式 】C18H25ClN2O5S 【 分 子 量 】416.92735 |
【开发单位】Yamanouchi (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, alpha1-Adrenoceptor Antagonists, beta-Adrenoceptor Antagonists |
合成路线1
The condensation of 2-methoxyphenol (I) with ethylene oxide (II) gives 2-(2-methoxyphenoxy)ethanol (III), which is treated with SOCl2 to yield 2-(2-methoxyphenoxy)ethyl chloride (IV). The reaction of (IV) with benzylamine (A) gives N-[2-(2-methoxyphenoxy)ethyl]benzylamine (V), which is condensed with 2-methyl-5-bromoacetylbenzenesulfonamide (VI) affording N-[2-(2-methoxyphenoxy)ethyl]-N-[(4-methyl-3-aminosulfonylbenzoyl)methyl]benzylamine (VII). The reduction of (VII) with NaBH4 affords the corresponding protected carbinol (VIII), which is finally debenzylated by hydrogenation with H2 over Pd/C.
| 【1】 Arima, H.; Tamazawa, K.; Synthesis of 14C-labeled 5-[1-hydroxy-2-[2-(o-methoxyphenoxy)ethylamino]ethyl]-2-methylbenzenesulfonamide hydochloride (YM-09538). J Label Compd Radiopharm 1983, 20, 7, 803-811. |
| 【2】 Fujikura, T.; et al. (Yamanouchi Pharmaceutical Co., Ltd.); Phenylethanolamine derivatives. DE 2843016; ES 474149; ES 481549; FR 2405931; GB 2006772 . |
| 【3】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Leeson, P.A.; Mealy, N.E.; YM-09,538. Drugs Fut 1981, 6, 7, 425. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (I) | 13182 | Guaiacol; 2-Methoxyphenol | 90-05-1 | C7H8O2 | 详情 | 详情 |
| (II) | 10393 | Oxirane; Ethylene oxide | 75-21-8 | C2H4O | 详情 | 详情 |
| (III) | 30526 | 2-(2-methoxyphenoxy)-1-ethanol | C9H12O3 | 详情 | 详情 | |
| (IV) | 30527 | 2-(2-chloroethoxy)phenyl methyl ether; 1-(2-chloroethoxy)-2-methoxybenzene | C9H11ClO2 | 详情 | 详情 | |
| (V) | 30528 | N-benzyl-2-(2-methoxyphenoxy)-1-ethanamine; N-benzyl-N-[2-(2-methoxyphenoxy)ethyl]amine | C16H19NO2 | 详情 | 详情 | |
| (VI) | 30529 | 5-(2-bromoacetyl)-2-methylbenzenesulfonamide | C9H10BrNO3S | 详情 | 详情 | |
| (VII) | 30530 | 5-(2-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]acetyl)-2-methylbenzenesulfonamide | C25H28N2O5S | 详情 | 详情 | |
| (VIII) | 30531 | 5-(2-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-1-hydroxyethyl)-2-methylbenzenesulfonamide | C25H30N2O5S | 详情 | 详情 |