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【结 构 式】 
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【药物名称】YM-193489 【化学名称】N-(1,3-Benzodioxol-5-yl)-3-[3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-ylcarbonyl)piperidin-1-yl]propionamide 【CA登记号】312738-02-6 ((R)-isomer, anhydrous D-tartrate), 312738-08-2 ((S)-isomer, fumarate salt (1:1)), 312738-48-0 ((S)-isomer, fumarate 【 分 子 式 】C27H33N3O6 【 分 子 量 】495.58056 |
【开发单位】Yamanouchi (Originator) 【药理作用】Acute Myocardial Infarction, Treatment of, Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis |
合成路线1
Acylation of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (I) with N-Boc-nipecotic acid (II) by means of EDC/HOBt gives amide (III). Subsequent acidic cleavage of the Boc protecting group yields amine (IV). 3,4-Methylenedioxyaniline (V) is acylated by acryloyl chloride in the presence of Et3N to produce the acrylanilide (VI). Then, Michael addition of piperidine (IV) to the acrylanilide (VI) in boiling toluene provides the title compound.
| 【1】 Kakefuda, A.; Okazaki, T.; Watanabe, T.; et al.; Structure-activity relationships of novel 1,2,3,4-tetrahydroisoquinolin derivatives as bradycardic agents. Drugs Fut 2002, 27, Suppl. A. |
| 【2】 Okazaki, T.; Watanabe, T.; Wada, K.; Kakefuda, A.; Masuda, N. (Yamanouchi Pharmaceutical Co., Ltd.); Novel isoquinoline derivs. or salts thereof. EP 1186601; WO 0075133 . |
| 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) | 25859 | 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline; 6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether | C11H15NO2 | 详情 | 详情 | |
| (II) | 57078 | Boc-nipecotic acid | C11H19NO4 | 详情 | 详情 | |
| (III) | 58821 | tert-butyl 3-{[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]carbonyl}-1-piperidinecarboxylate | C22H32N2O5 | 详情 | 详情 | |
| (IV) | 58822 | [6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl](3-piperidinyl)methanone | C17H24N2O3 | 详情 | 详情 | |
| (V) | 10984 | 1,3-Benzodioxol-5-amine; 1,3-Benzodioxol-5-ylamine.; 3,4-(Methylenedioxy)aniline | 14268-66-7 | C7H7NO2 | 详情 | 详情 |
| (VI) | 58823 | N-(1,3-benzodioxol-5-yl)acrylamide | C10H9NO3 | 详情 | 详情 |