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【结 构 式】 
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【药物名称】Mepirodipine hydrochloride, Barnidipine hydrochloride, EU-730, YM-730, YM-09730-5, Cyress, Vasexten, Hypoca 【化学名称】2,6-Dimethyl-4(S)-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[1-benzylpyrrolidin-3(S)-yl] 5-methyl diester hydrochloride 【CA登记号】104713-75-9 (free base), 71863-55-3 (undefined stereoch.) 【 分 子 式 】C27H30ClN3O6 【 分 子 量 】528.00965 |
【开发单位】Yamanouchi (Originator) 【药理作用】Angina pectoris, Treatment of, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Calcium Channel Blockers |
合成路线1
By cyclocondensation of 3-nitrobenzaldehyde (I) with methyl 3-aminocrotonate (II) and 1-benzyl-3-(acetoacetoxy)pyrrolidine (III) in refluxing isopropanol. The pyrrolidine (III) is obtained as follows: The condensation of 2-hydroxysuccinic acid (IV) with benzylamine (VI), which is reduced with LiAlH4 in dry THF yielding N-benzyl-3-hydroxypyrrolidine (VIII). Finally, this compound is condensed with diketene (VII) by means of sodium acetate at 80 C.
| 【1】 Tamazawa, K.; Takeuchi, M.; Arima, H.; Synthesis of 14C-and 2H-labeled (3S)-1-benzyl-3-py. J Label Compd Radiopharm 1988, 25, 2, 161. |
| 【2】 Kojima, T.; Takenaka, T. (Yamanouchi Pharmaceutical Co., Ltd.); 1,4-Dihydropyridine-3,5-dicarboxylic acid ester de. DE 2904552; US 4220649 . |
| 【3】 Prous, J.; Castaner, J.; YM-09730-5. Drugs Fut 1988, 13, 7, 634. |
| 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) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (II) | 11372 | Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate | C5H9NO2 | 详情 | 详情 | |
| (III) | 22742 | 2-Oxobutyric acid 1-benzylpyrrolidin-3-yl ester | C15H19NO3 | 详情 | 详情 | |
| (IV) | 22743 | Hydroxysuccinic acid; Malic acid; Hydroxybutanedioic acid | 617-48-1 | C4H6O5 | 详情 | 详情 |
| (V) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (VI) | 22745 | 1-Benzyl-3-hydroxypyrrolidine-2,5-dione | C11H11NO3 | 详情 | 详情 | |
| (VII) | 22746 | 1-benzyl-3-pyrrolidinol | C11H15NO | 详情 | 详情 | |
| (VIII) | 11367 | 4-Methylene-2-oxetanone; Acetyl ketene | 674-82-8 | C4H4O2 | 详情 | 详情 |