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【结 构 式】 
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【药物名称】 【化学名称】trans-3-Propyl-5,6,6a,7,8,12b-hexahydronaphtho[1,2-f][1,7]naphthyridine-10,11-diol 【CA登记号】197007-99-1, 197007-53-7 (diHBr) 【 分 子 式 】C19H22N2O2 【 分 子 量 】310.39939 |
【开发单位】Abbott (Originator) 【药理作用】Antiparkinsonian Drugs, Extrapyramidal Disorders, Treatment of, NEUROLOGIC DRUGS, Dopamine D1 Agonists |
合成路线1
6-Propyl-2-pyridinecarboxylic acid (I) was activated as the mixed anhydride with pivaloyl chloride, and then condensed with tert-butylamine to afford amide (II). After treatment of (II) with butyllithium, the resulting dianion equilibrated to the trans isomer upon treatment with Et3N in MeOH. Reduction of (IV) with concomitant cyclization in the presence of Zn and HCl furnished the tetracyclic compound (V). Finally, cleavage of the methyl ethers of (V) using BBr3 yielded the was condensed with nitroolefin (III) to provide a cis/trans mixture of adducts (VI), which was target compound.
| 【1】 Bayburt, E.K.; Michaelides, M.R.; Shiosaki, K.; Lin, C.W.; Gu, Y.G.; trans-2,6-, 3,6- and 4,6-diaza-5,6,6a,7,8,12b-hexahydro-benzo[c]phenanthrene-10,11-diols as dopamine agonists. Bioorg Med Chem Lett 1999, 9, 10, 1341. |
| 【2】 Michaelides, M.; Gu, Y.G.; Shiosaki, K. (Abbott Laboratories Inc.); Trans-2,6-, 3,6- and 4,6-diaza-5,6,6a,7,8,12b-hexahydrobenzo[c]phenanthrene cpds. as dopamine agonists. US 5668141; WO 9736902 . |
| 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) | 31384 | 6-propyl-2-pyridinecarboxylic acid | C9H11NO2 | 详情 | 详情 | |
| (II) | 31385 | N-(tert-butyl)-6-propyl-2-pyridinecarboxamide | C13H20N2O | 详情 | 详情 | |
| (III) | 16966 | 3-methoxy-6-nitro-7,8-dihydro-2-naphthalenyl methyl ether; 6,7-dimethoxy-3-nitro-1,2-dihydronaphthalene | C12H13NO4 | 详情 | 详情 | |
| (IV) | 31386 | N-(tert-butyl)-3-(6,7-dimethoxy-2-nitro-1,2,3,4-tetrahydro-1-naphthalenyl)-6-propyl-2-pyridinecarboxamide | C25H33N3O5 | 详情 | 详情 | |
| (V) | 31387 | (6aR,12bS)-10,11-dimethoxy-3-propyl-5,6,6a,7,8,12b-hexahydronaphtho[1,2-f][1,7]naphthyridine; (6aR,12bS)-10-methoxy-3-propyl-5,6,6a,7,8,12b-hexahydronaphtho[1,2-f][1,7]naphthyridin-11-yl methyl ether | C21H26N2O2 | 详情 | 详情 |