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【结 构 式】 
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【分子编号】35834 【品名】dimethyl 1-(3-bromo-4,5-dimethoxyphenyl)-5-chloro-2,3-naphthalenedicarboxylate 【CA登记号】 |
【 分 子 式 】C22H18BrClO6 【 分 子 量 】493.73802 【元素组成】C 53.52% H 3.67% Br 16.18% Cl 7.18% O 19.44% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Lithiation of 2-chloro-N-methylbenzamide (I) using sec-butyllithium and tetramethyl ethylenediamine, followed by addition of the resulting organolithium derivative to 3-bromo-4,5-dimethoxybenzaldehyde (II) produced hydroxy amide (III), which was cyclized to lactone (IV) upon refluxing with HCl/dioxan. Reduction of the lactone function of (IV) employing DIBAL yielded lactol (V). The intermediate isobenzofuran generated by acidic treatment of lactol (V) experienced a Diels-Alder addition with dimethyl fumarate (VI) to afford adduct (VII). Subsequent aromatization of (VII) to give naphthalene (VIII) was carried out by treatment with boron trifluoride etherate in hot acetonitrile. Selective saponification of the less hindered ester group of (VIII) provided acid (IX). After coupling of (IX) with N-(2-hydroxyethyl)piperazine (X) by means of DCC and HOBt, the title compound was converted to the hydrochloride salt.
| 【1】 Takahashi, M.; Yamamoto, Y.; Nakamura, Y.; Kubo, A.; Kotera, J.; Ukita, T.; Ikeo, T.; 1-Arylnaphthalene lignan: A novel scaffold for type 5 phosphodiesterase inhibitor. J Med Chem 1999, 42, 7, 1293. |
| 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) | 35828 | 2-chloro-N-methylbenzamide | C8H8ClNO | 详情 | 详情 | |
| (II) | 35829 | 3-bromo-4,5-dimethoxybenzaldehyde | 6948-30-7 | C9H9BrO3 | 详情 | 详情 |
| (III) | 35830 | 2-[(3-bromo-4,5-dimethoxyphenyl)(hydroxy)methyl]-6-chloro-N-methylbenzamide | C17H17BrClNO4 | 详情 | 详情 | |
| (IV) | 35831 | 3-(3-bromo-4,5-dimethoxyphenyl)-7-chloro-2-benzofuran-1(3H)-one | C16H12BrClO4 | 详情 | 详情 | |
| (V) | 35832 | 3-(3-bromo-4,5-dimethoxyphenyl)-7-chloro-1,3-dihydro-2-benzofuran-1-ol | C16H14BrClO4 | 详情 | 详情 | |
| (VI) | 35018 | dimethyl (E)-2-butenedioate | 624-49-7 | C6H8O4 | 详情 | 详情 |
| (VII) | 35823 | 7-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline; methyl 2,3,4,9-tetrahydro-1H-beta-carbolin-7-yl ether | C12H14N2O | 详情 | 详情 | |
| (VIII) | 35834 | dimethyl 1-(3-bromo-4,5-dimethoxyphenyl)-5-chloro-2,3-naphthalenedicarboxylate | C22H18BrClO6 | 详情 | 详情 | |
| (IX) | 35835 | 4-(3-bromo-4,5-dimethoxyphenyl)-8-chloro-3-(methoxycarbonyl)-2-naphthoic acid | C21H16BrClO6 | 详情 | 详情 | |
| (X) | 21893 | 2-(1-piperazinyl)-1-ethanol; 1-piperazineethanol; 1-(2-Hydroxyethyl)piperazine | 103-76-4 | C6H14N2O | 详情 | 详情 |