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【结 构 式】 
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【分子编号】28720 【品名】2,3-dimethoxy-5-[(Z)-2-(4-methoxy-3-nitrophenyl)ethenyl]phenyl methyl ether; 1,2,3-trimethoxy-5-[(Z)-2-(4-methoxy-3-nitrophenyl)ethenyl]benzene 【CA登记号】 |
【 分 子 式 】C18H19NO6 【 分 子 量 】345.352 【元素组成】C 62.6% H 5.55% N 4.06% O 27.8% |
合成路线1
该中间体在本合成路线中的序号：(IV)Wittig reaction of 3,4,5-trimethoxybenzyl phosphonium bromide (I) with benzaldehyde (II) in the presence of NaH in toluene yielded a 1:1 mixture of E (III) and Z (IV) stilbenes, from which the Z isomer was separated by crystallization from EtOAc and then from EtOH. Then, nitro group of (IV) was reduced with Zn in AcOH at room temperature to give anilino compound (V), which was converted to the hydrochloride salt with HCl in dioxane-methylene chloride.
| 【1】 Suga, Y.; Ohsumi, K.; Fukuda, Y.; Nihei, Y.; Hatanaka, T.; Tsuji, T.; Nakagawa, R.; Morrinaga, Y.; Ohishi, K.; Akiyama, Y.; Novel combretastatin analogue effective against murine solid tumors: Design and structure-activity relationships. J Med Chem 1998, 41, 16, 3022. |
| 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) | 18224 | triphenyl(3,4,5-trimethoxybenzyl)phosphorane; 2,3-dimethoxy-5-[(triphenylphosphoranyl)methyl]phenyl methyl ether | C28H29O3P | 详情 | 详情 | |
| (II) | 18225 | 4-METHOXY-3-NITROBENZALDEHYDE | 31680-08-7 | C8H7NO4 | 详情 | 详情 |
| (III) | 18226 | 2,3-dimethoxy-5-[(E)-2-(4-methoxy-3-nitrophenyl)ethenyl]phenyl methyl ether; 1,2,3-trimethoxy-5-[(E)-2-(4-methoxy-3-nitrophenyl)ethenyl]benzene | C18H19NO6 | 详情 | 详情 | |
| (IV) | 28720 | 2,3-dimethoxy-5-[(Z)-2-(4-methoxy-3-nitrophenyl)ethenyl]phenyl methyl ether; 1,2,3-trimethoxy-5-[(Z)-2-(4-methoxy-3-nitrophenyl)ethenyl]benzene | C18H19NO6 | 详情 | 详情 | |
| (V) | 18228 | 2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]aniline; 2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenylamine | C18H21NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Wittig reaction of phosphonium bromide (I) with 4-methoxy-3-nitrobenzaldehyde (II) in the presence of NaOMe provided an approximately equimolecular mixture of Z- and E-stilbenes (III) and (IV), from which the E-isomer was isolated by crystallization. Stilbene (IV) was converted to bromohydrin (V) by treatment with N-bromosuccinimide in aqueous DMSO. Further Swern oxidation of (V) with DMSO-trifluoroacetic anhydride (TFAA) yielded bromoketone (VI), which was then cyclized with thiourea (VII) in the presence of K2CO3 in DMF to give aminothiazole (VIII). Finally, the nitro of (VIII) group was reduced to the target amine by treatment with Zn in AcOH.
| 【1】 Ohsumi, K.; Hatanaka, T.; Fujita, K.; Nakagawa, R.; Fukuda, Y.; Nihei, Y.; Suga, Y.; Morinaga, Y.; Akiyama, Y.; Tsuji, T.; Syntheses and antitumor activity of cis-restricted combretastatins: 5-Membered heterocyclic analogues. Bioorg Med Chem Lett 1998, 8, 22, 3153. |
| 【2】 Suga, Y.; Ohsumi, K.; Fukuda, Y.; Nihei, Y.; Hatanaka, T.; Tsuji, T.; Nakagawa, R.; Morrinaga, Y.; Ohishi, K.; Akiyama, Y.; Novel combretastatin analogue effective against murine solid tumors: Design and structure-activity relationships. J Med Chem 1998, 41, 16, 3022. |
| 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) | 19866 | triphenyl(3,4,5-trimethoxybenzyl)phosphonium bromide | C28H28BrO3P | 详情 | 详情 | |
| (II) | 18225 | 4-METHOXY-3-NITROBENZALDEHYDE | 31680-08-7 | C8H7NO4 | 详情 | 详情 |
| (III) | 28720 | 2,3-dimethoxy-5-[(Z)-2-(4-methoxy-3-nitrophenyl)ethenyl]phenyl methyl ether; 1,2,3-trimethoxy-5-[(Z)-2-(4-methoxy-3-nitrophenyl)ethenyl]benzene | C18H19NO6 | 详情 | 详情 | |
| (IV) | 18226 | 2,3-dimethoxy-5-[(E)-2-(4-methoxy-3-nitrophenyl)ethenyl]phenyl methyl ether; 1,2,3-trimethoxy-5-[(E)-2-(4-methoxy-3-nitrophenyl)ethenyl]benzene | C18H19NO6 | 详情 | 详情 | |
| (V) | 18226 | 2,3-dimethoxy-5-[(E)-2-(4-methoxy-3-nitrophenyl)ethenyl]phenyl methyl ether; 1,2,3-trimethoxy-5-[(E)-2-(4-methoxy-3-nitrophenyl)ethenyl]benzene | C18H19NO6 | 详情 | 详情 | |
| (V) | 19870 | 2-bromo-2-(4-methoxy-3-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)-1-ethanol | C18H20BrNO7 | 详情 | 详情 | |
| (VI) | 19871 | 2-bromo-2-(4-methoxy-3-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)-1-ethanone | C18H18BrNO7 | 详情 | 详情 | |
| (VII) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (VIII) | 19873 | 5-(4-methoxy-3-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,3-thiazol-2-amine; 5-(4-methoxy-3-nitrophenyl)-4-(3,4,5-trimethoxyphenyl)-1,3-thiazol-2-ylamine | C19H19N3O6S | 详情 | 详情 |