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【结 构 式】 
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【分子编号】14658 【品名】methyl (8S)-8-(bromomethyl)-4-hydroxy-2-methyl-1-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate 【CA登记号】 |
【 分 子 式 】C26H26BrN3O8 【 分 子 量 】588.41186 【元素组成】C 53.07% H 4.45% Br 13.58% N 7.14% O 21.75% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of 8(S)-(bromomethyl)-4-hydroxy-2-methyl-1-oxo-6-(5,6,7-trimethoxyindol-2-ylcarbonyl)-1,2,3,6,7,8-hexahydrobenzo[1,2-b:4,3-b']dipyrrole-2-carboxylic acid methyl ester (I) with tert-butyl-dimethylsilyl chloride in DMF gives the corresponding O-silyl derivative (II), which is treated with camphorsulfonic acid (CPS) in hot chloroform to afford 8(S)-(bromomethyl)-4-hydroxy-2-methyl-6-(5,6,7-trimethoxyindol-2-ylcarbonyl)-3,6,7,8-tetrahydrobenzo[1,2-b:4,3-b']dipyrrole-1-carboxylic acid methyl ester (III). Finally, this compound is desilylated with tetrabutylammonium fluoride in THF and condensed with N-methylpiperazine (IV) and 4-nitrophenyl chloroformate by means of triethylamine in dichloromethane.
| 【1】 Kanda, Y.; Uosaki, Y.; Saito, H.; Sano, H.; Kobayashi, E.; Morimoto, M.; Nagamura, S. (Kyowa Hakko Kogyo Co., Ltd.); DC-88A derivs. EP 0406749; JP 1991128379; US 5070092; US 5187186 . |
| 【2】 Castaner, J.; Hoshi, A.; KW-2189. Drugs Fut 1993, 18, 12, 1112. |
| 【3】 Saito, H.; Gomi, K.; Nagamura, S.; Kanda, Y.; Asai, A.; Kobayashi, E.; Synthesis, antitumor activity and DNA alkylation of duocarmycin analogs. Development of KW2189. 203rd ACS Natl Meet (April 5-10, San Francisco) 1992, Abst MEDI 44. |
| 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) | 14658 | methyl (8S)-8-(bromomethyl)-4-hydroxy-2-methyl-1-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate | C26H26BrN3O8 | 详情 | 详情 | |
| (II) | 14659 | methyl (8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate | C32H40BrN3O8Si | 详情 | 详情 | |
| (III) | 14660 | methyl (8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate | C32H40BrN3O7Si | 详情 | 详情 | |
| (IV) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |