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【结 构 式】 
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【分子编号】61776 【品名】methyl (8S)-8-(bromomethyl)-2-methyl-4-{[(4-nitrophenoxy)carbonyl]oxy}-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate 【CA登记号】 |
【 分 子 式 】C33H29BrN4O11 【 分 子 量 】737.51762 【元素组成】C 53.74% H 3.96% Br 10.83% N 7.6% O 23.86% |
合成路线1
该中间体在本合成路线中的序号：(XIV)The condensation of indoline (I) with methyl acetoacetate (II) by means of Ts-OH in refluxing benzene gives the adduct (III), which is cyclized by means of Pd(OAc)2 in hot DMA to yield the pyrroloindole (IV). The hydrolysis of the acetate group of (IV) by means of K2CO3 in methanol affords the hydroxymethyl compound (V), which is treated with CCl4 and PPh3 to provide the chloromethyl derivative (VI). The cleavage of the benzyl protecting group of (VI) by means of HCOONH4 and Pd/C in THF gives the hydroxy derivative (VII), which is N-deprotected by means of HCl in ethyl acetate to yield the intermediate (VIII). The condensation of (VIII) with 5,6,7-trimethoxy-1H-indole-2-carboxylic acid (IX) by means of EDC in DMF affords the carboxamide (X), which is treated with DBU in acetonitrile to provide the cyclopropapyrroloindole (XI). The reaction of (XI) with HBr in acetonitrile gives the bromomethyl derivative (XII), which is treated with 4-nitrophenyl chloroformate (XIII) to yield the active carbonate ester (XIV). Finally, this compound is treated with 1-methylpiperazine (XV) to provide the target Pibrozelesin.
| 【1】 Fukuda, Y.; et al.; Novel syntheses of optically active CC-1065, U-73,975 (adozelesin), U-80,244 (carzelesin), U-77,779 (bizelesin), KW-2189, and DU-86. Heterocycles 1997, 45, 12, 2303. |
| 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) | 59123 | tert-butyl (3S)-3-[(acetyloxy)methyl]-5-amino-6-(benzyloxy)-2,3-dihydro-1H-indole-1-carboxylate | C23H28N2O5 | 详情 | 详情 | |
| (II) | 11791 | methyl 3-oxobutanoate; Methyl acetoacetate | 105-45-3 | C5H8O3 | 详情 | 详情 |
| (III) | 61767 | tert-butyl (3S)-3-[(acetyloxy)methyl]-6-(benzyloxy)-5-{[(E)-3-methoxy-1-methyl-3-oxo-1-propenyl]amino}-2,3-dihydro-1H-indole-1-carboxylate | C28H34N2O7 | 详情 | 详情 | |
| (IV) | 61768 | 6-(tert-butyl) 1-methyl (8S)-8-[(acetyloxy)methyl]-4-(benzyloxy)-2-methyl-7,8-dihydropyrrolo[3,2-e]indole-1,6(3H)-dicarboxylate | C28H32N2O7 | 详情 | 详情 | |
| (V) | 61769 | 6-(tert-butyl) 1-methyl (8S)-4-(benzyloxy)-8-(hydroxymethyl)-2-methyl-7,8-dihydropyrrolo[3,2-e]indole-1,6(3H)-dicarboxylate | C26H30N2O6 | 详情 | 详情 | |
| (VI) | 61770 | 6-(tert-butyl) 1-methyl (8S)-4-(benzyloxy)-8-(chloromethyl)-2-methyl-7,8-dihydropyrrolo[3,2-e]indole-1,6(3H)-dicarboxylate | C26H29ClN2O5 | 详情 | 详情 | |
| (VII) | 61771 | 6-(tert-butyl) 1-methyl (8S)-8-(chloromethyl)-4-hydroxy-2-methyl-7,8-dihydropyrrolo[3,2-e]indole-1,6(3H)-dicarboxylate | C19H23ClN2O5 | 详情 | 详情 | |
| (VIII) | 61772 | methyl (8S)-8-(chloromethyl)-4-hydroxy-2-methyl-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate | C14H15ClN2O3 | 详情 | 详情 | |
| (IX) | 61773 | 5,6,7-trimethoxy-1H-indole-2-carboxylic acid | C12H13NO5 | 详情 | 详情 | |
| (X) | 61774 | methyl (8S)-8-(chloromethyl)-4-hydroxy-2-methyl-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate | C26H26ClN3O7 | 详情 | 详情 | |
| (XI) | 40881 | methyl (3bR,4aS)-2-methyl-8-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate | C26H25N3O7 | 详情 | 详情 | |
| (XII) | 61775 | methyl (8S)-8-(bromomethyl)-4-hydroxy-2-methyl-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate | C26H26BrN3O7 | 详情 | 详情 | |
| (XIII) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
| (XIV) | 61776 | methyl (8S)-8-(bromomethyl)-2-methyl-4-{[(4-nitrophenoxy)carbonyl]oxy}-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate | C33H29BrN4O11 | 详情 | 详情 | |
| (XV) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |