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【结 构 式】 
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【分子编号】40978 【品名】1,2,2a,3,9,9a-hexahydro-4H-benzo[e]cyclopropa[c]indol-4-one 【CA登记号】 |
【 分 子 式 】C13H13NO 【 分 子 量 】199.25236 【元素组成】C 78.36% H 6.58% N 7.03% O 8.03% |
合成路线1
该中间体在本合成路线中的序号：(II)Treatment of the cyclopropabenzindole derivative (CBI) (I) with hydrochloric acid in ethyl acetate affords the chloromethyl derivative (II). The final step is the condensation of (II) with the acid (VIII) by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) in DMF. The acid (VIII) was prepared as follows: Ethyl 5-nitroindole-2-carboxylate (III) is reductively transformed to its corresponding amine (IV) by hydrogenation over Pd/C. The amine (IV) is then converted to its acetamido ester (V) by treatment with acetic anhydride in ethyl acetate. Ester (V) is then hydrolyzed using NaOH to afford the corresponding acid (VI), which is coupled to amine (IV) in the presence of EDCI to yield ester (VII). Finally (VII) is converted to acid (VIII) by treatment with NaOH.
| 【1】 Wang, Y.; Ye, W.; Wright, S.C.; Larrick, J.W.; Wang, H.; Yuan, H.; Synthesis and preliminary biological evaluations of CC-1065 analogues: Effects of different linkers terminal amides on biological activity. J Med Chem 2000, 43, 8, 1541. |
| 【2】 Larrick, J.W.; Wright, S.C.; Wang, Y. (Panorama Research, Inc.); DNA-binding indole derivs., their prodrugs and immunoconjugates as anticancer agents. WO 9744000 . |
| 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) | 40977 | 1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol | C13H12ClNO | 详情 | 详情 | |
| (II) | 40978 | 1,2,2a,3,9,9a-hexahydro-4H-benzo[e]cyclopropa[c]indol-4-one | C13H13NO | 详情 | 详情 | |
| (III) | 38163 | ethyl 5-nitro-1H-indole-2-carboxylate | 16732-57-3 | C11H10N2O4 | 详情 | 详情 |
| (IV) | 38164 | ethyl 5-amino-1H-indole-2-carboxylate | C11H12N2O2 | 详情 | 详情 | |
| (V) | 40973 | ethyl 5-(acetamido)-1H-indole-2-carboxylate | C13H14N2O3 | 详情 | 详情 | |
| (VI) | 40974 | 5-(acetamido)-1H-indole-2-carboxylic acid | C11H10N2O3 | 详情 | 详情 | |
| (VII) | 40975 | ethyl 5-([[5-(acetamido)-1H-indol-2-yl]carbonyl]amino)-1H-indole-2-carboxylate | C22H20N4O4 | 详情 | 详情 | |
| (VIII) | 40976 | 5-([[5-(acetamido)-1H-indol-2-yl]carbonyl]amino)-1H-indole-2-carboxylic acid | C20H16N4O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Coupling between ethyl 5-aminoindole-2-carboxylate (I) and 5-nitrobenzofuran-2-carboxylic acid (II) by means of HBTU affords amide (III). Subsequent ethyl ester hydrolysis under alkaline conditions yields the carboxylic acid (IV). Ring opening of the cyclopropane-fused compound (V) with anhydrous HCl in EtOAc leads to the chloromethyl compound (VI). Acid (IV) is finally coupled to amine (VI) in the presence of EDC to furnish the title compound.
| 【1】 Wang, Y.; Li, L.; Ye, W.; Tian, Z.; Jiang, W.; Wang, H.; Wright, S.C.; Larrick, J.W.; CC-1065 analogues bearing different DNA-binding subunits: Synthesis, antitumor activity, and preliminary toxicity study. J Med Chem 2003, 46, 4, 634. |
| 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) | 38164 | ethyl 5-amino-1H-indole-2-carboxylate | C11H12N2O2 | 详情 | 详情 | |
| (II) | 63365 | 5-nitro-1-benzofuran-2-carboxylic acid | 10242-12-3 | C9H5NO5 | 详情 | 详情 |
| (III) | 63366 | ethyl 5-{[(5-nitro-1-benzofuran-2-yl)carbonyl]amino}-1H-indole-2-carboxylate | C20H15N3O6 | 详情 | 详情 | |
| (IV) | 63367 | 5-{[(5-nitro-1-benzofuran-2-yl)carbonyl]amino}-1H-indole-2-carboxylic acid | C18H11N3O6 | 详情 | 详情 | |
| (V) | 40978 | 1,2,2a,3,9,9a-hexahydro-4H-benzo[e]cyclopropa[c]indol-4-one | C13H13NO | 详情 | 详情 | |
| (VI) | 40977 | 1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol | C13H12ClNO | 详情 | 详情 |