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【结 构 式】 
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【分子编号】68969 【品名】ethyl 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-carboxylate 【CA登记号】 |
【 分 子 式 】C14H15NO2 【 分 子 量 】229.27864 【元素组成】C 73.34% H 6.59% N 6.11% O 13.96% |
合成路线1
该中间体在本合成路线中的序号：(XXII)The 2,3-disubstituted maleimide intermediate (X) is prepared by N-alkylation of 1,2,3,4-tetrahydroquinoline (XIX) with ethyl 3-bromopyruvate (XX) in THF to give ethyl 3-(3,4-dihydro-2H-quinolin-1-yl)-2-oxopropionate (XXI), which by intramolecular cyclocondensation by means of MgCl2 in 2-methoxyethanol at 125 °C affords ethyl 5,6-dihydropyrrolo[3,2,1-ij]quinoline-1-carboxylate (XXII). Hydrolysis of ethyl ester (XXII) with NaOH in EtOH/H2O provides the corresponding carboxylic acid (XXIII), which is then decarboxylated to 5,6-dihydropyrrolo[3,2,1-ij]quinoline (lilolidine) (XVII) by heating to 185 °C in quinoline in the presence of CuO·Cr2O3 . Acylation of lilolidine (XVII) with (COCl)2 in Et2O, and subsequent quenching of the resulting glyoxylyl chloride with MeOH or NaOMe/MeOH affords the oxoester (XXIV), which is finally cyclocondensed with indole-3-acetamide (XXV) in the presence of t-BuOK in THF .
| 【1】 Li, C.J., Ashwell, M.A., Hill, J., Moussa, M.M., Munshi, N. (ArQule, Inc.). Maleimide derivatives, pharmaceutical compositions and methods for treatment of cancer. CN 10194970, EP 1846406, EP 2289892, JP 2008530026, US 2006223760, US 7713969, WO 2006086484. |
| 【2】 Chan, T.C.K., France, D.S., Ishii, K. (ArQule, Inc.; Kyowa Hakko Kirin Co., Ltd.). Combinational compositions and methods for treatment of cancer. KR 2011118817, US 2010297075, WO 2010093789. |
| 【3】 Reed, D.P., Barnes, N.R., Kane, J.C., Lee, C.A., Chen, J.-X., Redmon, M.P.(ArQule, Inc.). Purified pyrroloquinolinyl-pyrrolidine-2,5-dione compositions and methods for preparing and using same. US 201116022, WO 2011079142. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 68960 | 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione | C23H17N3O2 | 详情 | 详情 | |
| (XVII) | 68966 | 5,6-dihydropyrrolo[3,2,1-ij]quinoline;5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline;1,7-Trimethyleneindol;1,8-Trimethyleneindole | 5840-01-7 | C11H11N | 详情 | 详情 |
| (XIX) | 23859 | 1,2,3,4-tetrahydroquinoline | 635-46-1 | C9H11N | 详情 | 详情 |
| (XX) | 25183 | ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate | 70-23-5 | C5H7BrO3 | 详情 | 详情 |
| (XXI) | 68968 | ethyl 3-(3,4-dihydro-2H-quinolin-1-yl)-2-oxopropionate | C14H17NO3 | 详情 | 详情 | |
| (XXII) | 68969 | ethyl 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-carboxylate | C14H15NO2 | 详情 | 详情 | |
| (XXIII) | 68970 | 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1-carboxylic acid | C12H11NO2 | 详情 | 详情 | |
| (XXIV) | 68971 | methyl 2-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-2-oxoacetate | C14H13NO3 | 详情 | 详情 | |
| (XXV) | 48682 | Indole-3-acetamide;3-Indoleacetamide;2-(1H-indol-3-yl) | 879-37-8 | C10H10N2O | 详情 | 详情 |