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【结 构 式】

【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information