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【结 构 式】

【分子编号】67563

【品名】1-(6-chloro-5-fluoro-1H-indol-3-yl)propan-2-amine

【CA登记号】 

【 分 子 式 】C11H12ClFN2

【 分 子 量 】226.681

【元素组成】C 58.28% H 5.33% Cl 15.64% F 8.38% N 12.36%

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:(XVII)

Vilsmeier-Haack formylation of 6-chloro-5-fluoroindole (I) with dimethylformamide (XIII) by means of POCl3 gives 6-chloro-5-fluoroindole-3-carbaldehyde (XIV), which by Henry reaction with nitroethane (XV) in the presence of NH4OAc yields 6-chloro-5-fluoro-3-(2-nitroprop-1-enyl)indole (XVI). Reduction of the unsaturated nitro compound (XVI) by means of LiAlH4 in refluxing THF provides the trypt amine derivative (XVII), which is then subjected to Pictet-Spengler cyclization with 5-chloroisatin (XII) by means of p-TsOH in EtOH at 110 °C to afford spiro racemate (XVIII). Finally, chiral chromatography of racemate (XVIII) affords the desired (1R,3S)-enantiomer .

1 Ang, S.H., Krastel, P., Leong, S.Y., Tan, L.J., Wong, W.L.J., Yeung, B.K.S., Zou, B. (Novartis AG). Spiro-indole derivatives for the treatment of parasitic diseases. CN 102015711; EP 2722333; KR 2010135320; EP 2285808;JP 2011518852; US 8399453; US 2011275613; WO 2009132921; US 2009275560; US 8053442.
2 Yeung, B.K., Zou, B., Rottmann, M. et al. Spirotetrahydro beta-carbolines (spiroindolones): a new class of potent and orally efficacious compounds for the treatment of malaria. J Med Chem 2010, 53(14): 5155-64.
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) 30025 6-Chloro-5-fluoroindole; 6-Chloro-5-fluoro-1H-indole 122509-72-2 C8H5ClFN 详情 详情
(XII) 14099 5-Chloro-1H-indole-2,3-dione; 5-Chloroisatin 17630-76-1 C8H4ClNO2 详情 详情
(XIII) 33491 Dimethylformamide 68-12-2 C3H7NO 详情 详情
(XIV) 67561 6-chloro-5-fluoroindole-3-carbaldehyde   C9H5ClFNO 详情 详情
(XV) 12117 Nitroethane; 1-Nitroethane 79-24-3 C2H5NO2 详情 详情
(XVI) 67562 (Z)-6-chloro-5-fluoro-3-(2-nitroprop-1-en-1-yl)-1H-indole   C11H8ClFN2O2 详情 详情
(XVII) 67563 1-(6-chloro-5-fluoro-1H-indol-3-yl)propan-2-amine   C11H12ClFN2 详情 详情
(XVIII) 67564 5,7'-dichloro-6'-fluoro-3'-methyl-2',3',4',9'-tetrahydrospiro[indoline-3,1'-pyrido[3,4-b]indol]-2-one   C19H14Cl2FN3O 详情 详情
Extended Information