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【结 构 式】 
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【药物名称】LENVATINIB MESYLATE 【化学名称】4-[3-Chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy]-7-methoxyquinoline-6-carboxamide methanesulfonate 【CA登记号】857890-39-2;417716-92-8 (as free base) 【 分 子 式 】C21H19ClN4O4.CH4O3 【 分 子 量 】522.959 |
【开发单位】University of Kansas, Division of Hematology/Oncology, Westwood, Kansas, USA 【药理作用】Multikinase inhibitor; Oncolytic |
合成路线1
Lenvatinib is prepared by condensation of 4-chloro-7-methoxyquinoline-6-carbonitrile (I) with 3-chloro-4-nitrophenol (II) in hot 2,6-lutidine to afford the 4-aryloxy quinoline (III), which by reduction of its nitro group by means of iron and ammonium chloride yields aniline (IV). Aniline (IV) is then condensed with cyclopropyl isocyanate (V), producing urea (VI), which is finally submitted to partial hydrolysis of the nitrile group under basic conditions .
| 【1】 Funahashi, Y., Arimoto, I., Matsukura, M. et al. (Eisai R&D Management Co., Ltd.). Nitrogenous aromatic ring compounds. CA 2426461, EP 1415987, EP1506962, EP 1777218, JP 2005272474, JP 2009215313, US 2004953908, US 2006160832, US 2006247259, US 7253286, US 7612092, US 2010197911, US 2011118470, US 7973160, US 8372981, WO 2002032872. |
| 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) | 67702 | 4-chloro-7-methoxyquinoline-6-carbonitrile | C11H7ClN2O | 详情 | 详情 | |
| (II) | 12599 | 3-Chloro-4-nitrophenol | 491-11-2 | C6H4ClNO3 | 详情 | 详情 |
| (III) | 67703 | 4-(3-chloro-4-nitrophenoxy)-7-methoxyquinoline-6-carbonitrile | C17H10ClN3O4 | 详情 | 详情 | |
| (IV) | 67704 | 4-(4-amino-3-chlorophenoxy)-7-methoxyquinoline-6-carbonitrile | C17H12ClNO2 | 详情 | 详情 | |
| (V) | 67705 | cyclopropyl isocyanate | 4747-72-2 | C4H5NO | 详情 | 详情 |
| (VI) | 67706 | 1-(2-chloro-4-((6-cyano-7-methoxyquinolin-4-yl)oxy)phenyl)-3-cyclopropylurea | C21H17ClN4O3 | 详情 | 详情 |