|
【结 构 式】 
|
【分子编号】52776 【品名】N-(8-amino-6-fluoro-5-methyl-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)acetamide 【CA登记号】 |
【 分 子 式 】C13H15FN2O2 【 分 子 量 】250.2727832 【元素组成】C 62.39% H 6.04% F 7.59% N 11.19% O 12.79% |
合成路线1
该中间体在本合成路线中的序号：(XXI)The pyranoindolizine acetal (XVIII) was hydrolyzed to the trione (XIX) in 90% trifluoroacetic acid. Condensation of (XIX) with amino ketone (XVII) in refluxing toluene produced the hexacyclic compound (XX) as a diastereomeric mixture. The title compound was then obtained by acidic hydrolysis of the trifluoroacetamido group, followed by isolation of the desired isomer by preparative HPLC. The synthesis of the title compound was also reported by condensation of trione (XIX) with the acetamido tetralone (XXI). The resultant hexacyclic acetamide (XXII) was subsequently hydrolyzed with methanesulfonic acid, and the diastereomeric mixture of mesylate salts was finally separated by fractional crystallization.
| 【1】 Chilman-Blair, K.; Mealy, N.E.; Castaner, J.; Bayes, M.; Exatecan Mesilate. Drugs Fut 2004, 29, 1, 9. |
| 【2】 Terasawa, H.; Ejima, A.; Ohsuki, S.; Uoto, K. (Daiichi Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.); Hexacyclic cpd.. EP 0495432; JP 1993059061; US 5834476; US 6407115 . |
| 【3】 Kamihara, S.; Kanai, K.; Noguchi, S.; Terasawa, H.; Kitaoka, H. (Daiichi Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.); Campthothecin deriv. with antitumour activity. CA 2173671; EP 0737686; JP 1996337584 . |
| 【4】 Terasawa, H.; Sato, K.; Mitsui, I. (Daiichi Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.); Antitumor agents. JP 1994087746 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 52774 | N-(8-amino-6-fluoro-5-methyl-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)-2,2,2-trifluoroacetamide | C13H12F4N2O2 | 详情 | 详情 | |
| (XVIII) | 52775 | C15H17NO6 | 详情 | 详情 | ||
| (XIX) | 10841 | (4S)-4-Ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione | C13H13NO5 | 详情 | 详情 | |
| (XX) | 52777 | N-[(9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl]-2,2,2-trifluoroacetamide | C26H21F4N3O5 | 详情 | 详情 | |
| (XXI) | 52776 | N-(8-amino-6-fluoro-5-methyl-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)acetamide | C13H15FN2O2 | 详情 | 详情 | |
| (XXII) | 52778 | N-[(9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl]acetamide | C26H24FN3O5 | 详情 | 详情 |