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【结 构 式】 
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【分子编号】64761 【品名】7-fluoro-5-(trifluoromethyl)-5,10-dihydrobenzo[b][1,8]naphthyridin-5-ol 【CA登记号】 |
【 分 子 式 】C13H8F4N2O 【 分 子 量 】284.2130128 【元素组成】C 54.94% H 2.84% F 26.74% N 9.86% O 5.63% |
合成路线1
该中间体在本合成路线中的序号：(VI)The condensation of 2-chloropyridine (I) with ethyl trifluoroacetate (II) by means of LDA in THF gives 2-chloro-3-(trifluoroacetyl)pyridine (III), which is condensed with 4-fluoroaniline (IV) by means of refluxing aqueous acetic acid to yield the diarylamine (V). The cyclization of (V) by means of concentrated H2SO4 affords 7-fluoro-5-hydroxy-5-(trifluoromethyl)-5,10-dihydro-benzo[b]-1,8-naphthyridine (VI), which is dehydrated in THF to give 7-fluoro-5-(trifluoromethyl)benzo[b]-1,8-naphthyridine (VII). The condensation of (VII) with cyclopropylmethanol (VIII) by means of anhydrous HCl in dichloromethane yields the 5-(cyclopropylmethoxy)-7-fluoro-5-(trifluoromethyl)-5,10-dihydro-benzo[b]-1,8-naphthyridine (IX), which is oxidated by means of MCPBA in dichloromethane to afford the N-oxide (X) (1, 2). Finally, this racemic compound is submitted to chiral HPLC to obtain the target enantiomer (1).
| 【1】 Novel 5,10-dihydrobenzo[B][1,8]napthyridine N-oxides as non-nucleoside reverse transcriptase inhibitors of HIV-1 with high potency against clinically relevant mutants variants. 226th ACS Natl Meet (Sept 7 2003, New York) 2003, Abst MEDI 129. |
| 【2】 Patel, M.; Rodgers, J.D.; Wang, H.; Johnson, B.L. (Bristol-Myers Squibb Co.); Tricyclic cpds. useful as HIV reverse transcriptase inhibitors. JP 2003512375; US 6593337; WO 0129037 . |
| 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) | 17503 | 2-chloropyridine | 109-09-1 | C5H4ClN | 详情 | 详情 |
| (II) | 14588 | Ethyl 2,2,2-trifluoroacetate; Trifluoroethyl acetate | 383-63-1 | C4H5F3O2 | 详情 | 详情 |
| (III) | 64759 | 1-(2-chloro-3-pyridinyl)-2,2,2-trifluoro-1-ethanone | C7H3ClF3NO | 详情 | 详情 | |
| (IV) | 37690 | 4-fluorophenylamine; 4-fluoroaniline | 371-40-4 | C6H6FN | 详情 | 详情 |
| (V) | 64760 | 2,2,2-trifluoro-1-[2-(4-fluoroanilino)-3-pyridinyl]-1-ethanone | C13H8F4N2O | 详情 | 详情 | |
| (VI) | 64761 | 7-fluoro-5-(trifluoromethyl)-5,10-dihydrobenzo[b][1,8]naphthyridin-5-ol | C13H8F4N2O | 详情 | 详情 | |
| (VII) | 64762 | 7-fluoro-5-(trifluoromethyl)benzo[b][1,8]naphthyridine | C13H6F4N2 | 详情 | 详情 | |
| (VIII) | 64763 | cyclopropylmethanol | C4H8O | 详情 | 详情 | |
| (IX) | 64764 | 5-(cyclopropylmethoxy)-7-fluoro-5-(trifluoromethyl)-5,10-dihydrobenzo[b][1,8]naphthyridine; cyclopropylmethyl 7-fluoro-5-(trifluoromethyl)-5,10-dihydrobenzo[b][1,8]naphthyridin-5-yl ether | C17H14F4N2O | 详情 | 详情 | |
| (X) | 64765 | 5-(cyclopropylmethoxy)-7-fluoro-5-(trifluoromethyl)-5,10-dihydrobenzo[b][1,8]naphthyridin-1-ium-1-olate | C17H14F4N2O2 | 详情 | 详情 |