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【结 构 式】 
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【分子编号】40697 【品名】4-(2-chloroethyl)-7-fluoro-2(1H)-quinolinone 【CA登记号】 |
【 分 子 式 】C11H9ClFNO 【 分 子 量 】225.6497032 【元素组成】C 58.55% H 4.02% Cl 15.71% F 8.42% N 6.21% O 7.09% |
合成路线1
该中间体在本合成路线中的序号：(VII)Condensation of 3-fluoroaniline (I) with the cyclic anhydride (II) in AcOH gave amide (III). Subsequent cyclization of (III) in hot H2SO4 produced quinolineacetic acid (IV). After esterification of (IV) with methanol in the presence of SOCl2, the resulting methyl ester (V) was reduced to alcohol (VI) using NaBH4 in refluxing THF. Treatment of alcohol (VI) with SOCl2 afforded chloride (VII), which was condensed with 4-(1-piperazinyl)thieno[3,2-c]pyridine (VIII) yielding adduct (IX), isolated as the dihydro-chloride salt. Finally, alkylation of the quinoline N atom of (IX) with bromoacetamide (A) under phase-transfer conditions furnished the title compound.
| 【1】 McCort, G.; et al.; Synthesis and SAR of 3- and 4-substituted quinolin-2-ones: Discovery of mixed 5-HT1b/5-HT2A receptor antagonists. Bioorg Med Chem 2001, 9, 8, 2129. |
| 【2】 Demarquay, D.; Lavergne, O.; Bailly, C.; et al.; Topoisomerase I-mediated antiproliferative activity of enantiomerically pure fluorinated homocamptothecins. J Med Chem 2000, 43, 11, 2285. |
| 【3】 Mc Cort, G.; Hoornaert, C.; Dellac, G.; Aletru, M. (Sanofi-Synthelabo ); Quinolein-2(1H)-one derivs. as serotonin antagonists. EP 0850235; FR 2738822; FR 2739100; JP 1999514982; US 5958924; WO 9710238 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 38747 | 2-bromoacetamide | 683-57-8 | C2H4BrNO | 详情 | 详情 |
| (I) | 20697 | 3-fluoroaniline; 3-fluorophenylamine | 372-19-0 | C6H6FN | 详情 | 详情 |
| (II) | 40692 | 2,6-dioxo-3,6-dihydro-2H-pyran-4-yl acetate | C7H6O5 | 详情 | 详情 | |
| (III) | 40693 | (Z)-3-(acetoxy)-5-(3-fluoroanilino)-5-oxo-2-pentenoic acid | C13H12FNO5 | 详情 | 详情 | |
| (IV) | 40694 | 2-(7-fluoro-2-oxo-1,2-dihydro-4-quinolinyl)acetic acid | C11H8FNO3 | 详情 | 详情 | |
| (V) | 40695 | methyl 2-(7-fluoro-2-oxo-1,2-dihydro-4-quinolinyl)acetate | C12H10FNO3 | 详情 | 详情 | |
| (VI) | 40696 | 7-fluoro-4-(2-hydroxyethyl)-2(1H)-quinolinone | C11H10FNO2 | 详情 | 详情 | |
| (VII) | 40697 | 4-(2-chloroethyl)-7-fluoro-2(1H)-quinolinone | C11H9ClFNO | 详情 | 详情 | |
| (VIII) | 40698 | 4-(1-piperazinyl)thieno[3,2-c]pyridine | C11H13N3S | 详情 | 详情 | |
| (IX) | 40699 | 7-fluoro-4-[2-(4-thieno[3,2-c]pyridin-4-yl-1-piperazinyl)ethyl]-2(1H)-quinolinone | C22H21FN4OS | 详情 | 详情 |