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【结 构 式】 
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【分子编号】15537 【品名】2-ethyl-4(1H)-quinolinone 【CA登记号】 |
【 分 子 式 】C11H11NO 【 分 子 量 】173.21448 【元素组成】C 76.28% H 6.4% N 8.09% O 9.24% |
合成路线1
该中间体在本合成路线中的序号：(III)1) The cyclization of aniline (I) with propionylacetic acid methyl ester (II) by means of p-toluenesulfonic acid in refluxing cyclohexane gives 2-ethylquinolin-4(1H)-one (III), which is condensed with 5-[4'-(bromomethyl)biphenyl-2-yl]-2-(triphenylmethyl)tetrazole (IV) by means of NaH in DMF, yielding 2-ethyl-4-[2'-[1-(triphenylmethyl)tetrazol-5-yl]biphenyl-4-ylmethoxy] quinoline (V). Finally, this compound is deprotected with HCl in ethanol - methanol. 2) The condensation of 4-methylphenylboronic acid (VI) with 2-bromobenzonitrile (VII) by means of Na2CO3 and PdCl2 in toluene - methanol gives 2-(4-methylphenyl)benzonitrile (VIII), which is brominated with N-bromosuccinimide (NBS) and azobis(isobutyronitrile) (AIBN) in hot chlorobenzene, yielding the bromomethyl derivative (IX). The condensation of (IX) with quinolone (III) by means of K2CO3 in N-methylpyrrolidone affords 4-(2'-cyanobiphenyl-4-ylmethoxy)-2-ethylquinoline (X), which is treated with tributyltin hydrazide in refluxing toluene to afford 2-ethyl-4-[2'-[2-(tributyltin)tetrazol-5-yl]biphenyl-4-ylmethoxy] quinoline (XI). Finally, this compound is deprotected with NaNO2 and HCl in cool water.
| 【1】 Roberts, D.A.; Russell, S.T.; Pearce, R.J. (AstraZeneca plc); Quinoline derivs., process for their preparation and their use as medicaments. AU 9160955; EP 0412848; GB 2234748; JP 1991169863; US 5444071 . |
| 【2】 Prous, J.; Castaner, J.; Graul, A.; ICI-D8731. Drugs Fut 1993, 18, 5, 428. |
| 【3】 Bradbury, R.H.; Allott, C.P.; Dennis, M.; et al.; New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)quinoline derivatives. J Med Chem 1992, 35, 22, 4027. |
| 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) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (II) | 15536 | methyl 3-oxopentanoate | 30414-53-0 | C6H10O3 | 详情 | 详情 |
| (III) | 15537 | 2-ethyl-4(1H)-quinolinone | C11H11NO | 详情 | 详情 | |
| (IV) | 15538 | 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-2-trityl-2H-1,2,3,4-tetraazole | 124750-51-2 | C33H25BrN4 | 详情 | 详情 |
| (V) | 15539 | 2-ethyl-4-quinolinyl [2'-(2-trityl-2H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl ether; 2-ethyl-4-[[2'-(2-trityl-2H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methoxy]quinoline | C44H35N5O | 详情 | 详情 | |
| (VI) | 15540 | 4-methylphenylboronic acid; p-Tolylboronic acid | 5720-05-8 | C7H9BO2 | 详情 | 详情 |
| (VII) | 15541 | o-bromobenzonitrile; 2-bromobenzonitrile | 2042-37-7 | C7H4BrN | 详情 | 详情 |
| (VIII) | 13929 | 2-Cyano-4'-methylbiphenyl; 4'-Methyl[1,1'-biphenyl]-2-carbonitrile | 114772-53-1 | C14H11N | 详情 | 详情 |
| (IX) | 15332 | 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile; 4'-bromomethyl-2-cyanobiphenyl | 114772-54-2 | C14H10BrN | 详情 | 详情 |
| (X) | 15544 | 4'-[[(2-ethyl-4-quinolinyl)oxy]methyl][1,1'-biphenyl]-2-carbonitrile | C25H20N2O | 详情 | 详情 | |
| (XI) | 15545 | 5-[4'-(2-Ethylquinolin-4-yloxymethyl)biphenyl-2-yl]-2-(tributylstannyl)-2H-tetrazole | C37H47N5OSn | 详情 | 详情 |