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【结 构 式】 
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【分子编号】32799 【品名】1-[8-methoxy-4-(2-toluidino)-3-quinolinyl]-1-butanone 【CA登记号】 |
【 分 子 式 】C21H22N2O2 【 分 子 量 】334.41796 【元素组成】C 75.42% H 6.63% N 8.38% O 9.57% |
合成路线1
该中间体在本合成路线中的序号：(XII)This compound has been obtained by several related ways: 1) The reaction of ethyl butyrylacetate (I) with triethyl orthoformate and Ac2O gives acrylate (II), which by reaction with o-toluidine (III) yields the aminoacrylate (IV). The cyclization of (IV) by heating at 255 C in diphenyl ether affords the quinolone (V), which is treated with refluxing POCl3 to give 1-(4-chloro-8-methoxyquinolin-3-yl)-1-butanone (VI). The demethylation of (VI) with AlCl3 or BBr3 yields the 8-hydroxyquinoline (VII), which is condensed with o-toluidine (VIII) in refluxing dioxane affording 1-[8-hydroxy-4-(2-methylphenylamino)quinolin-3-yl-1-butanone (IX). Finally, this compound is condensed with 2-bromomethanol (X) by means of potassium tert-butoxide or with ethylene carbonate (XI) by means of K2CO3. 2) The condensation of chloroquinoline (VI) with o-toluidine (VIII) in refluxing dioxane gives 1-[8-methoxy-4-(2-methylphenylamino)quinolin-3-yl-1-butanone (XII), which is demethylated with AlCl3 or BBr3 as before yielding the previously reported 1-[8-hydroxy-4-(2-methylphenylamino)quinolin-3-yl-1-butanone (IX).
| 【1】 Atkins, R.J.; et al.; Synthetic routes to quinoline derivatives: Novel syntheses of 3-butyryl-8-methoxy-4-[(2-methylphenyl)amini]quinoline and 3-butyryl-8-(2-hydroxyethoxy)-4-[(2-methylphenyl)amino]quin. Org Process Res Dev 1997, 1, 3, 185. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 21304 | Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether | 122-51-0 | C7H16O3 | 详情 | 详情 | |
| (I) | 12516 | ethyl 3-oxohexanoate; ethyl butyrylacetate | 3249-68-1 | C8H14O3 | 详情 | 详情 |
| (II) | 12517 | ethyl (E)-2-butyryl-3-ethoxy-2-propenoate | C11H18O4 | 详情 | 详情 | |
| (III) | 25193 | 2-methoxyphenylamine; 2-methoxyaniline | 517-28-2 | C7H9NO | 详情 | 详情 |
| (IV) | 12518 | ethyl (Z)-2-butyryl-3-(2-methoxyanilino)-2-propenoate | C16H21NO4 | 详情 | 详情 | |
| (V) | 12519 | 3-Butyryl-8-methoxy-4(1H)-quinolinone | C14H15NO3 | 详情 | 详情 | |
| (VI) | 12520 | 1-(4-Chloro-8-methoxy-3-quinolinyl)-1-butanone | C14H14ClNO2 | 详情 | 详情 | |
| (VII) | 32800 | 1-(4-chloro-8-hydroxy-3-quinolinyl)-1-butanone | C13H12ClNO2 | 详情 | 详情 | |
| (VIII) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (IX) | 32801 | 1-[8-hydroxy-4-(2-toluidino)-3-quinolinyl]-1-butanone | C20H20N2O2 | 详情 | 详情 | |
| (X) | 10059 | Ethylene bromohydrin; 2-Bromo-1-ethanol | 540-51-2 | C2H5BrO | 详情 | 详情 |
| (XI) | 32802 | 1,3-dioxolan-2-one | 96-49-1 | C3H4O3 | 详情 | 详情 |
| (XII) | 32799 | 1-[8-methoxy-4-(2-toluidino)-3-quinolinyl]-1-butanone | C21H22N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)The condensation of 8-methoxyquinolin-4(1H)-one (XXI) with o-toluidine (VIII) gives the secondary amine (XXII), which is brominated with NBS to the 3-bromo derivative (XXIII). Finally, this compound is condensed with N-methoxy-N-methylbutyramide (XXIV) by means of BuLi to afford intermediate (XII).
| 【1】 Atkins, R.J.; et al.; Synthetic routes to quinoline derivatives: Novel syntheses of 3-butyryl-8-methoxy-4-[(2-methylphenyl)amini]quinoline and 3-butyryl-8-(2-hydroxyethoxy)-4-[(2-methylphenyl)amino]quin. Org Process Res Dev 1997, 1, 3, 185. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (XII) | 32799 | 1-[8-methoxy-4-(2-toluidino)-3-quinolinyl]-1-butanone | C21H22N2O2 | 详情 | 详情 | |
| (XXI) | 32780 | 8-methoxy-4(1H)-quinolinone | C10H9NO2 | 详情 | 详情 | |
| (XXII) | 32781 | 8-methoxy-N-(2-methylphenyl)-4-quinolinamine; N-(8-methoxy-4-quinolinyl)-N-(2-methylphenyl)amine | C17H16N2O | 详情 | 详情 | |
| (XXIII) | 32782 | N-(3-bromo-8-methoxy-4-quinolinyl)-N-(2-methylphenyl)amine; 3-bromo-8-methoxy-N-(2-methylphenyl)-4-quinolinamine | C17H15BrN2O | 详情 | 详情 | |
| (XXIV) | 32783 | N-methoxy-N-methylbutanamide | C6H13NO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XII)The condensation of ethoxymethylenemalonic acid diethyl ester (XXV) with 2-methoxyaniline (XXVI) in hot toluene gives the aminomethylene derivative (XXVII), which is cyclized with POCl3 and polyphosphoric acid (PPA) at 100 C yielding 8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (XXVIII), which is hydrolyzed with NaOH in methanol to the corresponding free acid (XXIX), and treated with refluxing SOCl2 to afford 4-chloro-8-methoxyquinoline-3-carbonyl chloride (XXX). The reaction of (XXX) with dimethylamine gives the corresponding amide (XXXI), which is condensed with o-toluidine (VIII) in refluxing dioxane yielding the expected secondary amine (XXXII). Finally, this compound is treated with propylmagnesium chloride (XXXIII) to afford the intermediate (XII).
| 【1】 Atkins, R.J.; et al.; Synthetic routes to quinoline derivatives: Novel syntheses of 3-butyryl-8-methoxy-4-[(2-methylphenyl)amini]quinoline and 3-butyryl-8-(2-hydroxyethoxy)-4-[(2-methylphenyl)amino]quin. Org Process Res Dev 1997, 1, 3, 185. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 19443 | N-methylmethanamine; N,N-dimethylamine | 124-40-3 | C2H7N | 详情 | 详情 | |
| 40593 | Sulfurous oxychloride; Thionyl chloride | 7719-09-7 | Cl2OS | 详情 | 详情 | |
| (VIII) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (XII) | 32799 | 1-[8-methoxy-4-(2-toluidino)-3-quinolinyl]-1-butanone | C21H22N2O2 | 详情 | 详情 | |
| (XXV) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
| (XXVI) | 25193 | 2-methoxyphenylamine; 2-methoxyaniline | 517-28-2 | C7H9NO | 详情 | 详情 |
| (XXVII) | 32784 | diethyl 2-[(2-methoxyanilino)methylene]malonate | C15H19NO5 | 详情 | 详情 | |
| (XXVIII) | 32785 | ethyl 8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C13H13NO4 | 详情 | 详情 | |
| (XXIX) | 32786 | 8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | C11H9NO4 | 详情 | 详情 | |
| (XXX) | 32787 | 4-chloro-8-methoxy-3-quinolinecarbonyl chloride | C11H7Cl2NO2 | 详情 | 详情 | |
| (XXXI) | 32788 | 4-chloro-8-methoxy-N,N-dimethyl-3-quinolinecarboxamide | C13H13ClN2O2 | 详情 | 详情 | |
| (XXXII) | 32789 | 8-methoxy-N,N-dimethyl-4-(2-toluidino)-3-quinolinecarboxamide | C20H21N3O2 | 详情 | 详情 | |
| (XXXIII) | 32790 | Chloro(propyl)magnesium | 2234-82-4 | C3H7ClMg | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XII)The reaction of acyl chloride (XXX) with propylmagnesium chloride (XXXIII) gives 1-(4-chloro-8-methoxyquinolin-3-yl)-1-butanone (XXXIV), which is finally condensed with o-toluidine (VIII) in refluxing dioxane to afford the intermediate (XII).
| 【1】 Atkins, R.J.; et al.; Synthetic routes to quinoline derivatives: Novel syntheses of 3-butyryl-8-methoxy-4-[(2-methylphenyl)amini]quinoline and 3-butyryl-8-(2-hydroxyethoxy)-4-[(2-methylphenyl)amino]quin. Org Process Res Dev 1997, 1, 3, 185. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (XII) | 32799 | 1-[8-methoxy-4-(2-toluidino)-3-quinolinyl]-1-butanone | C21H22N2O2 | 详情 | 详情 | |
| (XXX) | 32787 | 4-chloro-8-methoxy-3-quinolinecarbonyl chloride | C11H7Cl2NO2 | 详情 | 详情 | |
| (XXXIII) | 32790 | Chloro(propyl)magnesium | 2234-82-4 | C3H7ClMg | 详情 | 详情 |
| (XXXIV) | 12520 | 1-(4-Chloro-8-methoxy-3-quinolinyl)-1-butanone | C14H14ClNO2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XII)The cyclization of (XXVII) in refluxing POCl3 gives 4-chloro-8-methoxyquinoline-3-carboxylic acid ethyl ester (XXXV), which is condensed with o-toluidine (VIII) in refluxing dioxane yielding the secondary amine (XXXVI). Finally, this compound is condensed with propylmagnesium chloride (XXXIII) to afford the intermediate (XII).
| 【1】 Atkins, R.J.; et al.; Synthetic routes to quinoline derivatives: Novel syntheses of 3-butyryl-8-methoxy-4-[(2-methylphenyl)amini]quinoline and 3-butyryl-8-(2-hydroxyethoxy)-4-[(2-methylphenyl)amino]quin. Org Process Res Dev 1997, 1, 3, 185. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (XII) | 32799 | 1-[8-methoxy-4-(2-toluidino)-3-quinolinyl]-1-butanone | C21H22N2O2 | 详情 | 详情 | |
| (XXVII) | 32784 | diethyl 2-[(2-methoxyanilino)methylene]malonate | C15H19NO5 | 详情 | 详情 | |
| (XXXIII) | 32790 | Chloro(propyl)magnesium | 2234-82-4 | C3H7ClMg | 详情 | 详情 |
| (XXXV) | 32791 | ethyl 4-chloro-8-methoxy-3-quinolinecarboxylate | C13H12ClNO3 | 详情 | 详情 | |
| (XXXVI) | 32792 | ethyl 8-methoxy-4-(2-toluidino)-3-quinolinecarboxylate | C20H20N2O3 | 详情 | 详情 |