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【结 构 式】 
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【分子编号】32788 【品名】4-chloro-8-methoxy-N,N-dimethyl-3-quinolinecarboxamide 【CA登记号】 |
【 分 子 式 】C13H13ClN2O2 【 分 子 量 】264.7112 【元素组成】C 58.99% H 4.95% Cl 13.39% N 10.58% O 12.09% |
合成路线1
该中间体在本合成路线中的序号：(XXII)The condensation of ethoxymethylenemalonic acid diethyl ester (XVI) with 2-methoxyaniline (XVII) in hot toluene gives the aminomethylene derivative (XVIII), 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 (XIX), which is hydrolyzed with NaOH in methanol to the corresponding free acid (XX), and treated with refluxing SOCl2 to afford 4-chloro-8-methoxyquinoline-3-carbonyl chloride (XXI). The reaction of (XXI) with dimethylamine gives the corresponding amide (XXII), which is condensed with o-toluidine (VII) in refluxing dioxane yielding the expected secondary amine (XXIII). Finally, this compound is treated with propylmagnesium chloride (XXIV) to afford the target compound.
| 【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 | |
| (VII) | 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 |
| (XVI) | 14088 | Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate | 87-13-8 | C10H16O5 | 详情 | 详情 |
| (XVII) | 25193 | 2-methoxyphenylamine; 2-methoxyaniline | 517-28-2 | C7H9NO | 详情 | 详情 |
| (XVIII) | 32784 | diethyl 2-[(2-methoxyanilino)methylene]malonate | C15H19NO5 | 详情 | 详情 | |
| (XIX) | 32785 | ethyl 8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C13H13NO4 | 详情 | 详情 | |
| (XX) | 32786 | 8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | C11H9NO4 | 详情 | 详情 | |
| (XXI) | 32787 | 4-chloro-8-methoxy-3-quinolinecarbonyl chloride | C11H7Cl2NO2 | 详情 | 详情 | |
| (XXII) | 32788 | 4-chloro-8-methoxy-N,N-dimethyl-3-quinolinecarboxamide | C13H13ClN2O2 | 详情 | 详情 | |
| (XXIII) | 32789 | 8-methoxy-N,N-dimethyl-4-(2-toluidino)-3-quinolinecarboxamide | C20H21N3O2 | 详情 | 详情 | |
| (XXIV) | 32790 | Chloro(propyl)magnesium | 2234-82-4 | C3H7ClMg | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXI)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 |