【结 构 式】 |
【分子编号】32790 【品名】Chloro(propyl)magnesium 【CA登记号】2234-82-4 |
【 分 子 式 】C3H7ClMg 【 分 子 量 】102.84628 【元素组成】C 35.04% H 6.86% Cl 34.47% Mg 23.63% |
合成路线1
该中间体在本合成路线中的序号:(XXIV)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:(XXIV)The reaction of acyl chloride (XXI) with propylmagnesium chloride (XXIV) gives 1-(4-chloro-8-methoxyquinolin-3-yl)-1-butanone (XXV), which is finally condensed with o-toluidine (VII) in refluxing dioxane 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 |
---|---|---|---|---|---|---|
(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 |
(XXI) | 32787 | 4-chloro-8-methoxy-3-quinolinecarbonyl chloride | C11H7Cl2NO2 | 详情 | 详情 | |
(XXIV) | 32790 | Chloro(propyl)magnesium | 2234-82-4 | C3H7ClMg | 详情 | 详情 |
(XXV) | 12520 | 1-(4-Chloro-8-methoxy-3-quinolinyl)-1-butanone | C14H14ClNO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号:(XXIV)The cyclization of (XVIII) in refluxing POCl3 gives 4-chloro-8-methoxyquinoline-3-carboxylic acid ethyl ester (XXVI), which is condensed with o-toluidine (VII) in refluxing dioxane yielding the secondary amine (XXVII). Finally, this compound is condensed 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 |
---|---|---|---|---|---|---|
(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 |
(XVIII) | 32784 | diethyl 2-[(2-methoxyanilino)methylene]malonate | C15H19NO5 | 详情 | 详情 | |
(XXIV) | 32790 | Chloro(propyl)magnesium | 2234-82-4 | C3H7ClMg | 详情 | 详情 |
(XXVI) | 32791 | ethyl 4-chloro-8-methoxy-3-quinolinecarboxylate | C13H12ClNO3 | 详情 | 详情 | |
(XXVII) | 32792 | ethyl 8-methoxy-4-(2-toluidino)-3-quinolinecarboxylate | C20H20N2O3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号:(XXXIII)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5
该中间体在本合成路线中的序号:(XXXIII)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6
该中间体在本合成路线中的序号:(XXXIII)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 |