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【结 构 式】 
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【分子编号】12595 【品名】isopropyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate 【CA登记号】 |
【 分 子 式 】C14H15NO5 【 分 子 量 】277.27684 【元素组成】C 60.64% H 5.45% N 5.05% O 28.85% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of isopropyl acetoacetate (I) with 3-nitrobenzaldehyde (II) gives isopropyl 2-(3-nitrobenzylidene)acetoacetate (III), which is cyclized with methyl 3-amino-4,4-dimethoxycrotonate (IV) at 100 C yielding 5-isopropyl-3-methyl-2-(dimethoxymethyl)-6-methyl-4-(3-nitropheny)-1,4-dihydropyridine-3,5-dicarboxylate (V). The hydrolysis of the acetal group of (V) with HCl in acetone affords the corresponding 2-formyl derivative (VI), which is finally treated with hydroxylamine and acetic anhydride in acetic acid at 100 C.
| 【1】 Satu, Y. (Fujisawa Pharmaceutical Co., Ltd.); 1,4-Dihydropyridine derivatives and pharmaceutical method of the same. BE 0879263; DE 2940833; FR 2438654; GB 2036722; US 4284634; US 4338322 . |
| 【2】 Blancafort, P.; Castaner, J.; Serradell, M.N.; FR-34,235. Drugs Fut 1983, 8, 9, 776. |
| 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) | 13332 | isopropyl 3-oxobutanoate; Isopropyl acetoacetate | 542-08-5 | C7H12O3 | 详情 | 详情 |
| (II) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (III) | 12595 | isopropyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate | C14H15NO5 | 详情 | 详情 | |
| (IV) | 31096 | methyl (E)-3-amino-4,4-dimethoxy-2-butenoate | C7H13NO4 | 详情 | 详情 | |
| (V) | 31097 | 5-isopropyl 3-methyl 2-(dimethoxymethyl)-6-methyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate | C21H26N2O8 | 详情 | 详情 | |
| (VI) | 31098 | 5-isopropyl 3-methyl 2-formyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate | C19H20N2O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)By cyclocondensation of a mixture of isopropyl(m-nitrobenzylidene)acetylacetate (II), 2-methoxyethyl acetylacetate (I) and NH3 in refluxing ethanol.
| 【1】 Meyer, H.; et al.; Unsymmetrical esters of 1,4-dihydropyridine-3,5-dicarboxylic acid. BE 0781878; DE 2117571; FR 2132830; GB 1358951; US 3799934 . |
| 【2】 Castaner, J.; Serradell, M.N.; Mealy, N.E.; Blancafort, P.; Leeson, P.A.; Nimodipine. Drugs Fut 1981, 6, 2, 98. |
合成路线3
该中间体在本合成路线中的序号：(V)The esterification of cyanacetic acid (I) with 1-(diphenylmethyl)azetidin-3-ol (II) by means of dicyclohexylcarbodiimide (DCC) in hot THF gives the corresponding cyanacetic ester (III), which is treated with HCl and then with NH3 to afford amidinoacetic acid (1-diphenylmethyl)azetidin-3-yl ester (IV). Finally, this compound is cyclized with 2-(3-nitrobenzylidene)acetoacetic acid isopropyl ester (V) by means of sodium methoxide in refluxing isopropanol.
| 【1】 Koike, H.; Yoshimoto, M.; Nishino, H. (Sankyo Co., Ltd.; Ube Industries, Ltd.); Dihydropyridine derivs., their preparation and their use. EP 0266922; EP 0529702; JP 1988253082; US 4772596 . |
| 【2】 Prous, J.; Castaner, J.; CS-905. Drugs Fut 1990, 15, 7, 1671. |
| 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) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (II) | 12592 | 1-Benzhydryl-3-azetidinol; 1-Benzhydryl-3-hydroxyazetidine；1-benzhydrylazetidin-3-ol | 18621-17-5 | C16H17NO | 详情 | 详情 |
| (III) | 12593 | 1-benzhydryl-3-azetidinyl 2-cyanoacetate | C19H18N2O2 | 详情 | 详情 | |
| (IV) | 12594 | 1-benzhydryl-3-azetidinyl 3-amino-3-iminopropanoate | C19H21N3O2 | 详情 | 详情 | |
| (V) | 12595 | isopropyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate | C14H15NO5 | 详情 | 详情 |