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【结 构 式】 
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【分子编号】20790 【品名】Methyl (Z)-2,3-dichlorobenzyldeneacetoacetate; Methyl (Z)-2-acetyl-3-(2,3-dichlorophenyl)-2-propenoate 【CA登记号】74073-22-6 |
【 分 子 式 】C12H10Cl2O3 【 分 子 量 】273.115 【元素组成】C 52.77% H 3.69% Cl 25.96% O 17.57% |
与该中间体有关的原料药合成路线共 5 条
合成路线1
该中间体在本合成路线中的序号：(I)By cyclization of methyl 2,3-dichlorobenzyldeneacetoacetate (I) with ethyl 3-aminocrotonate (II) in tert-butanol at room temperature.
| 【1】 Carter, R.E.; Berntsson, P.; Determination of te conformation of felodipine by 1H NMR-spinlattice relaxation time measurements. Acta Pharm Suec 1981, 18, 221-226. |
| 【2】 Bernston, P.B.; Carlsson, S.A.I.; Gaarder, J.O.; Ljung, B.R. (AstraZeneca AB); 2,6-Dimethyl-4-2,3-disubstituted phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid-3,5-asymmetric diesters having hypotensive properties, as well as method for treating hypertensive conditions and pharmaceutical preparations containing same. CA 1117530; EP 0007293; JP 55009083; US 4264611 . |
| 【3】 Blancafort, P.; Serradell, M.N.; Sneddon, J.M.; Castaner, J.; Felodipine. Drugs Fut 1982, 7, 3, 160. |
合成路线2
该中间体在本合成路线中的序号：(IV)By cyclization of 2-(2,3-dichlorobenzylidene)acetyl acetic acid methyl ester (IV) with acetylacetic acid ethyl ester (V) and ammonia (VI) in tert-butanol.
| 【1】 Bernston, P.B.; Carlsson, S.A.I.; Gaarder, J.O.; Ljung, B.R. (AstraZeneca AB); 2,6-Dimethyl-4-2,3-disubstituted phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid-3,5-asymmetric diesters having hypotensive properties, as well as method for treating hypertensive conditions and pharmaceutical preparations containing same. CA 1117530; EP 0007293; JP 55009083; US 4264611 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 20790 | Methyl (Z)-2,3-dichlorobenzyldeneacetoacetate; Methyl (Z)-2-acetyl-3-(2,3-dichlorophenyl)-2-propenoate | 74073-22-6 | C12H10Cl2O3 | 详情 | 详情 |
| (V) | 11819 | ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate | 141-97-9 | C6H10O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)1) By cyclization of methyl 2-(2,3-dichlorobenzylidene)acetoacetate (I) with isopropyl 3-amino-4-(carbamoyloxy)crotonate (II).
| 【1】 Migano, T. et al. (Banyu Pharmaceutical Co., Ltd.); 2-N-Substd. or unsubstd.-carbamoyloxy-alkyl-1, 4-dihydropyridine-3,5-dicarboxylic acid symmetrical or asymmetrical diester deriv. and its preparation. JP 1984152373 . |
| 【2】 Prous, J.; Castaner, J.; NB-818. Drugs Fut 1989, 14, 4, 331. |
合成路线4
该中间体在本合成路线中的序号：(I)2) By cyclization of (I) with isopropyl 4-(carbamoyloxy)-2-butynoate (III) and ammonium acetate (IV).
| 【1】 Migano, T. et al. (Banyu Pharmaceutical Co., Ltd.); 2-N-Substd. or unsubstd.-carbamoyloxy-alkyl-1, 4-dihydropyridine-3,5-dicarboxylic acid symmetrical or asymmetrical diester deriv. and its preparation. JP 1984152373 . |
| 【2】 Prous, J.; Castaner, J.; NB-818. Drugs Fut 1989, 14, 4, 331. |
合成路线5
该中间体在本合成路线中的序号：(I)
| 【1】 Andersson KH, Nordlander M, Westerlund RC, (AstraZeneca plc). Short-acting dihydropyridines. EP 0726894; JP 1997504542; US 5856346; WO 9512578. |
| 【2】 Kosugi Y, Hori M, Nagasaka T. 1994. Synthesis of optically pure 1,4-dihydropyridine derivatives by means od diastereoisomeric separation of the Hantzsch intermediates bearing (R) -1-phenylethylamino group. Heterocycles, 39(2) : 591～602. |
| 【3】 Mattson A, Svensson C, Thonblom K, et al. (AstraZeneca AB). New manufacturing process. CA 2349195; EP 1133473; US 6350877; WO 0031035. |
| 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) | 20790 | Methyl (Z)-2,3-dichlorobenzyldeneacetoacetate; Methyl (Z)-2-acetyl-3-(2,3-dichlorophenyl)-2-propenoate | 74073-22-6 | C12H10Cl2O3 | 详情 | 详情 |
| (II) | 67067 | (Z)-allyl 3-((1-phenylethyl)amino)but-2-enoate | C15H19NO2 | 详情 | 详情 | |
| (III) | 67068 | 1-methyl 5-vinyl 2-acetyl-3-(2,3-dichlorophenyl)-4-(1-((1-phenylethyl)amino)ethylidene)pentanedioate | C27H29Cl2NO5 | 详情 | 详情 | |
| (IV) | 67069 | 3-allyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate | C19H19Cl2NO4 | 详情 | 详情 | |
| (V) | 17945 | 4-(2,3-dichlorophenyl)-5-(methoxycarbonyl)-2,6-dimethyl-1,4-dihydro-3-pyridinecarboxylic acid | 105580-45-8 | C16H15Cl2NO4 | 详情 | 详情 |
| (VI) | 17946 | chloromethyl butyrate | 33657-49-7 | C5H9ClO2 | 详情 | 详情 |
Extended Information