【结 构 式】 |
【药物名称】Clevidipine, Clevelox, Cleviprex 【化学名称】(±)-4-(2,3-Dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid butyryloxymethyl methyl diester 【CA登记号】167221-71-8, 166432-28-6 (deleted CAS) 【 分 子 式 】C21H23Cl2NO6 【 分 子 量 】456.32656 |
【开发单位】AstraZeneca (Originator), The Medicines Co. (Licensee) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Calcium Channel Blockers |
合成路线1
Clevidipine is prepared by esterification of 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester (I) with chloromethyl butyrate (II) by means of NaHCO3 in DMF at 80 oC (1) or refluxing acetonitrile (2).
【1】 Andersson, K.H.; Nordlander, M.; Westerlund, R.C. (AstraZeneca plc); Short-acting dihydropyridines. EP 0726894; JP 1997504542; US 5856346; WO 9512578 . |
【2】 Mattson, A.; Svensson, C.; Thornblom, K.; Odman, C. (AstraZeneca AB); New manufacturing process. CA 2349195; EP 1133473; US 6350877; WO 0031035 . |
【3】 Castañer, J., Sorbera, L.A.; Clevidipine. Drugs Fut 2004, 29 (2): 105 |
合成路线2
【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