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【结 构 式】 
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【分子编号】12277 【品名】3-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl] 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate 【CA登记号】 |
【 分 子 式 】C22H26N2O8 【 分 子 量 】446.45712 【元素组成】C 59.19% H 5.87% N 6.27% O 28.67% |
合成路线1
该中间体在本合成路线中的序号：(VI)This compound can be obtained in two different ways: 1) The reaction of 8-(4-chlorophenyl)-8-aza-1,4-dioxaspiro[4.5]decane-2-methanol (I) with 5-acetyl-2,2-dimethyl-1,3-dioxane-4,6-dione (acetylated Meldrum's acid, II) in refluxing toluene gives the corresponding acetylacetic ester (III), which by reaction with NH3 in dry dichloromethane is converted into the 3-aminocrotonic ester (IV). Finally, this compound is cyclized with methyl 2-(3-nitrobenzylidene)acetylacetate (V) in refluxing tert-butanol. 2) The partial hydrolysis of 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl) 5-methyl diester (VI) with HCl 1N in methanol gives the corresponding glycerol ester (VII), which is then spiranized with 1-(4-chlorophenyl)-4-piperidone (VIII) by means of p-toluenesulfonic acid in refluxing methanol.
| 【1】 Robin, J.; Pruneau, D.; Bellamy, F. (SORI); Disymetric derivs. of 1,4-dihydropyridine-3,5-dicarboxylic acid, method of preparation and use in therapeutics. EP 0240398; FR 2596760; JP 1988017883; US 4806544 . |
| 【2】 Prous, J.; Castaner, J.; CRONIDIPINE. Drugs Fut 1990, 15, 4, 341. |
| 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) | 12272 | [8-(4-Chlorophenyl)-1,4-dioxa-8-azaspiro[4.5]dec-2-yl]methanol | C14H18ClNO3 | 详情 | 详情 | |
| (II) | 12273 | 5-Acetyl-2,2-dimethyl-1,3-dioxane-4,6-dione | C8H10O5 | 详情 | 详情 | |
| (III) | 12274 | [8-(4-chlorophenyl)-1,4-dioxa-8-azaspiro[4.5]dec-2-yl]methyl 3-oxobutanoate | C18H22ClNO5 | 详情 | 详情 | |
| (IV) | 12275 | [8-(4-chlorophenyl)-1,4-dioxa-8-azaspiro[4.5]dec-2-yl]methyl (E)-3-amino-2-butenoate | C18H23ClN2O4 | 详情 | 详情 | |
| (V) | 12276 | methyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate | C12H11NO5 | 详情 | 详情 | |
| (VI) | 12277 | 3-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl] 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate | C22H26N2O8 | 详情 | 详情 | |
| (VII) | 12278 | 3-(2,3-dihydroxypropyl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate | C19H22N2O8 | 详情 | 详情 | |
| (VIII) | 12279 | 1-(4-Chlorophenyl)tetrahydro-4(1H)-pyridinone | C11H12ClNO | 详情 | 详情 |