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【结 构 式】 
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【分子编号】22088 【品名】2-[4-(3,4-dichlorophenyl)-1-piperazinyl]ethyl 3-oxobutanoate 【CA登记号】 |
【 分 子 式 】C16H20Cl2N2O3 【 分 子 量 】359.25188 【元素组成】C 53.49% H 5.61% Cl 19.74% N 7.8% O 13.36% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of 1 2-benzenediamine (I) with methyltetrahydro-5-methyl 4-oxo-3-thiophenecarboxylate (II) in toluene using a Dean-Stark trap gives the triyclic system (III), which is dehydrogenated to 4,9-dihydro-3-methyl-10H-thienol[3,4-b][1,5]benzodiazepin-10-one (IV). Treatment of (IV) with chloroacetyl chloride in dioxane in the presence of K2CO3 yields 4-chloroacetyl-4,9-dihydro-3-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one (V), which is finally reacted with N-methylpiperazine to produce telenzepine, which is isolated as the hydrochloride.
| 【1】 Borner, H.; Haffer, G.; Sauer, G. (Schering AG); Process for the preparation of 2-bromo-8-ergolinyl. DE 3340025; US 4970314 . |
| 【2】 Galvan, M.; Eltze, M.; Figala, V.; TELENZEPINE HYDROCHLORIDE < Rec INN >. Drugs Fut 1988, 13, 4, 327. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (A) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (I) | 12824 | 2-Aminophenylamine; o-Phenylenediamine; 1,2-Benzenediamine | 95-54-5 | C6H8N2 | 详情 | 详情 |
| (II) | 11372 | Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate | C5H9NO2 | 详情 | 详情 | |
| (II) | 22082 | methyl (5R)-5-methyl-4-oxotetrahydro-3-thiophenecarboxylate | C7H10O3S | 详情 | 详情 | |
| (III) | 22083 | (3R)-3-methyl-1,3,4,9-tetrahydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-one | C12H12N2OS | 详情 | 详情 | |
| (III) | 22088 | 2-[4-(3,4-dichlorophenyl)-1-piperazinyl]ethyl 3-oxobutanoate | C16H20Cl2N2O3 | 详情 | 详情 | |
| (IV) | 22084 | 3-methyl-4,9-dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-one | C12H10N2OS | 详情 | 详情 | |
| (V) | 22085 | 4-(2-chloroacetyl)-3-methyl-4,9-dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-one | C14H11ClN2O2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Hantzsch condensation of 2-[4-(3,4-dichlorophenyl)piperazin-1-yl]ethyl acetylacetate (III) with methyl 3-aminocrotonate (II) and 3-nitrobenzaldehyde (I) in eftuxing isopropanol affords title compound.
| 【1】 Zumin Tricerri, S.; Casagrande, C.; De Marchi, F.; Nicola, M. (Pierrel SpA); Dihydropyridines with an antagonistic activity to . EP 0097821; US 4894460 . |
| 【2】 Bani, M.; Favara, D.; P-0285. Drugs Fut 1988, 13, 4, 321. |