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【结 构 式】 
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【分子编号】11172 【品名】(1R,2S,6R,7S)-4-Oxatricyclo[5.2.1.0(2,6)]decane-3,5-dione 【CA登记号】6004-79-1 |
【 分 子 式 】C9H10O3 【 分 子 量 】166.1766 【元素组成】C 65.05% H 6.07% O 28.88% |
合成路线1
该中间体在本合成路线中的序号：(II)New syntheses of tandospirone have been described: 1) The hydrogenation of bicyclo[2.2.1]hept-5-ene-2,3-di-exo-carboxylic acid anhydride (I) with H2 over Pd/C in THF-water gives bicyclo[2.2.1]heptane-2,3-di-exo-carboxylic acid anhydride (II), which by reaction with ammonia in THF-water is converted into the imide (III). The reaction of (III) with 1,4-dibromobutane by means of K2CO3 in refluxing acetone yields N-(4-bromobutyl)bicyclo[2.2.1]heptane-2,3-di-exo-carboximide (IV), which is finally condensed with 1-(2-pyrimidinyl)piperazine (V) by means of K2CO3 and KI in hot DMF. 2) Imide (III) is condensed with propargyl bromide (VI) by means of K2CO3 in refluxing acetone affording N-propargylbicyclo[2.2.1]heptane-2,3-di-exo-carboximide (VII), which is allowed to react with piperazine (V) and formaldehyde by means of CuSO4 in dioxane to give N-[4-[4-(2-pyrimidinyl)piperazin-1-yl]-2-butynyl]bicyclo[2.2.1]heptane-2,3-di-exo-carboximide (VIII). Finally, this compound is reduced with H2 over Pd/C. 3) The condensation of piperazine (V) with 4-chlorobutyronitrile (IX) by means of NaOH in acetone gives 4-[4-(2-pyrimidinyl)piperazin-1-yl]butyronitrile (X), which is reduced with LiAlH4 in ether yielding 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine (XI). Finally, this compound is condensed with anhydride (II) in refluxing pyridine.
| 【1】 Kojima, A.; Ishizumi, K.; Antoku, F.; Synthesis and anxiolytic activity of N-substituted cyclic imides (1R*,2S*,3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3-bicyclo[2.2.1]heptanedicarboximide (tandospirone) and related compounds. Chem Pharm Bull 1991, 39, 9, 2288. |
| 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) | 11171 | (1R,2R,6S,7S)-4-Oxatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione | C9H8O3 | 详情 | 详情 | |
| (II) | 11172 | (1R,2S,6R,7S)-4-Oxatricyclo[5.2.1.0(2,6)]decane-3,5-dione | 6004-79-1 | C9H10O3 | 详情 | 详情 |
| (III) | 11173 | (1R,2S,6R,7S)-4-Azatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C9H11NO2 | 详情 | 详情 | |
| (IV) | 11174 | (1R,2S,6R,7S)-4-(4-Bromobutyl)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C13H18BrNO2 | 详情 | 详情 | |
| (V) | 11175 | 2-(1-Piperazinyl)pyrimidine; 2-Piperazinopyrimidine; N-(Pyrimidinyl)piperazine | 20980-22-7 | C8H12N4 | 详情 | 详情 |
| (VI) | 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 |
| (VII) | 11177 | (1R,2S,6R,7S)-4-(2-Propynyl)-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C12H13NO2 | 详情 | 详情 | |
| (VIII) | 11178 | (1R,2S,6R,7S)-4-[4-[4-(2-Pyrimidinyl)piperazino]-2-butynyl]-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C21H25N5O2 | 详情 | 详情 | |
| (IX) | 11179 | 4-Chlorobutanenitrile; 4-Chlorobutyronitrile | 628-20-6 | C4H6ClN | 详情 | 详情 |
| (X) | 11180 | 4-[4-(2-Pyrimidinyl)piperazino]butanenitrile | C12H17N5 | 详情 | 详情 | |
| (XI) | 11181 | 4-[4-(2-Pyrimidinyl)piperazino]butylamine; 4-[4-(2-Pyrimidinyl)piperazino]-1-butanamine | 33386-20-8 | C12H21N5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)By condensation of norbornane-2,3-di-endo-carboxylic anhydride (I) with 1-(4-aminobutyl)-4-(2 pyrimidinyl)piperazine (II) in refluxing pyridine.
| 【1】 Ishizumi, K.; Antoku, F.; Asami, Y. (Sumitomo Chemical Co., Ltd.); Succimide derivatives, compositions and method of use. CA 1184915; EP 0082402 . |
| 【2】 Castaner, J.; Prous, J.; SM-3997. Drugs Fut 1986, 11, 11, 949. |