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【结 构 式】 
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【药物名称】Aniracetam, Ro-13-5057, Reset, Ampamet, Sarpul, Draganon 【化学名称】1-p-Anisoyl-2-pyrrolidinone 【CA登记号】72432-10-1 【 分 子 式 】C12H13NO3 【 分 子 量 】219.24231 |
【开发单位】Roche (Originator), Biomedica Foscama (Licensee), Menarini (Licensee), Toyama (Licensee) 【药理作用】Cognition Disorders, Treatment of, Mood Disorders, Treatment of, NEUROLOGIC DRUGS, PSYCHOPHARMACOLOGIC DRUGS, Senile Dementia, Treatment of |
合成路线1
The silylation of 4-acetoxy-2-pyrrolidone (I) with trimethylchlorosilane (II) by means of triethyl amine in THF gives the corresponding N-trimethylsilyl derivative (III), which is condensed with 4-methoxybenzoyl chloride (IV) by means of NaHCO3 in THF yielding 1-(4-methoxybenzoyl)pyrrolin-2-one (V). Finally, this compound is reduced with H2 over Pd/C in ethyl acetate.
| 【1】 Kyburz, E.; Aschwanden, W. (F. Hoffmann-La Roche AG); 1-(p-Methoxy-p-hydroxy, and p-benzyloxybenzoyl)-2-pyrrolidinones. DD 141828; EP 0005143; EP 0044088; ES 477587; ES 483756; JP 54117468 . |
| 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) | 29095 | 4-Acetoxy-2-pyrrolidone; 5-Oxo-3-pyrrolidinyl acetate | C6H9NO3 | 详情 | 详情 | |
| (II) | 29096 | Chloro(trimethyl)silane; Trimethylsilyl chloride; Trimethylchlorosilane | 75-77-4 | C3H9ClSi | 详情 | 详情 |
| (III) | 29097 | 5-oxo-1-(trimethylsilyl)-3-pyrrolidinyl acetate | C9H17NO3Si | 详情 | 详情 | |
| (IV) | 22671 | 4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride | 100-07-2 | C8H7ClO2 | 详情 | 详情 |
| (V) | 29098 | 1-(4-methoxybenzoyl)-1,5-dihydro-2H-pyrrol-2-one | C12H11NO3 | 详情 | 详情 |
合成路线2
The condensation of 4-aminobutyric acid (VI) with acid chloride (IV) by means of NaOH in water gives 4-(4-methoxybenzoylamino)butyric acid (VII), which is then cyclized by means of P2O5 in phosphoric acid.
| 【1】 Kyburz, E.; Aschwanden, W. (F. Hoffmann-La Roche AG); 1-(p-Methoxy-p-hydroxy, and p-benzyloxybenzoyl)-2-pyrrolidinones. DD 141828; EP 0005143; EP 0044088; ES 477587; ES 483756; JP 54117468 . |
| 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) | 22671 | 4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride | 100-07-2 | C8H7ClO2 | 详情 | 详情 |
| (VI) | 13620 | 4-Amino-n-butyric acid; 4-Aminobutyric acid;Piperidinic acid;Piperidic acid | 56-12-2 | C4H9NO2 | 详情 | 详情 |
| (VII) | 29099 | 4-[(4-methoxybenzoyl)amino]butyric acid | C12H15NO4 | 详情 | 详情 |
合成路线3
By reaction of 2-pyrrolidinone (I) with p-methoxybenzoyl chloride (II) by means of triethylamine in ether or sodium hydride in DMF.
| 【1】 Kyburz, E.; Aschwanden, W.; 1-(P-Methoxy, p-hydroxy and p-benzyloxybenzoyl)-2-pyrrolidinones. EP 0005143; JP 54117468; US 4369139 . |
| 【2】 Blancafort, P.; Serradell, M.N.; Mealy, N.E.; Leeson, P.A.; Castaner, J.; Aniracetam. Drugs Fut 1981, 6, 3, 127. |