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【结 构 式】 
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【药物名称】Z-4105 【化学名称】N-(3-Carboxypropyl)-3-methylisoxazole-5-carboxamide 【CA登记号】119737-52-9 【 分 子 式 】C9H12N2O4 【 分 子 量 】212.20699 |
【开发单位】Zambon (Originator) 【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS |
合成路线1
Z-4105 was prepared according to the reaction sequence as follows: The isoxazole intermediate (III) was obtained by one-pot 1,3-dipolar cycloaddition between acetonitrile oxide, in situ generated from chlorooxime (II), and propargyl alcohol. The oxidation of compound (III) with potassium permanganate gave the acid (IV), which was subsequently converted into the acid chloride (V) by Burdett's method. Finally, Z-4105 was synthesized from (V) and gamma-aminobutyric acid by means of Schotten-Baumann procedure.
| 【1】 Burdett, K.A.; An improved acid chloride preparation via phase transfer catalysis. Synthesis 1991, 441-2. |
| 【2】 Casnati, G.; Ricca, A.; Aliphatic chloro oximes and their application in the synthesis of isoxazole and beta-furanone systems. Tetrahedron Lett 1967, 4, 327-30. |
| 【3】 Fusi, R.; Luperi, L.; Napoletano, M.; Ricciardi, S.; Masotto, C.; Z-4105. Drugs Fut 1995, 20, 6, 584. |
| 【4】 Carenzi, A.; Chiarino, D.; Della Bella, D.; Napoletano, M.; Sala, A. (Zambon Group SpA); Isoxazoles with nootropic activity. AU 8817869; EP 0317588; JP 1990500365; US 4985428; WO 8809330 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 13620 | 4-Amino-n-butyric acid; 4-Aminobutyric acid;Piperidinic acid;Piperidic acid | 56-12-2 | C4H9NO2 | 详情 | 详情 | |
| 16664 | Propargyl Alcohol; 2-propyn-1-ol | 107-19-7 | C3H4O | 详情 | 详情 | |
| (I) | 13341 | Acetaldehyde oxime | 107-29-9 | C2H5NO | 详情 | 详情 |
| (II) | 13342 | N-Hydroxyethanimidoyl chloride | C2H4ClNO | 详情 | 详情 | |
| (III) | 13343 | (3-Methyl-5-isoxazolyl)methanol | C5H7NO2 | 详情 | 详情 | |
| (IV) | 13344 | 3-Methyl-5-isoxazolecarboxylic acid | C5H5NO3 | 详情 | 详情 | |
| (V) | 13345 | 3-Methyl-5-isoxazolecarbonyl chloride | C5H4ClNO2 | 详情 | 详情 |