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【结 构 式】 
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【药物名称】Fezolamine fumarate, Win-41528-2 【化学名称】N,N-Dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine (E)-2-butenedioate (1:1) 【CA登记号】80410-37-3, 80410-36-2 (free base) 【 分 子 式 】C24H27N3O4 【 分 子 量 】421.50049 |
【开发单位】Sanofi-synthélabo (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS |
合成路线1
1) The condensation of 3,4-diphenylpyrazole (I) with acrylonitrile (II) by means of benzyl-trimethyl-ammonium hydroxide (Triton B) in dioxane gives 1-(2-cyanoethyl)-3,4-diphenylpyrazole (III), which is then reductocondensed with dimethylamine by means of H2 over Pd/C in ethanol.
| 【1】 Feigenson, M.E.; Hansen, P.E.; Bailey, D.M.; Pearl, J.; DeFelice, A.F.; Hlavac, A.G.; Baizman, E.R.; 3,4-Diphenyl-1H-pyrazole-1-propanamine antidepressants. J Med Chem 1985, 28, 256. |
| 【2】 Bailey, D.M. (Sanofi-Synthelabo); 1-Amino-lower-alkyl-3,4-diphenyl-1H-pyrazoles. US 4182895 . |
| 【3】 Prous, J.; Castaner, J.; Fezolamine fumarate. Drugs Fut 1988, 13, 10, 913. |
合成路线2
2) The condensation of (I) with methyl acrylate (IV) by means of Triton B as before gives methyl 3-(3,4-diphenylpyrazol-1-yl)propionate (V), which is saponified with KOH in refluxing methanol yielding the corresponding free acid (VI). The reaction of (VI) with SOCl2 in refluxing CHCl3 affords the acyl chloride (VII), which is treated with dimethylamine in THF to give N,N-dimethyl-3-(3,4-diphenylpyrazol-1-yl)propionamide (VIII). Finally, this compound is reduced with LiAlH4 in refluxing THF.
| 【1】 Bailey, D.M. (Sanofi-Synthelabo); 1-Amino-lower-alkyl-3,4-diphenyl-1H-pyrazoles. US 4182895 . |
| 【2】 Prous, J.; Castaner, J.; Fezolamine fumarate. Drugs Fut 1988, 13, 10, 913. |
| 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) | 23190 | 3,4-diphenyl-1H-pyrazole | C15H12N2 | 详情 | 详情 | |
| (IV) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
| (V) | 23194 | methyl 3-(3,4-diphenyl-1H-pyrazol-1-yl)propanoate | C19H18N2O2 | 详情 | 详情 | |
| (VI) | 23195 | 3-(3,4-diphenyl-1H-pyrazol-1-yl)propionic acid | C18H16N2O2 | 详情 | 详情 | |
| (VII) | 23196 | 3-(3,4-diphenyl-1H-pyrazol-1-yl)propanoyl chloride | C18H15ClN2O | 详情 | 详情 | |
| (VIII) | 23197 | 3-(3,4-diphenyl-1H-pyrazol-1-yl)-N,N-dimethylpropanamide | C20H21N3O | 详情 | 详情 |