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【结 构 式】 
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【药物名称】Ciclazindol, Wy-23409 【化学名称】10-(m-Chlorophenyl)-2,3,4,10-tetrahydropyrimido[1,2-a]indol-10-ol 【CA登记号】37751-39-6 【 分 子 式 】C17H15ClN2O 【 分 子 量 】298.7749 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS |
合成路线1
The reaction of 2-amino-3'-chlorobenzophenone (I) with dichloroacetyl chloride (II) in acetone gives o-(m'-chlorobenzoyl)-2,2-dichloroacetanilide (III), which is cyclized with potassium cyanide in water yielding 2-amino-3-(m-chlorophenyl-3H-indol-3-ol (IV). Finally, this compound is condensed with 1,3-dibromopropane (A) in refluxing ethanol.
| 【1】 White, A.C.; Bell, S.C. (John Wyeth & Brother Ltd.); Process for the preparation of diazepino[1,2-a]indoles. CH 590286; DE 2417917; FR 2247227; GB 1427066; US 3931226 . |
| 【2】 Weetman, D.F.; Castaner, J.; Ciclazindol. Drugs Fut 1977, 2, 8, 508. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (I) | 40184 | (2-aminophenyl)(3-chlorophenyl)methanone | C13H10ClNO | 详情 | 详情 | |
| (II) | 17829 | 2,2-dichloroacetyl chloride; dichloroacetyl chloride | 79-36-7 | C2HCl3O | 详情 | 详情 |
| (III) | 40185 | 2,2-dichloro-N-[2-(3-chlorobenzoyl)phenyl]acetamide | C15H10Cl3NO2 | 详情 | 详情 | |
| (IV) | 40186 | 2-amino-3-(3-chlorophenyl)-3H-indol-3-ol | C14H11ClN2O | 详情 | 详情 |
合成路线2
The reduction of 2'-oxospiro-(1,3-dioxolane-2,3'-indoline)-1'-propionitrile (V) with H2 over Raney-Ni in NH3 saturated ethanol gives 2'-oxospiro-(1,3-dioxolane-2,3'-indoline)-1'-propanamine (VI), which, without isolation, is cyclized in refluxing xylene yielding 3',4'-dihydrospiro[1,3-dioxolane-2,10'(2H,10H)pyrimido-[1,2-a]indole] (VII). The hydrolysis of (VII) with aqueous HCl at 85 C affords 3,4-dihydropyrimido[1,2-a]indole-10(2H)-one (VIII), which is finally treated with m-chlorophenylmagnesium bromide (IX) in refluxing ethyl ether.
| 【1】 White, A.C.; Black, R.M. (John Wyeth & Brother Ltd.); Fused ring indole derivatives. DE 2200584; ES 398678; ES 409296; FR 2121699; GB 1366133 . |
| 【2】 Weetman, D.F.; Castaner, J.; Ciclazindol. Drugs Fut 1977, 2, 8, 508. |