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【结 构 式】 
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【药物名称】Ritanserin, R-55667, Tiserton 【化学名称】6-[2-[4-[Bis(p-fluorophenyl)methylene]piperidino]ethyl]-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 【CA登记号】87051-43-2 【 分 子 式 】C27H25F2N3OS 【 分 子 量 】477.5806 |
【开发单位】Janssen (Originator) 【药理作用】Antidepressants, Antipsychotic Drugs, Anxiolytics, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Treatment of Alcohol Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, 5-HT2A Antagonists |
合成路线1
The Grignard condensation of ethyl 1-benzyl-piperidine-4-carboxylate (I) with 4-fluorophenylmagnesium bromide (II) in THF gives a-bis(4-fluorophenyl)-1-benzylpiperidine-4-methanol (III), which is dehydrated with HCl in refluxing acetic acid yielding 1-benzyl-4-[bis(4 fluorophenyl)methylene]piperidine (IV). Elimination of the benzyl group of (IV) by hydrogenation with H2 over rhodium/carbon in methanol affords 4-[bis(4 fluorophenyl)metlylene] piperidine (V), which is finally condensed with 6-(2-chloroethyl)-7-methyl 5H thiazolo[3,2-a]pyrimidin-5-one (VI) by means of Na2CO3 and KI lo refluxing 4-methyl-2-pentanone. Compound (VI) is obtained by cyclocondensation of 2-thiazolylamine (VII) with 3 acetyl 4,5 dihydro-2(3H)furanone (VIII) by means of aqueous concentrated HCl in refluxing toluene.
| 【1】 Kennis, L.E.J.; Mertens, J.C.; Vandenberk, J. (Janssen Pharmaceutica NV); Novel ((bis(aryl)methylene)-1-piperidinyl)alkyl-pyrimidinones. EP 0110435; ES 8601965; US 4485107 . |
| 【2】 Prous, J.; Castaner, J.; Ritanserin. Drugs Fut 1986, 11, 5, 391. |
| 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) | 22600 | ethyl 1-benzyl-4-piperidinecarboxylate; N-Benzyl-4-carbethoxy piperidine | 24228-40-8 | C15H21NO2 | 详情 | 详情 |
| (II) | 13643 | 4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide | 352-13-6 | C6H4BrFMg | 详情 | 详情 |
| (III) | 22601 | (1-benzyl-4-piperidinyl)[bis(4-fluorophenyl)]methanol | C25H25F2NO | 详情 | 详情 | |
| (IV) | 24705 | 1-benzyl-4-[bis(4-fluorophenyl)methylene]piperidine | C25H23F2N | 详情 | 详情 | |
| (V) | 24706 | 4-[bis(4-fluorophenyl)methylene]piperidine | C18H17F2N | 详情 | 详情 | |
| (VI) | 24707 | 6-(2-chloroethyl)-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one | C9H9ClN2OS | 详情 | 详情 | |
| (VIII) | 24709 | 3-acetyldihydro-2(3H)-furanone | 517-23-7 | C6H8O3 | 详情 | 详情 |