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【结 构 式】 
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【药物名称】Setoperone(Rec INN; USAN), R-52245 【化学名称】6-[2-[4-(4-Fluorobenzoyl)piperidino]ethyl]-2,3-dihydro-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 【CA登记号】86487-64-1 【 分 子 式 】C21H24FN3O2S 【 分 子 量 】401.50673 |
【开发单位】Janssen (Originator) 【药理作用】Antipsychotic Drugs, PSYCHOPHARMACOLOGIC DRUGS |
合成路线1
By condensation of 4-(4-fluorobenzoyl)piperidine (IX) with 6-(2-bromo ethyl)-7-methyl-2,3-dihydro-5H-thiazolo[2,3-a]pyrimidin-5-one (IV) by means of Na2CO3 in refluxing 4-methyl-2-pentanone. The starting products are obtained as follows: The cyclization of 4-hydroxy-5-(2-hydroxyethyl)-6-methyl-2-mercaptopyrimidine (I) with 1,2-dibromo ethane (II) by means of K2CO3 in hot dimethylacetamide gives 2,3-dihydro-6-(2-hydroxyethyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one (II), which by reaction with HBr in refluxing acetic acid is converted to the corresponding 6-(2-bromoethyl) derivative (IV). The Grignard reaction of 4-bromofluorobenzene (V) with N benzyl-4 cyanopiperidine (VI) by means of Mg in dimethoxyethane gives 4-(4-fluorobenzoyl)-N-benzylpiperidine (VII), which is treated with ethyl chlorocarbo-nate in refluxing toluene to afford ethyl 4-(4-fluorobenzoyl)piperidine-1-carboxylate (VIII). Finally, this compound is treated with HBr in refluxing 48% HBr to give (IX).
| 【1】 Kennis, L.; Mertens, J.C. (Janssen Pharmaceutica NV); Bicyclic pyrimidin-5-one derivatives. DD 215553; EP 0070053; US 4443451 . |
| 【2】 Serradell, M.N.; Castaner, J.; Setoperone. Drugs Fut 1985, 10, 1, 40. |
| 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) | 29009 | 5-(2-hydroxyethyl)-6-methyl-2-sulfanyl-4-pyrimidinol | C7H10N2O2S | 详情 | 详情 | |
| (II) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
| (III) | 29010 | 6-(2-hydroxyethyl)-7-methyl-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one | C9H12N2O2S | 详情 | 详情 | |
| (IV) | 29011 | 6-(2-bromoethyl)-7-methyl-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one | C9H11BrN2OS | 详情 | 详情 | |
| (V) | 29012 | 1-bromo-4-fluorobenzene | 460-00-4 | C6H4BrF | 详情 | 详情 |
| (VI) | 29013 | 1-benzyl-4-piperidinecarbonitrile | C13H16N2 | 详情 | 详情 | |
| (VII) | 29014 | (1-benzyl-4-piperidinyl)(4-fluorophenyl)methanone | C19H20FNO | 详情 | 详情 | |
| (VIII) | 29015 | ethyl 4-(4-fluorobenzoyl)-1-piperidinecarboxylate | C15H18FNO3 | 详情 | 详情 | |
| (IX) | 21497 | (4-Fluorophenyl)(4-piperidinyl)methanone; 4-(4-Fluorobenzoyl)piperidine; 4-(p-Fluorobenzoyl)piperidine | 56346-57-7 | C12H14FNO | 详情 | 详情 |