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【结 构 式】 
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【药物名称】Sabeluzole, R-58735 【化学名称】1-[4-[N-(2-Benzothiazolyl)-N-methylamino]piperidin-1-yl]-3-(4-fluorophenoxy)propan-2-ol 【CA登记号】104383-17-7, 104153-38-0 (deleted CAS) 【 分 子 式 】C22H26FN3O2S 【 分 子 量 】415.53382 |
【开发单位】Janssen (Originator) 【药理作用】Alzheimer's Dementia, Treatment of , Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Glutamate Ionotropic Antagonists |
合成路线1
The reductocondensation of ethyl 4-oxopiperidine-1-carboxylate (I) with methylamine by means of H2 over Pd/C in thiophene gives ethyl 4-(methylamino)piperidine-1-carboxylate (II), which is then condensed with phenyl isothiocyanate (III) in diisopropyl ether to yield the substituted thiourea (IV). The cyclization of (IV) with Br2 in refluxing CCl4 affords N-[4-(ethoxycarbonyl)piperidin-l-yl]-N methylbenzo-thiazol-2-amine (V), which is decarboxylated with refluxing 48% HBr to N-methyl-N-(4-piperidyl)benzo thiazol-2-amine (VI). Finally, this compound is condensed with 1,2-epoxy-3-(4-fluorophenoxypropane) (VII) in refluxing toluene methanol.
| 【1】 Stokbroekx, R.A.; Luyckx, M.G.M.; Janssens, F.E. (Janssen Pharmaceutica NV); Benzoxazol- and benzothiazolamine derivs.. EP 0184257; US 4861785 . |
| 【2】 Prous, J.; Castaner, J.; SABELUZOLE < Rec INN >. Drugs Fut 1988, 13, 6, 529. |
| 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) | 13486 | Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone | 29976-53-2 | C8H13NO3 | 详情 | 详情 |
| (II) | 22145 | ethyl 4-(methylamino)-1-piperidinecarboxylate | C9H18N2O2 | 详情 | 详情 | |
| (III) | 22146 | 1-isothiocyanatobenzene; phenyl isothiocyanate | 103-72-0 | C7H5NS | 详情 | 详情 |
| (IV) | 22147 | ethyl 4-[(anilinocarbothioyl)(methyl)amino]-1-piperidinecarboxylate | C16H23N3O2S | 详情 | 详情 | |
| (V) | 22148 | ethyl 4-[1,3-benzothiazol-2-yl(methyl)amino]-1-piperidinecarboxylate | C16H21N3O2S | 详情 | 详情 | |
| (VI) | 16742 | N-(1,3-benzothiazol-2-yl)-N-methyl-N-(4-piperidinyl)amine; N-methyl-N-(4-piperidinyl)-1,3-benzothiazol-2-amine | C13H17N3S | 详情 | 详情 | |
| (VII) | 22150 | 2-[(4-fluorophenoxy)methyl]oxirane; 4-fluorophenyl 2-oxiranylmethyl ether | 18123-82-5 | C9H9FO2 | 详情 | 详情 |