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【结 构 式】 
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【药物名称】E-5842 【化学名称】4-(4-Fluorophenyl)-1-[4-(1,2,4-triazol-1-yl)butyl]-1,2,3,6-tetrahydropyridine citrate 【CA登记号】177945-46-9 (free base), 177945-45-8 (HCl) 【 分 子 式 】C23H29FN4O7 【 分 子 量 】492.50858 |
【开发单位】Esteve (Originator) 【药理作用】Antipsychotic Drugs, PSYCHOPHARMACOLOGIC DRUGS, sigma-Receptor Ligands |
合成路线1
E-5842 was prepared by reacting (I) with citric acid monohydrate in ethanol. The base (I) can be obtained by two ways: 1) By condensation of 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (III) or 8-(4-fluorophenyl)-5-azoniaspiro[4.5]dec-7-ene chloride (IV) with 1-(4-chlorobutyl)-1H-1,2,4-triazole (V) or 1H-1,2,4-triazole, respectively, in dimethylformamide in the presence of potassium hydrogencarbonate. 2) By dehydration of 1-[4-[4-(4-fluorophenyl)-4-hydroxy-1-piperidyl]butyl]-1H-1,2,4-triazole (VI) in refluxing hydrochloric acid/ethanol. The piperidinol (VI) can be obtained by two procedures: a) By condensation of 4-(4-fluorophenyl)-4-hydroxypiperidine (II) with 1-(4-chlorobutyl)-1H-1,2,4-triazole (V) in dimethylformamide in the presence of potassium hydrogencarbonate. b) By condensation of 1,4-dioxa-8-azaspiro[4.5]decane (VII) with 1-(4-chlorobutyl)-1H-1,2,4-triazole (V) and hydrolysis of the acetal to give 1-[4-(4-oxo-1-piperidyl)butyl]-1H-1,2,4-triazole (VIII), followed by addition of 4-fluorophenyllithium or 4-fluorophenyl magnesium bromide in ether or tetrahydrofuran to yield (VI).
| 【1】 Merce-Vidal, R.; Frigola-Constansa, J. (Laboratorios del Dr. Esteve, SA); Tetrahydropyridine-(or -4-hydroxypiperidine)alkyla. EP 0721455; FR 2723091; JP 1997503230; US 5731331; WO 9604287 . |
| 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) | 23463 | 4-(4-fluorophenyl)-1-[4-(1H-1,2,4-triazol-1-yl)butyl]-1,2,3,6-tetrahydropyridine | C17H21FN4 | 详情 | 详情 | |
| (II) | 15723 | 4-(4-fluorophenyl)-4-piperidinol; 4-(4-Fluorophenyl)-4-hydroxypiperidine | 3888-65-1 | C11H14FNO | 详情 | 详情 |
| (III) | 23465 | 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine | 1978-59-2 | C11H12FN | 详情 | 详情 |
| (IV) | 23466 | 8-(4-fluorophenyl)-5-azoniaspiro[4.5]dec-7-ene | C15H19FN | 详情 | 详情 | |
| (V) | 23467 | 1-(4-chlorobutyl)-1H-1,2,4-triazole | C6H10ClN3 | 详情 | 详情 | |
| (VI) | 23468 | 4-(4-fluorophenyl)-1-[4-(1H-1,2,4-triazol-1-yl)butyl]-4-piperidinol | C17H23FN4O | 详情 | 详情 | |
| (VII) | 11338 | 1,4-Dioxa-8-azaspiro[4.5]decane; 4-Piperidone ethylene ketal | 177-11-7 | C7H13NO2 | 详情 | 详情 |
| (VIII) | 23470 | 1-[4-(1H-1,2,4-triazol-1-yl)butyl]-4-piperidinone | C11H18N4O | 详情 | 详情 | |
| (IX) | 13135 | 1H-1,2,4-Triazole; 1,2,4-Triazole | 288-88-0 | C2H3N3 | 详情 | 详情 |