【结 构 式】 |
【药物名称】EF-7412 【化学名称】N-[3-[4-[4-(1,3-Dioxoperhydro-1H-pyrrolo[1,2-c]imidazol-2-yl)butyl]piperazin-1-yl]phenyl]ethanesulfonamide 【CA登记号】 【 分 子 式 】C22H33N5O4S 【 分 子 量 】463.60341 |
【开发单位】Universidad Complutense de Madrid (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, 5-HT1A Antagonists, Dopamine D2 Antagonists |
合成路线1
Perhydropyrrolo[1,2-c]imidazole-1,3-dione (II) was prepared by Urech synthesis upon condensation of proline (I) with potassium cyanate, followed by acid cyclization. Subsequent alkylation of (II) with 1-bromo-4-chlorobutane (III) in the presence of NaH in DMF provided the chlorobutyl derivative (IV). This was finally coupled with aryl piperazine (V) to yield the title compound.
【1】 Lopez Rodriguez, M.L.; Rosado Samitier, M.L.; Benahmu Salama, B.; Fernandez Velando, E.; Morcillo Ortega, M.J. (Universidad Complutense de Madrid); New arylpiperazine derivs.. ES 2095811; WO 9606846 . |
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) | 16731 | L-proline | 147-85-3 | C5H9NO2 | 详情 | 详情 |
(II) | 25216 | tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione | C6H8N2O2 | 详情 | 详情 | |
(III) | 16141 | 1-bromo-4-chlorobutane | 6940-78-9 | C4H8BrCl | 详情 | 详情 |
(IV) | 25217 | 2-(4-chlorobutyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione | C10H15ClN2O2 | 详情 | 详情 | |
(V) | 25218 | N-[3-(1-piperazinyl)phenyl]-1-ethanesulfonamide | C12H19N3O2S | 详情 | 详情 |
合成路线2
The condensation of perhydropyrrolo[1,2-c]imidazole-2,7-dione (I) with 1,4-dibromobutane (II) by means of NaH in DMF gives the expected 4-bromobutyl derivative (III), which is condensed with 1-(3-nitrophenyl)piperazine (IV) by means of triethylamine in hot acetonitrile yielding 2-[4-[4-(3-nitrophenyl)piperazin-1-yl]butyl]perhydropyrrolo[1,2-c]imidazole-2,7-dione (V). The reduction of the nitro group of (V) with H2 over Pd/C in methanol affords the corresponding amino derivative (VI), which is finally sulfonated with ethanesulfonyl chloride and pyridine in acetone.
【1】 López-Rodríguez, M.L.; et al.; Design and synthesis of 2-[4-[4-(m-(ethylsulfonamido)-penhyl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole (EF-7412) using neural networks. A selective derivative with mixed 5-HT1A/D2 antagonist properties. Bioorg Med Chem Lett 1999, 9, 12, 1679. |
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) | 25216 | tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione | C6H8N2O2 | 详情 | 详情 | |
(II) | 11883 | 1,4-Dibromobutane; 1,4-Butylene bromide | 110-52-1 | C4H8Br2 | 详情 | 详情 |
(III) | 26724 | 2-(4-bromobutyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione | C10H15BrN2O2 | 详情 | 详情 | |
(IV) | 26725 | 1-(3-nitrophenyl)piperazine | C10H13N3O2 | 详情 | 详情 | |
(V) | 26726 | 2-[4-[4-(3-nitrophenyl)-1-piperazinyl]butyl]tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione | C20H27N5O4 | 详情 | 详情 | |
(VI) | 26727 | 2-[4-[4-(3-aminophenyl)-1-piperazinyl]butyl]tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione | C20H29N5O2 | 详情 | 详情 |