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【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
Extended Information