|
【结 构 式】 
|
【药物名称】DR-4365 【化学名称】N,N-Dimethyl-2-[4-[2-oxo-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-2-yl]butyl]-2,3,4,9-tetrahydro-1H-beta-carboline-9-carboxamide 【CA登记号】230300-64-8, 247082-25-3 ((S)-isomer) 【 分 子 式 】C29H34N4O2 【 分 子 量 】470.61993 |
【开发单位】Meiji Seika (Originator) 【药理作用】Antipsychotic Drugs, Pharmacological Tools, PSYCHOPHARMACOLOGIC DRUGS, 5-HT7 Antagonists |
合成路线1
Intermediate (III) is prepared by the following route. Acylation of 2-Boc-tetrahydropyridoindole (I) with dimethylcarbamoyl chloride provides the 9-carbamoyl derivative (II). Subsequent Boc group cleavage under acidic conditions furnishes amine (III).
| 【1】 Koyama, M.; Okuno, M.; Hiranuma, T.; Ando, T.; Fuji, K.; Ushiroda, O.; Kikuchi, C.; Shiiyama, M.; Satoh, E. (Meiji Seika Kaisha, Ltd.); Tetrahydrobenzindole derivs.. EP 1057814; JP 1999189585; US 6498251; WO 9933804 . |
| 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) | 60191 | 1,1-dimethylethyl 1,3,4,9-tetrahydro-2H-beta-carboline-2-carboxylate | C16H20N2O2 | 详情 | 详情 | |
| (II) | 60192 | 1,1-dimethylethyl 9-[(dimethylamino)carbonyl]-1,3,4,9-tetrahydro-2H-beta-carboline-2-carboxylate | C19H25N3O3 | 详情 | 详情 | |
| (III) | 60193 | N,N-dimethyl-1,2,3,4-tetrahydro-9H-beta-carboline-9-carboxamide | C14H17N3O | 详情 | 详情 |
合成路线2
Tetrahydrobenzo[cd]indol-2-one (IV) is selectively alkylated at position 2a with 1,4-dibromobutane (V) in the presence of NaH to provide the bromobutyl derivative (VI). Then, condensation of bromide (VI) with amine (III) employing K2CO3 in DMF leads to the title compound.
| 【1】 Kikuchi, C.; et al.; 2a-[4-(Tetrahydropyridondol-2-yl)butyl]tetrahydrobenzindole derivatives: New selective antagonists of the 5-hydroxytryptamine7 receptor. J Med Chem 2002, 45, 11, 2197. |
| 【2】 Koyama, M.; Okuno, M.; Hiranuma, T.; Ando, T.; Fuji, K.; Ushiroda, O.; Kikuchi, C.; Shiiyama, M.; Satoh, E. (Meiji Seika Kaisha, Ltd.); Tetrahydrobenzindole derivs.. EP 1057814; JP 1999189585; US 6498251; WO 9933804 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 60193 | N,N-dimethyl-1,2,3,4-tetrahydro-9H-beta-carboline-9-carboxamide | C14H17N3O | 详情 | 详情 | |
| (IV) | 25590 | 2a,3,4,5-tetrahydrobenzo[cd]indol-2(1H)-one | 96933-21-0 | C11H11NO | 详情 | 详情 |
| (V) | 11883 | 1,4-Dibromobutane; 1,4-Butylene bromide | 110-52-1 | C4H8Br2 | 详情 | 详情 |
| (VI) | 25591 | 2a-(4-bromobutyl)-2a,3,4,5-tetrahydrobenzo[cd]indol-2(1H)-one | C15H18BrNO | 详情 | 详情 |