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【结 构 式】 
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【分子编号】47511 【品名】N-[(3aS,9bR)-7-methoxy-3a,4,5,9b-tetrahydro-1H-benzo[e]indol-2-yl]-4-[[(phenylsulfonyl)amino]methyl]cyclohexanecarboxamide 【CA登记号】 |
【 分 子 式 】C27H33N3O4S 【 分 子 量 】495.64284 【元素组成】C 65.43% H 6.71% N 8.48% O 12.91% S 6.47% |
合成路线1
该中间体在本合成路线中的序号：(IX)The condensation of 6-methoxy-2-tetralone (I) with pyrrolidine (II) in methanol gives the enamine (III), which is treated with 2-bromoacetonitrile (IV) to yield the pyrrolidinium salt (V). The hydrolysis of (V) with acetic acid in dichloromethane/methanol affords 2-(2-oxo-1,2,3,4-tetrahydronaphthalen-1-yl)acetonitrile (VI), which is cyclized with ammonium acetate and NaBH3CN in refluxing methanol to provide the benzoindole derivative (VII). The condensation of (VII) with trans-4-(phenylsulfonamidomethyl)cyclohexanecarboxylic acid (VIII) by means of HBTU and DIEA in DMF gives the corresponding amide (IX), which is reduced with LiAlH4 in THF to yield the secondary amine (X). Finally, this compound is demethylated by means of BBr3 in dichloromethane.
| 【1】 Dax, S.; McNally, J. (Ortho-McNeil Pharmaceutical, Inc.); 3a,4,5,9b-Tetrahydro-1H-benz[e]indol-2-yl amine-derived neuropeptide Y receptor ligands useful in the treatment of obesity and other disorders. WO 0068197 . |
| 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) | 47506 | 6-Methoxy-2-tetralone; 6-methoxy-3,4-dihydro-2(1H)-naphthalenone | 2472-22-2 | C11H12O2 | 详情 | 详情 |
| (II) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (III) | 47507 | methyl 6-(1-pyrrolidinyl)-7,8-dihydro-2-naphthalenyl ether; 1-(6-methoxy-3,4-dihydro-2-naphthalenyl)pyrrolidine | C15H19NO | 详情 | 详情 | |
| (IV) | 31883 | 2-bromoacetonitrile | 590-17-0 | C2H2BrN | 详情 | 详情 |
| (V) | 47508 | 1-[1-(cyanomethyl)-6-methoxy-3,4-dihydro-2(1H)-naphthalenylidene]pyrrolidinium | C17H21N2O | 详情 | 详情 | |
| (VI) | 47509 | 2-(6-methoxy-2-oxo-1,2,3,4-tetrahydro-1-naphthalenyl)acetonitrile | C13H13NO2 | 详情 | 详情 | |
| (VII) | 47510 | (3aS,9bR)-7-methoxy-3a,4,5,9b-tetrahydro-1H-benzo[e]indol-2-amine; (3aS,9bR)-7-methoxy-3a,4,5,9b-tetrahydro-1H-benzo[e]indol-2-ylamine | C13H16N2O | 详情 | 详情 | |
| (VIII) | 37020 | 4-[[(phenylsulfonyl)amino]methyl]cyclohexanecarboxylic acid | C14H19NO4S | 详情 | 详情 | |
| (IX) | 47511 | N-[(3aS,9bR)-7-methoxy-3a,4,5,9b-tetrahydro-1H-benzo[e]indol-2-yl]-4-[[(phenylsulfonyl)amino]methyl]cyclohexanecarboxamide | C27H33N3O4S | 详情 | 详情 | |
| (X) | 47512 | N-[[4-([[(3aS,9bR)-7-methoxy-3a,4,5,9b-tetrahydro-1H-benzo[e]indol-2-yl]amino]methyl)cyclohexyl]methyl]benzenesulfonamide | C27H35N3O3S | 详情 | 详情 |