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【结 构 式】 
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【分子编号】48540 【品名】benzyl (1R)-1-[(2R)-5-oxo-2,5-dihydro-2-furanyl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate 【CA登记号】 |
【 分 子 式 】C21H19NO4 【 分 子 量 】349.3862 【元素组成】C 72.19% H 5.48% N 4.01% O 18.32% |
合成路线1
该中间体在本合成路线中的序号：(IV)Reaction of 3,4-dihydroisoquinoline (I) with benzyl chloroformate in acetonitrile afforded the isoquinolinium salt (II), which was coupled in situ with 2-(tert-butyldimethylsilyloxy)furan (III) to produce a diastereomeric mixture of threo (IV) and erythro (V) adducts. After chromatographic isolation of the desired threo-isomer (IV), catalytic hydrogenation of the furanone double bond and simultaneous removal of the carbobenzoxy group furnished the tetrahydroisoquinoline (VI). This was converted to the target sulfonamide using p-toluenesulfonyl chloride (VII) and triethylamine. The enantiomers were then separated by means of chiral HPLC.
| 【1】 Razet, R.; et al.; 5-[1'-(2'-N-arylsulfonyl-1',2',3',4'-tetrahydroisoquinoly)]-4,5-dihydro-2(3H)-furanones: Positive allosteric modulators of the GABAA receptor with a new mode of action. J Med Chem 2000, 43, 23, 4363. |
| 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) | 48537 | 3,4-dihydroisoquinoline | C9H9N | 详情 | 详情 | |
| (II) | 48538 | 2-[(benzyloxy)carbonyl]-3,4-dihydroisoquinolinium chloride | C17H16ClNO2 | 详情 | 详情 | |
| (III) | 48539 | tert-butyl(dimethyl)silyl 2-furyl ether; tert-butyl(2-furyloxy)dimethylsilane | C10H18O2Si | 详情 | 详情 | |
| (IV) | 48540 | benzyl (1R)-1-[(2R)-5-oxo-2,5-dihydro-2-furanyl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate | C21H19NO4 | 详情 | 详情 | |
| (V) | 48541 | benzyl (1R)-1-[(2S)-5-oxo-2,5-dihydro-2-furanyl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate | C21H19NO4 | 详情 | 详情 | |
| (VI) | 48542 | (5R)-5-[(1R)-1,2,3,4-tetrahydro-1-isoquinolinyl]dihydro-2(3H)-furanone | C13H15NO2 | 详情 | 详情 | |
| (VII) | 13975 | p-Toluenesulfonyl chloride;p-tosyl chloride;Toluene-4-sulfonyl chloride;4-Toluene sulfochloride;tosyl chloride; 4-Methylbenzenesulfonyl chloride | 98-59-9 | C7H7ClO2S | 详情 | 详情 |