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【结 构 式】 
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【分子编号】21129 【品名】(1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2-carbaldehyde O-methyloxime 【CA登记号】 |
【 分 子 式 】C15H18Cl2N2O 【 分 子 量 】313.2262 【元素组成】C 57.52% H 5.79% Cl 22.64% N 8.94% O 5.11% |
合成路线1
该中间体在本合成路线中的序号：(XIV)Synthesis of 8-[11C-methyl]-brasofensine: The demethylation of the previously described intermediate (VI) by means of 2,2,2-trichloroethyl chloroformate in refluxing toluene gives the expected ester (IX), which is protected with di-tert-butyl dicarbonate in THF, affording (1R,2R,3S,5S)-8-(tert-butoxycarbonyl)-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester (X). The reduction of (X) with LiAlH4 in ethyl ether gives (1R,2R,3S,5S)-8-(tert-butoxycarbonyl)-[3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-2-yl]methanol (XI), which is oxidized with oxalyl chloride in dichloromethane, affording the aldehyde (XII). The reaction of (XII) with methoxyammonium chloride and Na2CO3 in methanol gives the O-methyloxime (XIII), which is deprotected with trifluoroacetic acid in dichloromethane, yielding (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2-carbadehyde O-methyloxime (XIV). Finally, this compound is methylated with [11C]-methyl iodide in DMSO at 130 C.
| 【1】 Gjedde, A.; Moldt, P.; Gee, A.D.; The labelling of a novel tropane derivative [C-11]NS 2214 (BMS-204756) - An inhibitor of the dopamine transporter. J Label Compd Radiopharm 1997, 39, 12, 959. |
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【2】
Castañer, J.; Graul, A.; Brasofensine Sulfate |
| 【3】 Moldt, P.; Watjen, F.; Scheel-Kruger, J. (NeuroSearch A/S); Tropane-2-aldoxine derivs. as neurotransmitter reuptake inhibitors. EP 0756596; JP 1997505607; US 5736556; WO 9528401 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 21121 | methyl (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate | C16H19Cl2NO2 | 详情 | 详情 | |
| (IX) | 21124 | methyl (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate | C15H17Cl2NO2 | 详情 | 详情 | |
| (X) | 21125 | 8-(tert-butyl) 2-methyl (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate | C20H25Cl2NO4 | 详情 | 详情 | |
| (XI) | 21126 | tert-butyl (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(hydroxymethyl)-8-azabicyclo[3.2.1]octane-8-carboxylate | C19H25Cl2NO3 | 详情 | 详情 | |
| (XII) | 21127 | tert-butyl (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-formyl-8-azabicyclo[3.2.1]octane-8-carboxylate | C19H23Cl2NO3 | 详情 | 详情 | |
| (XIII) | 21128 | tert-butyl (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-[(methoxyimino)methyl]-8-azabicyclo[3.2.1]octane-8-carboxylate | C20H26Cl2N2O3 | 详情 | 详情 | |
| (XIV) | 21129 | (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2-carbaldehyde O-methyloxime | C15H18Cl2N2O | 详情 | 详情 |