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【结 构 式】

【分子编号】21124

【品名】methyl (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate

【CA登记号】

【 分 子 式 】C15H17Cl2NO2

【 分 子 量 】314.21092

【元素组成】C 57.34% H 5.45% Cl 22.57% N 4.46% O 10.18%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

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.
2 Castañer, J.; Graul, A.; Brasofensine Sulfate . Drugs Fut 1999, 24, 2, 128.
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
Extended Information