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【结 构 式】 
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【药物名称】 【化学名称】4-[N-[8-(1,3-Benzodioxol-5-ylmethyl)-8-azabicyclo[3.2.1]oct-3endo-yl]-N-phenylamino]-N,N-diethylbenzamide 【CA登记号】 【 分 子 式 】C32H37N3O3 【 分 子 量 】511.66999 |
【开发单位】R.W. Johnson (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Opioid Analgesics, delta-Opioid Agonists |
合成路线1
The reductive alkylation of tropinone (I) with aniline (II) using either NaBH4 or NaBH(OAc)3 as the reducing agent furnished the endo-isomer (III). Arylation of amine (III) with t-butyl 4-bromobenzoate (IV) produced the (diarylamino)tropane (V). Acid cleavage of the tert-butyl ester of (V) gave acid (VI), which was further coupled to diethylamine, yielding amide (VII). Demethylation of tropane (VII) with 1-chloroethyl chloroformate, followed by methanolysis of the resulting carbamate (VIII), provided the secondary amine (IX). This was finally subjected to reductive alkylation with 3,4-methylenedioxybenzaldehyde (X) to give the title compound.
| 【1】 Gauthier, A.D.; Neilson, L.A.; Carson, J.R.; Codd, E.E.; Zhang, S.-P.; Boyd, R.E.; Synthesis and binding affinities of 4-diarylaminotropanes, a new class of delta opioid agonists. Bioorg Med Chem Lett 2000, 10, 10, 1109. |
| 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) | 16443 | (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-one | C8H13NO | 详情 | 详情 | |
| (II) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (III) | 51368 | (1R,5S)-8-methyl-N-phenyl-8-azabicyclo[3.2.1]octan-3-amine; N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-N-phenylamine | C14H20N2 | 详情 | 详情 | |
| (IV) | 14286 | tert-butyl 4-bromobenzoate | C11H13BrO2 | 详情 | 详情 | |
| (V) | 51369 | tert-butyl 4-[[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]anilino]benzoate | C25H32N2O2 | 详情 | 详情 | |
| (VI) | 51370 | 4-[[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]anilino]benzoic acid | C21H24N2O2 | 详情 | 详情 | |
| (VII) | 51371 | N,N-diethyl-4-[[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]anilino]benzamide | C25H33N3O | 详情 | 详情 | |
| (VIII) | 51372 | 1-chloroethyl (1R,5S)-3-[4-[(diethylamino)carbonyl](phenyl)anilino]-8-azabicyclo[3.2.1]octane-8-carboxylate | C27H34ClN3O3 | 详情 | 详情 | |
| (IX) | 51373 | 4-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylanilino]-N,N-diethylbenzamide | C24H31N3O | 详情 | 详情 | |
| (X) | 10127 | 1,3-Benzodioxole-5-carbaldehyde; Heliotropine | 120-57-0 | C8H6O3 | 详情 | 详情 |