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【结 构 式】 
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【分子编号】25807 【品名】(1R,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-4-phenyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfoxide; (1S,2R,3R,5R,7R)-8-methyl-3-(4-methylphenyl)-7-[(4-methylphenyl)sulfinyl]-2-phenyl-8-azabicyclo[3.2.1]octane 【CA登记号】 |
【 分 子 式 】C28H31NOS 【 分 子 量 】429.62628 【元素组成】C 78.28% H 7.27% N 3.26% O 3.72% S 7.46% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Dipolar cycloaddition of hydroxypyridinium betaine (I) with R-(+)-p-tolyl vinyl sulfoxide (II) furnished the chiral tropenone (III). Subsequent copper-catalyzed conjugate addition of phenyl-magnesium bromide on the beta-face of (III) provided the trans diaryltropanone (IV). Then, ketone reduction of (IV) with LiAlH4 gave alcohol (V), which was condensed with phenyl thionochloroformate (VI) to afford thiocarbonate (VII). This was reduced with tributyltin hydride and azobis(isobutyronitrile) to produce tropane (VIII). The sulfoxide group of (VIII) was further reduced to sulfide (IX) with PCl3 in DMF. Finally, Raney Nickel-promoted desulfurization in boiling EtOH yielded the title compound.
| 【1】 Kozikowski, A.P.; Araldi, G.L.; Prakash, K.R.; Zhang, M.; Johnson, K.M.; Synthesis and biological properties of new 2beta-alkyl- and 2beta-aryl-3-(substituted phenyl)tropane derivatives: Stereochemical effect of C-3 on affinity and selectivity for neuronal dopamine and serotonin transporters. J Med Chem 1998, 41, 25, 4973. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17616 | bromo(phenyl)magnesium; Phenyl Magnesium Bromide | 100-58-3 | C6H5BrMg | 详情 | 详情 | |
| (I) | 25800 | 1-methyl-4-(4-methylphenyl)-3-pyridiniumolate | C13H13NO | 详情 | 详情 | |
| (II) | 25801 | (4-methylphenyl)(oxo)vinyl-lambda(4)-sulfane; 4-methylphenyl vinyl sulfoxide | C9H10OS | 详情 | 详情 | |
| (III) | 25802 | (1S,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-8-azabicyclo[3.2.1]oct-3-en-2-one | C22H23NO2S | 详情 | 详情 | |
| (IV) | 25803 | (1S,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-4-phenyl-8-azabicyclo[3.2.1]octan-2-one | C28H29NO2S | 详情 | 详情 | |
| (V) | 25804 | (1S,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-4-phenyl-8-azabicyclo[3.2.1]octan-2-ol | C28H31NO2S | 详情 | 详情 | |
| (VI) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (VII) | 25806 | O-[(1S,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-4-phenyl-8-azabicyclo[3.2.1]oct-2-yl] O-phenyl carbonothioate | C35H35NO3S2 | 详情 | 详情 | |
| (VIII) | 25807 | (1R,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-4-phenyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfoxide; (1S,2R,3R,5R,7R)-8-methyl-3-(4-methylphenyl)-7-[(4-methylphenyl)sulfinyl]-2-phenyl-8-azabicyclo[3.2.1]octane | C28H31NOS | 详情 | 详情 | |
| (IX) | 25808 | (1R,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-4-phenyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfide; (1S,2R,3R,5R,7R)-8-methyl-3-(4-methylphenyl)-7-[(4-methylphenyl)sulfanyl]-2-phenyl-8-azabicyclo[3.2.1]octane | C28H31NS | 详情 | 详情 |