新产品编号:1742291

Chemical Name: (1R,2R,3R,5S)-3-(4-Methylphenyl)-8-(2-phenylethyl)-2-phenyl-8-azabicyclo[3.2.1]octane
项目整合开发状态: Biological Testing
项目研究机构: Georgetown University (Originator), UT Medical Branch at Galveston (Originator)
合成路线: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.

合成路线:The cycloaddition of the oxidopyridinium (I) with p-tolyl(vinyl)sulfoxide (II) in refluxing dioxane gives the tropenone derivative (III),which is treated with phenylmagnesium bromide and CuBr in THF yielding the diaryl tropanone derivative (IV).The reduction of (IV) with LiAlH4 in THF affords the corresponding alcohol (V),which is deoxigenated by reaction first with O-phenyl chlorothioformate and then with tributyltin hydride and AIBN in hot toluene to provide the diaryltropane (VI).The elimination of the sulfoxide group of (VI) with PCl3 and Raney-Ni in refluxing ethanol gives the diaryl tropane (VII) (1),which is submitted to N-demethylation with alpha-chloroethyl chloroformate and proton sponge in refluxing dichloroethane yielding the intermediate (VIII),which is finally N-alkylated with 2-phenylethyl bromide (IX) and K2CO3 in DMF.