合成路线:Treatment of ethyl cyanoacetate derivative (I) with cyanoacetamide (II) in EtOH in the presence of NaOEt provides dicyano derivative (III),which is then converted into diimide (IV) by treatment with refluxing sulfuric acid.Alternatively,(IV) can also be obtained by reaction between cyclopentanone (V),cyanoacetamide (II) and piperidine by means of KOH or NaOH in H2O (or H2O/EtOH) to provide mononitrile derivative (VI),which is then refluxed with H2SO4.Double N-alkylation of compound (IV) with chloride (VII) by heating with NaH or alkaline carbonate in DMF yields dialkylated compound (VIII),which is reduced with LiAlH4 or Red-Al in refluxing THF/toluene to furnish the free base (IX).Finally,(IX) is converted into the desired dihydrochloride by treatment with HCl in isopropanol.
参考文献标题:Medicament containing crystalline fumaric acid salts or 9,9-alkylen-3-7-diazabicyclononane cpds.
文献作者:Sch鰊,U.; Heitmann,W.; M鋞zel,U.(Kali-Chemie AG)
参考来源:DE 4139763; EP 0550383; JP 1993247040
合成路线:Treatment of ethyl cyanoacetate derivative (I) with cyanoacetamide (II) in EtOH in the presence of NaOEt provides dicyano derivative (III),which is then converted into diimide (IV) by treatment with refluxing sulfuric acid.Alternatively,(IV) can also be obtained by reaction between cyclopentanone (V),cyanoacetamide (II) and piperidine by means of KOH or NaOH in H2O (or H2O/EtOH) to provide mononitrile derivative (VI),which is then refluxed with H2SO4.Double N-alkylation of compound (IV) with chloride (VII) by heating with NaH or alkaline carbonate in DMF yields dialkylated compound (VIII),which is reduced with LiAlH4 or Red-Al in refluxing THF/toluene to furnish the free base (IX).Finally,(IX) is converted into the desired dihydrochloride by treatment with HCl in isopropanol.
参考文献标题:Synthesis,pharmacological characterization,and quantitative structure-activity relationship analyses of 3,7,9,9-tetraalkylbispidines: Derivatives with specific bradycardic activity
文献作者:Sch鰊,U.; Antel,J.; Bruckner,R.; Messinger,J.; Franke,R.; Gruska,A.
参考来源:J Med Chem 1998,41(3),318
合成路线:Treatment of ethyl cyanoacetate derivative (I) with cyanoacetamide (II) in EtOH in the presence of NaOEt provides dicyano derivative (III),which is then converted into diimide (IV) by treatment with refluxing sulfuric acid.Alternatively,(IV) can also be obtained by reaction between cyclopentanone (V),cyanoacetamide (II) and piperidine by means of KOH or NaOH in H2O (or H2O/EtOH) to provide mononitrile derivative (VI),which is then refluxed with H2SO4.Double N-alkylation of compound (IV) with chloride (VII) by heating with NaH or alkaline carbonate in DMF yields dialkylated compound (VIII),which is reduced with LiAlH4 or Red-Al in refluxing THF/toluene to furnish the free base (IX).Finally,(IX) is converted into the desired dihydrochloride by treatment with HCl in isopropanol.
参考文献标题:Piperidine derivatives.XXX.1,4-Dialkyl-4-arylpiperidines
文献作者:McElvain,S.M.; Clemens,D.H.
参考来源:J Am Chem Soc 1958,803915
合成路线:Treatment of ethyl cyanoacetate derivative (I) with cyanoacetamide (II) in EtOH in the presence of NaOEt provides dicyano derivative (III),which is then converted into diimide (IV) by treatment with refluxing sulfuric acid.Alternatively,(IV) can also be obtained by reaction between cyclopentanone (V),cyanoacetamide (II) and piperidine by means of KOH or NaOH in H2O (or H2O/EtOH) to provide mononitrile derivative (VI),which is then refluxed with H2SO4.Double N-alkylation of compound (IV) with chloride (VII) by heating with NaH or alkaline carbonate in DMF yields dialkylated compound (VIII),which is reduced with LiAlH4 or Red-Al in refluxing THF/toluene to furnish the free base (IX).Finally,(IX) is converted into the desired dihydrochloride by treatment with HCl in isopropanol.
参考文献标题:The formation and reactions of imino-compounds.Part XV.The production of imino-derivatives of piperidine leading to the formation of the betabeta-disubstituted glutaric acids
文献作者:Thole,F.B.; Thorpe,J.F.
参考来源:J Chem Soc 1911,99422
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