PD-123497, RSD-921
Chemical Name: (+)-(1R,2R)-N-Methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzo[b]thiophene-4-acetamide
CAS No. 114419-77-1
项目整合开发状态: Phase II
项目研究机构: Pfizer (Originator), Cardiome (Licensee), Chemical Company of Malaysia (Licensee)
合成路线:Ring opening of cyclohexene oxide (I) with aqueous methylamine gave trans 2-(methylamino)cyclohexanol (II),which was further cyclized to the aziridine (III) upon treatment with chlorosulfonic acid and then with NaOH.Subsequent condensation of (III) with pyrrolidine (IV) yielded the racemic trans diamine (V).Resolution was achieved by fractional crystallization of the 2,3-di-p-toluoyl-D-tartaric acid salt in MeOH.The required (-)-(R,R) enantiomer was finally coupled with 4-benzothiopheneacetyl chloride (VI) to provide the corresponding amide.
📌 参考资料/链接：
参考文献标题:Aminocyclohexylamides for antiarrhythmic and anaesthetic uses
文献作者:MacLeod,B.A.; Walker,M.J.A.; Wall,R.A.(University of British Columbia)
参考来源:EP 0632806; JP 1995505151; US 5506257; WO 9319056
📄 详细内容
合成路线:Ring opening of cyclohexene oxide (I) with aqueous methylamine gave trans 2-(methylamino)cyclohexanol (II),which was further cyclized to the aziridine (III) upon treatment with chlorosulfonic acid and then with NaOH.Subsequent condensation of (III) with pyrrolidine (IV) yielded the racemic trans diamine (V).Resolution was achieved by fractional crystallization of the 2,3-di-p-toluoyl-D-tartaric acid salt in MeOH.The required (-)-(R,R) enantiomer was finally coupled with 4-benzothiopheneacetyl chloride (VI) to provide the corresponding amide.
参考文献标题:Mixtures of enantiomers of aminocyclohexylamides to produce simultaneous analgesia with local anaesthesia or antiarrhythmia
文献作者:Bain,A.I.(Nortran Pharmaceuticals Inc.)
参考来源:WO 9916431
合成路线:Ring opening of cyclohexene oxide (I) with aqueous methylamine gave trans 2-(methylamino)cyclohexanol (II),which was further cyclized to the aziridine (III) upon treatment with chlorosulfonic acid and then with NaOH.Subsequent condensation of (III) with pyrrolidine (IV) yielded the racemic trans diamine (V).Resolution was achieved by fractional crystallization of the 2,3-di-p-toluoyl-D-tartaric acid salt in MeOH.The required (-)-(R,R) enantiomer was finally coupled with 4-benzothiopheneacetyl chloride (VI) to provide the corresponding amide.
参考文献标题:Highly selective kappa opioid analgesics.Synthesis and structure-activity relationships of novel N-[(2-aminocyclohexyl)aryl]acetamide and N-[(2-aminocyclohexyl)aryloxy]acetamide derivatives
文献作者:Clark,C.R.; Halfpenny,P.R.; Hill,R.G.; Horwell,D.C.; Hughes,J.; Jarvis,T.C.; Rees,D.C.; Schofield,D.
参考来源:J Med Chem 1988,31(4),831