新产品编号:364369
Chemical Name: (-)-1-[2(S)-[3-(2,3-Dihydro-1H-inden-2-yloxy)-4-methoxyphenyl]propyl]-2,3-dihydro-1H-imidazol-2-ylidenecyanamide
CAS No. 205699-43-0 (undefined stereochem.)
项目整合开发状态: Preclinical
项目研究机构: Janssen (Originator)
合成路线:Alkylation of isovanillin (I) with 2-indanyl tosylate (II) produces the corresponding indanyl ether (III).Subsequent reduction of the aldehyde function of (III) with NaBH4 yields the benzylic alcohol (IV),which is converted to chloride (V) by treatment with SOCl2.Displacement of chloride (V) by KCN in hot DMF gives nitrile (VI).The phenylacetonitrile (VI) is then converted to the homologous phenylpropionitrile derivative (VII) by alkylation with iodomethane in the presence of LDA.Further cyano group reduction in (VII) by hydrogenation over Raney Ni provides amine (VIII).Condensation of amine (VIII) with diphenyl N-cyanocarbonimidate affords the N-cyano isourea (IX) which,after reaction with 2,2-dimethoxyethylamine (X),yields the cyano guanidine (XI).Finally,cyclization of (XI) under acidic conditions gives rise to the target 2-(cyanoimino)imidazole derivative.
📌 参考资料/链接：
参考文献标题:PDE IV inhibiting 2-cyanoiminoimidazole derivs.
文献作者:Freyne,E.J.E.; Fernandez-Gadea,F.J.; Andres-Gil,J.I.(Janssen Pharmaceutica NV)
参考来源:WO 9814432
📄 详细内容
合成路线:Alkylation of isovanillin (I) with 2-indanyl tosylate (II) produces the corresponding indanyl ether (III).Subsequent reduction of the aldehyde function of (III) with NaBH4 yields the benzylic alcohol (IV),which is converted to chloride (V) by treatment with SOCl2.Displacement of chloride (V) by KCN in hot DMF gives nitrile (VI).The phenylacetonitrile (VI) is then converted to the homologous phenylpropionitrile derivative (VII) by alkylation with iodomethane in the presence of LDA.Further cyano group reduction in (VII) by hydrogenation over Raney Ni provides amine (VIII).Condensation of amine (VIII) with diphenyl N-cyanocarbonimidate affords the N-cyano isourea (IX) which,after reaction with 2,2-dimethoxyethylamine (X),yields the cyano guanidine (XI).Finally,cyclization of (XI) under acidic conditions gives rise to the target 2-(cyanoimino)imidazole derivative.
参考文献标题:Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole derivatives: Novel series of PDE4 inhibitors
文献作者:Andr閟,J.I.; Alonso,J.M.; D韆z,A.; Fernandez,J.; Iturrino,L.; Martinez,P.; Matesanz,E.; Freyne,E.J.; Deroose,F.; Boeckx,G.; Petit,D.; Diels,G.; Megens,A.A.; Somers,M.V.F.; Van Wauwe,J.; Stoppie,P.; Cools,M.; De Clerck,F.; et al.
参考来源:Bioorg Med Chem Lett 2002,12(4),653