-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	54727
标题:	PDE IV inhibiting 2-cyanoiminoimidazole derivs.
作者:	Freyne, E.J.E.; Fernandez-Gadea, F.J.; Andres-Gil, J.I. (Janssen Pharmaceutica NV)
来源:	WO 9814432

合成路线图解说明: 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No.	666171
标题:	Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole derivatives: Novel series of PDE4 inhibitors
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.
来源:	Bioorg Med Chem Lett 2002,12(4),653

合成路线图解说明: 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.