T-607, T-900607
N-(4-甲氧基-3-脲苯基)-2,3,4,5,6-五氟苯磺酰胺Chemical Name: N-(4-Methoxy-3-ureidophenyl)-2,3,4,5,6-pentafluorobenzenesulfonamide; N-[2-Methoxy-4-(2,3,4,5,6-pentafluorobenzenesulfonamido)phenyl]urea
CAS No. 261944-52-9, 261944-58-5 (monoK salt), 261944-77-8 (monoNa salt)
项目整合开发状态: Phase II
项目研究机构: Amgen (Originator)
合成路线:Formylation of 2-methoxy-5-nitroaniline (I) with formic acid (II) in Ac2O/THF yields formamide (III),whose nitro group is then hydrogenated over Pd/C in MeOH to provide aniline (IV).Treatment of (IV) with pentafluorophenylsulfonyl chloride (V) in acetone in the presence of 2,6-lutidine affords sulfonamide (VI),which is then deformylated to hydrochloride (VII) by treatment with acetyl chloride and HCl in EtOH.The target compound is finally obtained by reaction of (VII) with potassium cyanate (KCNO) in H2O/HOAc.An analogous route can be also followed for the synthesis of the target product: Treatment of 3-nitro-4-fluoroaniline (VIII) with sodium methoxide (NaOMe) in refluxing MeOH furnishes 4-methoxy-3-nitroaniline (IX),which is then condensed with pentafluorophenylsulfonyl chloride (V) in MeOH to give sulfonamide (X).Reduction of the nitro moiety of (X) by hydrogenation over Pd/C in EtOH yields aniline (XI),which is finally treated with potassium cyanate (KCNO) in H2O/HOAc.
📌 参考资料/链接：
参考文献标题:Arylsulfonanilide ureas
文献作者:Houze,J.B.(Tularik Inc.)
参考来源:EP 1115701; US 6214880; WO 0017159
📄 详细内容
合成路线:Formylation of 2-methoxy-5-nitroaniline (I) with formic acid (II) in Ac2O/THF yields formamide (III),whose nitro group is then hydrogenated over Pd/C in MeOH to provide aniline (IV).Treatment of (IV) with pentafluorophenylsulfonyl chloride (V) in acetone in the presence of 2,6-lutidine affords sulfonamide (VI),which is then deformylated to hydrochloride (VII) by treatment with acetyl chloride and HCl in EtOH.The target compound is finally obtained by reaction of (VII) with potassium cyanate (KCNO) in H2O/HOAc.An analogous route can be also followed for the synthesis of the target product: Treatment of 3-nitro-4-fluoroaniline (VIII) with sodium methoxide (NaOMe) in refluxing MeOH furnishes 4-methoxy-3-nitroaniline (IX),which is then condensed with pentafluorophenylsulfonyl chloride (V) in MeOH to give sulfonamide (X).Reduction of the nitro moiety of (X) by hydrogenation over Pd/C in EtOH yields aniline (XI),which is finally treated with potassium cyanate (KCNO) in H2O/HOAc.
参考文献标题:T900607: Design and evaluation of a second-generation irreversible binder of beta-tubulin
文献作者:Houze,J.; Medina,J.; Gergely,J.; et al.
参考来源:Clin Cancer Res 2000,6(Suppl.),Abst 562
产品链接: CAS No. 261944-52-9›› 产品链接: CAS No.261944-77-8››