DB-075, DB-75

7-氧杂二环[4.1.0]庚烷-2-醇,6-甲基- 呋喃二脒二盐酸盐 Chemical Name: 4,4'-(2,5-Furandiyl)bis(benzamidine)
CAS No. 73819-26-8, 55368-40-6 (as dihydrochloride)
项目整合开发状态: Preclinical
项目研究机构: Georgia State University (Originator), University of North Carolina (Originator), Immtech (Licensee), CombinatoRx (Codevelopment)
合成路线:The reaction of 2-(p-toluenesulfonyloxymethyl)-4-triphenylmethylmorpholine (I) with the potassium salt of 4-hydroxy-1-indanone (II) in DMSO at 100 C gives 2-(1-oxoindan-4-yloxymethyl)-4-triphenylmethylmorpholine (III),which is hydrolyzed with trifluoroacetic acid yielding 2-(1-oxoindan-4-yloxymethyl)morpholine (IV).The reduction of (IV) with LiAlH4-THF affords 2-(1-hydroxyindan-4-yloxymethyl)morpholine (V),which is finally dehydrated by treatment with p-toluenesulfonic acid in refluxing toluene.

合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V) which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with ammonia in ethanol to yield the target bis benzamidine.
📌 参考资料/链接:
参考文献标题:Novel indene derivs.or their salts
文献作者:Niigata,K.; Murakami,M.; Kagami,S.; Fujikura,S.; Kojima,A.; Tachikawa,S.; Nozaki,J.; Takahashi,K.(Yamanouchi Pharmaceutical Co.,Ltd.)
参考来源:JP 1977111580

📄 详细内容


合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V),which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with O-methylhydroxylamine to yield the target bis O-methylamidooxime.

合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V) which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with ammonia in ethanol to yield the target bis benzamidine.

参考文献标题:Anti-pneumocystis activity of bis-amidoximes and bis-O-alkylamidoximes prodrugs
文献作者:Boykin,D.W.; et al.
参考来源:Bioorg Med Chem Lett 1996,6(24),3017


合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V),which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with O-methylhydroxylamine to yield the target bis O-methylamidooxime.

合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V) which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with ammonia in ethanol to yield the target bis benzamidine.

参考文献标题:2,5-Bis[4-(N-alkylamidino)phenyl]furans as anti-Pneumocystis carinii agents
文献作者:Boykin,D.W.; Kumar,A.; Xiao,G.; Wilson,W.D.; Bender,B.C.; McCurdy,D.R.; Hall,J.E.; Tidwell,R.R.
参考来源:J Med Chem 1998,41(1),124


合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V) which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with ammonia in ethanol to yield the target bis benzamidine.

合成路线:2,5-Bis(p-bromophenyl)furan (II) was prepared by cyclodehydration of diketone (I) in refluxing acetic anhydride.Displacement of both bromine atoms by copper(I) cyanide in boiling quinoline generated the dicyano derivative (V).Alternatively,furan (V) was prepared by addition of p-cyanobenzaldehyde (III) to divinyl sulfone (IV) in the presence of a thiazolium catalyst.After conversion of the cyano groups of (V) into bis-imidate (VI),reaccion with ethanolic ammonia furnished amidine (VII).The stable symmetrical carbonate (X) was obtained by reaction of p-fluorophenyl chloroformate (VIII) with p-fluorophenol (IX) in the presence of pyridine.Finally,reaction of the bis(amidine) compound (VII) with carbonate (X) yielded the title compound.

参考文献标题:Synthesis and antiprotozoal activity of 2,5-bis (4-guanylphenyl) furans
文献作者:Das,B.P.; Boykin,D.W.
参考来源:J Med Chem 1977,20(4),531-536


合成路线:The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III),which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV).The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V) which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI).The reaction of (VI) with HCl in ethanol gives the bis imidate (VII),which is finally treated with ammonia in ethanol to yield the target bis benzamidine.
参考文献标题:Trypanocidal diamidines with three isolated ring systems
文献作者:Dann,O.; et al.
参考来源:Liebigs Ann Chem 1975,(1),160


产品链接: CAS No. 73819-26-8››

产品链接: CAS No.55368-40-6››