RWJ-51204
5-(乙氧基甲基)-7-氟-N-(2-氟苯基)-3-氧代-1,2-二氢吡啶并[1,2-a]苯并咪唑-4-甲酰胺Chemical Name: 5-(Ethoxymethyl)-7-fluoro-N-(2-fluorophenyl)-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxamide
CAS No. 205701-85-5
项目整合开发状态: Phase II
项目研究机构: R.W. Johnson (Originator)
合成路线:Michael addition of acrylonitrile (II) to 4-fluoro-2-nitroaniline (I) in the presence of Triton B provided nitrile (III).The nitro group of (III) was then reduced to the amine (IV) by hydrogenation over Pd/C.Further cyclization of amine (IV) with ethyl (ethoxycarbonyl)acetimidate (V) furnished the benzimidazole (VI).Diester (VII) (prepared by refluxing the nitrile (VI) with ethanolic HCl),was submitted to Dieckmann cyclization in the presence of NaOEt to produce the pyridobenzimidazole (VIII).Reaction of the ester group of (VIII) with 2-fluoroaniline (IX) in boiling xylene yielded the corresponding anilide (X),which was finally alkylated with ethoxymethyl chloride (XI) in the presence of NaH and crown ether.
📌 参考资料/链接：
参考文献标题:5-Heteroatom-containing alkyl substd.-3-oxo-pyrido(1,2-a)benzimidazole-4-carboxamide derivs.useful in treating central nervous system disorders
文献作者:Reitz,A.B.; Jordan,A.D.; Sanfilippo,P.J.; Scott,M.K.(Ortho-McNeil Pharmaceutical,Inc.)
参考来源:EP 0935598; US 5817668; WO 9815553
📄 详细内容
合成路线:Michael addition of acrylonitrile (II) to 4-fluoro-2-nitroaniline (I) in the presence of Triton B provided nitrile (III).The nitro group of (III) was then reduced to the amine (IV) by hydrogenation over Pd/C.Further cyclization of amine (IV) with ethyl (ethoxycarbonyl)acetimidate (V) furnished the benzimidazole (VI).Diester (VII) (prepared by refluxing the nitrile (VI) with ethanolic HCl),was submitted to Dieckmann cyclization in the presence of NaOEt to produce the pyridobenzimidazole (VIII).Reaction of the ester group of (VIII) with 2-fluoroaniline (IX) in boiling xylene yielded the corresponding anilide (X),which was finally alkylated with ethoxymethyl chloride (XI) in the presence of NaH and crown ether.
参考文献标题:Process research for the synthesis of RWJ-51204,a novel anxiolytic agent
文献作者:Cohen,J.H.; et al.
参考来源:Org Process Res Dev 1999,3(4),260
合成路线:Michael addition of acrylonitrile (II) to 4-fluoro-2-nitroaniline (I) in the presence of Triton B provided nitrile (III).The nitro group of (III) was then reduced to the amine (IV) by hydrogenation over Pd/C.Further cyclization of amine (IV) with ethyl (ethoxycarbonyl)acetimidate (V) furnished the benzimidazole (VI).Diester (VII) (prepared by refluxing the nitrile (VI) with ethanolic HCl),was submitted to Dieckmann cyclization in the presence of NaOEt to produce the pyridobenzimidazole (VIII).Reaction of the ester group of (VIII) with 2-fluoroaniline (IX) in boiling xylene yielded the corresponding anilide (X),which was finally alkylated with ethoxymethyl chloride (XI) in the presence of NaH and crown ether.
参考文献标题:Potential anxiolytic agents.Part 4: Novel orally-active N(5)-substituted pyrido[1,2-a]benzimidazoles with high GABA-A receptor affinity
文献作者:Jordan,A.D.; Vaidya,A.H.; Rosenthal,D.I.; Dubinsky,B.; Kordik,C.P.; Sanfilippo,P.J.; Wu,W.-N.; Reitz,A.B.
参考来源:Bioorg Med Chem Lett 2002,12(17),2381
产品链接: CAS No. 205701-85-5››