LY-487379
2,2,2-三氟-N-[4-(2-甲氧基苯氧基)苯基]-N-(3-吡啶基甲基)-乙磺酰胺 LY487379盐酸盐 Chemical Name: 2,2,2-Trifluoro-N-[4-(2-methoxyphenoxy)phenyl]-N-(pyridin-3-ylmethyl)ethanesulfonamide
CAS No. 353231-17-1, 353229-59-1 (hydrochloride)
项目整合开发状态: Preclinical
项目研究机构: Lilly (Originator)
合成路线:The reductive alkylation of 4-(2-methoxyphenoxy)aniline (I) with pyridine-3-carboxaldehyde (II) in the presence of NaBH4 leads to the N-pyridylmethyl aniline adduct (III) (1).Alternatively,4-bromoaniline (IV) is reductively alkylated with pyridine-3-carboxaldehyde (II) to produce (V).Subsequent copper-catalyzed bromide displacement of (V) with guaiacol (VI) affords intermediate (III) (2).Finally,acylation of amine (III) with 2,2,2-trifluoroethylsulfonyl chloride (VII) gives rise to the target sulfonamide (1,2).
合成路线:Coupling of 2-methoxyphenol (I) with 3-fluoronitrobenzene (II) produced the diaryl ether (III).The nitro group of (III) was then reduced by catalytic hydrogenation over Raney-Ni,yielding aniline (IV).Reductive alkylation of (IV) with pyridine-3-carboxaldehyde (V) using NaBH4 furnished the secondary amine (VI).This was finally acylated with 2,2,2-trifluoroethylsulfonyl chloride to produce the title sufonamide.
📌 参考资料/链接：
参考文献标题:Potentiators of glutamate receptors
文献作者:Monn,J.A.; Hornback,W.J.; Schoepp,D.D.; Dressman,B.A.; Britton,T.C.; Tizzano,J.P.; Johnson,K.W.; Henry,S.S.; Coleman,D.S.; Jagdmann,G.E.J.; Johnson,M.P.; Large,T.H.; Barda,D.A.; Fichtner,M.W.(Eli Lilly and Company)
参考来源:WO 0156990
📄 详细内容
合成路线:The reductive alkylation of 4-(2-methoxyphenoxy)aniline (I) with pyridine-3-carboxaldehyde (II) in the presence of NaBH4 leads to the N-pyridylmethyl aniline adduct (III) (1).Alternatively,4-bromoaniline (IV) is reductively alkylated with pyridine-3-carboxaldehyde (II) to produce (V).Subsequent copper-catalyzed bromide displacement of (V) with guaiacol (VI) affords intermediate (III) (2).Finally,acylation of amine (III) with 2,2,2-trifluoroethylsulfonyl chloride (VII) gives rise to the target sulfonamide (1,2).
参考文献标题:Discovery of allosteric potentiators for the metabotropic glutamate 2 receptor: Synthesis and subtype selectivity of N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethylamine
文献作者:Johnson,M.P.; Baez,M.; Jagdmann,G.E.Jr.; Britton,T.C.; Large,T.H.; Callagaro,D.O.; Tizzano,J.P.; Monn,J.A.; Schoepp,D.D.
参考来源:J Med Chem 2003,46(15),3189
产品链接: CAS No. 353231-17-1›› 产品链接: CAS No.353229-59-1››