RO-66-0074
Chemical Name: 4-[2-Bromo-6-(1-pyrrolidinyl)pyridin-4-ylsulfonyl]phenylamine
CAS No. 231286-79-6
项目整合开发状态: Preclinical
项目研究机构: Roche (Originator)
合成路线:2,6-Dibromopyridine (I) is converted to its N-oxide (II),which undergoes electrophilic nitration at position 4 with HNO3/H2SO4 to yield compound (III).Subsequent selective reduction of the N-oxide group of (III) to afford 2,6-dibromo-4-nitropyridine (IV) is accomplished by treatment with PBr3 in acetonitrile (1).Nucleophilic displacement of the 4-nitro group of (IV) with potassium p-nitrothiophenoxide (V) leads to sulfide (VI).This is oxidized to sulfone (VII) with m-chloroperbenzoic acid,and followed by reduction of the nitro group of (VII) to amine (VIII) with Fe and NH4Cl.Finally,displacement of one bromo substituent of (VIII) with pyrrolidine (IX) in dioxane gives rise to the title pyrrolidinylpyridine derivative (1,2).
📌 参考资料/链接：
参考文献标题:Benzosulfone derivs.
文献作者:Hunkeler,W.; B,M.; Riemer,C.(F.Hoffmann-La Roche AG)
参考来源:CA 2258454; EP 0930302; JP 2000053635; US 5990105
📄 详细内容
合成路线:2,6-Dibromopyridine (I) is converted to its N-oxide (II),which undergoes electrophilic nitration at position 4 with HNO3/H2SO4 to yield compound (III).Subsequent selective reduction of the N-oxide group of (III) to afford 2,6-dibromo-4-nitropyridine (IV) is accomplished by treatment with PBr3 in acetonitrile (1).Nucleophilic displacement of the 4-nitro group of (IV) with potassium p-nitrothiophenoxide (V) leads to sulfide (VI).This is oxidized to sulfone (VII) with m-chloroperbenzoic acid,and followed by reduction of the nitro group of (VII) to amine (VIII) with Fe and NH4Cl.Finally,displacement of one bromo substituent of (VIII) with pyrrolidine (IX) in dioxane gives rise to the title pyrrolidinylpyridine derivative (1,2).
参考文献标题:Influence of the 5-HT6 receptor on acetylcholine release in the cortex: Pharmacological characterization of 4-(2-bromo-6-pyrrolidin-1-ylpyridine-4-sulfonyl)phenylamine,a potent and selective 5-HT6 receptor antagonist
文献作者:Riemer,C.; Borroni,E.; Levet-Trafit,B.; Martin,J.R.; Poli,S.; Porter,R.H.P.; B,M.
参考来源:J Med Chem 2003,46(7),1273
产品链接: CAS No. 231286-79-6››