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Dofetilide, UK-68798, Tikosyn, Xelide

多非利特Chemical Name: N-[4-[2-[N-[2-[4-(Methanesulfonamido)phenyl]ethyl]-N-methylamino]ethoxy]phenyl]methanesulfonamide
CAS No. 115256-11-6
项目整合开发状态: Launched-2000
项目研究机构: Pfizer (Originator)
合成路线:This compound can be prepared by several related ways:1) The condensation of N-methyl-2-(4-nitrophenyl)ethylamine (I) with 4-(2-chloroethoxy)nitrobenzene (II) by means of NaI and K2CO3 in refluxing acetonitrile gives 1-(4-nitrophenoxy)-5-(4-nitrophenyl)-3-methyl-3-azapentane (III),which is reduced with H2 over Pd/C in ethanol,yielding the corresponding diamino derivative (IV).Finally,this compound is acylated with methanesulfonyl anhydride in dichloromethane.2) The condensation of (I) with N-[4-(2-chloroethoxy)phenyl]methanesulfonamide (V) with NaI and K2CO3 as before gives 1-[4-(methanesulfonamide)phenoxy]-3-methyl-5-(4-nitrophenyl)-3-azapentane (VI),which is reduced with H2 over Pd/C as before,yielding the corresponding amino derivative (VII).Finally,this compound is acylated with methanesulfonyl anhydride as usual.3) The condensation of (II) with N-[4-[2-(methylamino)ethyl]phenyl]methanesulfonamide (VIII) with NaI and K2CO3 as usual gives 1-[4-(methanesulfonamido)phenyl]-3-methyl-5-(4-nitrophenoxy)-3-azapentane (IX),which is reduced with H2 and RaNi to the corresponding amino derivative (X).Finally,this compound is acylated with methanesulfonyl chloride and pyridine.4) By condensation of N-[4-[2-(methanesulfonyloxy)ethyl]phenyl]methanesulfonamide (XI) with N-[4-[2-(methylamino)ethoxy]phenyl]methanesulfonamide (XII) in refluxing ethanol.5) By condensation of (V) with (VIII) by means of NaHCO3.
📌 参考资料/链接:
参考文献标题:N-Substituted p-aminoethylsulphonanilides as antiarrhythmic agents,and intermediates therefor
文献作者:Arrowsmith,J.E.; Cross,P.E.; Thomas,G.N.(Pfizer Inc.)
参考来源:EP 0245997; JP 1987267250; US 4959366; US 5079248

📄 详细内容


合成路线:This compound can be prepared by several related ways:1) The condensation of N-methyl-2-(4-nitrophenyl)ethylamine (I) with 4-(2-chloroethoxy)nitrobenzene (II) by means of NaI and K2CO3 in refluxing acetonitrile gives 1-(4-nitrophenoxy)-5-(4-nitrophenyl)-3-methyl-3-azapentane (III),which is reduced with H2 over Pd/C in ethanol,yielding the corresponding diamino derivative (IV).Finally,this compound is acylated with methanesulfonyl anhydride in dichloromethane.2) The condensation of (I) with N-[4-(2-chloroethoxy)phenyl]methanesulfonamide (V) with NaI and K2CO3 as before gives 1-[4-(methanesulfonamide)phenoxy]-3-methyl-5-(4-nitrophenyl)-3-azapentane (VI),which is reduced with H2 over Pd/C as before,yielding the corresponding amino derivative (VII).Finally,this compound is acylated with methanesulfonyl anhydride as usual.3) The condensation of (II) with N-[4-[2-(methylamino)ethyl]phenyl]methanesulfonamide (VIII) with NaI and K2CO3 as usual gives 1-[4-(methanesulfonamido)phenyl]-3-methyl-5-(4-nitrophenoxy)-3-azapentane (IX),which is reduced with H2 and RaNi to the corresponding amino derivative (X).Finally,this compound is acylated with methanesulfonyl chloride and pyridine.4) By condensation of N-[4-[2-(methanesulfonyloxy)ethyl]phenyl]methanesulfonamide (XI) with N-[4-[2-(methylamino)ethoxy]phenyl]methanesulfonamide (XII) in refluxing ethanol.5) By condensation of (V) with (VIII) by means of NaHCO3.

参考文献标题:Selective class III antiarrhythmic agents.1.Bis(arylalkyl)amines
文献作者:Cross,P.E.; Thomas,G.N.; Gwilt,M.; Arrowsmith,J.E.; Burges,R.A.
参考来源:J Med Chem 1990,33(4),1151-5


合成路线:This compound can be prepared by several related ways:1) The condensation of N-methyl-2-(4-nitrophenyl)ethylamine (I) with 4-(2-chloroethoxy)nitrobenzene (II) by means of NaI and K2CO3 in refluxing acetonitrile gives 1-(4-nitrophenoxy)-5-(4-nitrophenyl)-3-methyl-3-azapentane (III),which is reduced with H2 over Pd/C in ethanol,yielding the corresponding diamino derivative (IV).Finally,this compound is acylated with methanesulfonyl anhydride in dichloromethane.2) The condensation of (I) with N-[4-(2-chloroethoxy)phenyl]methanesulfonamide (V) with NaI and K2CO3 as before gives 1-[4-(methanesulfonamide)phenoxy]-3-methyl-5-(4-nitrophenyl)-3-azapentane (VI),which is reduced with H2 over Pd/C as before,yielding the corresponding amino derivative (VII).Finally,this compound is acylated with methanesulfonyl anhydride as usual.3) The condensation of (II) with N-[4-[2-(methylamino)ethyl]phenyl]methanesulfonamide (VIII) with NaI and K2CO3 as usual gives 1-[4-(methanesulfonamido)phenyl]-3-methyl-5-(4-nitrophenoxy)-3-azapentane (IX),which is reduced with H2 and RaNi to the corresponding amino derivative (X).Finally,this compound is acylated with methanesulfonyl chloride and pyridine.4) By condensation of N-[4-[2-(methanesulfonyloxy)ethyl]phenyl]methanesulfonamide (XI) with N-[4-[2-(methylamino)ethoxy]phenyl]methanesulfonamide (XII) in refluxing ethanol.5) By condensation of (V) with (VIII) by means of NaHCO3.
参考文献标题:UK-68,798
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1991,16(6),521


产品链接: CAS No. 115256-11-6››