【结 构 式】 |
【分子编号】12395 【品名】N-Methyl-N-(4-nitrophenethyl)amine; N-Methyl-2-(4-nitrophenyl)-1-ethanamine 【CA登记号】 |
【 分 子 式 】C9H12N2O2 【 分 子 量 】180.20656 【元素组成】C 59.99% H 6.71% N 15.55% O 17.76% |
合成路线1
该中间体在本合成路线中的序号:(I)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.
【1】 Arrowsmith, J.E.; Cross, P.E.; Thomas, G.N. (Pfizer Inc.); N-Substituted p-aminoethylsulphonanilides as antiarrhythmic agents, and intermediates therefor. EP 0245997; JP 1987267250; US 4959366; US 5079248 . |
【2】 Cross, P.E.; Thomas, G.N.; Gwilt, M.; Arrowsmith, J.E.; Burges, R.A.; Selective class III antiarrhythmic agents. 1. Bis(arylalkyl)amines. J Med Chem 1990, 33, 4, 1151-5. |
【3】 Castaner, J.; Prous, J.; UK-68,798. Drugs Fut 1991, 16, 6, 521. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 12395 | N-Methyl-N-(4-nitrophenethyl)amine; N-Methyl-2-(4-nitrophenyl)-1-ethanamine | C9H12N2O2 | 详情 | 详情 | |
(II) | 12396 | 2-Chloroethyl 4-nitrophenyl ether; 1-(2-Chloroethoxy)-4-nitrobenzene | 3383-72-0 | C8H8ClNO3 | 详情 | 详情 |
(III) | 12397 | N-Methyl-N-(4-nitrophenethyl)-2-(4-nitrophenoxy)-1-ethanamine; N-Methyl-N-(4-nitrophenethyl)-N-[2-(4-nitrophenoxy)ethyl]amine | C17H19N3O5 | 详情 | 详情 | |
(IV) | 12398 | N-(4-Aminophenethyl)-N-[2-(4-aminophenoxy)ethyl]-N-methylamine; 4-[2-[(4-Aminophenethyl)(methyl)amino]ethoxy]aniline | C17H23N3O | 详情 | 详情 | |
(V) | 12399 | N-[4-(2-Chloroethoxy)phenyl]methanesulfonamide | C9H12ClNO3S | 详情 | 详情 | |
(VI) | 12400 | N-(4-[2-[Methyl(4-nitrophenethyl)amino]ethoxy]phenyl)methanesulfonamide | C18H23N3O5S | 详情 | 详情 | |
(VII) | 12401 | N-(4-[2-[(4-Aminophenethyl)(methyl)amino]ethoxy]phenyl)methanesulfonamide | C18H25N3O3S | 详情 | 详情 | |
(VIII) | 12402 | N-[4-[2-(Methylamino)ethyl]phenyl]methanesulfonamide | C10H16N2O2S | 详情 | 详情 | |
(IX) | 12403 | N-[4-(2-[Methyl[2-(4-nitrophenoxy)ethyl]amino]ethyl)phenyl]methanesulfonamide | C18H23N3O5S | 详情 | 详情 | |
(X) | 12404 | N-(4-[2-[[2-(4-Aminophenoxy)ethyl](methyl)amino]ethyl]phenyl)methanesulfonamide | C18H25N3O3S | 详情 | 详情 | |
(XI) | 12405 | 4-[(methylsulfonyl)amino]phenethyl methanesulfonate | C10H15NO5S2 | 详情 | 详情 | |
(XII) | 12406 | N-[4-[2-(Methylamino)ethoxy]phenyl]methanesulfonamide | C10H16N2O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(I)
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 12395 | N-Methyl-N-(4-nitrophenethyl)amine; N-Methyl-2-(4-nitrophenyl)-1-ethanamine | C9H12N2O2 | 详情 | 详情 | |
(VI) | 12400 | N-(4-[2-[Methyl(4-nitrophenethyl)amino]ethoxy]phenyl)methanesulfonamide | C18H23N3O5S | 详情 | 详情 | |
(VII) | 12401 | N-(4-[2-[(4-Aminophenethyl)(methyl)amino]ethoxy]phenyl)methanesulfonamide | C18H25N3O3S | 详情 | 详情 | |
(XIII) | 66267 | N-(4-(2-bromoethoxy)phenyl)methanesulfonamide | C9H12BrNO3S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号:(I)
【1】 Arrowsmith JE,Cross PE,et al.1987.Processes for the preparation of N-substituted p-aminoethylsufonanilides for use as antiarryhythmic agents. EP245997 |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 12395 | N-Methyl-N-(4-nitrophenethyl)amine; N-Methyl-2-(4-nitrophenyl)-1-ethanamine | C9H12N2O2 | 详情 | 详情 | |
(III) | 12397 | N-Methyl-N-(4-nitrophenethyl)-2-(4-nitrophenoxy)-1-ethanamine; N-Methyl-N-(4-nitrophenethyl)-N-[2-(4-nitrophenoxy)ethyl]amine | C17H19N3O5 | 详情 | 详情 | |
(IV) | 12398 | N-(4-Aminophenethyl)-N-[2-(4-aminophenoxy)ethyl]-N-methylamine; 4-[2-[(4-Aminophenethyl)(methyl)amino]ethoxy]aniline | C17H23N3O | 详情 | 详情 | |
(XVII) | 63398 | 1-[(2-bromoethyl)oxy]-4-nitrobenzene; 2-bromoethyl 4-nitrophenyl ether | 13288-06-7 | C8H8BrNO3 | 详情 | 详情 |