2-Chloroethyl 4-nitrophenyl ether; 1-(2-Chloroethoxy)-4-nitrobenzene -Drug Synthesis Database

【结构式】

【分子编号】12396

【品名】2-Chloroethyl 4-nitrophenyl ether; 1-(2-Chloroethoxy)-4-nitrobenzene

【CA登记号】3383-72-0

【分子式】C₈H₈ClNO₃

【分子量】201.60916

【元素组成】C 47.66% H 4% Cl 17.58% N 6.95% O 23.81%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

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.

参考文献中间体

合成目标

【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：(V)

The methylation of the 1-(4-benzyloxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline (I) with methyl iodide gives the isoquinolinium salt (II), which is reduced with potassium borohydride to afford 1-(4-benzyloxybenzyl)-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinoline (III). The treatment of (III) with HCl yields the phenol (IV), which is finally alkylated with 2-(4-nitrophenoxy)ethanol.

参考文献中间体

合成目标

【1】 He, L.W.; et al.; Synthesis and biological activity of 1-(4-alkyloxy)benzyl-1,2,3,4-tetrahydroisoquinolines and related compounds. Acta Pharm Sin 1998, 33, 10, 741.

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)	27671	benzyl 4-[(6,7-dimethoxy-3,4-dihydro-1-isoquinolinyl)methyl]phenyl ether		C₂₅H₂₅NO₃	详情	详情
(II)	27672	1-[4-(benzyloxy)benzyl]-6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolinium iodide		C₂₆H₂₈INO₃	详情	详情
(III)	27673	1-[4-(benzyloxy)benzyl]-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline		C₂₆H₂₉NO₃	详情	详情
(IV)	27674	4-[(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-1-isoquinolinyl)methyl]phenol		C₁₉H₂₃NO₃	详情	详情
(V)	12396	2-Chloroethyl 4-nitrophenyl ether; 1-(2-Chloroethoxy)-4-nitrobenzene	3383-72-0	C₈H₈ClNO₃	详情	详情

Extended Information