Tamsulosin hydrochloride, Amsulosin hydrochloride, Y-617, YM-12617-1, LY-253351, YM-617, EU-617, Josir, Omix, Harnal, Flomax, Alna, Flomax MR, Omic, Omnic, Pradif

合成路线:The condensation of 2-methoxy-5-(2-bromopropionyl)benzenesulfonamide (I) with N-benzyl-2-(2 ethoxyphenoxy)ethylamine (II) in refluxing butanone gives the tertiary amine (III),which is reduced with sodium in ethanol to the alcohol (IV).Debenzylation of (IV) with H2 over Pd/C in methanol affords the hydroxyamine (V),which by reaction with SOCl2 in acetonitrile is converted to the corresponding chloro derivative (VI).Finally,this compound is dechlorinated by hydrogenolysis with H2 over Pd/C in methanol.

合成路线:The condensation of 2-methoxyphenol (I) with ethylene oxide (II) gives 2-(2-methoxyphenoxy)ethanol (III),which is treated with SOCl2 to yield 2-(2-methoxyphenoxy)ethyl chloride (IV).The reaction of (IV) with benzylamine (A) gives N-[2-(2-methoxyphenoxy)ethyl]benzylamine (V),which is condensed with 2-methyl-5-bromoacetylbenzenesulfonamide (VI) affording N-[2-(2-methoxyphenoxy)ethyl]-N-[(4-methyl-3-aminosulfonylbenzoyl)methyl]benzylamine (VII).The reduction of (VII) with NaBH4 affords the corresponding protected carbinol (VIII),which is finally debenzylated by hydrogenation with H2 over Pd/C.

参考文献标题:Phenylethanolamine derivatives
文献作者:Fujikura,T.; et al.(Yamanouchi Pharmaceutical Co.,Ltd.)
参考来源:DE 2843016; ES 474149; ES 481549; FR 2405931; GB 2006772


合成路线:The condensation of 2-methoxy-5-(2-bromopropionyl)benzenesulfonamide (I) with N-benzyl-2-(2 ethoxyphenoxy)ethylamine (II) in refluxing butanone gives the tertiary amine (III),which is reduced with sodium in ethanol to the alcohol (IV).Debenzylation of (IV) with H2 over Pd/C in methanol affords the hydroxyamine (V),which by reaction with SOCl2 in acetonitrile is converted to the corresponding chloro derivative (VI).Finally,this compound is dechlorinated by hydrogenolysis with H2 over Pd/C in methanol.

参考文献标题:YM-12617
文献作者:Castar,J.; Mannhold,R.
参考来源:Drugs Fut 1986,11(4),293


合成路线:A new synthesis of YM-12617-1,the active R-isomer of YM-12617,has been described:The reductocondensation of 1-(4-methoxyphenyl)-2-propanone (I) with R-1-phenylethylamine (II) gives regioselectively the secondary amine (III) as the HCl salt,which by sulfonation with chlorosulfonic acid and treatment with NH4OH yields (R,R)-2-methoxy-5-[2-(1-phenylethylamino)propyl]benzenesulfonamide (IV).Eliminating the protecting group by hydrogenation,the free amine hydrochloride (V) is obtained,which is finally submitted to a reductocondensation with 2-(2-ethoxyphenoxy)acetaldehyde (VI) by means of sodium borohydride in methanol,and treated with HCl in ether.
参考文献标题:The synthesis of the 14C and 2H-isotopomers of (R)-N-[2-(2'-ethoxyphenoxy)-ethyl]-N-2-[3-(4'-methoxy-3'-sulfonamido)-phenyl]-propylamine hydrochloride,an alpha1-adrenoreceptor antagonist
文献作者:Hunden,D.C.; Wheller,W.J.; Schmiegel,K.K.
参考来源:J Label Compd Radiopharm 1989,26(2),171