MR-827, YS-035

N-(3,4-二甲氧基苯乙基)-2-(3,4-二甲氧基苯基)-N-甲基乙-1-胺Chemical Name: N,N-Bis[2-(3,4-dimethoxyphenyl)ethyl]methylamine hydrochloride; 3,3',4,4'-Tetramethoxy-N-methyldiphenethylamine hydrochloride
CAS No. 33978-72-2
项目整合开发状态: Preclinical
项目研究机构: Medea Research (Originator), SIR International (Originator)
合成路线:3,4-Dimethoxyphenylacetic acid (I) is dissotved in anhydrous chloroform free of ethanol and thionyl chloride is added.When the reaction is complete (4 h) and the solvent evaporated,the oily residue is distilled under reduced presaure (10 mm) and the fraction distilled at 170-2 C is collected.The pure 3,4-dimethoxyphenylacetic acid chloride is thus obtained with 81% yield (II).2-(3,4-Dimethoxyphenyl)ethylamine is dissolved in anhydrous chloroform and anhydrous triethylamine is added to the solution.3,4-Dimethoxyphenylacetyl chloride is added to the cooled solution,refluxed for 8 h,washed with diluted HCl,with water,the organic phase is dried over anhydrous sodium sulfate and the solvent is evaporated under reduced pressure.The final solid is recrystallized from absolute ethanol.The pure N-[2-(3,4-dimethoxyphenyl)ethyl]-3,4-dimethoxyphenylacetamide is obtained with a yield of 84% (III).The amide is reduced according to the method of Umino et al.(Tetrahedron Lett 1976; 763).The N-bis(3,4-dimethoxyphenylethyl)amine obtained (IV) is then dissolved in methanol and CH2O is added.The mixture is boiled under stirring,cooled,and NaBH4 is added in small portions.After evaporation under reduced pressure the residue is dissolved in water acidified with hydrochloric acid,cooled and made definitely alkaline with 4N sodium hydroxide.The alkaline solution is extracted with dichloromethane,the organic phase is isotated,washed and dried over Na2SO4.After filtration the solvent is evaporated under reduced pressure.The residue is crystallized twice from n-hexane,thus obtaining a pure base with a 62% yield.N,N-Bis[2-(3,4-dimethoxyphenyl)ethyl]methylamine hydrochloride (YS-035) is then prepared.