D-2343

Chemical Name: 1-(4-Hydroxyphenyl)-2-[1,1-dimethyl-3-(2-methoxyphenyl)propylamino]ethanol hydrochloride; 4-Hydroxy-alpha-[[[3-(2-methoxyphenyl)-1,1-dimethylpropyl]amino]methyl]benzenemethanol hydrochloride
CAS No. 72734-58-8, 72734-63-5 (free base)
项目整合开发状态: Biological Testing
项目研究机构: AstraZeneca (Originator)
合成路线:The condensation of acetone (VIII) with 2-methoxybenzaldehyde (IX) by means of NaOH gives 2-methoxybenzalacetone (X),which is reduced with H2 over Raney-Ni in ethanol to yield 4-(2-methoxyphenyl)-2-butanone (XI).The Grignard reaction of (XI) with methylmagnesium iodide in ether affords 1,1-dimethyl-3-(2-methoxyphenyl) propanol (XII),which by reaction with NaCN by means of H2SO4 in acetic acid affords N-[1,1-dimethyl-3-(2-methoxyphenyl)propyl]formamide (XIII).Finally,this compound is hydrolyzed with refluxing 5N NaOH to give (II).

合成路线:The bromination of 4-benzyloxyacetophenone (VI) with Br2 in dioxane gives 4-benzyloxyphenacyl bromide (VII),which by reduction with NaBH4 in dioxane and epoxidation with NaOH water is converted into (I).The condensation of 4-benzyloxystyrene oxide (I) with 1,1-dimethyl-3-(2-methoxyphenyl)propylamine (II) in refluxing isopropanol gives 1-(4-benzyloxyphenyl)-2-[1,1-dimethyl-3-(2-methoxyphenyl)propylamino]ethanol (III),which is debenzylated by reduction with H2 over Pd/C in ethanol,and treated with HCl.

合成路线:The oxidation of (VI) with SeO2 in hot dioxane-water gives 4-benzyloxyphenylglyoxal (IV).The condensation with (II) in refluxing ethanol,gives 4-benzyloxy-alpha-[1,1-dimethyl-3-(2-methoxyphenyl)propylimino]acetophenone (V),which is then reduced with NaBH4 in ethanol to afford (III),which is debenzylated by reduction with H2 over Pd/C in ethanol,and treated with HCl.