MDL-10222F(undefined isomer), MDL-101986
Chemical Name: (E)-N'-[4-(2-Chloro-1,2-diphenylvinyl)phenyl]-N,N-diethyl-1,2-ethanediamine citrate (1:1)
CAS No. 179552-06-8, 179552-05-7 (free base), 179552-10-4 (monoHCl), 155519-89-4 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator)
合成路线:The reaction of 4-aminobenzophenone (I) with benzylmagnesium bromide (II) in ether gives the carbinol (III),which by reaction with acetic anhydride in hot pyridine yields the olefinic acetamide (IV).The chlorination of (IV) with Cl2 in CCl4 followed by refluxing in the same solvent affords the chlorovinyl acetamide (V),which is alkylated at the amidic nitrogen with 2-chloroethyl(diethyl)amine (VI) by means of KOH in refluxing acetone giving the disubstituted acetamide (VII).Finally,the deacetylation of (VII) with hot 10% HCl and salification with citric acid affords the target compound.
📌 参考资料/链接：
参考文献标题:Non-metabolizable clomiphene analogs for treatment of tamoxifen-resistant tumors
文献作者:Bitonti,A.J.; Baumann,R.J.(Merrell Pharmaceuticals,Inc.)
参考来源:EP 0660821; JP 1997500863; WO 9406762
📄 详细内容
合成路线:The acetylation of 4-aminobenzophenone (I) with acetic anhydride and TEA in dichloromethane gives the acetamide (II),which is N-alkylated with 2-chlorethyl(diethyl)amine (III) by means of KOH in refluxing acetone yielding the disubstituted acetamide (IV).The reaction of the ketonic group of (IV) with benzylphosphonic acid diethyl ester (V) by means of butyllithium and benzenesulfonyl chloride in THF affords the chlorovinyl acetamide (VI),which is finally hydrolyzed with HCl and salified with citric acid to provide the target compound.
参考文献标题:Method of using triaryl-ethylene derivs.in the treatment and prevention of osteoporosis
文献作者:Bitonti,A.J.(Aventis Pharmaceuticals,Inc.)
参考来源:US 5691384; WO 9616646