LM-1669
Chemical Name: 2-(3-Benzoyl-5-ethylphenyl)ethenesulfonamide
项目整合开发状态: Biological Testing
项目研究机构: Menarini (Originator)
合成路线:An alternative method for the preparation of the precursor 3-bromo-5-ethylbenzophenone (VI) has been reported.Diazotization of diethyl 5-aminoisophthalate (I),followed by treatment with HBr/CuBr furnishes the bromo isophthalate (II).Partial hydrolysis of diester (II) by means of KOH provides mono-acid (VIII),which is further converted to acid chloride (IX) with PCl5.Subsequent Friedel-Crafts condensation of (IX) with benzene in the presence of AlCl3 leads to benzophenone (X).After protection of ketone (X) as the ethylene ketal (XI),addition of methylmagnesium chloride to (XI) affords the acetyl compound (XII).This is subsequently reduced to the corresponding ethyl derivative (XIII) under Wolff-Kishner conditions.The key benzophenone precursor (VI) is then obtained by acidic hydrolysis of ketal (XIII).
📌 参考资料/链接：
参考文献标题:Trisubstd.benzenes linked to amides,esters and carboxylic acids as new cyclooxygenase II inhibitors
文献作者:Palomer Benet,A.; Maule�?Casellas,D.; Garc�?P閞ez,M.L.; Pascual Avellana,J.
参考来源:ES 2164564
📄 详细内容
合成路线:Dimethyl 5-aminoisophthalate (I) is converted into the corresponding 5-bromo derivative (II) via diazotization,followed by Sandmeyer reaction with HBr/CuBr.Addition of methylmagnesium chloride to one of the carboxylate groups of diester (II) leads to methyl 3-acetyl-5-bromobenzoate (III).Ketone (III) reduction with concomitant ester hydrolysis under Wolff-Kishner conditions produces 3-bromo-5-ethylbenzoic acid (IV),which is further chlorinated to (V) by using PCl5 in CCl4.Friedel-Crafts condensation of acid chloride (V) with benzene gives rise to the benzophenone (VI).Finally,palladium-catalyzed coupling of aryl bromide (VI) with vinylsulfonamide (VII) yields the title compound.
参考文献标题:Structure-based design of cyclooxygenase-2 selectivity into ketoprofen
文献作者:Palomer,A.; Pascual,J.; Cabr? M.; Borr�? L.; Gonz醠ez,G.; Aparici,M.; Carabaza,A.; Cabr? F.; Garc�? M.L.; Maule�? D.
参考来源:Bioorg Med Chem Lett 2002,12(4),533