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    • 3. 发明申请
    • IMPROVED SYNTHESIS OF MACROCYCLIC TETRAAMIDO COMPOUNDS AND NEW METAL INSERTION PROCESS
    • 大分子四氯化钛化合物的改进合成和新金属插入过程
    • WO2004076425A1
    • 2004-09-10
    • PCT/US2004/004985
    • 2004-02-19
    • CARNEGIE MELLON UNIVERSITYHORWITZ, Colin, P.GHOSH, Anindya
    • HORWITZ, Colin, P.GHOSH, Anindya
    • C07D257/10
    • C07D257/10
    • An improved method of synthesizing a macrocyclic tetraamido compound includes protecting the amino portion of an amino carboxylic acid to form a protected amino carboxylic acid; exposing the protected amino carboxylic acid to a first solvent, preferably a hydrocarbon solvent, such as toluene or 1,2-dichloroethane, dichloromethane, dibromomethane and 1,2-dibromoethane. The carboxylic acid portion of the protected amino carboxylic acid is then converted to an activated carboxylic acid by one of esterification or acid halide formation, to form a protected amino activated carboxylic acid derivative. The protected amino activated carboxylic acid derivative is reacted with a diamine in the presence of a second solvent, such as THF or ,2-dichloroethane, dichloromethane, dibromomethane and 1,2-dibromoethane, to form a protected diamide diamine intermediate. Following deprotection, the diamide diamine intermediate is reacted with an activated diacid, such as an activated malonate, oxalate or succinate derivative to form the macrocyclic tetraamido compound. The macrocyclic tetraamido compound may further be complexed with a transition metal.
    • 合成大环四氨基化合物的改进方法包括保护氨基羧酸的氨基部分以形成受保护的氨基羧酸; 将保护的氨基羧酸暴露于第一溶剂,优选烃溶剂如甲苯或1,2-二氯乙烷,二氯甲烷,二溴甲烷和1,2-二溴乙烷。 然后通过酯化或酰卤形成之一将受保护的氨基羧酸的羧酸部分转化为活化的羧酸,形成受保护的氨基活化的羧酸衍生物。 保护的氨基活化的羧酸衍生物与二胺在第二溶剂如THF或2-二氯乙烷,二氯甲烷,二溴甲烷和1,2-二溴乙烷的存在下反应,形成受保护的二酰胺二胺中间体。 脱保护后,将二酰胺二胺中间体与活化的二酸例如活化的丙二酸酯,草酸酯或琥珀酸酯衍生物反应形成大环四氨基化合物。 大环四氨基化合物还可以与过渡金属络合。