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    • 28. 发明申请
    • PROCESS FOR THE PREPARATION OF DERIVATIVES OF 4-AMINO-3-HYDROXYPYRROLE-2-CARBOXYLIC ACID
    • 制备4-氨基-3-羟基吡咯-2-羧酸的衍生物的方法
    • WO02004417A1
    • 2002-01-17
    • PCT/US2001/021274
    • 2001-07-05
    • C07C229/30C07D207/36C07D207/42
    • C07D207/36C07C229/30C07D207/42
    • Novel processes and intermediates are provided for the synthesis of derivatives of 4-amino-3-hydroxypyrrole-2-carboxylic acids that are useful as monomers for polyamides capable of binding dsDNA. According to one preferred reaction scheme, an alkyl alkoxymethylene nitroacetate (Formula VIII) is prepared by reaction of a trialkyl orthoformate or orthoacetate with a nitroacetate ester in the presence of a carboxylic anhydride. The compound of Formula VIII is condensed with an N-substituted glycine to yield an N-substituted(2-nitro-2-alkoxycarbonyl)vinyl glycinate ester (Formula VII). Ring closure in the presence of an alkali metal alkoxide yields a 4-nitro-3-hydroxypyrrole-2-carboxylic ester (Formula V). After blocking of the 3-hydroxy group to produce a further intermediate (Formula IV), the 4-nitro group is reduced to a 4-amino group (Formula III), and the 4-amino group is then blocked by reaction with a dicarbonate diester to produce the fully blocked intermediate (Formula II). Saponification of the 2-carboxylic acid ester yields a monomer having a free 2-carboxylic ester moiety (Formula I).
    • 提供新的方法和中间体用于合成可用作能够结合dsDNA的聚酰胺单体的4-氨基-3-羟基吡咯-2-羧酸衍生物。 根据一个优选的反应方案,烷基烷氧基亚甲基硝基乙酸酯(式VIII)是通过在羧酸酐存在下,原甲酸三烷基酯或原乙酸酯与硝基乙酸酯反应来制备的。 式VIII的化合物与N-取代的甘氨酸缩合,得到N-取代的(2-硝基-2-烷氧基羰基)乙烯基甘氨酸酯(式VII)。 在碱金属醇盐存在下闭环,得到4-硝基-3-羟基吡咯-2-羧酸酯(式Ⅴ)。 在封闭3-羟基以产生另外的中间体(式IV)后,将4-硝基还原成4-氨基(式III),然后通过与二碳酸酯反应来阻断4-氨基 二酯以产生完全封闭的中间体(式II)。 2-羧酸酯的皂化产生具有游离的2-羧酸酯部分的单体(式I)。