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    Process for the preparation of substituted cyanophenoxy-pyrimidinyloxy-phenyl acrylate derivatives
    3.
    发明授权
    Process for the preparation of substituted cyanophenoxy-pyrimidinyloxy-phenyl acrylate derivatives 有权
    取代氰基苯氧基 - 嘧啶氧基 - 苯基丙烯酸酯衍生物的制备方法

    公开(公告)号：US08471013B2

    公开(公告)日：2013-06-25

    申请号：US12519436

    申请日：2007-12-16

    申请人： David Ovadia ,  Raya Sturkovich ,  David Leonov

    发明人： David Ovadia ,  Raya Sturkovich ,  David Leonov

    IPC分类号： C07D239/54 ,  C07D213/30 ,  C07C43/205

    CPC分类号： C07D239/52 ,  C07D239/54

    摘要： The present invention provides a process for reacting between a phenol derivative and an aromatic substrate under phenolate forming conditions comprising the following steps: (a) reacting a phenol derivative with a base in a polar organic solvent to obtain a phenolate salt, wherein water is removed form the reaction mixture during the reaction, (b) adding the aromatic substrate to the reaction mixture obtained in step (a), (c) heating the reaction mixture of step (b) to a temperature in the range of 80° to 1300° C., preferably, 90° to 1000° C. for 2 to 7 hours to obtain a phenoxy substituted aromatic substrate, (d) removing the solvent from the mixture of step (c) and optionally further isolating an purifying the phenoxy substituted aromatic substrate. Optionally, the removal of water during step (a) is in conjunction with partial removal of the organic solvent.

    摘要翻译： 本发明提供一种苯酚衍生物和芳族底物在酚盐形成条件下的反应方法，包括以下步骤：（a）使苯酚衍生物与碱在极性有机溶剂中反应得到酚盐，其中除去水 在反应期间形成反应混合物，（b）将芳族底物加入到步骤（a）中获得的反应混合物中，（c）将步骤（b）的反应混合物加热至80℃至1300℃ 优选在90℃至1000℃下反应2至7小时以获得苯氧基取代的芳族底物，（d）从步骤（c）的混合物中除去溶剂，并任选进一步分离纯化苯氧基取代的芳族底物 。 任选地，步骤（a）期间除去水与有机溶剂的部分去除结合在一起。

    PROCESS FOR THE PREPARATION OF SUBSTITUTED CYANOPHENOXY-PYRIMIDINYLOXY-PHENYL ACRYLATE DERIVATIVES
    5.
    发明申请
    PROCESS FOR THE PREPARATION OF SUBSTITUTED CYANOPHENOXY-PYRIMIDINYLOXY-PHENYL ACRYLATE DERIVATIVES 有权
    制备取代的氰基苯氧基 - 丙烯酰氧基 - 苯基丙烯酸酯衍生物的方法

    公开(公告)号：US20090281316A1

    公开(公告)日：2009-11-12

    申请号：US12519436

    申请日：2007-12-16

    申请人： David Ovadia ,  Raya Sturkovich ,  David Leonov

    发明人： David Ovadia ,  Raya Sturkovich ,  David Leonov

    IPC分类号： C07D239/24

    CPC分类号： C07D239/52 ,  C07D239/54

    摘要： The present invention provides a process for reacting between a phenol derivative and an aromatic substrate under phenolate forming conditions comprising the following steps: (a) reacting a phenol derivative with a base in a polar organic solvent to obtain a phenolate salt, wherein water is removed form the reaction mixture during the reaction, (b) adding the aromatic substrate to the reaction mixture obtained in step (a), (c) heating the reaction mixture of step (b) to a temperature in the range of 80° to 1300° C., preferably, 90° to 1000° C. for 2 to 7 hours to obtain a phenoxy substituted aromatic substrate, (d) removing the solvent from the mixture of step (c) and optionally further isolating an purifying the phenoxy substituted aromatic substrate. Optionally, the removal of water during step (a) is in conjunction with partial removal of the organic solvent.

    摘要翻译： 本发明提供一种苯酚衍生物和芳族底物在酚盐形成条件下的反应方法，包括以下步骤：（a）使苯酚衍生物与碱在极性有机溶剂中反应得到酚盐，其中除去水 在反应期间形成反应混合物，（b）将芳族底物加入到步骤（a）中获得的反应混合物中，（c）将步骤（b）的反应混合物加热至80℃至1300℃ 优选在90℃至1000℃下反应2至7小时以获得苯氧基取代的芳族底物，（d）从步骤（c）的混合物中除去溶剂，并任选进一步分离纯化苯氧基取代的芳族底物 。 任选地，在步骤（a）期间除去水与有机溶剂的部分去除结合在一起。

    Torsemide polymorphs
    7.
    发明授权
    Torsemide polymorphs 失效
    泰索米多晶型物

    公开(公告)号：US06465496B1

    公开(公告)日：2002-10-15

    申请号：US09638106

    申请日：2000-08-11

    申请人： Judith Aronhime ,  David Leonov ,  Marko Kordova ,  Anchel Schwartz ,  Ben-Zion Dolitzky

    发明人： Judith Aronhime ,  David Leonov ,  Marko Kordova ,  Anchel Schwartz ,  Ben-Zion Dolitzky

    IPC分类号： A61K3144

    CPC分类号： C07D213/74 ,  A61K31/64

    摘要： The present invention is directed to the novel forms of torsemide, designated Form V, amorphous torsemide, Dupont Form 2 solvent adduct, Dupont Form 2 ethanol adduct and Dupont Form 2 isopropanol adduct. Methods for their preparation are also disclosed. The present invention also relates to processes for making torsemide modification I. Pharmaceutical compositions containing the new forms of torsemide and methods of using them are also disclosed.

    摘要翻译： 本发明涉及形式为V，无定形托塞米特，杜邦2型溶剂加合物，杜邦2型乙醇加合物和杜邦2型异丙醇加合物的新型托马斯。 还公开了它们的制备方法。 本发明还涉及制备托塞米特改性的方法I.还公开了含有新形式的托塞米的药物组合物及其使用方法。

    PROCESS FOR THE PREPARATION OF SUBSTITUTED CYANOPHENOXY-PYRIMIDINYLOXY-PHENYL ACRYLATE DERIVATIVES
    8.
    发明申请
    PROCESS FOR THE PREPARATION OF SUBSTITUTED CYANOPHENOXY-PYRIMIDINYLOXY-PHENYL ACRYLATE DERIVATIVES 审中-公开
    制备取代的氰基苯氧基 - 丙烯酰氧基 - 苯基丙烯酸酯衍生物的方法

    公开(公告)号：US20130261303A1

    公开(公告)日：2013-10-03

    申请号：US13905447

    申请日：2013-05-30

    申请人： David OVADIA ,  Raya STURKOVICH ,  David LEONOV

    发明人： David OVADIA ,  Raya STURKOVICH ,  David LEONOV

    IPC分类号： C07D239/52

    CPC分类号： C07D239/52 ,  C07D239/54

    摘要： The present invention provides a process for reacting between a phenol derivative and an aromatic substrate under phenolate forming conditions comprising the following steps: (a) reacting a phenol derivative with a base in a polar organic solvent to obtain a phenolate salt, wherein water is removed from the reaction mixture during the reaction, (b) adding the aromatic substrate to the reaction mixture obtained in step (a), (c) heating the reaction mixture of step (b) to a temperature in the range of 80° to 1300° C., preferably, 90° to 1000° C. for 2 to 7 hours to obtain a phenoxy substituted aromatic substrate, (d) removing the solvent from the mixture of step (c) and optionally further isolating and purifying the phenoxy substituted aromatic substrate. Optionally, the removal of water during step (a) is in conjunction with partial removal of the organic solvent.

    摘要翻译： 本发明提供一种苯酚衍生物和芳族底物在酚盐形成条件下的反应方法，包括以下步骤：（a）使苯酚衍生物与碱在极性有机溶剂中反应得到酚盐，其中除去水 （b）将芳族底物加入到步骤（a）中获得的反应混合物中，（c）将步骤（b）的反应混合物加热至80℃至1300℃的温度 （d）从步骤（c）的混合物中除去溶剂，任选地进一步分离和纯化苯氧基取代的芳香族底物， 。 任选地，在步骤（a）期间除去水与有机溶剂的部分去除结合在一起。

    Process for the isolation of pseudomonic acid A from pseudomonic acid complex-containing culture broth
    9.
    发明授权
    Process for the isolation of pseudomonic acid A from pseudomonic acid complex-containing culture broth 失效
    用于从含有假单胞菌酸的复合物的培养液中分离假单胞菌酸A的方法

    公开(公告)号：US06245921B1

    公开(公告)日：2001-06-12

    申请号：US09497806

    申请日：2000-02-03

    申请人： Istvan Barta ,  Aniko Tegdes ,  Valeria Szell ,  Csaba Szabo ,  Edit Nagy Nee Arvai ,  Vilmos Keri ,  David Leonov ,  IIdiko Lang ,  Margit Bidlo Nee Igloy ,  Gyula Jerkovich ,  Janos Salat

    发明人： Istvan Barta ,  Aniko Tegdes ,  Valeria Szell ,  Csaba Szabo ,  Edit Nagy Nee Arvai ,  Vilmos Keri ,  David Leonov ,  IIdiko Lang ,  Margit Bidlo Nee Igloy ,  Gyula Jerkovich ,  Janos Salat

    IPC分类号： C07D31500

    CPC分类号： C12P17/162

    摘要： A process for the isolation of the pseudomonic acid A antibiotic of pharmaceutical quality from the culture broth of one of the pseudomonic acid A-producing species of the Pseudomonas bacterium genus comprising the extraction of the biosynthesized pseudomonic acid A from the culture broth at acidic pH with a chlorinated aliphatic hydrocarbon or isobutyl acetate, followed by purification, is disclosed. The invention includes processes for purification of the isolated pseudomonic acid A, including (a) by the distribution of the evaporated extract residue between the aqueous-alcohol and some aliphatic or aromatic hydrocarbon, and then the extraction of the increased water-containing aqueous-alcoholic phase with methylene chloride, ethyl acetate, or isobutyl acetate; (b) by the extraction of the extract with aqueous ammonium hydrogen carbonate, alkali metal hydroxide or ammonium hydroxide solution and the acidification of the resulting alkaline aqueous extract, then reextraction again with a chlorinated aliphatic hydrocarbon or isobutyl acetate; and (c) by the concentration of the extract and the recrystallization of the crystalline pseudomonic acid A in a mixture of isobutyl acetate and petroleum ether, or acetonitrile, or aqueous acetonitrile.

    摘要翻译： 从假单胞菌属的假单胞菌素A产生物种之一的培养液中分离出假单胞菌A抗生素药物质量的方法，包括在酸性pH下从培养液中提取生物合成的假单胞菌酸A， 公开了氯化脂族烃或乙酸异丁酯，然后纯化。 本发明包括纯化分离的假单胞菌酸A的方法，包括（a）通过在含水醇和某些脂族或芳族烃之间分配蒸发的提取物残渣，然后提取含水的含水醇 与二氯甲烷，乙酸乙酯或乙酸异丁酯反应; （b）通过用碳酸氢铵水溶液，碱金属氢氧化物或氢氧化铵溶液萃取提取物，并将得到的碱性水提取物酸化，然后用氯化脂族烃或乙酸异丁酯再次萃取; 和（c）通过提取物的浓度和结晶假单胞菌酸A在乙酸异丁酯和石油醚或乙腈或乙腈水溶液的混合物中的重结晶。