(2Z)-2-[[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]methylidene]-3-oxobutanedioic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: (2Z)-2-[[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]methylidene]-3-oxobutanedioic acid
• 化学式: C₁₁H₁₆N₂O₇
• 分子量: 288.25
• InChiKey: OXGDWTMWEQQVBF-WAYWQWQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  133
• 氢给体数：
  3
• 氢受体数：
  8

文献信息

• PROCESS FOR THE PREPARATION OF PYRAZOLE CARBOXYLIC ACID DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150158818A1

  公开（公告）日：2015-06-11

  The present invention relates to a novel process for the preparation of a pyrazole carboxylic acid derivative of the formula wherein R 1 is C 1-7 -alkyl and R 3 is C 1-7 -alkyl which is optionally substituted with halogen or C 1-4 -alkoxy. The pyrazole carboxylic acid derivative of the formula I can be used as building block in the preparation of pharmaceutically active principles e.g. for compounds acting as phosphodiesterase (PDE) inhibitors, particularly PDE10 inhibitors. PDE10 inhibitors have the potential to treat psychotic disorders like schizophrenia.

  本发明涉及一种新型制备吡唑羧酸衍生物的方法，其化学式如下：其中R1为C1-7烷基，R3为C1-7烷基，可选地被卤素或C1-4烷氧基取代。化合物I的吡唑羧酸衍生物可用作制备药用活性原理的构建块，例如用于作为磷酸二酯酶（PDE）抑制剂的化合物，特别是PDE10抑制剂。PDE10抑制剂具有治疗精神分裂症等精神障碍的潜力。
• [EN] PROCESS FOR THE PREPARATION OF PYRAZOLE CARBOXYLIC ACID DERIVATIVES<br/>[FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS D'ACIDE PYRAZOLE CARBOXYLIQUE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014027009A1

  公开（公告）日：2014-02-20

  The present invention relates to a novel process for the preparation of a pyrazole carboxylic acid derivative of the formula (I) wherein R1 is C1-7-alkyl and R3 is C1-7-alkyl which is optionally substituted with halogen or C1-4-alkoxy. The pyrazole carboxylic acid derivative of the formula I can be used as building block in the preparation of pharmaceutically active principles, e.g. for compounds acting as phosphodiesterase (PDE) inhibitors, particularly PDE10 inhibitors. PDE10 inhibitors have the potential to treat psychotic disorders like schizophrenia (Int. Patent Publication WO 2011/117264). A synthetic approach to the pyrazole carboxylic acid derivative of the formula I has been described in scheme 3 of the Int. Patent Publication WO 2011/117264 applying a method disclosed in Hanzlowsky et al, J. Heterocyclic Chem. 2003, 40(3), 487-489. However, under the acid-catalyzed cyclocondensation conditions described, besides of the desired isomer, also a substantial amount of the undesired N-1 substituted isomer was formed. In many cases, especially on larger scale, this undesired isomer is the major product in the reaction mixture with ratios of up to 70:30 in favor of the undesired isomer, leading to isolated yields of ca. 30% of the undesired isomer, along with ca. 25% of the desired isomer.

  本发明涉及一种新颖的制备吡唑羧酸衍生物的方法，其化学式为（I），其中R1为C1-7烷基，R3为C1-7烷基，可以选择性地取代卤素或C1-4烷氧基。化学式I的吡唑羧酸衍生物可用作制备药用活性原理的构建块，例如用于作为磷酸二酯酶（PDE）抑制剂的化合物，尤其是PDE10抑制剂。PDE10抑制剂具有治疗精神分裂症等精神障碍的潜力（国际专利出版物WO 2011/117264）。已经描述了一种制备化学式I的吡唑羧酸衍生物的合成方法，该方法在国际专利出版物WO 2011/117264的方案3中应用了Hanzlowsky等人在J. Heterocyclic Chem. 2003, 40(3), 487-489中披露的方法。然而，在所描述的酸催化环缩合条件下，除了期望的异构体外，还形成了相当数量的不希望的N-1取代异构体。在许多情况下，特别是在较大规模上，这种不希望的异构体是反应混合物中的主要产物，不希望的异构体与期望的异构体的比例可高达70:30，导致不希望的异构体的分离产率约为30％，同时还伴随着约为25％的期望的异构体。
• US9346763B2
  申请人：——

  公开号：US9346763B2

  公开（公告）日：2016-05-24