3-(difluoromethyl)-5-methyl-1H-pyrazole-4-carboxylic acid | 1703774-35-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(difluoromethyl)-5-methyl-1H-pyrazole-4-carboxylic acid
• CAS: 1703774-35-9
• 化学式: C₆H₆F₂N₂O₂
• mdl: MFCD21602446
• 分子量: 176.123
• InChiKey: VCVMMDKNWZFRIP-UHFFFAOYSA-N

物化性质

• 沸点：
  374.7±42.0 °C(Predicted)
• 密度：
  1.495±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl 5-(difluoromethyl)-3-methyl-1H-pyrazole-4-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以90%的产率得到3-(difluoromethyl)-5-methyl-1H-pyrazole-4-carboxylic acid
  参考文献：
  名称：

  氟代烷基取代的吡唑-4-羧酸的多克合成

  摘要：

  3-（甲基氨基）丁-2-烯酸叔丁酯与氟化乙酸酐的酰化发生在烯胺碳原子上。所得的 3-(甲基氨基)-2-(RFCO)but-2-enoates 叔丁酯与烷基肼的反应产生了异构吡唑的混合物，这些混合物很容易通过柱色谱分离。以多克规模获得目标氟化吡唑-4-羧酸。

  DOI：

  10.1002/ejoc.201403295

文献信息

• [EN] KCNT1 INHIBITORS AND METHODS OF USE<br/>[FR] INHIBITEURS DE KCNT1 ET PROCÉDÉS D'UTILISATION
  申请人：PRAXIS PREC MEDICINES INC

  公开号：WO2020227101A1

  公开（公告）日：2020-11-12

  The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.

  本发明部分涉及用于预防和/或治疗神经系统疾病或紊乱、与过度神经元兴奋性有关的疾病或病况，以及基因（例如KCNT1）中的功能增强突变的化合物和组合物。本文还提供了治疗神经系统疾病或紊乱、与过度神经元兴奋性有关的疾病或病况，以及基因如KCNT1中的功能增强突变的方法。
• [EN] PROCESS FOR THE PREPARATION OF 4,4-DIFLUORO-3-OXOBUTANOIC ACID ESTERS<br/>[FR] PROCEDE DE PREPARATION D'ESTERS D'ACIDE 4,4-DIFLUORO-3-OXOBUTANOIQUE
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2006005612A1

  公开（公告）日：2006-01-19

  The present invention relates to a process for the preparation of a compound of the formula (I), wherein R is C1-12 alkyl, by the contact of a compound of the general formula (II) , wherein R1 and R2 are each, independently, C1-12 alkyl; or R1 and R2 join together with the nitrogen atom to which they are attached to form an alicyclic amine ring containing 4 to 7 carbon atoms or a morpholine ring, with an acetic acid ester of the general formula (III) CH3COOR, wherein R is as defined under formula (I), in the presence of a base.

  本发明涉及一种制备式(I)化合物的方法，其中R为C1-12烷基，通过将一般式(II)化合物与一般式(III)CH3COOR的乙酸酯在碱的存在下接触，其中R1和R2各自独立地为C1-12烷基；或者R1和R2与它们连接的氮原子结合在一起形成含有4到7个碳原子的脂环胺环或吗啉环。
• [EN] IMPROVED PROCESS FOR THE PREPARATION OF ESTERS OF 1-H-PYRAZOLE-4-CARBOXYLIC ACIDS<br/>[FR] PROCÉDÉ PERFECTIONNÉ POUR LA PRÉPARATION D'ESTERS D'ACIDES 1H-PYRAZOLE-4-CARBOXYLIQUES
  申请人：SOLVAY

  公开号：WO2012025469A1

  公开（公告）日：2012-03-01

  Process for the manufacture of an ester of a 1-H-pyrazole-4-carboxylic acid of formula (I) wherein - R1 is H or an organic residue - R2 is H or an organic residue - R3 is H, an alkyl group having from 1 to 12 carbon atoms, an halogenated alkyl group having from 1 to 12 carbon atoms, an aralkyl group, an aryl group, a halogen. which comprises reacting a compound of formula (II): wherein R4 is C1-C8-alkyl, C3-C8-cycloalkyl, C2-C8-alkenyl, benzyl or phenyl,R1 and R3, are as defined above with a hydrazine of formula (III): R2NHNH2 (III) wherein R2 is as defined above, in the presence of an organic solvent comprising at least one halogen.

  制备1-H-吡唑-4-羧酸酯（化学式（I））的方法如下：其中- R1为H或有机残基，- R2为H或有机残基，- R3为H、含有1至12个碳原子的烷基、含有1至12个碳原子的卤代烷基、芳基烷基、芳基、卤素。该方法包括将化合物（II）与化学式（III）的肼在至少含有一种卤素的有机溶剂中反应。其中化合物（II）的化学式为：其中R4为C1-C8-烷基、C3-C8-环烷基、C2-C8-烯基、苄基或苯基，R1和R3如上定义，R2如上定义。
• [EN] PROCESS FOR THE PREPARATION OF ESTERS OF 1-SUBSTITUTED-3-FLUOROALKYL-PYRAZOLE-4-CARBOXYLIC ACIDS<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ESTERS D'ACIDES 3-FLUOROALKYL-PYRAZOLE-4-CARBOXYLIQUES SUBSTITUÉS EN POSITION 1
  申请人：SOLVAY

  公开号：WO2012010692A1

  公开（公告）日：2012-01-26

  Process for the manufacture of an ester or the respective free acid of a 1-substituted-3-fluoroalkyl-pyrazole-4-carboxylic acid of formula (I) wherein - Y is H, F or an alkyl group having from 1 to 12 carbon atoms which is optionally substituted by at least one halogen atom, an aralkyl group or an aryl group, - R1 is H or an organic residue, - R2 is H or an organic residue, which comprises submitting a compound of formula (II) wherein Y is as defined above - X is CI, Br or I, - R1 is H or an organic residue, - R2 is H or an organic residue, to a reduction reaction.

  制备1-取代-3-氟烷基吡唑-4-羧酸酯或相应的1-取代-3-氟烷基吡唑-4-羧酸的过程，其化学式为(I)，其中- Y为H，F或含有1至12个碳原子的烷基基团，该基团可选择地被至少一个卤素原子取代，也可以是芳基烷基基团或芳基基团，- R1为H或有机残基，- R2为H或有机残基，包括将化学式(II)的化合物进行还原反应，其中Y如上定义，- X为Cl，Br或I，- R1为H或有机残基，- R2为H或有机残基。
• [EN] PROCESS FOR THE REGIOSELECTIVE SYNTHESIS OF 1,3, 4 -SUBSTITUTED PYRAZOLES<br/>[FR] PROCÉDÉ DE SYNTHÈSE RÉGIOSÉLECTIVE DE PYRAZOLES SUBSTITUÉS EN POSITIONS 1,3,4
  申请人：ISAGRO SPA

  公开号：WO2015155713A1

  公开（公告）日：2015-10-15

  A process is described for the synthesis of pyrazoles having general formula (I) comprising the following steps: a) a mixture comprising an alkyl-hydrazine having formula (II) RNH-NH2 and a compound having general formula (III) Rx1 -X1 -Rx-X2-Rx2, b) the mixture obtained in step a) is reacted with a compound having formula (IV), obtaining a 1,3,4-substituted pyrazole having general formula (I), according to the reaction scheme 1.

  描述一种合成一般式为(I)的吡唑的过程，包括以下步骤：a)混合物包括具有公式(II)的烷基肼RNH-NH2和具有公式(III)Rx1-X1-Rx-X2-Rx2的化合物，b)将步骤a)中获得的混合物与具有公式(IV)的化合物反应，根据反应方案1获得一般式为(I)的1,3,4-取代吡唑。