1-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethanone | 189300-85-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethanone
• 英文别名: 1-(3-(trifluoromethyl)-1-methyl-1H-pyrazol-4-yl)ethanone；3-trifluoromethyl-1-methyl-4-acetylpyrazole；3-trifluoromethyl-1-methyl-4-acetylpyrazol；Ethanone, 1-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-；1-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]ethanone
• CAS: 189300-85-4
• 化学式: C₇H₇F₃N₂O
• 分子量: 192.141
• InChiKey: BXPYXUULYZZKNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethanone 在 双氧水 、 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 5.0h， 生成 1-甲基-3-三氟甲基-1H-吡唑-4-羧酸
  参考文献：
  名称：

  [EN] OXIDATION OF A PYRAZOLYL KETONE COMPOUND TO THE CORRESPONDING CARBOXYLIC ACID
  [FR] OXYDATION D'UN COMPOSÉ DE PYRAZOLYL CÉTONE EN ACIDE CARBOXYLIQUE CORRESPONDANT

  摘要：

  这项发明涉及一种用于制造羧酸或羧酸衍生物的过程，以及一种用于制造农药和药用活性化合物的过程，包括制造羧酸或其衍生物的过程。制造公式（II）的羧酸或羧酸衍生物的过程包括在至少一种公式（III）R6-C（O）O-OH存在的情况下氧化公式（I）的化合物的步骤。

  公开号：

  WO2019110795A1
• 作为产物：
  描述：

  methyl 2-(ethoxymethylidene)-4,4,4-trifluoro-3-oxobutanoate 在 甲基肼 作用下， 以 四氢呋喃 为溶剂， 反应 2.25h， 以70%的产率得到1-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethanone
  参考文献：
  名称：

  Lead Optimization toward Proof-of-Concept Tools for Huntington’s Disease within a 4-(1H-Pyrazol-4-yl)pyrimidine Class of Pan-JNK Inhibitors

  摘要：

  Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole.

  DOI：

  10.1021/jm5013598

文献信息

• 3-氟代烷基-1-甲基吡唑-4-羧酸的制备方法
  申请人：常州市卜 弋科研化工有限公司

  公开号：CN106554311B

  公开（公告）日：2019-03-01

  本发明涉及一种3‑氟代烷基‑1‑甲基吡唑‑4‑羧酸的制备方法，包括以下步骤：步骤一、以式I所示的氟代乙酰卤衍生物与二甲胺基乙烯基甲基酮缩合反应，生成式II所示的3‑二甲胺基亚甲基‑1,1‑二氟代‑2,4‑戊二酮衍生物；步骤二、以所述式II所示的3‑二甲胺基亚甲基‑1,1‑二氟代‑2,4‑戊二酮衍生物与甲基肼关环反应，生成式III所示的3‑氟代烷基‑1‑甲基‑4‑乙酰基吡唑衍生物；步骤三、以所述式III所示的3‑氟代烷基‑1‑甲基‑4‑乙酰基吡唑衍生物在碱性条件下氧化，再酸化，生成式IV所示的3‑氟代烷基‑1‑甲基吡唑‑4‑羧酸。本发明的制备方法反应路线较短，原料成本较低，各步骤反应收率高，适于工业化生产。
• METHOD FOR THE PREPARATION OF 3-FLUOROALKYL-1-METHYLPYRAZOL-4-CARBOXYLIC ACID
  申请人：SOLVAY FLUOR GmbH

  公开号：US20180273486A1

  公开（公告）日：2018-09-27

  The present invention relates to method for the preparation of 3-fluoroalkyl-1-methylpyrazol-4-carboxylic acid, wherein it comprises the following steps: step 1, fluoroacetyl fluoride derivative shown in Formula I undergoes condensation with dimethylamino vinyl methyl ketone, as a result, 3-dimethylamino methylene-fluoro-2,4-pentanedione derivative shown in Formula II is formed; step 2, ring closing reaction takes place between said 3-dimethylamino methylene-fluoro-2,4-pentanedione shown in Formula II and methylhydrazine, in this way, 3-fluoroalkyl-1-methyl-4-acetyl pyrazol derivative shown in Formula III is obtained; step 3, the said 3-fluoroalkyl-1-methyl-4-acetyl pyrazol derivative shown in Formula III is oxidized in the presence of alkali, and then acidified, in this way, 3-fluoroalkyl-1-methylpyrazol-4-carboxylic acid shown in Formula IV is formed. Preparing method of present invention, wherein the required preparing route is simple, the raw material cost is low, the resulting yield of each step is high, and it is suitable for industrialization.

  本发明涉及一种制备3-氟烷基-1-甲基吡唑-4-羧酸的方法，其中包括以下步骤：步骤1，式I所示的氟乙酰氟衍生物与二甲基氨基乙烯基甲基酮发生缩合反应，从而形成式II所示的3-二甲基氨基亚甲基-氟-2,4-戊二酮衍生物；步骤2，式II所示的3-二甲基氨基亚甲基-氟-2,4-戊二酮与甲基肼发生环合反应，得到式III所示的3-氟烷基-1-甲基-4-乙酰吡唑衍生物；步骤3，式III所示的3-氟烷基-1-甲基-4-乙酰吡唑衍生物在碱的存在下被氧化，然后酸化，从而形成式IV所示的3-氟烷基-1-甲基吡唑-4-羧酸。本发明的制备方法，所需制备路线简单，原料成本低，每个步骤的产率高，适合工业化生产。
• N-(Ortho-Phenyl)-1-Methyl -3-Trifluoromethlpyrazole-4-Carboxanilides and Their Use as Fungicides
  申请人：Gewehr Markus

  公开号：US20090036509A1

  公开（公告）日：2009-02-05

  The present invention relates to N-(ortho-phenyl)-1-methyl-3-trifluoromethylpyrazole-4-carboxanilides of the formula I in which the substituents are as defined below: R 1 and R 2 independently of one another are halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, cyano, nitro, methoxy, trifluoromethoxy or difluoromethoxy; with the proviso that when R 2 is chlorine in position 4, R 1 is not trifluoromethyl in position 3.

  本发明涉及公式I中的N-(邻苯基)-1-甲基-3-三氟甲基吡唑-4-羧酰胺，其中取代基如下所定义：R1和R2独立地为卤素，C1-C6烷基，C1-C6卤代烷基，氰基，硝基，甲氧基，三氟甲氧基或二氟甲氧基；但是当R2在位置4上为氯时，R1在位置3上不是三氟甲基。
• COMPOUNDS FOR THE TREATMENT OF HIV
  申请人：Bondy Steven S.

  公开号：US20140142085A1

  公开（公告）日：2014-05-22

  The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating a Retroviridae viral infection including an infection caused by the HIV virus.

  本发明提供了以下式子（I）的化合物或其盐，如本文所述。本发明还提供了包括式子（I）化合物的制药组合物，制备式子（I）化合物的方法，用于制备式子I化合物的中间体以及治疗逆转录病毒感染的治疗方法，包括由HIV病毒引起的感染。
• Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein–Protein Interaction
  作者：John M. Ketcham、Jacob Haling、Shilpi Khare、Vickie Bowcut、David M. Briere、Aaron C. Burns、Robin J. Gunn、Anthony Ivetac、Jon Kuehler、Svitlana Kulyk、Jade Laguer、J. David Lawson、Krystal Moya、Natalie Nguyen、Lisa Rahbaek、Barbara Saechao、Christopher R. Smith、Niranjan Sudhakar、Nicole C. Thomas、Laura Vegar、Darin Vanderpool、Xiaolun Wang、Larry Yan、Peter Olson、James G. Christensen、Matthew A. Marx

  DOI：10.1021/acs.jmedchem.2c00741

  日期：2022.7.28

  “off” states. Disrupting the SOS1:KRASG12C protein–protein interaction (PPI) can increase the proportion of GDP-loaded KRASG12C, providing a strong mechanistic rationale for combining inhibitors of the SOS1:KRAS complex with inhibitors like MRTX849 that target GDP-loaded KRASG12C. In this report, we detail the design and discovery of MRTX0902─a potent, selective, brain-penetrant, and orally bioavailable

  SOS1 是主要的鸟嘌呤核苷酸交换因子之一，可调节 KRAS 循环通过其“开”和“关”状态的能力。破坏 SOS1:KRAS G12C蛋白质-蛋白质相互作用 (PPI) 可以增加负载 GDP 的 KRAS G12C 的比例，为将 SOS1:KRAS 复合物的抑制剂与靶向 GDP 负载的 KRAS G12C的抑制剂（如 MRTX849）组合提供强有力的机制原理。在本报告中，我们详细介绍了 MRTX0902 的设计和发现——一种有效、选择性、脑渗透性和口服生物可利用的 SOS1 结合剂，可破坏 SOS1:KRAS G12C生产者价格指数。MRTX0902 与 MRTX849 联合口服给药相对于任一单一药物的抗肿瘤活性显着增加，包括 MIA PaCa-2 肿瘤小鼠异种移植模型中一部分动物的肿瘤消退。