3-羧基-5-氟苯硼酸频那醇酯 | 936728-22-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-羧基-5-氟苯硼酸频那醇酯
• 中文别名: 3-羧基-5-氟苯基硼酸,频哪醇酯
• 英文名称: 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid
• 英文别名: 2-(3'-carboxy-5'-fluorophenyl)-4,4,5,5-tetramethyl[1,3,2]dioxaborolane
• CAS: 936728-22-2
• 化学式: C₁₃H₁₆BFO₄
• 分子量: 266.077
• InChiKey: NMYIHYHALOHVHV-UHFFFAOYSA-N

物化性质

• 熔点：
  212-215 °C
• 沸点：
  396.7±32.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.82
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340+P312,P305+P351+P338,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335
• 储存条件：
  2-8°C，干燥

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Carboxy-5-fluorophenylboronic acid, pinacol ester
Synonyms: 3-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 3-Carboxy-5-fluorophenylboronic acid, pinacol ester
CAS number: 936728-22-2

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C13H16BFO4
Molecular weight: 266.1

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, hydrogen fluoride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  3-羧基-5-氟苯硼酸频那醇酯 在 四(三苯基膦)钯 、 sodium carbonate 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 1.83h， 生成 methyl 1-(3’-fluoro-5’-((R)-2-propylpiperidine-1-carbonyl)-[1,1‘-biphenyl]-3-yl)-2-(trans)-(2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrrole-3-carboxylate
  参考文献：
  名称：

  [EN] 3-CARBOXYLIC ACID PYRROLES AS NRF2 REGULATORS
  [FR] PYRROLES D'ACIDE 3-CARBOXYLIQUE UTILISÉS EN TANT QUE RÉGULATEURS DE NRF2

  摘要：

  本发明涉及3-羧基吡咯烷酸化合物，制备它们的方法，含有它们的药物组合物以及它们作为NRF2调节剂的用途。具体来说，本发明的化合物包括式（I）的化合物。

  公开号：

  WO2018109641A1
• 作为产物：
  描述：

  3-溴-5-氟苯甲酸 、 联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-羧基-5-氟苯硼酸频那醇酯
  参考文献：
  名称：

  Discovery of Acylsulfonohydrazide-Derived Inhibitors of the Lysine Acetyltransferase, KAT6A, as Potent Senescence-Inducing Anti-Cancer Agents

  摘要：

  A high-throughput screen designed to discover new inhibitors of histone acetyltransferase KAT6A uncovered CTX-0124143 (1), a unique aryl acylsulfonohydrazide with an IC50 of 1.0 mu M. Using this acylsulfonohydrazide as a template, we herein disclose the results of our extensive structure-activity relationship investigations, which resulted in the discovery of advanced compounds such as 55 and 80. These two compounds represent significant improvements on our recently reported prototypical lead WM-8014 (3) as they are not only equivalently potent as inhibitors of KAT6A but are less lipophilic and significantly more stable to microsomal degradation. Furthermore, during this process, we discovered a distinct structural subclass that contains key 2-fluorobenzenesulfonyl and phenylpyridine motifs, culminating in the discovery of WM-1119 (4). This compound is a highly potent KAT6A inhibitor (IC50 = 6.3 nM; K-D = 0.002 mu M), competes with Ac-CoA by binding to the Ac-CoA binding site, and has an oral bioavailability of 56% in rats.

  DOI：

  10.1021/acs.jmedchem.9b02071

文献信息

• One-Pot Generation of Lithium (Lithiophenyl)trialkoxyborates from Substituted Dihalobenzenes (Hal = Br, I) and Their Derivatization with Electrophiles
  作者：Paweł Kurach、Sergiusz Luliński、Janusz Serwatowski

  DOI：10.1002/ejoc.200800245

  日期：2008.6

  (halophenyl)trialkoxyborates were then subjected to halogen–lithium exchange in situ with a second equivalent of nBuLi to give dianionic lithium (lithiophenyl)trialkoxyborates. Treatment with selected electrophiles afforded substituted arylboronic acids and/or their pinacol esters as final products in moderate-to-good yields.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

  从 1,3- 和 1,4- 二碘苯以及几种活化的二溴苯和溴碘苯开始，已经开发出一种简单的一锅法合成有用的苯环上带有锂的苯基三烷氧基硼酸盐。转化的一般顺序包括使用 nBuLi 进行卤素-锂交换，然后用三烷基硼酸盐进行硼化。然后将所得（卤代苯基）三烷氧基硼酸锂与第二当量的 nBuLi 进行卤素-锂原位交换，得到双离子（硫代苯基）三烷氧基硼酸锂。用选定的亲电子试剂处理，以中等至良好的产率提供取代的芳基硼酸和/或其频哪醇酯作为最终产品。（© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008）
• Discovery of Acylsulfonohydrazide-Derived Inhibitors of the Lysine Acetyltransferase, KAT6A, as Potent Senescence-Inducing Anti-Cancer Agents
  作者：Daniel L. Priebbenow、David J. Leaver、Nghi Nguyen、Benjamin Cleary、H. Rachel Lagiakos、Julie Sanchez、Lian Xue、Fei Huang、Yuxin Sun、Prashant Mujumdar、Ramesh Mudududdla、Swapna Varghese、Silvia Teguh、Susan A. Charman、Karen L. White、David M. Shackleford、Kasiram Katneni、Matthew Cuellar、Jessica M. Strasser、Jayme L. Dahlin、Michael A. Walters、Ian P. Street、Brendon J. Monahan、Kate E. Jarman、Helene Jousset Sabroux、Hendrik Falk、Matthew C. Chung、Stefan J. Hermans、Natalie L. Downer、Michael W. Parker、Anne K. Voss、Tim Thomas、Jonathan B. Baell

  DOI：10.1021/acs.jmedchem.9b02071

  日期：2020.5.14

  A high-throughput screen designed to discover new inhibitors of histone acetyltransferase KAT6A uncovered CTX-0124143 (1), a unique aryl acylsulfonohydrazide with an IC50 of 1.0 mu M. Using this acylsulfonohydrazide as a template, we herein disclose the results of our extensive structure-activity relationship investigations, which resulted in the discovery of advanced compounds such as 55 and 80. These two compounds represent significant improvements on our recently reported prototypical lead WM-8014 (3) as they are not only equivalently potent as inhibitors of KAT6A but are less lipophilic and significantly more stable to microsomal degradation. Furthermore, during this process, we discovered a distinct structural subclass that contains key 2-fluorobenzenesulfonyl and phenylpyridine motifs, culminating in the discovery of WM-1119 (4). This compound is a highly potent KAT6A inhibitor (IC50 = 6.3 nM; K-D = 0.002 mu M), competes with Ac-CoA by binding to the Ac-CoA binding site, and has an oral bioavailability of 56% in rats.
• [EN] 3-CARBOXYLIC ACID PYRROLES AS NRF2 REGULATORS<br/>[FR] PYRROLES D'ACIDE 3-CARBOXYLIQUE UTILISÉS EN TANT QUE RÉGULATEURS DE NRF2
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018109641A1

  公开（公告）日：2018-06-21

  The present invention relates to 3-carboxylic acid pyrrole compounds, methods of making them, pharmaceutical compositions containing them and their use as NRF2 regulators. In particular, the compounds of this invention include a compound of Formula (I)

  本发明涉及3-羧基吡咯烷酸化合物，制备它们的方法，含有它们的药物组合物以及它们作为NRF2调节剂的用途。具体来说，本发明的化合物包括式（I）的化合物。