2-氟-6-羟基苯硼酸 | 1256345-60-4

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 2-氟-6-羟基苯硼酸
• 英文名称: (2-fluoro-6-hydroxyphenyl)boronic acid
• 英文别名: 2-Fluoro-6-hydroxyphenylboronic acid
• CAS: 1256345-60-4
• 化学式: C₆H₆BFO₃
• 分子量: 155.921
• InChiKey: FPXQHZPCFRQWCP-UHFFFAOYSA-N

物化性质

• 熔点：
  114-116°C
• 沸点：
  333.3±52.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• pKa：
  8.40±0.58 (Predicted,Most Acidic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.79
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  存储条件为2-8°C，并需置于惰性气体环境中。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2-Fluoro-6-hydroxyphenylboronic acid
Synonyms:

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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: 2-Fluoro-6-hydroxyphenylboronic acid
CAS number: 1256345-60-4

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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, under −20◦C.
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: C6H6BFO3
Molecular weight: 155.9

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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

制备方法与用途

2-氟-6-羟基苯硼酸是一种羧酸类衍生物，常被用作医药中间体。

反应信息

• 作为反应物：
  描述：

  2-氟-6-羟基苯硼酸 在 potassium phosphate 、 lithium hydroxide monohydrate 、 SPhos Pd G2 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 40.5h， 生成 tert-butyl 4-(6-chloro-2-((1-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxyphenyl)-11-methyl-1,12-dioxo-5,8-dioxa-2,11-diazatetradecan-14-yl)amino)-8-fluoro-7-((S)-2-fluoro-6-hydroxyphenyl)quinazolin-4-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  WO2019/195609

  摘要：

  公开号：
• 作为产物：
  描述：

  2-氟-6-甲氧基苯硼酸 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 2-氟-6-羟基苯硼酸
  参考文献：
  名称：

  Rh / Pd催化与手性和非手性配体：氮杂二氢二苯并xepines的多米诺合成。

  摘要：

  多米诺骨牌游戏：通过在单个锅中将Rh催化的芳基化和Pd催化的C-O偶联相结合，描述了合成氮杂二氢二苯并xepinepines的合成途径。首次实现了将手性和非手性配体结合到两组分，两种金属的转化中的能力，从而使产品具有中等至良好的收率，并具有出色的对映选择性。

  DOI：

  10.1002/anie.201303659

文献信息

• [EN] NOVEL THYROMIMETICS<br/>[FR] NOUVEAUX THYROMIMÉTIQUES
  申请人：AUTOBAHN THERAPEUTICS INC

  公开号：WO2021108549A1

  公开（公告）日：2021-06-03

  Compounds are provided having the structure of Formula (I) or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein R1, R2, X1, X2, Y1, and Y2 are as defined herein. Such compounds function as thyromimetics and have utility for treating diseases such as neurodegenerative disorders and fibrotic diseases. Pharmaceutical compositions containing such compounds are also provided, as are methods of their use and preparation.

  提供具有Formula (I)结构或其药学上可接受的异构体、拉克酸盐、水合物、溶剂化合物、同位素或盐的化合物，其中R1、R2、X1、X2、Y1和Y2如本文所定义。这些化合物作为甲状腺类似物发挥作用，并可用于治疗神经退行性疾病和纤维化疾病等疾病。还提供含有这些化合物的药物组合物，以及它们的使用和制备方法。
• [EN] INHIBITORS OF KRAS G12C MUTANT PROTEINS<br/>[FR] INHIBITEURS DE PROTÉINES MUTANTES KRAS G12C
  申请人：ARAXES PHARMA LLC

  公开号：WO2017058915A1

  公开（公告）日：2017-04-06

  Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein A, B R1, R2a, R2b, R3a, R3b, R4a, R4b, G1, G2, m1, m2, L1, L2 and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

  提供了作为G12C突变KRAS蛋白抑制剂活性的化合物。这些化合物具有以下结构（I）：或其药用可接受的盐、互变异构体、立体异构体或前药，其中A、B、R1、R2a、R2b、R3a、R3b、R4a、R4b、G1、G2、m1、m2、L1、L2和E如本文所定义。还提供了与制备和使用这些化合物相关的方法，包括包含这些化合物的药物组合物以及调节G12C突变KRAS蛋白活性的方法，用于治疗癌症等疾病。
• Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRASG12C inhibitors
  作者：Xuanzheng Xiao、Mengzhen Lai、Zilan Song、Meiyu Geng、Jian Ding、Hua Xie、Ao Zhang

  DOI：10.1016/j.ejmech.2020.113082

  日期：2021.3

  clinical KRASG12C inhibitor AMG510, a scaffold hopping strategy was conducted including a F-OH cyclization approach and a pyridinyl N-atom working approach leading to new tetracyclic and bicyclic analogues. Compound 26a was identified possessing binding potency of 1.87 μM against KRASG12C and cell growth inhibition of 0.79 μM in MIA PaCa-2 pancreatic cancer cells. Treatment of 26a with NCI-H358 cells

  KRAS 是 RAS 家族中最常见改变的癌基因，尤其是 G12C 突变体 (KRAS G12C )，它已成为许多癌症的有前途的药物靶点。在首创临床KRAS G12C抑制剂AMG510的双环吡啶并嘧啶酮框架的基础上，进行了支架跳跃策略，包括F-OH环化方法和吡啶基N原子工作方法，从而产生新的四环和双环类似物。化合物26a经鉴定对 KRAS G12C具有 1.87 μM 的结合效力，并且在 MIA PaCa-2 胰腺癌细胞中具有 0.79 μM 的细胞生长抑制作用。用 NCI-H358 细胞处理26a导致 KRAS-GTP 水平下调以及下游 ERK 和 AKT 磷酸化的减少，呈剂量依赖性。分子对接表明26a的氟苯酚部分占据疏水口袋区域，从而与Arg68形成氢键。这些结果将有助于指导进一步的结构修饰。
• [EN] IMMUNOPHILIN BINDING AGENTS AND USES THEREOF<br/>[FR] AGENTS DE LIAISON À L'IMMUNOPHILINE ET LEURS UTILISATIONS
  申请人：UNIV CALIFORNIA

  公开号：WO2020163594A1

  公开（公告）日：2020-08-13

  Described herein, inter alia, are immunophilin binding compounds and methods of treating CNS diseases, including co-administering outside the CNS of a subject an anti-CNS disease drug and a compound described herein.

  本文描述了免疫蛋白结合化合物以及治疗中枢神经系统疾病的方法，包括在主体的中枢神经系统外联合给予一种抗中枢神经系统疾病药物和本文描述的化合物。
• Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRAS^G12C
  作者：Jason G. Kettle、Sharan K. Bagal、Sue Bickerton、Michael S. Bodnarchuk、Jason Breed、Rodrigo J. Carbajo、Doyle J. Cassar、Atanu Chakraborty、Sabina Cosulich、Iain Cumming、Michael Davies、Andrew Eatherton、Laura Evans、Lyman Feron、Shaun Fillery、Emma S. Gleave、Frederick W. Goldberg、Stephanie Harlfinger、Lyndsey Hanson、Martin Howard、Rachel Howells、Anne Jackson、Paul Kemmitt、Jennifer K. Kingston、Scott Lamont、Hilary J. Lewis、Songlei Li、Libin Liu、Derek Ogg、Christopher Phillips、Radek Polanski、Graeme Robb、David Robinson、Sarah Ross、James M. Smith、Michael Tonge、Rebecca Whiteley、Junsheng Yang、Longfei Zhang、Xiliang Zhao

  DOI：10.1021/acs.jmedchem.9b01720

  日期：2020.5.14

  efforts across industry and academia. The KRASG12C mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small molecules that bind the mutant cysteine and create an allosteric pocket on GDP-bound RAS, locking it in an inactive state. A weak inhibitor at this site was optimized through conformational locking of a piperazine-quinazoline motif and linker modification

  尽管工业界和学术界做出了许多努力，但直接为重要的癌基因KRAS服药的尝试取得了有限的成功。KRASG12C突变体代表“致命弱点”，最近已与小分子共价靶向，这些小分子与突变体半胱氨酸结合并在GDP结合的RAS上形成一个变构口袋，从而将其锁定在非活性状态。通过哌嗪-喹唑啉基序的构象锁定和接头修饰优化了该位点的弱抑制剂。随后在哌嗪中引入关键甲基会导致效力，通透性，清除率和反应性增强，从而鉴定出具有高选择性，出色的跨物种药代动力学参数和体内功效的有效KRASG12C抑制剂。