2,6-二氟吡啶-4-硼酸 | 401816-16-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2,6-二氟吡啶-4-硼酸
• 英文名称: (2,6-difluoropyridin-4-yl)boronic acid
• 英文别名: (2,6-difluoro-4-pyridyl)boronic acid；2,6-difluoropyridin-4-ylboronic acid；2,6-difluoro-4-pyridineboronic acid；2,6-difluoropyridine-4-boronic acid；2,6-difluoro-pyridine-4-boronic acid；2,6-difluoro-4-pyridyl-boronic acid
• CAS: 401816-16-8
• 化学式: C₅H₄BF₂NO₂
• mdl: MFCD04114289
• 分子量: 158.9
• InChiKey: KMEJCVYIVUQTSP-UHFFFAOYSA-N

物化性质

• 沸点：
  334.0±52.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.52
• 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：
  53.4
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S39
• 危险类别码：
  R37/38,R41
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2,6-Difluoropyridine-4-boronic acid
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H318: Causes serious eye damage
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P280: Wear protective gloves/protective clothing/eye protection/face protection
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

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Section 3. Composition/information on ingredients.
Ingredient name: 2,6-Difluoropyridine-4-boronic acid
CAS number: 401816-16-8

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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
No data
Boiling point:
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H4BF2NO2
Molecular weight: 158.9

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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, nitrogen oxides, 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：

  2,6-二氟吡啶-4-硼酸 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 氯化铵 、 caesium carbonate 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 6.33h， 生成 1-(2-(4-(2,6-difluoropyridin-4-yl)-7-methoxy-3,3-dimethylindolin-1-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea
  参考文献：
  名称：

  [EN] 7-HYDROXY-INDOLINYL ANTAGONISTS OF P2Y1 RECEPTOR
  [FR] ANTAGONISTES DE 7-HYDROXY-INDOLINYLE DU RÉCEPTEUR P2Y1

  摘要：

  本发明提供了Formula (I)的化合物：如规范中定义的Formula (I)，以及包含任何此类新化合物的组合物。这些化合物是P2Y1受体的拮抗剂，可用作药物。

  公开号：

  WO2014022343A1
• 作为产物：
  描述：

  2,6-二氟-4-溴吡啶 、 硼酸三异丙酯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 以33%的产率得到2,6-二氟吡啶-4-硼酸
  参考文献：
  名称：

  Substituted pyridines

  摘要：

  提供了一类包括新颖化合物的2,4-；2,3,4-；2,4,6-；2,3,4,5,6-取代吡啶。这些取代是通过本文披露的方法实现的，其中金属化的吡啶与亲电试剂发生反应。适当的亲电试剂包括CO2、SO2、二烷基碳酸酯、脲、甲酰胺、酰胺、羧酸酯、单烷基和二卤代烷基、氯、氟、溴和碘等卤素、金属盐、磺酮、磺酰基、醛、酮、酸酐、亚硝酸盐和亲电硼化合物，包括但不限于硼三烷氧化物和硼三卤化物。该发明更具体地披露了一种合成2,6-二氟吡啶-4-基硼酸的方法，包括：(1)将2,4,6-三氟吡啶与单水合肼反应，生成2,6-二氟-4-肼基吡啶，(2)将2,6-二氟-4-肼基吡啶与元素溴反应，生成4-溴-2,6-二氟吡啶，(3)将4-溴-2,6-二氟吡啶与有机锂化合物和硼酸盐在约0°C以下的温度下反应，生成2,6-二氟吡啶-4-基硼酸，其中所述过程在有机溶剂中进行。

  公开号：

  US07087755B1

文献信息

• [EN] 5-AZAINDAZOLE COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS 5-AZAINDAZOLE ET MÉTHODES D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014001377A1

  公开（公告）日：2014-01-03

  5-Azaindazole compounds of Formula (I), including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式（I）的5-氮杂吲唑化合物，包括立体异构体、几何异构体、互变异构体和其药学上可接受的盐，用于抑制Pim激酶，并用于治疗由Pim激酶介导的癌症等疾病。公开了使用公式（I）化合物在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗此类疾病或相关病理条件的方法。
• COMPOUNDS AND COMPOSITIONS AS KINASE INHIBITORS
  申请人：Burger Matthew T.

  公开号：US20160075727A1

  公开（公告）日：2016-03-17

  The present invention provides a compound of Formula I: wherein X, Y, Z, R 1 and R 2 are as described herein, and salts thereof and therapeutic uses of these compounds for treatment of disorders associated with RAF kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.

  本发明提供了一种I式化合物： 其中X、Y、Z、R1和R2如本文所述，并其盐以及这些化合物用于治疗与RAF激酶活性相关的疾病的治疗用途。该发明还提供了包含这些化合物的药物组合物，以及包含这些化合物和治疗协同剂的组合物。
• Design and Discovery of <i>N</i>-(3-(2-(2-Hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide, a Selective, Efficacious, and Well-Tolerated RAF Inhibitor Targeting RAS Mutant Cancers: The Path to the Clinic
  作者：Savithri Ramurthy、Benjamin R. Taft、Robert J. Aversa、Paul A. Barsanti、Matthew T. Burger、Yan Lou、Gisele A. Nishiguchi、Alice Rico、Lina Setti、Aaron Smith、Sharadha Subramanian、Victoriano Tamez、Huw Tanner、Lifeng Wan、Cheng Hu、Brent A. Appleton、Mulugeta Mamo、Laura Tandeske、John E. Tellew、Shenlin Huang、Qin Yue、Apurva Chaudhary、Hung Tian、Raman Iyer、A. Quamrul Hassan、Lesley A. Mathews Griner、Laura R. La Bonte、Vesselina G. Cooke、Anne Van Abbema、Hanne Merritt、Kalyani Gampa、Fei Feng、Jing Yuan、Yuji Mishina、Yingyun Wang、Jacob R. Haling、Sepideh Vaziri、Mohammad Hekmat-Nejad、Valery Polyakov、Richard Zang、Vijay Sethuraman、Payman Amiri、Mallika Singh、William R. Sellers、Emma Lees、Wenlin Shao、Michael P. Dillon、Darrin D. Stuart

  DOI：10.1021/acs.jmedchem.9b00161

  日期：2020.3.12

  target CRAF have been challenging due to the complex nature of RAF signaling, downstream of activated RAS, and the poor overall kinase selectivity of putative RAF inhibitors. Herein, we describe 15 (LXH254, Aversa, R.; et al. Int. Patent WO2014151616A1, 2014), a selective B/C RAF inhibitor, which was developed by focusing on drug-like properties and selectivity. Our previous tool compound, 3 (RAF709; Nishiguchi

  RAS的直接药理抑制作用仍然难以捉摸，由于RAF信号的复杂性质，活化RAS的下游以及假定的RAF抑制剂的总体激酶选择性较差，因此针对CRAF的努力一直具有挑战性。在本文中，我们描述了15（LXH254，Aversa，R .；等人，国际专利WO2014151616A1，2014），一种选择性的B / C RAF抑制剂，其通过关注药物样性质和选择性而开发。我们以前的工具化合物，3（RAF709;西口，GA;等人，J.医学化学式。2017年，60（4969），在临床前模型中是有效的，选择性的，有效的和良好的耐受性，但是人类固有的高清除率阻止了进一步的发展，并促使人们进一步研究紧密的类似物。基于结构的方法产生了带有醇侧链的吡啶系列，该侧链可以与DFG环相互作用并显着提高了细胞效能。进一步缓解人类固有的清除和时间依赖性抑制导致15的发现。由于其优异的性能，它已经通过毒理学研究进展，并正在1期临床试验中进行测试。
• N-(1-(SUBSTITUTED-PHENYL)ETHYL)-9H-PURIN-6-AMINES AS PI3K INHIBITORS
  申请人：Li Yun-Long

  公开号：US20120157430A1

  公开（公告）日：2012-06-21

  The present invention provides N-(1-(substituted-phenyl)ethyl)-9H-purin-6-amines derivatives that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.

  本发明提供了调节磷脂酰肌醇3-激酶（PI3Ks）活性并且在治疗与PI3Ks活性相关的疾病方面有用的N-(1-(取代苯基)乙基)-9H-嘌呤-6-胺衍生物，例如炎症性疾病、免疫性疾病、癌症和其他疾病。
• [EN] GSM INTERMEDIATES<br/>[FR] INTERMÉDIAIRES GSM
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2009052341A1

  公开（公告）日：2009-04-23

  The present invention relates the use of compounds having the general Formula I, wherein the definitions or R1 and R2 are provided in the specification. Said compounds of Formula I are useful for the synthesis of a variety of g-secretase modulators, which are in turn useful for the treatment of diseases associated with y-secretase activity, including Alzheimer´s disease.

  本发明涉及具有通用公式I的化合物的使用，其中R1和R2的定义在说明书中提供。所述公式I的化合物可用于合成多种γ-分泌酶调节剂，这些调节剂又可用于治疗与γ-分泌酶活性相关的疾病，包括阿尔茨海默病。