2,6-二氯吡啶-4-硼酸 | 1072951-54-2

• 物质功能分类: 医药中间体 - 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: 2,6-二氯吡啶-4-硼酸
• 英文名称: (2,6-dichloropyridin-4-yl)boronic acid
• 英文别名: (2,6-dichloro-4-pyridine)boronic acid
• CAS: 1072951-54-2
• 化学式: C₅H₄BCl₂NO₂
• mdl: MFCD09751352
• 分子量: 191.809
• InChiKey: JFUQZFQJFYZZGY-UHFFFAOYSA-N

物化性质

• 沸点：
  396.8±52.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.11
• 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：
  3

安全信息

• 海关编码：
  2933399090
• 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-Dichloropyridine-4-boronic acid
Synonyms: 2,6-Dichloropyridin-4-ylboronic 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: 2,6-Dichloropyridine-4-boronic acid
CAS number: 1072951-54-2

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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, 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: C5H4BCl2NO2
Molecular weight: 191.8

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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 chloride.

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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

化学性质

2,6-二氯吡啶-4-硼酸是一种白色或类白色的结晶性粉末，不溶于水，但易溶于有机溶剂。在化学结构上，它具有显著的稳定性，在各种化学反应中都能保持原有的性质。此外，该化合物还表现出较高的热稳定性和化学稳定性，能够在较高温度和复杂的化学环境中保持其结构和性质的稳定。

用途

2,6-二氯吡啶-4-硼酸可用作医药合成中间体。它可通过将2,6-二氯-4-碘吡啶作为反应原料，在正丁基锂的作用下制备得到。此化合物还可用于Suzuki反应，进而合成医药中间体2,6-二氯-4-[5-(三氟甲基)吡啶-2-基]吡啶。

制备方法

在氮气保护条件下，将正丁基锂（3 mL，2.5 M己烷溶液，1.50当量）逐滴加入至2,6-二氯-4-碘吡啶（1.40 g，5.112 mmol，1.00当量）的四氢呋喃（20 mL）溶液中，并在-78℃搅拌30分钟。随后，在-78℃下加入硼酸三甲酯（580 mg，5.582 mmol，1.10当量），继续在-78℃下搅拌1小时。之后，将得到的混合物在室温下再搅拌12小时，并用1.6 g频哪醇和醋酸（AcOH）0.6 mL进行淬灭处理。最后，过滤出固体并减压浓缩液体以获得标题化合物2,6-二氯吡啶-4-硼酸（粗制品），呈黄色固体。

反应信息

• 作为反应物：
  描述：

  2,6-二氯吡啶-4-硼酸 在 tris-(dibenzylideneacetone)dipalladium(0) 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 19.0h， 生成 N-(4-(4-benzyl-6-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2-yl)phenyl)acrylamide
  参考文献：
  名称：

  Novel Phenylpyridine Derivative and Pharmaceutical Composition Comprising the Same

  摘要：

  本公开涉及一种由化学式1表示的新型苯基吡啶衍生物以及包含该衍生物的药物组合物，根据本公开的化合物可用于预防或治疗自身免疫疾病或癌症。

  公开号：

  US20200223821A1
• 作为产物：
  描述：

  2,6-二氯-4-碘吡啶 在 正丁基锂 、 频哪醇 、 硼酸三甲酯 、 溶剂黄146 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 0.5h， 以74%的产率得到2,6-二氯吡啶-4-硼酸
  参考文献：
  名称：

  亚氟杂芳基三氟硼酸盐在接近中性pH的水性条件下的水解稳定性

  摘要：

  杂芳基三氟硼酸酯在生理条件下的水解稳定性已通过19 F NMR光谱分析，发现由于存在环内环氮而大大提高。环外吸电子取代基的存在进一步提高了稳定性。与芳基三氟硼酸酯一样，NMR分析表明水解反应通过单个速率确定步骤进行，反映了第一个氟原子的损失。这些络合物的稳定性在金属催化的交叉偶联反应以及产生基于硼酸的18 F-PET显像剂方面均具有重要意义。

  DOI：

  10.1016/j.jfluchem.2008.12.006

文献信息

• [EN] SUBSTITUTED HETEROCYCLIC SULFONAMIDE COMPOUNDS USEFUL AS TRPA1 MODULATORS<br/>[FR] COMPOSÉS DE SULFONAMIDE HÉTÉROCYCLIQUES SUBSTITUÉS UTILES COMME MODULATEURS DE TRPA1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015052264A1

  公开（公告）日：2015-04-16

  The invention is concerned with the compounds of formula I or II: and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

  本发明涉及式I或II的化合物及其盐。此外，本发明还涉及制备这些化合物的方法以及使用这些化合物的方法，以及含有这些化合物的药物组合物。这些化合物可能对治疗由TRPA1介导的疾病和状况，如疼痛，具有用途。
• [EN] PROTEIN KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉINES KINASES
  申请人：ORION CORP

  公开号：WO2014162039A1

  公开（公告）日：2014-10-09

  A compound of formula (I), wherein R1 to R5, A, B, Z, Z1 and Z2 are as defined in the claims, and pharmaceutically acceptable salts thereof are disclosed. The compounds of formula (I) possess utility as FGFR inhibitors and are useful in the treatment of a condition, where FGFR kinase inhibition is desired, such as cancer.

  公式（I）的化合物，其中R1至R5，A，B，Z，Z1和Z2如权利要求中所定义，并公开其药学上可接受的盐。公式（I）的化合物具有作为FGFR抑制剂的效用，并在需要FGFR激酶抑制的情况下，如癌症治疗中是有用的。
• A Highly Efficient Dimeric Manganese‐Catalyzed Selective Hydroarylation of Internal Alkynes
  作者：Yubo Pang、Gengtu Liu、Congcong Huang、Xiang‐Ai Yuan、Weipeng Li、Jin Xie

  DOI：10.1002/anie.202004950

  日期：2020.7.27

  inherent double controlled strategy of sterically hindered propargyl alcohols without the installing of external directing groups. Its synthetic robustness and practicality have been illustrated by the concise synthesis of bervastatin, a hypolipidemic drug, and late‐stage modification of complex alkynes with precise regioselectivity.

  在水存在下，在没有配体参与的空气气氛下，我们已经开发了一种通用且可预测的锰催化内部炔烃加氢芳基化反应。与其他广泛使用的过渡金属催化剂（包括钯，铑，镍或铜）相比，该反应具有独特的催化特性。简单的操作，高效和出色的官能团兼容性使该协议可用于90多种结构不同的内部炔烃，克服了炔烃的电子和空间效应的影响。其独特的区域选择性和化学选择性来自于锰基催化剂对固有的双重控制策略（受阻炔丙基醇）的固有反应性，而无需安装外部引导基团。
• Gram-Scale Synthesis of β-(Hetero)arylethenesulfonyl Fluorides <i>via</i> a Pd(OAc)₂ Catalyzed Oxidative Heck Process with DDQ or AgNO₃ as an Oxidant
  作者：Gao-Feng Zha、Grant A. L. Bare、Jing Leng、Zhen-Peng Shang、Zhixiong Luo、Hua-Li Qin

  DOI：10.1002/adsc.201700688

  日期：2017.9.18

  gram‐scale operation without the requirement for strict anhydrous or oxygen‐free conditions. Furthermore, this procedure discriminates against the formation of arylboronic acids homo‐coupling byproducts. In addition, the preparation of the first aryl vinylsulfonate polymer, a material with functionalizable Michael acceptor sites, from a starting arylboronic acid is described.

  开发了一种实用的有机硼酸与乙磺酰氟（ESF）之间的氧化Heck反应。在催化量的Pd（OAc）2和2,3-二氯-5,6-二氰基对苯醌（DDQ）或AgNO 3在AcOH中存在的情况下，芳基和杂芳基硼酸与ESF高效且立体选择性地反应负担相应的Eβ-芳烷基磺酰氟产品的异构体。该反应的实用性在47个实例的扩展范围中得到了体现，其中包括含N，O和S的杂芳族化合物，证明了对芳基碘化物的化学选择性以及克级操作，而无需严格的无水或无氧条件。此外，此程序可区别芳基硼酸均偶联副产物的形成。另外，描述了由起始芳基硼酸制备第一芳基乙烯基磺酸酯聚合物，其是具有可官能化的迈克尔受体位点的材料。
• Rhodium-Catalyzed Asymmetric Conjugate Pyridylation with Pyridylboronic Acids
  作者：Bihai Ye、Jian Yao、Changhui Wu、Huilong Zhu、Weijun Yao、Lili Jin、Xiaowei Dou

  DOI：10.1021/acscatal.1c05732

  日期：2022.2.18

  asymmetric arylation reaction has been extensively studied for chiral Csp2–Csp3 bond formation, the asymmetric pyridylation reaction remains a great challenge. In this study, the rhodium-catalyzed asymmetric conjugate pyridylation of α,β-unsaturated carbonyl compounds with pyridylboronic acids is reported. The bifunctional chiral amide-diene ligand, which dramatically accelerated the reaction via possible

  尽管不对称芳基化反应已被广泛研究用于手性 Csp 2 -Csp 3键的形成，但不对称吡啶基化反应仍然是一个巨大的挑战。在这项研究中，报道了铑催化的 α,β-不饱和羰基化合物与吡啶基硼酸的不对称共轭吡啶化反应。双功能手性酰胺-二烯配体通过可能的氢键活化显着加速反应，醇溶剂在铑催化下显着抑制吡啶基硼酸的竞争性原去硼化反应，共同促进反应，从而能够生产吡啶化产物的高产率（高达 99%）和良好的对映选择性（高达 >99% ee）。