3-氰基-2-甲氧基吡啶-5-硼酸频那醇酯 | 1073354-05-8

• 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: 3-氰基-2-甲氧基吡啶-5-硼酸频那醇酯
• 中文别名: 3-氰-2-甲氧基吡啶-5-硼酸频哪醇酯
• 英文名称: 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile
• 英文别名: 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carbonitrile
• CAS: 1073354-05-8
• 化学式: C₁₃H₁₇BN₂O₃
• 分子量: 260.101
• InChiKey: JIDHBYJKXYDCDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.26
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933399090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Cyano-2-methoxypyridine-5-boronic acid, pinacol ester
Synonyms: 2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile

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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-Cyano-2-methoxypyridine-5-boronic acid, pinacol ester
CAS number: 1073354-05-8

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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, refrigerated.
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: C13H17BN2O3
Molecular weight: 260.1

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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, nitrogen oxides.

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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-氰基-2-甲氧基吡啶-5-硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 ethyl (S)-2-(3-((6-(5-cyano-6-methoxypyridin-3-yl)quinazolin-4-yl)amino)piperidin-1-yl)acetate
  参考文献：
  名称：

  4-（哌啶-3-基）氨基取代的6-吡啶基喹唑啉类化合物作为强效PI3Kδ抑制剂的合成及生物学评估。

  摘要：

  PI3Kδ是开发抗癌药物的引人入胜的目标。在这项研究中，合成了一系列新的4-（哌啶-3-基）氨基取代的6-吡啶基喹唑啉衍生物。经过生物学评估后，化合物A5和A8被确定为有效的PI3Kδ抑制剂，IC 50值分别为1.3和0.7 nM，与艾屈拉西布相当或更好（IC 50  = 1.2 nM）。进一步的PI3K同工型选择性评估表明，化合物A5相对于PI3Kα，PI3Kβ和PI3Kγ具有优异的PI3Kδ选择性。A8表现出优于PI3Kα和PI3Kβ的PI3Kδ/γ选择性。此外，化合物A5和A8选择性地表现出对SU-DHL-6的体外抗增殖，IC 50值为0.16和0.12μM。Western印迹分析表明，A8可以减弱AKT S473的磷酸化。分子对接研究表明，A8与PI3Kδ形成了三个关键的H键作用，这可能解释了其对PI3Kδ的有效抑制作用。这些发现表明4-（哌啶-3-基）氨基取代的6-吡啶基喹唑啉衍

  DOI：

  10.1016/j.bmc.2019.07.051
• 作为产物：
  描述：

  5-溴-2-甲氧基烟腈 、 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， 反应 2.5h， 生成 3-氰基-2-甲氧基吡啶-5-硼酸频那醇酯
  参考文献：
  名称：

  4-（哌啶-3-基）氨基取代的6-吡啶基喹唑啉类化合物作为强效PI3Kδ抑制剂的合成及生物学评估。

  摘要：

  PI3Kδ是开发抗癌药物的引人入胜的目标。在这项研究中，合成了一系列新的4-（哌啶-3-基）氨基取代的6-吡啶基喹唑啉衍生物。经过生物学评估后，化合物A5和A8被确定为有效的PI3Kδ抑制剂，IC 50值分别为1.3和0.7 nM，与艾屈拉西布相当或更好（IC 50  = 1.2 nM）。进一步的PI3K同工型选择性评估表明，化合物A5相对于PI3Kα，PI3Kβ和PI3Kγ具有优异的PI3Kδ选择性。A8表现出优于PI3Kα和PI3Kβ的PI3Kδ/γ选择性。此外，化合物A5和A8选择性地表现出对SU-DHL-6的体外抗增殖，IC 50值为0.16和0.12μM。Western印迹分析表明，A8可以减弱AKT S473的磷酸化。分子对接研究表明，A8与PI3Kδ形成了三个关键的H键作用，这可能解释了其对PI3Kδ的有效抑制作用。这些发现表明4-（哌啶-3-基）氨基取代的6-吡啶基喹唑啉衍

  DOI：

  10.1016/j.bmc.2019.07.051

文献信息

• Use of Inhibitors of the Activity or Function of PI3K
  申请人：NOVARTIS AG

  公开号：US20150342951A1

  公开（公告）日：2015-12-03

  The invention relates to new uses of PI3K inhibitors, wherein said inhibitors have an inhibitory action on the PI3K isoform delta for the treatment of immunopathology in a subject suffering from a disease or disorder selected from malaria, leishmaniasis, trypanosomiasis, toxoplasmosis and/or neurocysticercosis, via functional inhibition of TLR9 of the infected subject.

  该发明涉及PI3K抑制剂的新用途，其中所述抑制剂对PI3K同工酶δ具有抑制作用，用于治疗患有疟疾、利什曼病、锥虫病、弓形虫病和/或神经囊虫病等疾病或紊乱的受试者的免疫病理学，通过对感染受试者的TLR9的功能抑制。
• “On‐Water” Palladium‐Catalyzed Tandem Cyclization Reaction for the Synthesis of Biologically Relevant 4‐Arylquinazolines
  作者：Shuo Yuan、Bin Yu、Hong‐Min Liu

  DOI：10.1002/chem.201903464

  日期：2019.10.11

  The quinazoline scaffold is prevalent in pharmaceutically relevant molecules that show diverse biological activities. Herein, we report an efficient "on-water" palladium-catalyzed tandem cyclization reaction from commercially available arylboronic acids and benzonitriles that enable the rapid access to 4-arylquinazoline scaffolds in good to excellent yields (45 examples, up to 98 % yield). This protocol

  喹唑啉支架普遍存在于具有各种生物学活性的药学相关分子中。在本文中，我们报道了由市售的芳基硼酸和苄腈进行的有效的“水上”钯催化的串联环化反应，该反应能够以良好至优异的产率（45个实例，高达98％的产率）快速获得4-芳基喹唑啉骨架。该协议显示出良好的官能团耐受性和广泛的底物范围。该反应也以克为单位进行，并成功地应用于高效和选择性PI3Kδ抑制剂N11的合成，显示了该方案的实用性和合成实用性。在该反应中，通过同时形成一个CC键和一个CN键有效地构建了喹唑啉支架。总的来说，
• [EN] SUBSTITUTED PYRROLOPYRIDINE-DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRROLOPYRIDINE SUBSTITUÉS
  申请人：BAYER PHARMA AG

  公开号：WO2019016071A1

  公开（公告）日：2019-01-24

  The present invention relates to protein-inhibitory substituted pyrrolopyridine derivatives of formula (I), in which A, X, R1, R2a, R2b, R3a, R3b, R4a and R4b are as defined herein, to pharmaceutical compositions and combinations comprising the compounds according to the invention, and to the prophylactic and therapeutic use of the inventive compounds, respectively to the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular for neoplastic disorders, repectively cancer or conditions with dysregulated immune responses or other disorders associated with aberrant MAP4K1 signaling, as a sole agent or in combination with other active ingredients. The present invention further relates to the use, respectively to the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of protein inhibitors in benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, in neurodegenerative disorders, in inflammatory disorders, in atherosclerotic disorders and in male fertility control.

  本发明涉及式(I)的蛋白抑制取代吡咯吡啶衍生物，其中A、X、R1、R2a、R2b、R3a、R3b、R4a和R4b如本文所定义，以及包含根据本发明的化合物的药物组合物和药物组合物，以及创新化合物的预防和治疗用途，分别用于制造用于治疗或预防疾病的药物组合物，特别是用于肿瘤性疾病、癌症或与MAP4K1信号异常相关的其他疾病的治疗或预防，作为单一药剂或与其他活性成分组合使用。本发明还涉及用途，分别用于制造用于治疗或预防良性增生、动脉粥样硬化疾病、败血症、自身免疫性疾病、血管疾病、病毒感染、神经退行性疾病、炎症性疾病、动脉粥样硬化疾病和男性生育控制的蛋白抑制剂的药物组合物。
• [EN] Use of inhibitors of the activity or function of PI3K<br/>[FR] UTILISATION D'INHIBITEURS DE L'ACTIVITÉ OU DE LA FONCTION DE PI3K
  申请人：NOVARTIS AG

  公开号：WO2013088404A1

  公开（公告）日：2013-06-20

  The invention relates to new uses of PI3K inhibitors, wherein said inhibitors have an inhibitory action on the PI3K isoform delta for the treatment of immunopathology in a subject suffering from a disease or disorder selected from malaria, leishmaniasis, trypanosomiasis, toxoplasmosis and/or neurocysticercosis, via functional inhibition of TLR9 of the infected subject.

  该发明涉及 PI3K 抑制剂的新用途，其中所述抑制剂对 PI3K 亚型δ具有抑制作用，用于治疗患有疟疾、利什曼病、锥虫病、弓形虫病和/或神经囊虫病等疾病或紊乱的受试者的免疫病理学，通过对感染受试者的 TLR9 的功能抑制。
• [EN] QUINAZOLINE DERIVATIVES AS PI3K MODULATORS<br/>[FR] DÉRIVÉS DE QUINAZOLINE EN TANT QUE MODULATEURS DES PI3K
  申请人：NOVARTIS AG

  公开号：WO2013057711A1

  公开（公告）日：2013-04-25

  The invention relates to substituted quinazoline derivative of the formula (I), wherein A, X1, X2, X3, X4 and R5 are as defined in the description. Such compounds are suitable for the treatment of a disorder or disease which is mediated by the activity of the PI3K enzymes.

  这项发明涉及公式（I）的取代喹唑啉衍生物，其中A、X1、X2、X3、X4和R5如描述中所定义。这些化合物适用于治疗由PI3K酶活性介导的疾病或疾病。