3-(4-吗啉羰基)苯硼酸频那醇酯 | 1036991-25-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 3-(4-吗啉羰基)苯硼酸频那醇酯
• 中文别名: 3-(4-吗啉基羰基)苯基硼酸频哪醇酯
• 英文名称: morpholino(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanone
• 英文别名: morpholin-4-yl-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone
• CAS: 1036991-25-9
• 化学式: C₁₇H₂₄BNO₄
• 分子量: 317.193
• InChiKey: PKONGXZPUDFPPH-UHFFFAOYSA-N

物化性质

• 熔点：
  78-84 °C
• 沸点：
  478.7±40.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.46
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P362,P403+P233,P501,P330,P361,P363,P391,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
3-(4-Morpholinylcarbonyl)phenylboronic acid pinacol ester
Product Name:
Synonyms: 3-(4-Morpholinylcarbonyl)phenylboronic acid pinacol ester

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
3-(4-Morpholinylcarbonyl)phenylboronic acid pinacol ester
Ingredient name:
CAS number: 1036991-25-9

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.
Storage: Store in closed vessels.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C17H24BNO4
Molecular weight: 317.2

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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-(4-吗啉羰基)苯硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 三异丙基硅烷 、 四丁基溴化铵 、 cesium fluoride 、 三氟乙酸 作用下， 以 四氢呋喃 、 水 为溶剂， 20.0~120.0 ℃ 、1.72 MPa 条件下， 反应 1.5h， 生成 4-bromo-2-hydroxy-3-[3-(morpholine-4-carbonyl)phenyl]-2H-furan-5-one
  参考文献：
  名称：

  Identification of new γ-hydroxybutenolides that preferentially inhibit the activity of mPGES-1

  摘要：

  Microsomal prostaglandin E-2 synthase-1 (mPGES-1) has been recognized as novel, promising drug target for anti-inflammatory and anticancer drugs. mPGES-1 catalyzes the synthesis of the inducible prostaglandin E-2 in response to pro-inflammatory stimuli, rendering this enzyme extremely interesting in drug discovery process owing to the drastic reduction of the severe side effects typical for traditional non-steroidal anti-inflammatory drugs. In the course of our investigations focused on this topic, we identified two interesting molecules bearing the gamma-hydroxybutenolide scaffold which potently inhibit the activity of mPGES-1. Notably, the lead compound 2c that inhibited mPGES-1 with IC50 = 0.9 mu M, did not affect other related enzymes within the arachidonic acid cascade. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.032
• 作为产物：
  描述：

  3-羧基苯硼酸 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 3-(4-吗啉羰基)苯硼酸频那醇酯
  参考文献：
  名称：

  Design and synthesis of a second series of triazole-based compounds as potent dual mPGES-1 and 5-lipoxygenase inhibitors

  摘要：

  Microsomal prostaglandin E-2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO) are pivotal enzymes in the biosynthesis of the pro-inflammatory PGE(2) and leukotrienes, respectively. The design and synthesis of a second series of mPGES-1 inhibitors based on a triazole scaffold are described. Our studies allowed us to draw a tentative SAR profile and to optimize this series with the identification of compounds 10, 11 and 14-15 which displayed potent mPGES-1 inhibition in a cell-free assay. In addition, compounds 5, 10, 12 and 14-16 also blocked 5-LO activity in cell-free and cell-based test systems, emerging as very promising candidates for the development of safer and more effective anti-inflammatory drugs. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.05.014

文献信息

• One-Pot Palladium-Catalyzed Cross-Coupling Treble of Borylation, the Suzuki Reaction and Amination
  作者：Howard Jong、Stanley T.-C. Eey、Yee Hwee Lim、Sangeeta Pandey、Nurul Azmah Bte Iqbal、Fui Fong Yong、Edward G. Robins、Charles W. Johannes

  DOI：10.1002/adsc.201600708

  日期：2017.2.20

  A methodology for a sequential palladium‐catalyzed cross‐coupling procedure consisting of borylation, the Suzuki reaction and amination has been developed for the assembly of molecules with multi‐aryl backbones. The linchpin of this development is the meta‐terarylphosphine ligand, Cy*Phine, which has been employed as an air‐ and moisture‐stable precatalyst, Pd(Cy*Phine)2Cl2, to improve the efficiency

  已经开发了一种由硼化，Suzuki反应和胺化组成的顺序钯催化交叉偶联程序的方法，用于组装具有多芳基骨架的分子。这一发展的关键是间-叔芳基膦配体Cy * Phine，已被用作对空气和湿气稳定的前催化剂Pd（Cy * Phine）2 Cl 2，以提高一锅硼化-铃木反应的效率。此外，可以调整Pd-Cy * Phine系统的反应性，以提供一锅，硼化-铃木反应-胺化（BSA）交叉耦合的三重峰。该方法成功地整合了三个截然不同的模块化反应的互补条件。每个区段的平均产量可达到74-94％，在一个锅中，在整个三步过程中累计提供50-84％的产量。
• <i>para</i> ‐Selective C−H Borylation of (Hetero)Arenes by Cooperative Iridium/Aluminum Catalysis
  作者：Lichen Yang、Kazuhiko Semba、Yoshiaki Nakao

  DOI：10.1002/anie.201701238

  日期：2017.4.18

  para‐Selective C−H borylation of benzamides and pyridines has been achieved by cooperative iridium/aluminum catalysis. A combination of iridium catalysts commonly employed for arene C−H borylation and bulky aluminum‐based Lewis acid catalysts provides an unprecedented strategy for controlling the regioselectivity of C−H borylation to give variously substituted (hetero)arylboronates, which are versatile

  苯甲酰胺和吡啶的对位C-H硼化已通过铱/铝协同催化实现。芳烃CH硼化中常用的铱催化剂和庞大的铝基路易斯酸催化剂的结合提供了一种空前的策略，可控制CH硼化的区域选择性，从而得到各种取代的（杂）芳基硼酸酯，它们是复杂的多用途合成中间体多取代的芳族化合物。
• Amide Effects in C−H Activation: Noncovalent Interactions with L-Shaped Ligand for <i>meta</i> Borylation of Aromatic Amides
  作者：Ranjana Bisht、Md Emdadul Hoque、Buddhadeb Chattopadhyay

  DOI：10.1002/anie.201809929

  日期：2018.11.26

  A new concept for the meta‐selective borylation of aromatic amides is described. It has been demonstrated that while esters gave para borylations, amides lead to meta borylations. For achieving high meta selectivity, an L‐shaped bifunctional ligand has been employed and engages in an O⋅⋅⋅K noncovalent interaction with the oxygen atom of the moderately distorted amide carbonyl group. This interaction

  描述了芳族酰胺间选择性硼化的新概念。已经证明，尽管酯产生对硼烷基化，但是酰胺导致间硼烷基化。为了实现较高的间位选择性，使用了L型双功能配体，该配体与中度扭曲的酰胺羰基的氧原子发生O⋅⋅⋅K非共价相互作用。这种相互作用提供了对元CH活化/基化的特殊控制。
• Development of new highly potent imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1
  作者：Espérance Moine、Isabelle Dimier-Poisson、Cécile Enguehard-Gueiffier、Cédric Logé、Mélanie Pénichon、Nathalie Moiré、Claire Delehouzé、Béatrice Foll-Josselin、Sandrine Ruchaud、Stéphane Bach、Alain Gueiffier、Françoise Debierre-Grockiego、Caroline Denevault-Sabourin

  DOI：10.1016/j.ejmech.2015.10.004

  日期：2015.11

  Using a structure-based design approach, we have developed a new series of imidazo[1,2-b]pyridazines, targeting the calcium-dependent protein kinase-1 (CDPK1) from Toxoplasma gondii. Twenty derivatives were thus synthesized. Structure-activity relationships and docking studies confirmed the binding mode of these inhibitors within the ATP binding pocket of TgCDPK1. Two lead compounds (16a and 16f) were

  使用基于结构的设计方法，我们开发了一系列新的咪唑并[1,2- b ]哒嗪类药物，靶向弓形虫的钙依赖性蛋白激酶-1（CDPK1）。由此合成了二十种衍生物。结构活性关系和对接研究证实了这些抑制剂在Tg CDPK1的ATP结合口袋中的结合模式。然后鉴定了两种先导化合物（16a和16f），它们能够在低纳摩尔浓度下阻断Tg CDPK1的酶促活性，并且对一组哺乳动物激酶具有良好的选择性。这些抑制剂的潜力已在体外T上得到证实。刚地生长，EC 50值分别为100 nM和70 nM。这些最佳候选物还显示出对哺乳动物细胞的低毒性，并被选择用于急性弓形虫病小鼠模型的进一步体内研究。
• Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis
  作者：Gautam Patel、Caitlin E. Karver、Ranjan Behera、Paul J. Guyett、Catherine Sullenberger、Peter Edwards、Norma E. Roncal、Kojo Mensa-Wilmot、Michael P. Pollastri

  DOI：10.1021/jm400349k

  日期：2013.5.23

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.