5-溴-2-溴甲苯甲酸甲酯 | 79670-17-0

• 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 - 苯和取代衍生物
• 中文名称: 5-溴-2-溴甲苯甲酸甲酯
• 英文名称: methyl 5-bromo-2-(bromomethyl)benzoate
• 英文别名: 5-bromo-2-bromomethyl-benzoic acid methyl ester；methyl 2-bromomethyl-5-bromobenzoate
• CAS: 79670-17-0
• 化学式: C₉H₈Br₂O₂
• mdl: MFCD11505949
• 分子量: 307.969
• InChiKey: UVIJBFVFEGZZLQ-UHFFFAOYSA-N

物化性质

• 沸点：
  349.7±32.0 °C(Predicted)
• 密度：
  1.780±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2916399090
• 包装等级：
  II
• 危险类别：
  8
• 危险性防范说明：
  P501,P260,P270,P264,P280,P303+P361+P353,P301+P330+P331,P363,P301+P312+P330,P304+P340+P310,P305+P351+P338+P310,P405
• 危险品运输编号：
  3261
• 危险性描述：
  H302,H314
• 储存条件：
  存储条件：2-8°C，避光，保存于惰性气体中

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Methyl 5-bromo-2-(bromomethyl)benzoate
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: Methyl 5-bromo-2-(bromomethyl)benzoate
CAS number: 79670-17-0

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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: C9H8Br2O2
Molecular weight: 308.0

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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 bromide.

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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

用途

5-溴-2-溴甲苯甲酸甲酯是羧酸酯类衍生物，可用作医药中间体。

制备

取2-甲基-5-溴苯甲酸甲酯加入反应釜中，开启照射光源，在光照条件下滴加纯溴。在确保反应温度和反应速率等指标的控制下，通过光溴化反应生成5-溴-2-溴甲苯甲酸甲酯。依次经过结晶、过滤、离心和干燥处理后，最终得到目标产物——5-溴-2-溴甲苯甲酸甲酯。

反应信息

• 作为反应物：
  描述：

  5-溴-2-溴甲苯甲酸甲酯 在 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 79.0h， 生成 2-[(bis-pyridin-2-ylmethylamino)-methyl]-5-bromobenzoic acid
  参考文献：
  名称：

  含Co（II）槲皮素2,3-双加氧酶的ES（酶-底物）复合物的结构和功能模型系列

  摘要：

  一系列的单核的Co II -flavonolate络合物[CO II大号- [R（FLA）]（大号ř ħ = 2 - {[双（吡啶-2-基甲基）氨基]甲基} - p /米-R -苯甲酸; R = p -OMe（1），p -Me（2），m -Br（4）和m -NO 2（5）; fla =黄酮酸酯）被设计并合成为ES（酶-底物）复合物的结构和功能模型，以模拟含Co（II）的槲皮素2,3-二加氧酶（Co-2,3-QD）的活性位点。每个络合物中的金属中心Co（II）离子显示出相似的扭曲八面体几何形状。模型复合物在低温下显示出高的酶型双加氧反应性（配位底物黄酮酸酯的氧化O-杂环开环），这可能是由于配体中的羧酸酯基团所致。反应性表现出依赖于取代基的顺序-OMe（1）> -Me（2）> -H（3）14b> -Br（4）> -NO 2（5），而Hammett图是线性的（ρ= −0.78）。这可以解释为配体

  DOI：

  10.1021/ic402695c
• 作为产物：
  描述：

  对甲苯甲酸 在 四氯化碳 、 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 溴 、 铁粉 、 过氧化苯甲酰 作用下， 生成 5-溴-2-溴甲苯甲酸甲酯
  参考文献：
  名称：

  含Co（II）槲皮素2,3-双加氧酶的ES（酶-底物）复合物的结构和功能模型系列

  摘要：

  一系列的单核的Co II -flavonolate络合物[CO II大号- [R（FLA）]（大号ř ħ = 2 - {[双（吡啶-2-基甲基）氨基]甲基} - p /米-R -苯甲酸; R = p -OMe（1），p -Me（2），m -Br（4）和m -NO 2（5）; fla =黄酮酸酯）被设计并合成为ES（酶-底物）复合物的结构和功能模型，以模拟含Co（II）的槲皮素2,3-二加氧酶（Co-2,3-QD）的活性位点。每个络合物中的金属中心Co（II）离子显示出相似的扭曲八面体几何形状。模型复合物在低温下显示出高的酶型双加氧反应性（配位底物黄酮酸酯的氧化O-杂环开环），这可能是由于配体中的羧酸酯基团所致。反应性表现出依赖于取代基的顺序-OMe（1）> -Me（2）> -H（3）14b> -Br（4）> -NO 2（5），而Hammett图是线性的（ρ= −0.78）。这可以解释为配体

  DOI：

  10.1021/ic402695c

文献信息

• [EN] POLYCYCLIC COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES<br/>[FR] COMPOSÉS POLYCYCLIQUES ET MÉTHODES POUR LA DÉGRADATION CIBLÉE DE POLYPEPTIDES DU FIBROSARCOME RAPIDEMENT ACCÉLÉRÉ
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2020051564A1

  公开（公告）日：2020-03-12

  The present disclosure relates to bifunctional compounds, ULM— L—PTM, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A- RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物ULM—L—PTM，其作为快速加速纤维肉瘤（RAF，如c-RAF、A-RAF和/或B-RAF；目标蛋白）的调节剂具有实用性。具体而言，本公开涉及含有一端结合到相应E3泛素连接酶的Von Hippel-Lindau、cereblon、凋亡抑制蛋白或鼠双分子同源物2配体的双功能化合物，另一端结合到目标蛋白RAF的部分，使得目标蛋白与泛素连接酶靠近，以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性范围。本公开的化合物和组合物用于治疗或预防由目标蛋白的聚集或积累，或目标蛋白的构成性激活导致的疾病或紊乱。
• [EN] COMPOUNDS MODULATING PROTEIN RECRUITMENT AND/OR DEGRADATION<br/>[FR] COMPOSÉS MODULANT LE RECRUTEMENT ET/OU LA DÉGRADATION DE PROTÉINES
  申请人：ORIONIS BIOSCIENCES INC

  公开号：WO2021126973A1

  公开（公告）日：2021-06-24

  The invention provides cereblon binders for the degradation of proteins by the ubiquitin proteasome pathway for therapeutic applications.

  这项发明提供了用于通过泛素蛋白酶体途径降解蛋白质的 cereblon 结合物，用于治疗应用。
• Metal-free ¹⁸F-labeling of aryl-CF₂H via nucleophilic radiofluorination and oxidative C–H activation
  作者：Gengyang Yuan、Feng Wang、Nickeisha A. Stephenson、Lu Wang、Benjamin H. Rotstein、Neil Vasdev、Pingping Tang、Steven H. Liang

  DOI：10.1039/c6cc07913j

  日期：——

  A metal-free and selective method to form [18F]aryl-CF2H through nucleophilic radiofluorination of benzyl (pseudo)halides and oxidative C-H activation of benzylic C-H bonds has been developed.

  以形成[A和选择性的无金属的方法18 F]芳-CF 2通过苄基（伪）卤化物和苄基的CH键的氧化CH活化的亲核放射性氟化者H已被开发出来。
• 一种光催化连续溴代的方法
  申请人：凯莱英医药集团（天津）股份有限公司

  公开号：CN112592247A

  公开（公告）日：2021-04-02

  本发明提供了一种光催化连续溴代的方法。该方法包括：将包含具有结构通式I的芳香底物和溴化试剂的物料在第一连续光照反应器中进行第一阶段光催化连续溴代反应，形成第一连续体系；所得第一连续体系溢流至第二连续光照反应器中进行第二阶段光催化连续溴代反应，形成第二连续体系；对第二连续体系进行提纯，结构通式I为，R选自羧基、酯基、‑NO2、、‑CN、C1至C8的烷基、和烷氧基中的任意一种，R1为C1至C8的烷基；n为1或2；X为N或C，溴化试剂为N‑溴代丁二酰亚胺或二溴海因。上述溴化试剂，提高了产物的选择性，进而提高了产物收率；两个阶段的光催化连续溴代反应，有效缓解了反应热积聚，提高了目标产物的收率。
• Synthesis and Broad Antiviral Activity of Novel 2-aryl-isoindolin-1-ones towards Diverse Enterovirus A71 Clinical Isolates
  作者：Yixuan Wang、Huiqiang Wang、Xinbei Jiang、Zhi Jiang、Tingting Guo、Xingyue Ji、Yanping Li、Yuhuan Li、Zhuorong Li

  DOI：10.3390/molecules24050985

  日期：——

  Enterovirus 71 (EV-A71) is the main causative pathogen of childhood hand, foot and mouth disease. Effective medicine is currently unavailable for the treatment of this viral disease. Using the fragment-hopping strategy, a series of 2-aryl-isoindolin-1-one compounds were designed, synthesized and investigated for their in vitro antiviral activity towards multiple EV-A71 clinical isolates (H, BrCr, Shenzhen98, Jiangsu52) in Vero cell culture in this study. The structure–activity relationship (SAR) studies identified 2-phenyl-isoindolin-1-ones as a new potent chemotype with potent antiviral activity against EV-A71. Ten out of the 24 tested compounds showed significant antiviral activity (EC50 < 10 µM) towards four EV-A71 strains. Compounds A3 and A4 exhibited broad and potent antiviral activity with the 50% effective concentration (EC50) values in the range of 1.23–1.76 μM. Moreover, the selectivity indices of A3 and A4 were significantly higher than those of the reference compound, pirodavir. The western blotting experiment indicated that the viral VP1 was significantly decreased at both the protein and RNA level in a dose-dependent manner following treatment with compound A3. Moreover, compound A3 inhibited the viral replication by acting on the virus entry stage. In summary, this study led to the discovery of 2-aryl-isoindolin-1-ones as a promising scaffold with potent anti-EV-A71 activities, which deserves further in-depth studies.

  肠道病毒71型(EV-A71)是儿童手足口病的主要病原体。目前还没有有效的药物治疗这种病毒性疾病。在本研究中，我们采用片段跳跃策略，设计、合成了一系列2-芳基-异吲哚啉-1-酮化合物，并研究了它们在Vero细胞培养中对多个EV-A71临床分离株(H、BrCr、深圳98、江苏52)的体外抗病毒活性。结构-活性关系(SAR)研究确定2-苯基-异吲哚啉-1-酮是一种对EV-A71具有强大抗病毒活性的新型有效化学型。在24个测试化合物中，有10个化合物对四种EV-A71毒株显示出显著的抗病毒活性(EC50<10µM)。化合物A3和A4表现出广泛而强大的抗病毒活性，50%有效浓度(EC50)值在1.23-1.76μM范围内。此外，A3和A4的选择性指数显著高于参照化合物皮罗达韦。western印迹实验表明，经化合物A3处理后，病毒的VP1在蛋白质和RNA水平上均显著降低，并呈剂量依赖性。此外，化合物A3通过作用于病毒进入阶段来抑制病毒复制。总的来说，本研究发现了2-芳基-异吲哚啉-1-酮作为一种具有强大抗EV-A71活性的有希望的结构，值得进一步深入研究。