4-溴甲基苯甲酸叔丁酯 | 108052-76-2

• 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: 4-溴甲基苯甲酸叔丁酯
• 中文别名: 对溴甲基苯甲酸叔丁酯
• 英文名称: 4-(bromomethyl)benzoic acid 1,1-dimethylethyl ester
• 英文别名: tert-butyl 4-bromomethylbenzoate；Tert-butyl 4-(bromomethyl)benzoate
• CAS: 108052-76-2
• 化学式: C₁₂H₁₅BrO₂
• 分子量: 271.154
• InChiKey: GSIBTIUXYYFCPU-UHFFFAOYSA-N

物化性质

• 熔点：
  53-55 °C
• 沸点：
  320.9±25.0 °C(Predicted)
• 密度：
  1.313±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：30mg/mL； DMSO：30mg/mL；乙醇：30mg/mL；乙醇:PBS (pH 7.2)(1:3): 0.25 mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 包装等级：
  III
• 危险类别：
  8
• 危险性防范说明：
  P260,P264,P270,P280,P301+P312+P330,P301+P330+P331,P303+P361+P353,P304+P340+P310,P305+P351+P338+P310,P362+P364,P405,P501
• 危险品运输编号：
  3261
• 危险性描述：
  H302+H312,H314
• 储存条件：
  存放在室温、干燥且密封的环境中。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Bromo methyl benzoic acid mono tert-butyl ester
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: 4-Bromo methyl benzoic acid mono tert-butyl ester
CAS number: 108052-76-2

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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.
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: C12H15BrO2
Molecular weight: 271.2

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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, 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
4-溴甲基苯甲酸叔丁酯是合成杀螨剂唑螨酯的中间体。

生产方法
其制备是在装有搅拌器和温度计的三口瓶中加入0.56 g 叔丁醇、0.395 g 吡啶和1.75 g 4-溴甲基苯甲酰氯，于10～30℃反应5小时。反应结束后向反应瓶中加入10 mL 水，移至分液漏斗中，用乙酸乙酯萃取。合并萃取液，以稀酸洗涤并分去酸水层后减压脱溶，最终得到0.98 g 4-溴甲基苯甲酸叔丁酯，收率为72.0%。

反应信息

• 作为反应物：
  描述：

  4-溴甲基苯甲酸叔丁酯 在 palladium on activated charcoal 六甲基磷酰三胺 、 正丁基锂 、 Davison sponge Ni 、 氢气 、 sodium methylate 、 二异丙胺 作用下， 以 甲苯 为溶剂， 反应 52.75h， 生成 4-[2-(3-Methoxycarbonyl-4-oxo-cyclohexyl)-ethyl]-benzoic acid tert-butyl ester
  参考文献：
  名称：

  (6R,6S)-5,8,10-Trideaza-5,6,7,8-tetrahydrofolate and (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-ornithine as potential antifolates and antitumor agents. 35

  摘要：

  (6R,6S)-5,8,10-三去氮-5,6,7,8-四氢蝶酰酸通过多步反应由4,4-(环氧乙烷氧基)-环己酮和[4-(叔丁基氧基羰基)苄基]三苯基𬭸溴化物合成，并进一步转化为(6R,6S)-5,8,10-三去氮-5,6,7,8-四氢蝶酰-L-谷氨酸和(6R,6S)-5,8,10-三去氮-5,6,7,8-四氢蝶酰-L-精氨酸。化合物1被发现是部分纯化的鼠肝叶酸多谷氨酸合成酶（FPGS）的良好底物，其米氏常数（Km = 15 μM）与报道的还原型叶酸底物（6S）-5,6,7,8-四氢蝶酰-L-谷氨酸以及(6R,6S)-5,10-二去氮-5,6,7,8-四氢蝶酰-L-谷氨酸（DDATHF）的值相当。然而，与具有强细胞毒性的DDATHF形成鲜明对比的是，化合物1在高达100 μM的浓度下未能抑制肿瘤细胞的生长。这些结果表明，DDATHF中位于8号位的NH对于细胞毒性活性至关重要，但并非多谷氨酸化的必要条件。与1作为FPGS的良好底物类似，精氨酸类似物2证明是迄今为止发现的对该酶的较强竞争性抑制剂之一，其Ki值为10 μM。尽管2与5,6,7,8-四氢蝶酰-L-精氨酸（H4PteOrn）相比结合亲和力较低，但在N5、N8和N10位被碳取代的情况下，仍观察到显著的FPGS抑制作用。这表明，FPGS对环B和桥区的生物等价替代表现出一定的耐受性。化合物1和2在高达100 μM的浓度下均未显示出抑制细胞生长的活性。作为潜在前药的化合物2的Nδ半邻苯二甲酰衍生物也未表现出活性。

  DOI：

  10.1021/jm00123a037
• 作为产物：
  描述：

  4-甲基苯甲酸叔丁酯 在 N-溴代丁二酰亚胺(NBS) 作用下， 生成 4-溴甲基苯甲酸叔丁酯
  参考文献：
  名称：

  用于基于Fmoc的固相肽合成的4-羧基苯丙氨酸及其衍生物的立体定向合成

  摘要：

  获得N α -苄氧羰基-L-酪氨酸（ø -三氟甲基）苄基酯，我们准备了使用钯（0）催化的羰基化反应对映体纯的4- carboxyphenylalanine和4- methoxycarbonylphenylalanine衍生物。这些非天然氨基酸被适当地保护，并用于使用Fmoc /叔丁基方法的固相肽合成中。

  DOI：

  10.1016/s0040-4039(96)01490-6

文献信息

• Structure-Guided Design, Synthesis, and Characterization of Next-Generation Meprin β Inhibitors
  作者：Daniel Ramsbeck、Antje Hamann、Georg Richter、Dagmar Schlenzig、Stefanie Geissler、Vera Nykiel、Holger Cynis、Stephan Schilling、Mirko Buchholz

  DOI：10.1021/acs.jmedchem.8b00330

  日期：2018.5.24

  The metalloproteinase meprin β emerged as a current drug target for the treatment of a number of disorders, among those fibrosis, inflammatory bowel disease and Morbus Alzheimer. A major obstacle in the development of metalloprotease inhibitors is target selectivity to avoid side effects by blocking related enzymes with physiological functions. Here, we describe the structure-guided design of a novel

  金属蛋白酶甲铁蛋白β已成为治疗许多疾病的当前药物靶标，这些疾病包括纤维化，炎性肠病和Morbus Alzheimer。开发金属蛋白酶抑制剂的主要障碍是靶标选择性，以通过阻断具有生理功能的相关酶来避免副作用。在这里，我们基于先前报道的高活性甲羟乙炔β抑制剂描述了一系列新型化合物的结构指导设计。磺酰胺支架的生物立体替代产生了新一代的meprin抑制剂。基于这种新型胺支架的选定化合物显示出对甲羟乙炔β的高活性，并且对相关的金属蛋白酶（即基质金属蛋白酶和A整联蛋白和金属蛋白酶）具有显着的选择性。
• PTG-0861: A novel HDAC6-selective inhibitor as a therapeutic strategy in acute myeloid leukaemia
  作者：Justyna M. Gawel、Andrew E. Shouksmith、Yasir S. Raouf、Nabanita Nawar、Krimo Toutah、Shazreh Bukhari、Pimyupa Manaswiyoungkul、Olasunkanmi O. Olaoye、Johan Israelian、Tudor B. Radu、Aaron D. Cabral、Diana Sina、Abootaleb Sedighi、Elvin D. de Araujo、Patrick T. Gunning

  DOI：10.1016/j.ejmech.2020.112411

  日期：2020.9

  ROS generation. In examining compound stability and cellular permeability, PTG-0861 revealed a promising in vitro pharmacokinetic (PK) profile. Altogether, in this study we identified a novel and potent HDAC6-selective inhibitor (∼4 × more selective than current clinical standards – citarinostat, ricolinostat), which achieves cellular target engagement, efficacy in hematological cancer cells with a promising

  在多种人类病理学中失调的组蛋白脱乙酰基酶（HDAC）活性突显了这一表观遗传酶家族作为关键的可药物靶向，适合小分子干预。尽管有效，但目前使用非选择性HDAC抑制剂（HDACi）的方法已显示出一系列不良的临床毒性。为了避免这种情况，最近的努力集中在设计高选择性HDACi作为一种新的治疗策略上。除了在调节转录中的作用外，独特的HDAC6（具有两个催化结构域）还调节了HDAC6的脱乙酰基作用。α-微管蛋白; 促进生长因子控制的细胞运动，细胞分裂和转移标志。最近的研究已将HDAC6异常功能与包括急性髓细胞性白血病和多发性骨髓瘤在内的多种血液学癌症联系起来。本文中，我们报告了新型PDAC-0861（JG-265）的发现，体外表征和生物学评估，PTG-0861是新型HDAC6选择性抑制剂，具有强同工酶选择性（〜36×）和低纳摩尔 浓度（IC 50 = 6 nM） ）针对HDAC6。通过计算机对接研究对这
• SUBSTITUTED BIPIPERIDINYL DERIVATIVES
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：US20160318866A1

  公开（公告）日：2016-11-03

  The invention relates to novel substituted bipiperidinyl derivatives, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of diabetic microangiopathies, diabetic ulcers on the extremities, in particular for promoting wound healing of diabetic foot ulcers, diabetic heart failure, diabetic coronary microvascular heart disorders, peripheral and cardiac vascular disorders, thromboembolic disorders and ischaemias, peripheral circulatory disturbances, Raynaud's phenomenon, CREST syndrome, microcirculatory disturbances, intermittent claudication, and peripheral and autonomous neuropathies.

  该发明涉及新型取代的双哌啶衍生物，涉及它们的制备方法，涉及它们用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物的用途，特别是用于治疗和/或预防糖尿病微血管病变、四肢糖尿病溃疡，特别是促进糖尿病足溃疡愈合、糖尿病心力衰竭、糖尿病冠状微血管心脏疾病、外周和心脏血管疾病、血栓栓塞疾病和缺血、外周循环障碍、雷诺现象、CREST综合征、微循环障碍、间歇性跛行以及外周和自主神经病变的治疗和/或预防。
• Matrix metalloproteinase inhibitors
  申请人：——

  公开号：US20030078276A1

  公开（公告）日：2003-04-24

  Compounds are provided that bind allosterically to the catalytic domain of MMP-13 and comprise a hydrophobic group, first and second hydrogen bond acceptors and at least one, and preferably both, of a third hydrogen bond acceptor and a second hydrophobic group. Cartesian coordinates for centroids of the above features are defined in the specification. When the ligand binds to MMP-13, the first, second and third (when present) hydrogen bond acceptors bond respectively with Thr245, Thr 247 and Met 253, the first hydrophobic group locates within the S1′ channel of MMP-13 and the second hydrophobic group (when present) is relatively open to solvent. The compounds specifically inhibit the matrix metalloproteinase-13 enzyme and thus are useful for treating diseases resulting from tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.

  提供了一些与MMP-13的催化结构域发生变构结合的化合物，包括一个疏水基团，第一和第二氢键受体，以及至少一个，最好是两个，第三氢键受体和第二疏水基团。上述特征的质心的笛卡尔坐标在说明书中定义。当配体与MMP-13结合时，第一、第二和第三（存在时）氢键受体分别与Thr245、Thr247和Met253结合，第一个疏水基团位于MMP-13的S1'通道内，第二疏水基团（存在时）相对于溶剂是开放的。这些化合物特异性地抑制基质金属蛋白酶-13酶，因此可用于治疗由组织分解引起的疾病，如心脏病、多发性硬化症、关节炎、动脉粥样硬化和骨质疏松症。
• COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：US20160235734A1

  公开（公告）日：2016-08-18

  Compounds of formula I, defined herein, act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for treating broncho-obstructive and inflammatory diseases.

  具有本公式I定义的化合物既作为毒蕈碱受体拮抗剂又作为β2肾上腺素能受体激动剂，并且用于治疗支气管阻塞和炎症性疾病。