5-(溴乙基)-2-(三氟甲基)吡啶 | 108274-33-5

• 物质功能分类: 医药中间体 - 杂环化合物 - 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: 5-(溴乙基)-2-(三氟甲基)吡啶
• 中文别名: 2-三氟甲基-5-溴甲基吡啶
• 英文名称: 5-(bromomethyl)-2-(trifluoromethyl)pyridine
• CAS: 108274-33-5
• 化学式: C₇H₅BrF₃N
• 分子量: 240.023
• InChiKey: IRQUWHXXVJARBK-UHFFFAOYSA-N

物化性质

• 沸点：
  218.4±35.0 °C(Predicted)
• 密度：
  1.647

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 包装等级：
  III
• 危险类别：
  8
• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险品运输编号：
  1759
• 危险性描述：
  H314

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 5-(Bromomethyl)-2-(trifluoromethyl)pyridine
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: 5-(Bromomethyl)-2-(trifluoromethyl)pyridine
CAS number: 108274-33-5

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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: C7H5BrF3N
Molecular weight: 240

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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 fluoride, 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

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  5-甲基-2-三氟甲基吡啶	5-methyl-2-(trifluoromethyl)pyridine	1620-71-9	C7H6F3N	161.127
  6-三氟甲基-3-吡啶甲醇	6-(trifluoromethyl)pyridin-3-ylmethanol	386704-04-7	C7H6F3NO	177.126
  6-三氟甲基吡啶-3-醛	6-(trifluoromethyl)pyridine-3-carbaldehyde	386704-12-7	C7H4F3NO	175.11
  6-三氟甲基烟酸	6-trifluoromethylnicotinic acid	231291-22-8	C7H4F3NO2	191.109

反应信息

• 作为反应物：
  描述：

  5-(溴乙基)-2-(三氟甲基)吡啶 在 bis(1,5-cyclooctadiene)nickel (0) 、 sodium hydride 、 三乙胺 、 三氟乙酸 、 4,4'-二叔丁基-2,2'-二吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 为溶剂， 反应 38.5h， 生成 培西达替尼
  参考文献：
  名称：

  由四嗪和光激发实现的脱烯基镍催化交叉偶联

  摘要：

  已经开发出一种新的通用方法来官能化烷基和烯烃键的 C(sp 3 )–C(sp 2 ) 键，导致碳中心自由基的脱烯基生成，这些自由基可以被截获以进行 Ni 催化的 C( sp 3 )–C(sp 2 ) 交叉耦合。这种一锅法利用易于获得的烯烃原料进行有机合成，具有出色的官能团兼容性，无需光氧化还原催化剂。

  DOI：

  10.1021/jacs.1c05092
• 作为产物：
  描述：

  6-三氟甲基-3-吡啶甲醇 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 以71%的产率得到5-(溴乙基)-2-(三氟甲基)吡啶
  参考文献：
  名称：

  口服生物利用和肝脏靶向性缺氧诱导因子脯氨酰羟化酶（HIF-PHD）抑制剂治疗贫血的发现。

  摘要：

  我们在此报告了一系列口服活性，肝脏靶向的缺氧诱导因子脯氨酰羟化酶（HIF-PHD）抑制剂的设计和合成，用于治疗贫血。为了减轻对潜在全身性副作用的担忧，我们寻求依赖于通过有机阴离子转运多肽（OATP）摄取的针对肝脏的HIF-PHD抑制剂。从系统性HIF-PHD抑制剂（1）开始，药物化学致力于降低通透性，同时保持口服吸收，导致了一系列结构多样的羟基吡啶酮类似物的合成。选择化合物28a进行进一步的分析，因为它具有出色的体外特性和肝选择性。长期口服QD后，该化合物可显着增加大鼠血红蛋白水平，

  DOI：

  10.1021/acsmedchemlett.8b00274

文献信息

• Lead Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series for the Treatment of Malaria
  作者：Sreekanth Kokkonda、Xiaoyi Deng、Karen L. White、Farah El Mazouni、John White、David M. Shackleford、Kasiram Katneni、Francis C. K. Chiu、Helena Barker、Jenna McLaren、Elly Crighton、Gong Chen、Inigo Angulo-Barturen、Maria Belen Jimenez-Diaz、Santiago Ferrer、Leticia Huertas-Valentin、Maria Santos Martinez-Martinez、Maria Jose Lafuente-Monasterio、Rajesh Chittimalla、Shatrughan P. Shahi、Sergio Wittlin、David Waterson、Jeremy N. Burrows、Dave Matthews、Diana Tomchick、Pradipsinh K. Rathod、Michael J. Palmer、Susan A. Charman、Margaret A. Phillips

  DOI：10.1021/acs.jmedchem.0c00311

  日期：2020.5.14

  Compounds with nanomolar potency versus Plasmodium DHODH and Plasmodium parasites were identified with good pharmacological properties. X-ray studies showed that the pyrroles bind an alternative enzyme conformation from 1 leading to improved species selectivity versus mammalian enzymes and equivalent activity on Plasmodium falciparum and Plasmodium vivax DHODH. The best lead DSM502 (37) showed in vivo efficacy

  疟疾使世界上近一半的人口面临风险，并导致撒哈拉以南非洲地区的高死亡率，而耐药性也威胁着现有的治疗方法。根据我们的发现，三唑并嘧啶 DSM265 (1) 在临床研究中显示出疗效，嘧啶生物合成酶二氢乳清酸脱氢酶 (DHODH) 是疟疾治疗的有效靶点。在此，我们描述了使用基于目标的 DHODH 筛选鉴定的基于吡咯的系列的优化。与疟原虫 DHODH 和疟原虫寄生虫相比具有纳摩尔效力的化合物已被鉴定具有良好的药理学特性。X 射线研究表明，吡咯与 1 的替代酶构象结合，从而提高了相对于哺乳动物酶的物种选择性，并且对恶性疟原虫和间日疟原虫 DHODH 具有同等活性。最好的先导 DSM502 (37) 在与 1 的血液暴露水平相似的情况下显示出体内功效，尽管代谢稳定性有所降低。总体而言，基于吡咯的 DHODH 抑制剂为新型抗疟化合物的开发提供了一种有吸引力的替代支架。
• [EN] IMIDAZOLIDINONE DERIVATIVES AS INHIBITORS OF PERK<br/>[FR] DÉRIVÉS D'IMIDAZOLIDINONE COMME INHIBITEURS DE PERK
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO 2) LTD

  公开号：WO2017046739A1

  公开（公告）日：2017-03-23

  The invention is directed to substituted imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I (I) wherein R1, R2, R3, R4, R5, R6, R7, X, Y1, Y2 and Z are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  这项发明涉及取代咪唑烷酮衍生物。具体而言，该发明涉及根据式I（I）中R1、R2、R3、R4、R5、R6、R7、X、Y1、Y2和Z所定义的化合物。该发明的化合物是PERK的抑制剂，可用于治疗癌症、癌前综合征、阿尔茨海默病、神经病性疼痛、脊髓损伤、创伤性脑损伤、缺血性中风、中风、帕金森病、糖尿病、代谢综合征、代谢紊乱、亨廷顿病、克雅氏病、致命性家族性失眠、格斯特曼-施特劳斯勒-谢因克症候群及相关朊蛋白病、肌萎缩侧索硬化、进行性核上性麻痹、心肌梗死、心血管疾病、炎症、器官纤维化、肝脏慢性和急性疾病、脂肪肝病、肝脂肪变性、肝纤维化、肺部慢性和急性疾病、肺纤维化、肾脏慢性和急性疾病、肾脏纤维化、慢性创伤性脑病（CTE）、神经退行性疾病、痴呆症、额颞叶痴呆症、tau蛋白病、皮克氏病、尼曼-皮克氏病、淀粉样变性、认知障碍、动脉粥样硬化、眼部疾病、心律失常、器官移植以及器官移植用途中的运输。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制PERK活性和治疗相关疾病的方法。
• Structure–Activity Relationship Studies Reveal New Astemizole Analogues Active against <i>Plasmodium falciparum</i> In Vitro
  作者：Dickson Mambwe、Malkeet Kumar、Richard Ferger、Dale Taylor、Mathew Njoroge、Dina Coertzen、Janette Reader、Mariëtte van der Watt、Lyn-Marie Birkholtz、Kelly Chibale

  DOI：10.1021/acsmedchemlett.1c00328

  日期：2021.8.12

  In the context of drug repositioning and expanding the existing structure–activity relationship around astemizole (AST), a new series of analogues were designed, synthesized, and evaluated for their antiplasmodium activity. Among 46 analogues tested, compounds 21, 30, and 33 displayed high activities against asexual blood stage parasites (PfNF54 IC50 = 0.025–0.043 μM), whereas amide compound 46 additionally

  在药物重新定位和扩大阿司咪唑 (AST) 周围现有构效关系的背景下，设计、合成了一系列新的类似物，并评估了它们的抗疟原虫活性。在测试的46 种类似物中，化合物 21、30 和 33显示出对无性血液期寄生虫的高活性（Pf NF54 IC 50 = 0.025–0.043 μM），而酰胺化合物46还显示出对晚期配子体（IV/V 期；Pf LG IC 50 = 0.6 ± 0.1 μM）和比 hERG 高 860 倍的选择性（46, SI = 43) 与 AST 相比。在中国仓鼠卵巢 (SI > 148) 细胞系中显示出高溶解度 (Sol > 100 μM) 和低细胞毒性的几种类似物也已被鉴定。
• POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M1
  申请人：Vanderbilt University

  公开号：US20200131180A1

  公开（公告）日：2020-04-30

  Described are positive allosteric modulators of muscarinic acetylcholine receptor M 1 (mAChR M 1 ), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating neurological disorders, psychiatric disorders, or a combination thereof.

  描述了甲型乙酰胆碱受体M1（mAChR M1）的正向变构调节剂，包括这些化合物的药物组合物，以及使用这些化合物和组合物治疗神经系统疾病、精神疾病或二者的方法。
• Azabicyclic heterocycles as cannabinoid receptor modulators
  申请人：Yu Guixue

  公开号：US20050143381A1

  公开（公告）日：2005-06-30

  The present application describes compounds according to Formula I, pharmaceutical compositions comprising at least one compound according to Formula I and optionally one or more additional therapeutic agents and methods of treatment using the compounds according to Formula I both alone and in combination with one or more additional therapeutic agents. The compounds have the general Formula I: including all prodrugs, pharmaceutically acceptable salts and stereoisomers, R 1 , R 2 , R 3 , R 6 , R 7 , m and n are described herein.

  本申请描述了符合I式的化合物，包括至少一种符合I式的化合物和可选地一种或多种额外治疗剂的药物组合物，以及使用符合I式的化合物进行治疗的方法，包括单独使用和与一种或多种额外治疗剂结合使用。这些化合物的一般式I如下： 包括所有的前药、药用盐和立体异构体，R1、R2、R3、R6、R7、m和n如本文所述。