3-溴-5-甲基-1H-吡唑 | 57097-81-1

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 中文名称: 3-溴-5-甲基-1H-吡唑
• 中文别名: 3-溴-5-甲基吡唑
• 英文名称: 3-bromo-5-methyl-1H-pyrazole
• 英文别名: 5-methyl-3-bromopyrazole
• CAS: 57097-81-1
• 化学式: C₄H₅BrN₂
• 分子量: 161.001
• InChiKey: SVRPUGWCOWUQOY-UHFFFAOYSA-N

物化性质

• 熔点：
  138-139 °C
• 沸点：
  270℃
• 密度：
  1.723
• 闪点：
  117℃

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  7
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933199090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  2-8°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Bromo-5-methyl-1H-pyrazole
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: 3-Bromo-5-methyl-1H-pyrazole
CAS number: 57097-81-1

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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: C4H5BrN2
Molecular weight: 161.0

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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, nitrogen oxides, 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

简介

3-溴-5-甲基-1H-吡唑是一个重要的杂环化合物，广泛存在于多种生物活性化合物中，并用于合成进一步功能化起始材料。它作为合成新型鱼尼丁受体杀虫剂氯虫酰胺的关键中间体尤为重要。此外，吡唑类衍生物对抑制腺嘌呤核苷三磷酸（ATP）敏感性钾通道在心脏肌肉中的作用表现出显著效果，适用于治疗心血管系统疾病、心律失常或心脏收缩力下降等病症，并特别适用于预防心脏性猝死。

用途

3-溴-5-甲基吡唑主要用于制备环丁二醇。

制备方法

1. 合成3-羟基-1H-吡唑-5-乙酸乙酯

   将丁炔二酸二乙酯溶解于乙醚中，并冷却至-10℃，滴加40%水合肼溶液。体系进行放热反应，保持温度低于0℃，滴加完毕后降温至-5℃反应30分钟。有大量白色固体析出，抽滤并用少量乙醚洗涤滤渣，低压快速旋干得到中间体。将上述中间体置于单口反应瓶中，放入预热的油浴锅中升温至100℃，反应30分钟后薄层色谱检测反应进度，待原料药反应结束后真空旋干，得产品3-羟基-1H-吡唑-5-乙酸乙酯。

2. 合成3-溴-1H-吡唑-5-乙酸乙酯

   将3-羟基-1H-吡唑-5-乙酸乙酯溶解于乙腈中，加入三溴氧磷，升温回流15小时。薄层色谱检测反应进度，待原料药反应结束后将反应液冷却至室温，并缓慢倒入预先冷却好的饱和碳酸钠水溶液中。抽滤滤液，用乙酸乙酯萃取多次，合并有机层后，有机层经无水硫酸钠干燥并减压浓缩得无色至微黄色油状物。冰箱放置后得到固体3-溴-1H-吡唑-5-乙酸酯。

3. 合成3-溴-1H-吡唑-5-乙酸

   在单口反应瓶中加入乙醇，将3-溴-1H-吡唑-5-乙酸乙酯溶解于其中，再加入10%的氢氧化钠水溶液。室温搅拌反应2小时后薄层色谱检测反应进度，待原料药反应结束后减压浓缩乙醇溶液，含水浓缩物用乙酸乙酯萃取多次合并有机层，水相用稀盐酸调节pH值为9，并加入乙酸乙酯进行多次萃取。合并有机层并经无水硫酸钠干燥，最终有机相减压浓缩得到白色固体即3-溴-1H-吡唑-5-乙酸。

4. 合成3-溴-5-甲基-1H-吡唑

   通过脱羧反应制备3-溴-5-甲基-1H-吡唑。将3-溴-1H-吡唑-5-乙酸在加热和碱性条件下与固体NaOH作用发生脱羧反应，生成目标产物3-溴-5-甲基-1H-吡唑。此过程包括加热、碱性条件以及两者共存的条件，脱羧反应是羧酸失去羧基并放出二氧化碳的过程。

反应信息

• 作为反应物：
  描述：

  3-溴-5-甲基-1H-吡唑 在 盐酸 、 potassium permanganate 作用下， 反应 3.0h， 生成 5-溴-1H-吡唑-3-羧酸
  参考文献：
  名称：

  通过用取代的氰基苯基取代氯吡啶基部分提高氯虫苯甲酰胺的杀虫活性

  摘要：

  昆虫兰尼碱受体 (RyRs) 是邻氨基苯二胺杀虫剂的分子靶标。在本研究中，以小菜蛾RyRs为受体，氯虫苯甲酰胺为配体，通过活性片段组装和计算机辅助设计，合理设计了一系列含有氰基苯基吡唑部分的邻氨基苯甲酸二酰胺。大多数标题化合物对Mythimna separate、P. xylostella和Spodoptera frugiperda显示出良好的毒性。化合物CN06、CN11和CN16对应的 LC 50值分别为 0.15、0.29 和 0.52 mg·L –1，对M. separate显示出与氯虫苯甲酰胺 (0.13 mg·L –1 ) 相当的活性。令人惊讶的是，CN06、CN11和CN16对小菜蛾的相应 LC 50值分别为 1.6 × 10 –5、3.0 × 10 –5和 2.8 × 10 –5 mg·L –1至少是小菜蛾的 5 倍比氯虫苯甲酰胺（1.5 × 10 –4 mg·L –1）更有效。在S

  DOI：

  10.1021/acs.jafc.2c03133
• 作为产物：
  描述：

  3-氨基-5-甲基吡唑 在 氢溴酸 、 copper(I) bromide 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 3.0h， 生成 3-溴-5-甲基-1H-吡唑
  参考文献：
  名称：

  通过用取代的氰基苯基取代氯吡啶基部分提高氯虫苯甲酰胺的杀虫活性

  摘要：

  昆虫兰尼碱受体 (RyRs) 是邻氨基苯二胺杀虫剂的分子靶标。在本研究中，以小菜蛾RyRs为受体，氯虫苯甲酰胺为配体，通过活性片段组装和计算机辅助设计，合理设计了一系列含有氰基苯基吡唑部分的邻氨基苯甲酸二酰胺。大多数标题化合物对Mythimna separate、P. xylostella和Spodoptera frugiperda显示出良好的毒性。化合物CN06、CN11和CN16对应的 LC 50值分别为 0.15、0.29 和 0.52 mg·L –1，对M. separate显示出与氯虫苯甲酰胺 (0.13 mg·L –1 ) 相当的活性。令人惊讶的是，CN06、CN11和CN16对小菜蛾的相应 LC 50值分别为 1.6 × 10 –5、3.0 × 10 –5和 2.8 × 10 –5 mg·L –1至少是小菜蛾的 5 倍比氯虫苯甲酰胺（1.5 × 10 –4 mg·L –1）更有效。在S

  DOI：

  10.1021/acs.jafc.2c03133

文献信息

• NAPHTHYRIDINES AS INHIBITORS OF HPK1
  申请人：Genentech, Inc.

  公开号：US20180282328A1

  公开（公告）日：2018-10-04

  Naphthyridine compounds and their use as inhibitors of HPK1 are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the naphthyridine compounds.

  萘啶化合物及其作为HPK1抑制剂的用途被描述。这些化合物在治疗HPK1依赖性疾病和增强免疫反应方面很有用。还描述了抑制HPK1的方法、治疗HPK1依赖性疾病的方法、增强免疫反应的方法以及制备萘啶化合物的方法。
• [EN] THERAPEUTIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS THÉRAPEUTIQUES ET LEURS UTILISATIONS
  申请人：GENENTECH INC

  公开号：WO2016055028A1

  公开（公告）日：2016-04-14

  The present invention relates to compounds of formula (I): and to salts thereof, wherein A has any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.

  本发明涉及式(I)的化合物及其盐，其中A具有规范中定义的任何值，以及其组合物和用途。这些化合物可用作CBP和/或EP300的抑制剂。还包括包含式(I)的化合物或其药学上可接受的盐的药物组合物，以及在治疗各种CBP和/或EP300介导的疾病中使用这些化合物和盐的方法。
• TRICYCLIC FUSED THIOPHENE DERIVATIVES AS JAK INHIBITORS
  申请人：Incyte Corporation

  公开号：US20140121198A1

  公开（公告）日：2014-05-01

  The present invention provides tricyclic fused thiophene derivatives, as well as their compositions and methods of use, that modulate the activity of Janus kinase (JAK) and are useful in the treatment of diseases related to the activity of JAK including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.

  本发明提供了三环融合噻吩衍生物，以及它们的组合物和使用方法，这些衍生物调节Janus激酶（JAK）的活性，并且在治疗与JAK活性相关的疾病方面具有用处，例如炎症性疾病、自身免疫性疾病、癌症和其他疾病。
• Modulators of STING (Stimulator of Interferon Genes)
  申请人：PFIZER INC.

  公开号：US20210087180A1

  公开（公告）日：2021-03-25

  Compounds of the general formula (I): or a pharmaceutically acceptable salt thereof, processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.

  通式（I）的化合物： 或其药用可接受盐，制备这些化合物的方法，含有这些化合物的组合物，以及这些化合物的用途。
• ISOQUINOLINES AS INHIBITORS OF HPK1
  申请人：Genentech, Inc.

  公开号：US20180282282A1

  公开（公告）日：2018-10-04

  Isoquinoline compounds and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibitng HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the isoquinoline compounds.

  描述了异喹啉化合物及其作为HPK1（造血激酶1）抑制剂的用途。这些化合物在治疗依赖于HPK1的疾病和增强免疫应答方面非常有用。还描述了抑制HPK1的方法、治疗依赖于HPK1的疾病的方法、增强免疫应答的方法，以及制备异喹啉化合物的方法。