2-氯-3-溴-6-甲氧基吡啶 | 777931-67-6

• 物质功能分类: 医药中间体
• 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: 2-氯-3-溴-6-甲氧基吡啶
• 中文别名: 3-溴-2-氯-6-甲氧基吡啶
• 英文名称: 3-bromo-2-chloro-6-methoxypyridine
• CAS: 777931-67-6
• 化学式: C₆H₅BrClNO
• 分子量: 222.469
• InChiKey: OSXXSYYRNKLDHE-UHFFFAOYSA-N

物化性质

• 沸点：
  243.8±35.0 °C(Predicted)
• 密度：
  1.650±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  储存条件为2-8°C，并需保存在惰性气体中。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Bromo-2-chloro-6-methoxypyridine
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-2-chloro-6-methoxypyridine
CAS number: 777931-67-6

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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: C6H5BrClNO
Molecular weight: 222.5

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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 chloride, 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

2-氯-6-甲氧基-3-溴吡啶可作为医药合成中间体。

应用

2-氯-6-甲氧基-3-溴吡啶可用于制备2-(6-(1-乙基-4-氟-1H-吲唑-6-基)-2-甲氧基吡啶-3-基)-3-甲基丁醛。具体步骤如下：将2-氯-6-甲氧基-3-溴吡啶（2.00g，8.900mmol，当量）溶解在1,4-二恶烷（20mL）中，并加入Pd(dppf)Cl2·CH2Cl2（0.36g，0.450mmol，0.05当量）和Zn(CH3)2（17mL，17.000mmol，2.00当量）。将混合物在90℃下搅拌16小时。随后，在真空条件下浓缩混合物，并通过硅胶色谱法进行纯化，用乙酸乙酯/石油醚（2:98）洗脱，最终得到黄色油状的2-(6-(1-乙基-4-氟-1H-吲唑-6-基)-2-甲氧基吡啶-3-基)-3-甲基丁醛。

反应信息

• 作为反应物：
  描述：

  2-氯-3-溴-6-甲氧基吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 lithium chloro-isopropyl-magnesium chloride 、 camphor-10-sulfonic acid 、 sodium acetate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 44.5h， 生成 methyl 3-(dimethoxymethyl)-6-methoxypicolinate
  参考文献：
  名称：

  实用的丙烯酸酯A和B的总合成。

  摘要：

  实际的丙烯醛酸A（1）和B（2）的总合成是Shirahama和Matsumoto从有毒蘑菇中分离出的稀有天然产物，以13个步骤（总收率36％）和17个步骤（总收率6.9％）完成，分别来自2,6-二氯吡啶（8）。从通过邻位锂化或溴化的对称体8的区域选择性转化开始，提供了硝基烯烃15和16。通过镍催化的α-酮酸酯的不对称共轭加成反应，将邻位立体中心在1和2的C-3,4位置上进行立体选择性构建。吡咯烷环的构建通过一系列步骤完成，该步骤包括以下步骤：硝基还原，与酮的分子内缩合和所得酮亚胺的还原。

  DOI：

  10.1248/cpb.c16-00009
• 作为产物：
  描述：

  2,6-二氯吡啶 在 N-溴代丁二酰亚胺(NBS) 、 sodium methylate 作用下， 以 乙腈 为溶剂， 反应 48.0h， 生成 2-氯-3-溴-6-甲氧基吡啶
  参考文献：
  名称：

  实用的丙烯酸酯A和B的总合成。

  摘要：

  实际的丙烯醛酸A（1）和B（2）的总合成是Shirahama和Matsumoto从有毒蘑菇中分离出的稀有天然产物，以13个步骤（总收率36％）和17个步骤（总收率6.9％）完成，分别来自2,6-二氯吡啶（8）。从通过邻位锂化或溴化的对称体8的区域选择性转化开始，提供了硝基烯烃15和16。通过镍催化的α-酮酸酯的不对称共轭加成反应，将邻位立体中心在1和2的C-3,4位置上进行立体选择性构建。吡咯烷环的构建通过一系列步骤完成，该步骤包括以下步骤：硝基还原，与酮的分子内缩合和所得酮亚胺的还原。

  DOI：

  10.1248/cpb.c16-00009

文献信息

• PYRIDIN-2-ONE DERIVATIVES OF FORMULA (I) USEFUL AS EP3 RECEPTOR ANTAGONISTS
  申请人：Janssen Pharmaceutica NV

  公开号：US20190047959A1

  公开（公告）日：2019-02-14

  The present invention is directed to pyridin-2-one derivatives, pharmaceutical compositions containing them and their use as antagonists of the EP3 receptor, for the treatment of for example, impaired oral glucose tolerance, elevated fasting glucose, Type II Diabetes Mellitus, Syndrome X (also known as Metabolic Syndrome) and related disorders and complications thereof.

  本发明涉及吡啶-2-酮衍生物，包含它们的药物组合物以及它们作为EP3受体的拮抗剂的使用，用于治疗例如受损的口服葡萄糖耐量、空腹血糖升高、2型糖尿病、综合征X（也称为代谢综合征）及其相关疾病和并发症。
• PYRIDIN-2-ONE DERIVATIVES OF FORMULA (III) USEFUL AS EP3 RECEPTOR ANTAGONISTS
  申请人：Janssen Pharmaceutica NV

  公开号：US20190047961A1

  公开（公告）日：2019-02-14

  The present invention is directed to pyridin-2-one derivatives, pharmaceutical compositions containing them and their use as antagonists of the EP3 receptor, for the treatment of for example, impaired oral glucose tolerance, elevated fasting glucose, Type II Diabetes Mellitus, Syndrome X (also known as Metabolic Syndrome) and related disorders and complications thereof.

  本发明涉及吡啶-2-酮衍生物，包含它们的药物组合物以及它们作为EP3受体的拮抗剂的使用，用于治疗例如受损的口服葡萄糖耐量，空腹血糖升高，2型糖尿病，综合征X（也称为代谢综合征）以及与之相关的疾病和并发症。
• [EN] FUSED FURANS FOR THE TREATMENT OF HEPATITIS C<br/>[FR] FURANES FUSIONNÉS POUR LE TRAITEMENT DE L'HÉPATITE C
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014159559A1

  公开（公告）日：2014-10-02

  The disclosure provides compounds of formula I or II, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV. [

  本公开提供了公式I或II的化合物，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物对丙型肝炎病毒（HCV）具有活性，可能对治疗HCV感染者有益。
• PYRIDIN-2-ONE DERIVATIVES OF FORMULA (II) USEFUL AS EP3 RECEPTOR ANTAGONISTS
  申请人：Janssen Pharmaceutica NV

  公开号：US20190047960A1

  公开（公告）日：2019-02-14

  The present invention is directed to pyridin-2-one derivatives, pharmaceutical compositions containing them and their use as antagonists of the EP3 receptor, for the treatment of for example, impaired oral glucose tolerance, elevated fasting glucose, Type II Diabetes Mellitus, Syndrome X (also known as Metabolic Syndrome) and related disorders and complications thereof.

  本发明涉及吡啶-2-酮衍生物，包含它们的药物组合物以及它们作为EP3受体的拮抗剂的使用，用于治疗例如受损的口服葡萄糖耐量，空腹血糖升高，2型糖尿病，综合征X（也称为代谢综合征）以及与之相关的疾病和并发症。
• Synthesis and bioevaluation of N-(3,4,5-trimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amines as tubulin polymerization inhibitors with anti-angiogenic effects
  作者：Shu-Yi Hao、Zhi-Yuan Qi、Shuai Wang、Xing-Rong Wang、Shi-Wu Chen

  DOI：10.1016/j.bmc.2020.115985

  日期：2021.2

  A new series of N-(3,4,5-trimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amine derivatives as tubulin polymerization inhibitors were synthesized, and evaluated for the anti-proliferative activities. A structure–activity relationship study revealed that the free amino moiety of 1H-pyrazolo[3,4-b]pyridin-3-amine played an essential role in the anti-proliferative activities. Especially, compound 15c displayed

  合成了一系列新的N- (3,4,5-三甲氧基苯基) -1H-吡唑并[3,4- b ]吡啶-3-胺衍生物作为微管蛋白聚合抑制剂，并评价了其抗增殖活性。构效关系研究表明，1 H- pyrazolo[3,4- b ]pyridin-3-amine的游离氨基部分在抗增殖活性中起重要作用。特别是，化合物15c对 MCF-7 细胞显示出最强的抗增殖作用，IC 50值为 0.067 ± 0.003 μM，并且对正常人胚胎肺 WI-38 细胞具有高选择性，IC 50值 23.41 ± 1.53 μM。进一步的机理研究表明，15c显示出很强的抗微管蛋白聚合活性，改变了微管蛋白的形态，并在 MCF-7 细胞的 G2/M 转换时阻止了细胞周期。分子对接分析表明15c很好地占据了微管蛋白的秋水仙碱结合口袋。此外，15c显示出抗血管生成活性，可阻断迁移、侵袭和管形成，破坏新形成的管，并调节 HUVEC 细胞中的 MMP-9