2-甲氧基-5-氟吡啶 | 51173-04-7

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-甲氧基-5-氟吡啶
• 中文别名: 3-甲氧基-5-氟吡啶；5-氟-2-甲氧基吡啶
• 英文名称: 5-fluoro-2-methoxypyridine
• 英文别名: 2-Methoxy-5-fluorpyridin
• CAS: 51173-04-7
• 化学式: C₆H₆FNO
• mdl: MFCD03095252
• 分子量: 127.118
• InChiKey: GYGABXVZIHADCT-UHFFFAOYSA-N

物化性质

• 沸点：
  144.8±20.0 °C(Predicted)
• 密度：
  1.146±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险等级：
  3
• 危险品标志：
  Xi,T
• 海关编码：
  2933399090
• 包装等级：
  III
• 危险类别：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险品运输编号：
  1993
• 危险性描述：
  H225,H315,H319,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: 5-Fluoro-2-methoxypyridine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H226: Flammable liquid and vapour
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

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Section 3. Composition/information on ingredients.
Ingredient name: 5-Fluoro-2-methoxypyridine
CAS number: 51173-04-7

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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.
Storage: Store in closed vessels.

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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
No data
Boiling point:
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C6H6FNO
Molecular weight: 127.1

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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.

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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
UN Number: UN1993 Class: 3 Packing group: III
Proper shipping name: FLAMMABLE LIQUIDS, N.O.S. (5-Fluoro-2-methoxypyridine)

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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-甲氧基-5-氟吡啶可用于制备2-甲氧基-3-溴-5-氟吡啶，是重要的医药中间体，为第二代TRK抑制剂LOXO-195的重要片段。当前国内外针对该靶点的新药研发正处于快速发展阶段，未来对该中间体的需求量将持续增加。

制备方法

将2-氯-5-硝基吡啶加入反应瓶中，加入5倍体积的甲醇，搅拌下分批加入2.0摩尔当量的氢化钠。加完后升温至60℃保温搅拌反应3小时，通过TLC检测确认2-氯-5-硝基吡啶已消失。随后降温、搅拌抽滤，并于50℃鼓风干燥烘干，得到类白色固体中间体1，摩尔收率为87%。

将中间体1加入到新的反应瓶中，再次加入5倍体积的甲醇并加入5%质量比的钯碳。进行氮气置换3次后通入氢气，升温至60℃保温搅拌反应4小时，通过TLC检测确认中间体1已消失。搅拌降温、抽滤，旋干滤液得到浅黄色固体中间体2，并于50℃鼓风干燥烘干，摩尔收率为81%。

将中间体2加入到另一个反应瓶中，加入5倍体积的质量分数为18%的盐酸。降温至0℃后加入1.5摩尔当量的硝酸钠，滴加完毕保温反应1小时。再升至室温搅拌反应2小时，并于其中加入1.5摩尔当量的四氟硼酸，升温至40℃搅拌反应2小时。通过TLC检测确认中间体2已消失后，进行乙酸乙酯萃取、有机相干燥处理并旋干滤液得到中间体3油状物，在50℃鼓风干燥烘干后，摩尔收率为61%。

反应信息

• 作为反应物：
  描述：

  2-甲氧基-5-氟吡啶 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以83%的产率得到2-甲氧基-3-溴-5-氟吡啶
  参考文献：
  名称：

  一种2-甲氧基-3-溴-5-氟吡啶的合成工艺

  摘要：

  本发明公开了一种2‑甲氧基‑3‑溴‑5‑氟吡啶的合成工艺，包括如下步骤：将2‑甲氧基‑5‑氨基吡啶溶于酸，加入亚硝酸或亚硝酸盐制得重氮化中间态，再与氟化试剂反应获得2‑甲氧基‑5‑氟吡啶；将2‑甲氧基‑5‑氟吡啶与溴代试剂进行溴代反应，获得2‑甲氧基‑3‑溴‑5‑氟吡啶。本发明提供的合成工艺原料廉价易得、反应条件温和、高收率、易于工业化生产等优点。

  公开号：

  CN111777549A
• 作为产物：
  描述：

  5-氨基-2-甲氧基吡啶 在 盐酸 、 sodium nitrite 、 tetrafluoroboric acid 作用下， 以 水 为溶剂， 反应 5.0h， 以61%的产率得到2-甲氧基-5-氟吡啶
  参考文献：
  名称：

  一种2-甲氧基-3-溴-5-氟吡啶的合成工艺

  摘要：

  本发明公开了一种2‑甲氧基‑3‑溴‑5‑氟吡啶的合成工艺，包括如下步骤：将2‑甲氧基‑5‑氨基吡啶溶于酸，加入亚硝酸或亚硝酸盐制得重氮化中间态，再与氟化试剂反应获得2‑甲氧基‑5‑氟吡啶；将2‑甲氧基‑5‑氟吡啶与溴代试剂进行溴代反应，获得2‑甲氧基‑3‑溴‑5‑氟吡啶。本发明提供的合成工艺原料廉价易得、反应条件温和、高收率、易于工业化生产等优点。

  公开号：

  CN111777549A

文献信息

• Crystal form of orexin receptor antagonist compound, and preparation method and application thereof
  申请人：Shanghai Haiyan Pharmaceutical Technology Co., Ltd.

  公开号：US10668066B2

  公开（公告）日：2020-06-02

  Disclosed are a preparation method of an orexin receptor antagonist compound 5-3, Crystalline forms I-IV of an orexin receptor antagonist compound 5-3 are provided. Also provided are processes of the preparing the orexin receptor antagonist compound 5-3 and its crystalline forms, as well as methods of using the crystalline forms I-IV for treating an orexin-related disease.

  揭示了一种促觉醒素受体拮抗剂化合物5-3的制备方法，提供了促觉醒素受体拮抗剂化合物5-3的I-IV晶型。还提供了制备促觉醒素受体拮抗剂化合物5-3及其晶型的方法，以及利用I-IV晶型治疗促觉醒素相关疾病的方法。
• Nucleophilic C–H Etherification of Heteroarenes Enabled by Base-Catalyzed Halogen Transfer
  作者：Thomas R. Puleo、Danielle R. Klaus、Jeffrey S. Bandar

  DOI：10.1021/jacs.1c06481

  日期：2021.8.18

  for the direct C–H etherification of N-heteroarenes. Potassium tert-butoxide catalyzes halogen transfer from 2-halothiophenes to N-heteroarenes to form N-heteroaryl halide intermediates that undergo tandem base-promoted alcohol substitution. Thus, the simple inclusion of inexpensive 2-halothiophenes enables regioselective oxidative coupling of alcohols with 1,3-azoles, pyridines, diazines, and polyazines

  我们报告了N-杂芳烃直接 C-H 醚化的一般方案。叔丁醇钾催化卤素从 2-卤代噻吩转移到N-杂芳烃以形成N-杂芳基卤化物中间体，该中间体经历串联碱促进的醇取代。因此，简单地包含廉价的 2-卤代噻吩能够在碱性反应条件下实现醇与 1,3-唑、吡啶、二嗪和多嗪的区域选择性氧化偶联。
• Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
  申请人：——

  公开号：US20040110785A1

  公开（公告）日：2004-06-10

  This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.

  这项发明提供了具有药物和生物影响特性的化合物，它们的药物组合物和使用方法。具体而言，该发明涉及吡啶并咪唑酮乙酰基哌嗪衍生物。这些化合物具有独特的抗病毒活性，无论是单独使用还是与其他抗病毒药物、抗感染剂、免疫调节剂或HIV进入抑制剂结合使用。更具体地，本发明涉及治疗HIV和艾滋病。
• 8-AZABICYCLO[3.2.1]OCTANE-8-CARBOXAMIDE DERIVATIVE
  申请人：Horiuchi Yoshihiro

  公开号：US20120225876A1

  公开（公告）日：2012-09-06

  Disclosed is a compound represented by formula (1) or a pharmacologically acceptable salt thereof (In the formula, A represents a group that is represented by formula (A-1); R 1a and R 1b may be the same or different and each independently represents a C 1-6 alkyl group which may be substituted by one to three halogen atoms; m and n each independently represents an integer of 0-5; X 1 represents a hydroxyl group or an aminocarbonyl group; Z 1 represents a single bond or the like; and R 2 represents an optionally substituted C 1-6 alkyl group, an optionally substituted C 6-10 aryl group or the like.)

  公开了一种由公式(1)表示的化合物或其药理可接受的盐(在公式中，A代表由公式(A-1)表示的基团；R1a和R1b可以相同或不同，每个独立地表示一个可以由一个到三个卤素原子取代的C1-6烷基；m和n各自独立地表示0-5之间的整数；X1代表羟基或氨基甲酰基；Z1代表单键等；R2代表一个可选地取代的C1-6烷基，一个可选地取代的C6-10芳基等)。
• COMPOUNDS USEFUL AGAINST KINETOPLASTIDEAE PARASITES
  申请人：Davioud-Charvet Elisabeth

  公开号：US20120214996A1

  公开（公告）日：2012-08-23

  Dibenzylidene and heterobenzylideneacetone derivatives, related 4-piperidones, related 4-thiopyranones and the corresponding sulfinyl- and sulfonyl-analogues for their use for prophylaxis or treatment of trypanosomiasis and leishmaniasis.

  二苄基亚烷和杂二苄基亚烷乙酮衍生物，相关的4-哌啶酮，相关的4-噻opyranones以及相应的亚磺酰基和磺酰基类似物，用于预防或治疗锥虫病和利什曼病。