2-溴-6-氟吡啶 | 144100-07-2

• 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: 2-溴-6-氟吡啶
• 中文别名: 2-氟-6-溴吡啶
• 英文名称: 2-bromo-6-fluoropyridine
• 英文别名: 2-fluoro-6-bromopyridine；6-bromo-2-fluoropyridine
• CAS: 144100-07-2
• 化学式: C₅H₃BrFN
• 分子量: 175.988
• InChiKey: ZIDIKYIZXMYHAW-UHFFFAOYSA-N

物化性质

• 熔点：
  30-32°C
• 沸点：
  162-164°C
• 密度：
  1.707±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  6.1
• 危险品标志：
  Xi
• 安全说明：
  S16,S26,S36,S36/37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2933399090
• WGK Germany：
  1
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温条件下。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2-Bromo-6-fluoropyridine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H302: Harmful if swallowed
H315: Causes skin irritation
H318: Causes serious eye damage
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P280: Wear protective gloves/protective clothing/eye protection/face protection
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: 2-Bromo-6-fluoropyridine
CAS number: 144100-07-2

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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.
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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H3BrFN
Molecular weight: 176.0

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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 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
UN Number: UN2811 Class: 6.1 Packing group: III
Proper shipping name: TOXIC SOLIDS, ORGANIC, N.O.S. (2-Bromo-6-fluoropyridine)

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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-溴-6-氟吡啶主要用于有机合成，在医药工业中用于合成心脏病类药物双异丙吡胺（磷酸丙吡胺）等。丙吡胺药物广泛应用于维持房颤和房扑的窦性节律，或预防室性心动过速和心室纤颤的复发，也可用于治疗房性早搏、阵发性房性心动过速及室性早搏。

合成方法

以2-溴吡啶为原料，经过混酸硝化、硝基还原、重氮化以及席曼反应引入氟原子等步骤合成2-溴-6-氟吡啶。该路线简化了实验操作，避免了文献报道中在原料2-氯-5-氨基吡啶的合成、中间产物的分离和最终产品的纯化过程中出现的收率低及纯度不高的问题。

各步反应较为适宜的工艺条件（反应温度、反应时间、摩尔收率）分别为：

• 硝化反应：45℃，2小时，41%；
• 硝基还原：回流，1小时，90%；
• 重氮化：-5℃至0℃，2小时，81.4%；
• 席曼反应：130℃，0.5小时。两步反应总收率为51.6%。

其合成反应式如下图：

反应信息

• 作为反应物：
  描述：

  2-溴-6-氟吡啶 在 硼烷四氢呋喃络合物 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 6-溴-2-氟-3-吡啶甲醇
  参考文献：
  名称：

  [EN] ARYL, HETEROARY, AND HETEROCYCLIC PHARMACEUTICAL COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
  [FR] COMPOSÉS PHARMACEUTIQUES ARYLE, HÉTÉROARYLES ET HÉTÉROCYCLIQUES POUR LE TRAITEMENT DE TROUBLES MÉDICAUX

  摘要：

  提供了抑制补体因子D的抑制剂、药物组合物及其用途，以及它们的制备方法。所提供的化合物包括公式I、公式II、公式III、公式IV和公式V，或其药学上可接受的盐、前药、同位素类似物、N-氧化物或其分离异构体，可选地在药学上可接受的组合物中。本文描述的抑制剂针对因子D并抑制或调节补体级联反应。

  公开号：

  WO2018160889A1
• 作为产物：
  描述：

  2,6-二溴吡啶 在 potassium fluoride 作用下， 生成 2-溴-6-氟吡啶
  参考文献：
  名称：

  2-Fluoropyridines, their preparation and their use in liquid crystal

  摘要：

  2-氟吡啶，其制备方法及其在铁电液晶混合物中的应用。式（I）的2-氟吡啶，其中符号具有以下含义：R1，R2，相互独立地，例如为H或直链或支链烷基；A1，A2，A3，A4，相同或不同，例如为1-苯基，吡啶-2,5-二基或反-1,4-环己基；M1，M2，M3，M4，相同或不同，例如为--O--或--CO--O--；R3，R4，R6，R7，相互独立地，例如为H或直链或支链烷基；M5，例如为--O--CO--或单键；k，l，m，n，o，p，q，r为零或一，但要求k+m+p+r的总和小于4且大于零，可优选地用作铁电液晶混合物中的组分。

  公开号：

  US05630962A1

文献信息

• NOVEL GPR119 AGONIST COMPOUNDS
  申请人：Mankind Pharma Ltd.

  公开号：US20170291894A1

  公开（公告）日：2017-10-12

  The present invention relates to novel compounds of formula (I), process for preparation of the same and composition comprising these compounds.

  本发明涉及公式（I）的新化合物，其制备方法以及包含这些化合物的组合物。
• [EN] 2,3-DISUBSTITUTED 1 -ACYL-4-AMINO-1,2,3,4-TETRAHYDROQUINOLINE DERIVATIVES AND THEIR USE AS BROMODOMAIN INHIBITORS<br/>[FR] DÉRIVÉS 2,3-DISUBSTITUÉS DE 1-ACYL-4-AMINO-1,2,3,4-TÉTRAHYDROQUINOLÉINE ET LEUR UTILISATION COMME INHIBITEURS DE BROMODOMAINES
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2014140076A1

  公开（公告）日：2014-09-18

  The present invention relates to novel compounds of formula (I), wherein R1 is C1-4alkyl; R2 is C1-4alkyl, C3-7cycloalkyl, -CH2CF3, -CH2OCH3 or heterocyclyl; R3 is C1-4alkyl, -CH2F, -CH2OH or -CH2O(O)CH3; R4 when present is as defined in claim 1; R5 when present is H, halo, hydroxy or C1-6alkoxy; A is -NH-, -O-, -S-, -SO-, -SO2-, -N(C1-4alkyl)- or -NC(O)(CH3)-; V is phenyl, heteroaromatic or pyridone any of which may be optionally substituted by 1, 2 or 3 substituents; W is CH or N; X is C or N; Y is C or N; and Z is CH or N; subject to the proviso that no more than 2 of W, X, Y and Z are N, pharmaceutical compositions containing such compounds and to their use as bromodomain inhibitors.

  本发明涉及式(I)的新化合物，其中R1为C1-4烷基；R2为C1-4烷基、C3-7环烷基、-CH2CF3、-CH2OCH3或杂环烷基；R3为C1-4烷基、-CH2F、-CH2OH或-CH2O(O)CH3；R4存在时如权利要求1所定义；R5存在时为H、卤素、羟基或C1-6烷氧基；A为-NH-、-O-、-S-、-SO-、-SO2-、-N(C1-4烷基)-或-NC(O)(CH3)-；V为苯基、杂芳基或吡啶酮，其中任何一个可以选择性地被1、2或3个取代基取代；W为CH或N；X为C或N；Y为C或N；Z为CH或N；但W、X、Y和Z中不超过2个为N，含有这种化合物的药物组合物以及它们作为溴结构域抑制剂的用途。
• Anthranilamide (aam)-substituted diboron: palladium-catalyzed selective B(aam) transfer
  作者：Shintaro Kamio、Ikuo Kageyuki、Itaru Osaka、Sayaka Hatano、Manabu Abe、Hiroto Yoshida

  DOI：10.1039/c8cc05645e

  日期：——

  An unsymmetrical diboron bearing an anthranilamide (aam) substituent was synthesized and was converted into arylboranes via Pd-catalyzed selective B(aam) transfer.

  一种含有蒽酰胺（aam）取代基的非对称二硼烷被合成，并通过Pd催化选择性B(aam)转移转化为芳基硼烷。
• [EN] PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION<br/>[FR] DÉRIVÉS D'ACIDE PYRIDIN-3-YLE ACÉTIQUE UTILISÉS EN TANT QU'INHIBITEURS DE LA RÉPLICATION DU VIRUS DE L'IMMUNODÉFICIENCE HUMAINE
  申请人：VIIV HEALTHCARE UK NO 5 LTD

  公开号：WO2018127800A1

  公开（公告）日：2018-07-12

  Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS. (I)

  公开了公式I的化合物，包括药用可接受的盐、包含这些化合物的药物组合物、制备这些化合物的方法，以及它们在抑制HIV整合酶和治疗HIV或艾滋病感染者中的用途。
• 苯并咪唑或氮杂苯并咪唑-6-羧酸类化合物及其应用
  申请人：广州必贝特医药股份有限公司

  公开号：CN113480534B

  公开（公告）日：2022-05-13

  本发明公开了一种苯并咪唑或氮杂苯并咪唑‑6‑羧酸类化合物及其应用，所述苯并咪唑或氮杂苯并咪唑‑6‑羧酸类化合物具有式(I)所示结构。该苯并咪唑或氮杂苯并咪唑‑6‑羧酸类化合物可以有效激活GLP‑1R下游信号通路，提高cAMP的表达，从而达到促进胰岛素分泌，治疗糖尿病及其并发症的作用，有较大的应用价值。

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