4-氟靛红 | 346-34-9

• 物质功能分类: 医药中间体 - 吲哚类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 4-氟靛红
• 中文别名: 4-氟吲哚满-2,3-二酮；4-氟-2,3-吲哚二酮；4-氟-1H-吲哚-2,3-二酮
• 英文名称: 4-fluoroindoline-2,3-dione
• 英文别名: 4-fluoroisatin；4-fluoro-1H-indole-2,3-dione
• CAS: 346-34-9
• 化学式: C₈H₄FNO₂
• mdl: MFCD01175824
• 分子量: 165.124
• InChiKey: VUPIFURSDLGPMH-UHFFFAOYSA-N

物化性质

• 密度：
  1.477

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P280
• 危险性描述：
  H302,H317
• 储存条件：
  室温且干燥

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Fluoroindoline-2,3-dione
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: 4-Fluoroindoline-2,3-dione
CAS number: 346-34-9

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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: C8H4FNO2
Molecular weight: 165.1

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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
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

应用

4-氟-2,3-吲哚二酮可用作有机合成中间体和医药中间体，主要用于实验室研发过程和化工生产过程中。

制备

在配有强力搅拌器的1L反应瓶内，加入600g浓硫酸，并温热至50℃。随后，分批加入异亚硝基乙酰间氟苯胺（75g，0.46mol），同时充分搅拌，并用冷水间接冷却，控制温度在60～75℃之间。加完后，将溶液加热至80℃并保持60分钟。通过薄层色谱跟踪监测（展开剂：正己烷:乙酸乙酯 = 2:1），直至反应完全。随后，将反应混合物冷却至室温，并加入相当于反应物体积3-4倍的碎冰中搅拌0.5小时。减压过滤后，用冷水洗涤数次至中性。

接下来，将得到的滤饼溶解于250g 10%氢氧化钠溶液中直至呈碱性。经活性炭脱色处理后，再用盐酸酸化至pH3～4，析出橘红色结晶。冷却放置24小时后，抽滤并用水洗涤至中性干燥。最终得到4-氟-2,3-吲哚二酮（60.5g，0.41mol），收率为89.5%，熔点为198℃～201℃。

反应信息

• 作为反应物：
  描述：

  4-氟靛红 在 氯化亚砜 、 potassium hydroxide 作用下， 以 水 为溶剂， 反应 35.0h， 生成 dimethyl 5-fluoroquinoline-2,4-dicarboxylate
  参考文献：
  名称：

  第一种高选择性GLUT1抑制剂BAY-876的鉴定和优化。

  摘要：

  尽管众所周知的事实是，即使在正常的氧气供应条件下，促进性葡萄糖转运蛋白GLUT1仍是保证许多肿瘤实体葡萄糖消耗增加的关键因素之一（被称为Warburg效应），但仅进行了很少的努力寻找一种GLUT1选择性小分子抑制剂。由于GLUT1家族的其他转运蛋白都参与关键过程，因此此类抑制剂不应解决这些转运蛋白。针对约300万种化合物的库进行了高通量筛选，以发现具有这种具有挑战性的效能和选择性的小分子。N-（1H-吡唑-4-基）喹啉-4-羧酰胺被确定为进一步优化化合物的理想起点。经过广泛的构效关系探索后，获得了对GLUT2，GLUT3和GLUT4的选择性因子> 100的个位数纳摩尔抑制剂。最有前途的化合物BAY-876 [N4- [1-（4-氰基苄基）-5-甲基-3-（三氟甲基）-1H-吡唑-4-基] -7-氟喹啉-2,4-二甲酰胺]在体外具有良好的代谢稳定性，在体内具有较高的口服生物利用度。

  DOI：

  10.1002/cmdc.201600276
• 作为产物：
  描述：

  3-氟苯胺 在 盐酸 、 硫酸 、 盐酸羟胺 、 sodium sulfate 作用下， 反应 2.25h， 生成 4-氟靛红
  参考文献：
  名称：

  Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases

  摘要：

  Pharmacological inhibitors of glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinases have a promising potential for applications against several neurodegenerative diseases such as Alzheimer's disease. Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3. Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. This modeling approach provided some insight into the molecular basis of indirubins' action and selectivity and allowed us to forecast some improvements of this family of bis-indoles as kinase inhibitors. Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1.

  DOI：

  10.1021/jm031016d

文献信息

• Counter-Current chromatography separation of isatin derivatives using the sandmeyer methodology
  作者：Márcia R. Almeida、Gilda G. Leitão、Bárbara V. Silva、Jussara P. Barbosa、Angelo C. Pinto

  DOI：10.1590/s0103-50532010000400025

  日期：——

  method, using high-speed counter-current chromatography (HSCCC) technique, was developed for the separation of isomeric isatin derivatives, prepared following the Sandmeyer route. The biphasic solvent system composed of hexane:ethyl acetate:ethanol:water 1:0.5:0.5:1 (v/v/v/v) was used for all separations.

  开发了一种快速高效的方法，使用高速逆流色谱（HSCCC）技术分离按照Sandmeyer路线制备的同分异构的Isatin衍生物。所有分离均使用由己烷：乙酸乙酯：乙醇：水1：0.5：0.5：1（v / v / v / v）组成的双相溶剂系统。
• Novel Synthesis of 4- or 6-Substituted Indirubin Derivatives
  作者：Aiying Zhang、Mingfeng Yu、Tian Lan、Zenglu Liu、Zhenmin Mao

  DOI：10.1080/00397910903318591

  日期：2010.9.30

  A simple and convenient route for synthesis of a series of 4- or 6-substituted indirubin derivatives by oxidation and subsequent condensation of indoxyl and isatin is described. Acidic reaction conditions are crucial to the condensation of 4-substituted derivatives, whereas for the condensation of 6-substituted derivatives, both acidic and basic conditions work well.

  描述了通过氧化和随后缩合吲哚酚和靛红来合成一系列 4-或 6-取代的靛玉红衍生物的简单方便的途径。酸性反应条件对 4-取代衍生物的缩合至关重要，而对于 6-取代衍生物的缩合，酸性和碱性条件都适用。
• Utilizing Solubility Differences to Achieve Regiocontrol in the Synthesis of Substituted Quinoline-4-carboxylic Acids
  作者：Peter Lindsay-Scott、Helen Barlow

  DOI：10.1055/s-0035-1561395

  日期：——

  A practical method for the regiocontrolled synthesis of substituted quinoline-4-carboxylic acids is described. Solubility differences between the product quinoline regioisomers enable their facile separation, thus avoiding any challenging chromatographic purifications and allowing access to highly substituted quinoline compounds in three steps from commercially available anilines.

  描述了一种用于区域控制合成取代喹啉-4-羧酸的实用方法。产品喹啉区域异构体之间的溶解度差异使其易于分离，从而避免了任何具有挑战性的色谱纯化，并允许通过三个步骤从市售苯胺中获得高度取代的喹啉化合物。
• ４−フルオロイサチン誘導体の製造方法
  申请人：キヤノンファインテック株式会社

  公开号：JP2016204312A

  公开（公告）日：2016-12-08

  【課題】４−フルオロイサチンを含む、４−フルオロイサチン誘導体を、高純度かつ高収率で製造する方法を提供すること。【解決手段】下記一般式（１）に示す４−フルオロイサチン誘導体の製造プロセスにおいて、下記一般式（２）に示すトルエン誘導体を出発原料とし、該トルエン誘導体をＤＭＦジアルキルアセタールを用いて増炭した後、還元剤および酸を用いて還元することで下記一般式（３）に示すインドール誘導体を合成する工程（Ａ）、および前記インドール誘導体を酸化する工程（Ｂ）を実施したことを特徴とする４−フルオロイサチン誘導体の製造方法。【選択図】なし

  提供一种以高纯度和高收率制备含有4-氟异丙基的4-氟异丙基衍生物的方法，其中包括以下步骤：在制备4-氟异丙基衍生物的过程中，以苯衍生物作为起始原料，使用DMF二烷基缩醛对该苯衍生物进行炭增后，使用还原剂和酸将其还原为所示的吲哚衍生物（3）的合成步骤（A），并进行将所述吲哚衍生物氧化的步骤（B）。
• 一种高纯度4-氟靛红的工业制备方法
  申请人：严学文

  公开号：CN110642773A

  公开（公告）日：2020-01-03

  本发明公开了一种高纯度4‑氟靛红的工业制备方法，先由间氟苯胺与盐酸羟胺、三氯乙醛反应，缩合制得肟基乙酰苯胺，再经浓硫酸环合、水解制得4‑氟靛红与6‑氟靛红的混合物，再通过碱溶酸析法对4‑氟靛红与6‑氟靛红的混合物进行分离纯化，得到高纯度4‑氟靛红；本发明工艺简单、收率高、生产成本低，适于工业化生产。