4-氯-6-乙基-5-氟嘧啶 | 137234-74-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-氯-6-乙基-5-氟嘧啶
• 中文别名: 4-乙基-5-氟-6-氯嘧啶；4-氯-5-氟-6-乙基嘧啶；V3；6-乙基-5-氟-4-氯嘧啶
• 英文名称: 4-chloro-6-ethyl-5-fluoropyrimidine
• 英文别名: 6-chloro-4-ethyl-5-fluoropyrimidine；6-ethyl-5-fluoro-4-chloropyrimidine；4-chloro-5-fluoro-6-ethylpyrimidine
• CAS: 137234-74-3
• 化学式: C₆H₆ClFN₂
• mdl: MFCD07782087
• 分子量: 160.578
• InChiKey: LKTGVRWVTAJGMS-UHFFFAOYSA-N

物化性质

• 沸点：
  211°C
• 密度：
  1.286
• 闪点：
  81°C
• 溶解度：
  可溶于氯仿、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  8
• 安全说明：
  S22,S36/37/39,S45
• 危险类别码：
  R20/21/22
• 海关编码：
  2933599090
• 危险类别：
  8
• 危险性防范说明：
  P305+P351+P338
• 危险性描述：
  H302,H319
• 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: 4-Chloro-6-ethyl-5-fluoropyrimidine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H314: Causes severe skin burns and eye damage
H318: Causes serious eye damage
H302: Harmful if swallowed
Combustible liquid
H227:
P210: Keep away from heat/sparks/open flames/hot surfaces. No smoking
P260: Do not breathe dust/fume/gas/mist/vapours/spray
P303+P361+P353: IF ON SKIN (or hair): Remove/Take off immediately all contaminated clothing. Rinse skin with
water/shower
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P405: Store locked up

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Section 3. Composition/information on ingredients.
Ingredient name: 4-Chloro-6-ethyl-5-fluoropyrimidine
CAS number: 137234-74-3

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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
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C6H6ClFN2
Molecular weight: 160.6

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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 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: UN3267 Class: 8 Packing group: III
Proper shipping name: CORROSIVE LIQUID, BASIC, ORGANIC, N.O.S. (4-Chloro-6-ethyl-5-fluoropyrimidine)

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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：伏立康唑中间体3

反应信息

• 作为反应物：
  描述：

  4-氯-6-乙基-5-氟嘧啶 在 sodium hydrogensulfide 作用下， 以 甲醇 为溶剂， 反应 4.25h， 生成 6-ethyl-5-fluoropyrimidine-4-thiol
  参考文献：
  名称：

  [EN] PROCESS FOR THE PRODUCTION OF VORICONAZOLE
  [FR] PROCÉDÉ DE PRODUCTION DU VORICONAZOLE

  摘要：

  描述了一种制备伏立康唑的过程，其中烷基硫代嘧啶是关键中间体。烷基硫代取代基使嘧啶特别适用于金属介导的加成到酮的反应。这在制备伏立康唑的交叉偶联反应中得到了证明。

  公开号：

  WO2009024214A1
• 作为产物：
  描述：

  2-chloro-6-ethyl-5-fluoro-4-hydroxypyrimidine ammonium salt 在 5%-palladium/activated carbon 、 氢气 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 40.0~50.0 ℃ 、344.75 kPa 条件下， 反应 8.0h， 生成 4-氯-6-乙基-5-氟嘧啶
  参考文献：
  名称：

  Process Development of Voriconazole:  A Novel Broad-Spectrum Triazole Antifungal Agent

  摘要：

  In the synthesis of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (voriconazole), the relative stereochemistry is set in the addition of a 4-(1-metalloethyl)-5-fluoropyrimidine derivative to 1-(2,4-difluorophenyl)-2-(1H-1 ,2,4-triazol-1-yl)-1-ethanone, The diastereo-control of this reaction has been examined by variation of pyrimidine substitution pattern and by changes in the metalation and reaction conditions. Excellent diastereoselection (12: ii is obtained using an organozinc derivative of 6-(1-bromoethyl)-4-chloro-5-fluoropyriminidine. lifter removal cf the chlorine from the pyrimidine ring? the absolute stereochemistry of voriconazole is established via a diastereomeric salt resolution process using (1R)-10 camphorsulfonic acid. Synthetic routes to the pyrimidine partner have also been evaluated. The initial six-step development route from 5-fluorouracil has been superseded by a four-step synthesis involving fluorination of methyl 3-oxopentanoate and cyclisation with formamidine acetate.

  DOI：

  10.1021/op0000879

文献信息

• Synthesis of 3-Azabicyclo[3.2.0]heptane-Derived Building Blocks via [3+2] Cycloaddition
  作者：Anton A. Homon、Oleksandr V. Hryshchuk、Serhii Trofymchuk、Oleg Michurin、Yuliya Kuchkovska、Dmytro S. Radchenko、Oleksandr O. Grygorenko

  DOI：10.1002/ejoc.201800972

  日期：2018.11.1

  Synthesis of 3‐azabicyclo[3.2.0]heptane‐derived building blocks via [3+2]cycloaddition of cyclobutene‐1‐carboxylate and azomethine ylide is described. It is shown that the title bicyclic scaffold is a three‐dimensional template which is well‐compatible with lead‐oriented parallel synthesis.

  描述了通过环丁烯-1-羧酸酯和甲亚胺叶立德的[3 + 2]环加成反应合成3-氮杂双环[3.2.0]庚烷的结构单元。结果表明标题双环支架是一个三维模板，与基于铅的平行合成很好地兼容。
• [EN] SUBSTITUTED (PIPERIDIN-1-YL)ARYL ANALOGUES FOR MODULATING AVILACTIVITY<br/>[FR] ANALOGUES DE (PIPÉRIDIN-1-YL)ARYLE SUBSTITUÉS POUR LA MODULATION DE L'ACTIVITÉ DE L'AVIL
  申请人：UNIV VIRGINIA PATENT FOUNDATION

  公开号：WO2020223715A1

  公开（公告）日：2020-11-05

  In one aspect, the disclosure relates to compounds useful to regulate, limit, or inhibit the expression of AVIL (advillin), methods of making same, pharmaceutical compositions comprising same, and methods of treating disorders associated with AVIL dysregulation using same. In aspects, the disclosed compounds, compositions and methods are useful for treating disorders or diseases in which the regulation, limitation, or inhibition of the expression of AVIL can be clinically useful, such as, for example, the treatment of cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

  在一个方面，该披露涉及到有用于调节、限制或抑制AVIL（advillin）表达的化合物，制备方法，包含相同化合物的药物组合物，以及使用相同化合物治疗与AVIL失调相关的疾病的方法。在披露的方面，所述的化合物、组合物和方法可用于治疗调节、限制或抑制AVIL表达在临床上有用的疾病或疾病，例如癌症的治疗。本摘要旨在作为在特定领域进行搜索的扫描工具，并不意味着限制本披露。
• [EN] INDOLE AND AZAINDOLE MODULATORS OF THE ALPHA 7 NACHR<br/>[FR] MODULATEURS INDOLES ET AZAINDOLES DU NACHR-?7
  申请人：PROXIMAGEN LTD

  公开号：WO2011045353A1

  公开（公告）日：2011-04-21

  This invention relates to modulation of the α7 nicotinic acetylcholine receptor (nAChR) by a compound of formula (I) or a pharmaceutically acceptable salt thereof.

  这项发明涉及利用式(I)的化合物或其药用可接受盐对α7尼古丁乙酰胆碱受体(nAChR)进行调节。
• 一种三氮唑醇类衍生物及其制备方法和应用
  申请人：中国人民解放军第二军医大学

  公开号：CN106336383B

  公开（公告）日：2019-05-14

  本发明涉及一种三氮唑醇类衍生物及其制备方法和应用，所述的三氮唑醇类衍生物的化学结构如式I所示。本发明还提供了所述化合物的盐类、药物组合物、制备方法和用途。本发明的化合物具有较强的抗真菌活性，且具有毒性低、抗菌谱广等优点，可用于制备抗真菌药物。
• High-Throughput Experimentation and Continuous Flow Evaluation of Nucleophilic Aromatic Substitution Reactions
  作者：Zinia Jaman、David L. Logsdon、Botond Szilágyi、Tiago J. P. Sobreira、Deborah Aremu、Larisa Avramova、R. Graham Cooks、David H. Thompson

  DOI：10.1021/acscombsci.9b00212

  日期：2020.4.13

  Nucleophilic aromatic substitution (SNAr) reactions were optimized using high-throughput experimentation techniques for execution under flow conditions. A total of 3072 unique reactions were evaluated with an analysis time of ∼3.5 s per reaction using a system that combines a liquid handling robot for reaction mixture preparation with desorption electrospray ionization (DESI) mass spectrometry (MS)

  亲核芳香族取代（S N使用高通量实验技术优化Ar）反应，以在流动条件下进行。使用结合了用于处理反应混合物的液体处理机器人和用于解析的解吸电喷雾电离（DESI）质谱仪的系统，总共对3072个独特反应进行了评估，每个反应的分析时间约为3.5 s。反应在有和没有孵育的情况下以大量微量滴定仪阵列进行。内部开发的软件用于处理数据并生成结果的热图。然后，该信息用于选择在微流体反应器条件下连续合成的最有希望的条件。我们的结果表明，这种HTE方法为缩小优化S N所需的条件范围提供了强有力的指导Ar反应。