2-氯-4-羟基-5-氟嘧啶 | 155-12-4

• 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: 2-氯-4-羟基-5-氟嘧啶
• 中文别名: 2-氯-5-氟-4-羟基嘧啶
• 英文名称: 2-chloro-5-fluoropyrimidin-4(3H)-one
• 英文别名: 2-chloro-5-fluoro-1H-pyrimidin-6-one
• CAS: 155-12-4
• 化学式: C₄H₂ClFN₂O
• mdl: MFCD01346689
• 分子量: 148.524
• InChiKey: FHTLMXYURUPWJB-UHFFFAOYSA-N

物化性质

• 熔点：
  176-177 °C(Solv: ethanol (64-17-5))
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  9
• 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：
  41.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,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: 2-Chloro-5-fluoropyrimidin-4-one
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: 2-Chloro-5-fluoropyrimidin-4-one
CAS number: 155-12-4

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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: C4H2ClFN2O
Molecular weight: 148.5

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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 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

反应信息

• 作为反应物：
  描述：

  2-氯-4-羟基-5-氟嘧啶 以 水 、 正丁醇 为溶剂， 以91.9%的产率得到2-butoxy-5-fluoropyrimidine-4(3H)-one
  参考文献：
  名称：

  5-Fluoropyrimidin-4-one compositions

  摘要：

  由以下公式表示的5-氟嘧啶-4-酮衍生物，其中R是直链或支链烷基，碳原子数为4至18，直链或支链烯基，碳原子数为2至18，氧化烷基，碳原子数为3至10，芳基或芳基烷基；制备该衍生物的方法；包含该衍生物作为有效成分和辅料的抗肿瘤组合物。

  公开号：

  US04080455A1
• 作为产物：
  描述：

  5-氟脲嘧啶 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 反应 2.0h， 以64%的产率得到2-氯-4-羟基-5-氟嘧啶
  参考文献：
  名称：

  用于功能分子二次扩增和释放的 DNA 电路和模板化反应的偶联

  摘要：

  基于 DNA 的电路支持逻辑门控操作和放大，但仅限于核酸输出。模板化反应能够将核酸线索翻译成不同的小分子输出，但其扩增受到更多限制。在此，我们展示了 DNA 回路与模板化反应的耦合，以响应核酸输入，在小分子的输出中实现高水平的扩增。我们证明 DNA 电路与模板反应的耦合允许检测分析物的 fM 浓度，并且可以响应细胞毒性药物的释放。

  DOI：

  10.1021/jacs.9b05688
• 作为试剂：
  描述：

  sodium hydroxide 、 2,4-二氯-5-氟嘧啶 、 盐酸 在 氯仿 、 magnesium sulfate 、 CHCl3 hexanes 、 2-氯-4-羟基-5-氟嘧啶 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 2-氯-4-羟基-5-氟嘧啶
  参考文献：
  名称：

  POLYMORPHS OF TARTRATE SALT OF 2-[2-(3-(R)-AMINO-PIPERIDIN-1-YL)-5-FLUORO-6-OXO-6H-PYRIMIDIN-1-YLMETHYL]-BENZONITRILE AND METHODS OF USE THEREFOR

  摘要：

  本发明涉及包含化合物I的组合物，其中化合物I以一种或多种多形态形式存在。本发明还提供了包含化合物I的一种或多种多形态形式的组合物的工具包和制造品，以及使用这些组合物治疗各种疾病的方法。

  公开号：

  US20070066636A1

文献信息

• [EN] BI-ARYL DIHYDROOROTATE DEHYDROGENASE INHIBITORS<br/>[FR] INHIBITEURS DE LA DIHYDROOROTATE DÉSHYDROGÉNASE BI-ARYLE
  申请人：JANSSEN BIOTECH INC

  公开号：WO2021070132A1

  公开（公告）日：2021-04-15

  Disclosed are compounds, compositions and methods for treating diseases, disorders, or medical conditions that are affected by the modulation of DHODH. Such compounds are represented by Formula I as follows: Formula I wherein R1, R2, R3, and Q are defined herein.

  披露了用于治疗受DHODH调制影响的疾病、失调或医疗条件的化合物、组合物和方法。这些化合物由以下式I表示：式I其中R1、R2、R3和Q在此定义。
• Novel 5-Fluorouracil Derivatives: Synthesis and Cytotoxic Activity of 2-Butoxy-4-Substituted 5-Fluoropyrimidines
  作者：Jian Sun、Shi-Jie Zhang、Hai-Bo Li、Wei Zhou、Wei-Xiao Hu、Shang Shan

  DOI：10.5012/bkcs.2013.34.5.1349

  日期：2013.5.20

  Twenty two new 5-fluorouracil (5-FU) derivatives, 2-butoxy-4-substituted 5-fluoropyrimidines, were synthesized and characterized by IR, 1 H NMR, MS, HRMS. All compounds were preliminarily evaluated by MTT assay on human liver BEL-7402 cancer cell line in vitro. Ten compounds were selected to test their cytotoxic activity against A549, HL-60 and MCF-7 cancer cell lines in vitro. These compounds were

  合成了 22 种新的 5-氟尿嘧啶 (5-FU) 衍生物，即 2-丁氧基-4-取代的 5-氟嘧啶，并通过 IR、1 H NMR、MS、HRMS 对其进行了表征。所有化合物均通过MTT法在体外对人肝BEL-7402癌细胞系进行初步评价。选择了十种化合物以在体外测试它们对 A549、HL-60 和 MCF-7 癌细胞系的细胞毒活性。这些化合物比其他细胞系对BEL-7402更敏感，特别是化合物6b、6d-f、6p、6s-u的细胞毒活性在亚微摩尔级。2-butoxy-4-chloro-5fluoropyrimidine (5) 显示对 A549、HL-60 和 MCF-7 的最高细胞毒性效力，IC50 值分别为 0.10、1.66 和 0.59 µM。化合物 6d 和 6e 对 MCF-7 有效，IC50 为 9.73 µM 和 HL-60，IC50 分别为 8.83 µM。
• Studies on antitumor agents. V. Syntheses and antitumor activities of 5-fluorouracil derivatives.
  作者：JUNICHI YAMASHITA、ICHIRO YAMAWAKI、SHUICHI UEDA、MITSUGI YASUMOTO、NORIO UNEMI、SADAO HASHIMOTO

  DOI：10.1248/cpb.30.4258

  日期：——

  Six types of 5-fluorouracil (5-FU) derivatives were synthesized ; namely, 2, 4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1, 3-disubstituted, 1-substituted and 3-substituted compounds. After oral administration of these compounds to rats, the blood levels of 5-FU were determined. Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined. The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4 (1H)-pyrimidone (11) and 2-benzyloxy-5-fluoro-4 (1H)-pyrimidone (19), were as effective as Thf-FU. The activities of 2, 4-di-O-substituted derivatives, 2, 4-dibutoxy-5-fluoropyrimidine (1) and 2, 4-dibenzyloxy-5-fluoropyrimidine (6), against Ehrlich carcinoma and against sarcoma 180, respectively, were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil (49) and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil (50), were found to be as effective as Thf-FU.

  合成了六类氟尿嘧啶（5-FU）衍生物，即2,4-二-O-取代、2-O-取代、4-O-取代、1,3-二取代、1-取代和3-取代的化合物。在大鼠口服这些化合物后，测定了5-FU的血药浓度。在O-取代衍生物中，4-O-取代衍生物最容易被激活为5-FU，其次是2-O-取代衍生物。在N-取代衍生物中，酰基和磺酰基衍生物显示出最高的5-FU释放能力，1-烷氧甲基取代衍生物的释放能力较低。N-烷基取代衍生物未被激活为5-FU。选择了几种在血中5-FU水平高于1-(四氢-2-呋喃基)-5-氟尿嘧啶（Thf-FU）的化合物，以及一些相关化合物，并对其抗肿瘤活性进行了检测。2-O-取代衍生物，2-丁氧基-5-氟-4(1H)-嘧啶酮（11）和2-苄氧基-5-氟-4(1H)-嘧啶酮（19），与Thf-FU一样有效。2,4-二-O-取代衍生物，2,4-二丁氧基-5-氟嘧啶（1）和2,4-二苄氧基-5-氟嘧啶（6），对艾氏癌和肉瘤180的活性与Thf-FU相同。1-取代衍生物，1-乙氧甲基-5-氟尿嘧啶（49）和1-(1-乙氧基-1-苯甲基)-5-氟尿嘧啶（50），发现与Thf-FU一样有效。
• Design and Synthesis of Pyrimidinone and Pyrimidinedione Inhibitors of Dipeptidyl Peptidase IV
  作者：Zhiyuan Zhang、Michael B. Wallace、Jun Feng、Jeffrey A. Stafford、Robert J. Skene、Lihong Shi、Bumsup Lee、Kathleen Aertgeerts、Andy Jennings、Rongda Xu、Daniel B. Kassel、Stephen W. Kaldor、Marc Navre、David R. Webb、Stephen L. Gwaltney

  DOI：10.1021/jm101016w

  日期：2011.1.27

  The discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4) inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral dose, these potent, selective, and noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and lowering of blood glucose in animal models of diabetes. Compounds 13a, 27b, and 27j were selected for development.

  描述了两类杂环二肽基肽酶IV（DPP-4）抑制剂嘧啶酮和嘧啶二酮的发现。单次口服剂量后，这些有效的，选择性的和非共价的抑制剂可在糖尿病动物模型中持续降低血浆DPP-4活性并降低血糖。选择化合物13a，27b和27j进行开发。
• 5-fluoro-uracil immunoassay
  申请人：Salamone Salvatore J.

  公开号：US09551724B2

  公开（公告）日：2017-01-24

  Novel conjugates of 5-fluoro-uracil and novel 5-fluoro-uracil immunogens and monoclonal antibodies generated by these immunogens which are useful in immunoassays for the quantification and monitoring of 5-fluoro-uracil in biological fluids.

  新型5-氟尿嘧啶的共轭物和新型5-氟尿嘧啶免疫原以及由这些免疫原产生的单克隆抗体，可用于免疫测定中定量和监测生物体液中的5-氟尿嘧啶。