2,4,6-三氯-5-嘧啶甲醛 | 50270-27-4

• 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: 2,4,6-三氯-5-嘧啶甲醛
• 中文别名: 2,3-二氢苯并呋喃-6-羧酸；2,4,6-三氯-5-醛基嘧啶；2,4,6-三氯嘧啶-5-甲醛
• 英文名称: 2,4,6-trichloropyrimidine-5-carbaldehyde
• 英文别名: 2,4,6-trichloropyrimidine-5-carboxaldehyde；2,4,6-trichloro-5-formylpyrimidine；2,4,6-trichloro-5-pyrimidinecarboxaldehyde；2,4,6-trichloropyrimidin-5-carbaldehyde
• CAS: 50270-27-4
• 化学式: C₅HCl₃N₂O
• mdl: MFCD02257700
• 分子量: 211.435
• InChiKey: KVJIRFGNHAAUNQ-UHFFFAOYSA-N

物化性质

• 熔点：
  131-132℃
• 沸点：
  278.6±35.0 °C(Predicted)
• 密度：
  1.713±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  6.1
• 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：
  存放于惰性气体中，避免与空气接触。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2,4,6-Trichloropyrimidine-5-carbaldehyde
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H302: Harmful if swallowed
H312: Harmful in contact with skin
H332: Harmful if inhaled
Causes skin irritation
H315:
H319: Causes serious eye irritation
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
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
Ingredient name: 2,4,6-Trichloropyrimidine-5-carbaldehyde
CAS number: 50270-27-4

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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.
Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
Eye contact:
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, refrigerated.

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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: C5HCl3N2O
Molecular weight: 211.4

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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.

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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. (2,4,6-Trichloropyrimidine-5-carbaldehyde)

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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

2,4,6-二氯-5-嘧啶甲醛是重要的医药中间体。它可以通过与水合肼的反应生成2-氯吡唑并嘧啶，后者是一种新的重要药物中间体。此外，该醛基可以被氧化成羧酸；同时，在其2,4,6位上的氯也可以发生亲核取代反应，进而形成嘧啶衍生物。

制备

2,4,6-二氯-5-嘧啶甲醛作为重要的药物中间体，其合成方法主要分为两类：

1. 以2,4,6-二氯-5-溴（碘）嘧啶为起始原料，通过与格氏试剂或丁基锂反应后，再与DMF、甲酸甲酯或N-甲酰基吗啉反应获得目标分子。此合成方法中，通常需要在低温下进行（-78℃），收率相对较低。
2. 以尿嘧啶为起始原料，在氢氧化钡催化下，首先与甲醛发生反应生成5-羟甲基尿嘧啶，接着用二氧化锰作为氧化剂将其转化为尿嘧啶-5-甲醛。最终通过三氯氧磷进行三次转化后得到目标分子。整个过程的摩尔收率为45%，重量收率则为33.2%。

反应信息

• 作为反应物：
  描述：

  2,4,6-三氯-5-嘧啶甲醛 在 吡啶 、 盐酸 、 tetraphosphorus decasulfide 、 水 、 一水合肼 、 肼 作用下， 以 乙醇 、 乙二醇甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.67h， 生成 4-{N'-[1-(2-Chloro-phenyl)-meth-(E)-ylidene]-hydrazino}-1,7-dihydro-pyrazolo[3,4-d]pyrimidin-6-one
  参考文献：
  名称：

  Novel xanthine oxidase inhibitor studies. Part 3. Convenient and general syntheses of 3-substituted 7H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidin-5(6H)-ones as a new class of potential xanthine oxidase inhibitors

  摘要：

  报道了一种方便且通用的合成方法，用于合成3取代的7H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidin-5(6H)-酮（12），这是一类新型的强效黄嘌呤氧化酶抑制剂。该合成涉及到以70%浓硝酸进行的6取代4-烯基氨基或4-芳基甲烯基氨基-1H-pyrazolo[3,4-d]pyrimidines（3和11）的氧化环化作为关键步骤。氢肼衍生物3和11是通过一个多功能合成路线获得的，该路线以关键中间体6-氯-4-氨基-1H-pyrazolo[3,4-d]pyrimidine（2）或氧嘌呤醇（4）为起始物，开始自2,4,6-三氯嘧啶-5-醛（1）。同时也描述了它们对牛乳黄嘌呤氧化酶的体外抑制活性；即，pyrazolotriazolopyrimidines（12）的活性比别嘌呤明显强几百倍。

  DOI：

  10.1039/a907673e
• 作为产物：
  描述：

  巴比妥酸 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 以60%的产率得到2,4,6-三氯-5-嘧啶甲醛
  参考文献：
  名称：

  在存在碱金属离子的情况下，带有氧乙烯型间隔基的胆固醇基嘧啶系统对凝胶化和液晶元形成的差异响应†

  摘要：

  合成了一系列新的2,4,6-三氯-嘧啶-5-甲醛的亲脂性胆固醇基衍生物。为了了解它们对这些化合物自组装的影响，在氢键促进嘧啶核心和胆固醇尾基之间插入了可变长度的氧乙烯间隔基。只有具有最短间隔基的化合物1a在有机溶剂（例如正丁醇和正十二烷）中形成凝胶。而其他具有较长间隔基的成员（1b和c）则导致正丁醇和n中的溶胶形成和沉淀-十二烷。使用依赖于温度的UV-Vis和CD光谱研究了与胶凝过程相关的自组装现象。通过扫描电子显微镜（SEM）和原子力显微镜（AFM）检查了从不同有机溶剂获得的冻干凝胶的形态特征。使用偏振光学显微镜（POM）和差示扫描量热法（DSC）探索了这些分子及其相关的碱金属离子配合物的固相行为。使用广角X射线衍射（WAXD）技术进一步探查了干凝胶和固态分子的排列方式。对广角X射线衍射数据的分析表明，这类分子在凝胶和固态时采用六边形柱状组织。这些六边形柱状结构的每个切片均由二聚体分子组

  DOI：

  10.1039/c4sm02792b

文献信息

• Radiosynthesis of [¹⁸F]ATPFU: a potential PET ligand for mTOR
  作者：Vattoly J. Majo、Norman R. Simpson、Jaya Prabhakaran、J. John Mann、J. S. Dileep Kumar

  DOI：10.1002/jlcr.3239

  日期：2014.11

  achieved from beta-chloroaldehyde 3 in 4 and 5 steps, respectively, with an overall yield of 25-28%. [(18)F]Fluoroethylamine was prepared by heating N-[2-(toluene-4-sulfonyloxy)ethyl]phthalimide with [(18)F]fluoride ion in acetonitrile. [(18)F]1 was obtained by slow distillation under argon of [(18) F]FCH2CH2NH2 into amine 10 that was pre-treated with triphosgene at 0-5 °C. The total time required for

  哺乳动物雷帕霉素靶蛋白 (mTOR) 在细胞增殖的许多方面起着关键作用，最近的证据表明，改变的 mTOR 信号通路在衰老、肿瘤进展、神经精神疾病和重度抑郁症的发病机制中起着核心作用。mTOR 特异性 PET 示踪剂的可用性将有助于监测对临床开发中的 mTOR 抑制剂治疗的早期反应。为此，我们开发了 [(18)F]1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2) -三氟乙基)-1H-吡唑并[3,4-d]嘧啶-6-基)苯基)-3-(2-氟乙基)脲[(18)F]ATPFU([(18)F]1)作为mTOR PET配体。参考文献 1 和放射性标记前体的合成，4-(4-8-oxa-3-azabicyclo[3.2.1]-octan-3yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3 ,4-d]嘧啶-6基）苯胺（10），分别通过
• 4-PHENOXY-6-ARYL-1H-PYRAZOLO[3,4-D]PYRIMIDINE AND N-ARYL-6-ARYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
  申请人：Bursavich Matthew Gregory

  公开号：US20100015141A1

  公开（公告）日：2010-01-21

  The invention relates to 4,6-disubstituted-1H-pyrazolo[3,4-d]pyrimidin-4-amine compounds, including 4-phenoxy-6-aryl-1H-pyrazolo[3,4-d]pyrimidine and N-aryl-6-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-amine compounds of the Formula I: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.

  本发明涉及4,6-二取代-1H-吡唑[3,4-d]嘧啶-4-胺化合物，包括4-苯氧基-6-芳基-1H-吡唑[3,4-d]嘧啶和N-芳基-6-芳基-1H-吡唑[3,4-d]嘧啶-4-胺的化合物，其化学式为I： 或其药用可接受盐，其中组成变量如本文所述，包含该化合物的组合物，以及制造和使用这些化合物的方法。
• [EN] AZOLOPYRIDINE AND AZOLOPYRIMIDINE COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS D'AZOLOPYRIDINE ET D'AZOLOPYRIMIDINE ET MÉTHODES D'UTILISATION ASSOCIÉES
  申请人：AMBIT BIOSCIENCES CORP

  公开号：WO2012030924A1

  公开（公告）日：2012-03-08

  Provided herein are azolopyridine and azolopyrimidine compounds for treatment of JAK kinase mediated diseases, including JAK2 kinase-, JAK3 kinase- or TYK2 kinase-mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

  本文提供了用于治疗JAK激酶介导疾病的咪唑吡啶和咪唑吡啶化合物，包括JAK2激酶、JAK3激酶或TYK2激酶介导的疾病。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的方法。
• Discovery of a potent protein kinase D inhibitor: insights in the binding mode of pyrazolo[3,4-d]pyrimidine analogues
  作者：Klaas Verschueren、Mathias Cobbaut、Joachim Demaerel、Lina Saadah、Arnout R. D. Voet、Johan Van Lint、Wim M. De Borggraeve

  DOI：10.1039/c6md00675b

  日期：——

  PKD inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold. The lead compound for this study was 1-NM-PP1, which was previously found by us and others to inhibit PKD. In our screening we identified one compound (3-IN-PP1) displaying a 10-fold increase in potency over 1-NM-PP1, opening new possibilities for specific protein kinase inhibitors for kinases that show sensitivity towards pyrazolo[3,4-d]pyrimidine

  在本研究中，我们着手基于吡唑并[3,4- d ]嘧啶支架合理优化PKD抑制剂。本研究的先导化合物是 1-NM-PP1，我们和其他人之前发现它可以抑制 PKD。在我们的筛选中，我们鉴定出一种化合物 (3-IN-PP1)，其效力比 1-NM-PP1 提高 10 倍，为对吡唑并显示敏感性的激酶的特定蛋白激酶抑制剂开辟了新的可能性[3,4- d ]嘧啶衍生的化合物。有趣的是，观察到的 SAR 与通常观察到的结合模式并不完全一致，其中吡唑并[3,4- d ]嘧啶化合物以与 PKD 天然配体 ATP 类似的方式结合。因此，我们建议采用另一种结合模式，其中化合物翻转 180 度。这种基于吡唑并[3,4- d ]嘧啶的化合物的可能的替代结合模式可以为用于对吡唑并[3,4- d ]嘧啶敏感的激酶的新型特异性蛋白激酶抑制剂铺平道路。
• Synthesis and Photophysical Properties of a Deazaflavin-Bridged Porphyrinatoiron(III) That Mimics the Interaction of a Deazaflavin Inhibitor with the Heme-Thiolate Cofactor of Cytochrome P450 3A4
  作者：Michael A. Müller、Martin Gaplovsky、Jakob Wirz、Wolf-D. Woggon

  DOI：10.1002/hlca.200690268

  日期：2006.12

  Cytochrome P450 3A4 metabolizes a majority of administered therapeutic agents in the human liver. We recently reported the synthesis of a new inhibitor, 1, whose binding to and displacement from the active site of CYP 3A4 can be conveniently followed by the associated changes in fluorescence intensity. Here we report the synthesis of a bichromophoric compound, 6, in which deazaflavin was strapped over

  细胞色素P450 3A4会在人肝中代谢大部分已给药的治疗药物。最近，我们报道了一种新抑制剂1的合成，该抑制剂与CYP 3A4活性位点的结合和从中的置换可以随后伴随着荧光强度的变化。在这里，我们报告了一种双发色化合物6的合成，其中去氮黄素被束缚在卟啉铁（III）配合物的远端，以模仿设想的活性位点内的酶-抑制剂相互作用。飞秒泵浦探针和荧光光谱法用于研究6的光物理过程。高自旋Fe III诱导的快速分子内能量转移和增强的系统间穿越过程中心离子负责完全抑制6中的脱氮黄素荧光。荧光淬灭是在自由铁类似物效率较低6，即，在21。