4,6-二氯嘧啶-5-乙酸甲酯 | 171096-33-6

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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: 4,6-二氯嘧啶-5-乙酸甲酯
• 英文名称: methyl 2-(4,6-dichloropyrimidin-5-yl)acetate
• CAS: 171096-33-6
• 化学式: C₇H₆Cl₂N₂O₂
• mdl: MFCD20526414
• 分子量: 221.043
• InChiKey: ORHWGOUAAWDYFP-UHFFFAOYSA-N

物化性质

• 沸点：
  305.9±37.0 °C(Predicted)
• 密度：
  1.448±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Methyl 2-(4,6-dichloropyrimidin-5-yl)acetate
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: Methyl 2-(4,6-dichloropyrimidin-5-yl)acetate
CAS number: 171096-33-6

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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, refrigerated.
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: C7H6Cl2N2O2
Molecular weight: 221.0

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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 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
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

4,6-二氯嘧啶-5-乙酸甲酯是一种医药中间体，可通过丙二酸二乙酯和溴乙酸乙酯作为起始物料，在三步反应中制备得到。它适用于实验室研发和化工生产过程。

制备 步骤一：乙烷-1,1,2-三羧酸三乙基酯

将400升丙酮加入反应器，然后缓慢添加71.17千克粉状碳酸钾，确保温度维持在25-30℃。随后，逐步加入55千克的丙二酸二乙酯，并保持同样的温度范围。加热至55-60℃，持续2.5小时后冷却至50-54℃。缓慢加入5.225千克碘化钠（维持温度在52-54℃），再逐步添加71.5千克溴乙酸乙酯，并保持52-54℃。在55-60℃下搅拌12-14小时，随后冷却至10-15℃进行过滤并用110升丙酮洗涤滤饼。将该混合物加热至45-50℃直至无馏出物，并在真空（0.4-0.5 mmHg）条件下以80℃蒸馏过量的未反应丙二酸二乙酯，最终得到45.5千克三乙基乙烷-1,1,2-三羧酸酯（收率53.72%，纯度93.2%），通过气相色谱验证。

步骤二：2-(4,6-二羟基嘧啶-5-基)乙酸甲酯

将74.75克乙烷-1,1,2-三羧酸三乙基酯（当量1.00，303.54毫摩尔）加入到含甲醇钠溶液中（139.6毫升25% wt甲醇溶液，4.35M，共131.2克）。随后在室温下逐步添加甲脒盐酸盐（25.19克，1.01当量），搅拌整夜。用37 % HCl酸化后过滤并真空干燥以获得白色固体状的标题化合物（收率99.99%）。通过核磁共振谱仪验证：1H NMR (300 MHz, DMSO): 8.03 (s, 1H), 3.55 (s, 3H), 3.24-3.15 (m, 2H)。

步骤三：4,6-二氯嘧啶-5-乙酸甲酯

将2-(4,6-二羟基嘧啶-5-基)乙酸甲酯（46.65克，1.00当量，253.33毫摩尔）悬浮于磷酰氯（235.41毫升，10.00当量，2.53摩尔），在回流温度下搅拌3小时。用真空蒸馏至原始体积的1/3后加入4℃磷酸氢二钾水溶液（2M，2.53升，20当量，5.07摩尔）。使用乙酸乙酯（EA）萃取并经硫酸镁干燥、过滤和浓缩。通过硅胶柱层析纯化粗制品以获得浅黄色固体状的标题化合物（收率137.17毫摩尔，54.15%）。

反应信息

• 作为反应物：
  描述：

  4,6-二氯嘧啶-5-乙酸甲酯 在 4-二甲氨基吡啶 potassium tert-butylate 、 二异丁基氢化铝 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 乙醚 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 23.0h， 生成 4-[7-(4-methoxy-benzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] AKT PROTEIN KINASE INHIBITORS
  [FR] INHIBITEURS DE LA PROTEINE KINASE AKT

  摘要：

  公开号：

  WO2005051304A3
• 作为产物：
  描述：

  1,1,2-乙烷三羧酸三乙酯 在 sodium methylate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 21.0h， 生成 4,6-二氯嘧啶-5-乙酸甲酯
  参考文献：
  名称：

  [EN] AKT PROTEIN KINASE INHIBITORS
  [FR] INHIBITEURS DE LA PROTEINE KINASE AKT

  摘要：

  公开号：

  WO2005051304A3

文献信息

• [EN] BICYCLIC HETEROCYCLE DERIVATIVES AND THEIR USE AS GPCR MODULATORS<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES BICYCLIQUES ET LEUR UTILISATION COMME MODULATEURS DE GPCR
  申请人：SCHERING CORP

  公开号：WO2010009207A1

  公开（公告）日：2010-01-21

  The present invention relates to Bicyclic Heterocycle Derivatives of Formula (I), compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a diabetic complication, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a G protein-coupled receptor (GPCR) in a patient.

  本发明涉及公式（I）的双环杂环衍生物，包括双环杂环衍生物的组合物，以及使用双环杂环衍生物治疗或预防肥胖、糖尿病、糖尿病并发症、代谢紊乱、心血管疾病或与患者中G蛋白偶联受体（GPCR）活性相关的疾病的方法。
• AKT AND P70 S6 KINASE INHIBITORS
  申请人：Shepherd Timothy Alan

  公开号：US20100120801A1

  公开（公告）日：2010-05-13

  The present invention provides AKT and p70 S6 kinase inhibitors of the formula: The present invention also provides pharmaceutical compositions comprising compounds of Formula I, uses of compounds of Formula I and methods of using compounds of Formula I.

  本发明提供了式子为AKT和p70 S6激酶抑制剂的药物。本发明还提供了包含式子I化合物的药物组合物，式子I化合物的用途以及使用式子I化合物的方法。
• [EN] PIPERIDINE DERIVATIVES AS INHIBITORS OF UBIQUITIN SPECIFIC PROTEASE 7<br/>[FR] DÉRIVÉS DE PIPÉRIDINE UTILISÉS COMME INHIBITEURS DE LA PROTÉASE SPÉCIFIQUE DE L'UBIQUITINE 7
  申请人：ALMAC DISCOVERY LTD

  公开号：WO2018073602A1

  公开（公告）日：2018-04-26

  The present invention concerns the identification of inhibitors of ubiquitin specific protease 7 (USP7), and methods of use thereof.

  这项发明涉及抑制泛素特异性蛋白酶7（USP7）的识别，以及其使用方法。
• .alpha.-pyrimidinyl acrylic acid derivatives
  申请人：Sandoz Ltd.

  公开号：US05547919A1

  公开（公告）日：1996-08-20

  The invention discloses compounds of formula I ##STR1## the use of such compounds for the control of phytopathogens, composition for facilitating such use, and the preparation of the compounds of formula I.

  该发明揭示了化合物I的公式 ##STR1## 这些化合物用于控制植物病原体，为促进此类使用的组合物，以及制备化合物I的方法。
• [EN] NOVEL HETEROCYCLIC COMPOUNDS AS INHIBITORS OF VANIN-1 ENZYME<br/>[FR] NOUVEAUX COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE L'ENZYME VANINE-1
  申请人：PFIZER

  公开号：WO2016193844A1

  公开（公告）日：2016-12-08

  Compounds, pharmaceutically acceptable salts thereof, are disclosed wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  揭示了具有规范中定义的Formula (I)结构的化合物及其在药学上可接受的盐。还揭示了相应的药物组合物、治疗方法、合成方法和中间体。