3-甲基异恶唑-5-甲酸 | 4857-42-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-甲基异恶唑-5-甲酸
• 英文名称: 3-methyl-5-isoxazolecarboxylic acid
• 英文别名: 3-methylisoxazole-5-carboxylic acid；3-methyl-1,2-oxazole-5-carboxylic acid；3-Methyl-5-carboxy-isoxazol
• CAS: 4857-42-5
• 化学式: C₅H₅NO₃
• mdl: MFCD00464222
• 分子量: 127.1
• InChiKey: HXIYCKAAQPHZBM-UHFFFAOYSA-N

物化性质

• 熔点：
  210-211 °C
• 沸点：
  307.8±22.0 °C(Predicted)
• 密度：
  1.348±0.06 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：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S36/37
• 危险类别码：
  R43
• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Methylisoxazole-5-carboxylic acid
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: 3-Methylisoxazole-5-carboxylic acid
CAS number: 4857-42-5

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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, under −20◦C.
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: C5H5NO3
Molecular weight: 127.1

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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.

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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

3-甲基异恶唑-5-甲酸是一种有机中间体，可通过乙醛肟和炔丙醇为原料先关环制备（3-甲基异恶唑-5-基）甲醇，随后进行氧化得到3-甲基异恶唑-5-甲酸。

用途

3-甲基异恶唑-5-甲酸作为羧酸类衍生物，主要用于医药中间体的合成。

制备

1. 在室温下，将乙醛肟（1 g，16.9 mmol）溶解于无水THF（15 mL）中，然后加入NCS（2.7 g，20 mmol）。搅拌2小时后，缓慢滴加炔丙醇（1.42 g，25 mmol）的无水THF（4 mL）稀释溶液。30分钟后，逐滴滴入TEA（2.78 mL，20 mmol）的无水THF稀释液。继续剧烈搅拌1小时后，加入水（10 mL）。悬浮液用EA（20 mL×3）萃取，有机层经MgSO₄干燥、过滤并真空浓缩。通过硅胶快速柱色谱法（EA / Hex 1：1）纯化残余物，得到（3-甲基异恶唑-5-基）甲醇。产率0.93 g，8.28 mmol，49%。

2. 在0℃下向（3-甲基异恶唑-5-基）甲醇（0.5 g，4.42 mmol）的丙酮（19 mL）溶液中加入Jones试剂（2.21 mL），混合物搅拌3小时。通过TLC监测反应，当反应终止后，用1N HCl溶液将混合物的pH调节至2。残余物用EA（20 mL×3）萃取，合并的有机层经MgSO₄干燥、过滤并真空浓缩。通过硅胶快速柱色谱法（EA / Hex 1：1）纯化残余物，得到所需产物3-甲基异恶唑-5-甲酸。产率0.63 g，4.97 mmol，100%。

反应信息

• 作为反应物：
  描述：

  3-甲基异恶唑-5-甲酸 在 lithium aluminium tetrahydride 、 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.25h， 生成 3-甲基-5-异恶唑甲醇乙酸酯
  参考文献：
  名称：

  [EN] SUBSTITUTED BICYCLIC COMPOUNDS AS BROMODOMAIN INHIBITORS
  [FR] COMPOSÉS BICYCLIQUES SUBSTITUÉS UTILISÉS COMME INHIBITEURS DE BROMODOMAINE

  摘要：

  本公开涉及替代双环化合物，这些化合物通过结合溴结构域来抑制BET蛋白的功能，并可用于治疗。

  公开号：

  WO2016097870A1
• 作为产物：
  描述：

  3-甲基异恶唑-5-甲醛 在 potassium dichromate 、 硫酸 作用下， 生成 3-甲基异恶唑-5-甲酸
  参考文献：
  名称：

  Panizzi, Gazzetta Chimica Italiana, 1942, vol. 72, p. 99,106

  摘要：

  DOI：

文献信息

• Usnic Acid. II. Methylusnic Acid
  作者：Kotaro Takahashi、Akie Arai、Kazuko Oshima、Yoshie Ueda、Shuichi Miyashita

  DOI：10.1248/cpb.10.607

  日期：——

  The constitution of methylusnic acid, the methylation product of usnic acid withdimethyl sulfate and sodium hydroxide, first reported by A. Robertson et al. was reinvestigated and elucidated as (I).

  甲氧基次叶松酸（即由A. Robertson等人首次报道的，由次叶松酸与二甲基硫酸和氢氧化钠反应得到的甲基化产物）的结构被重新研究并阐明为（I）。
• [EN] DOPAMINE D3 RECEPTOR ANTAGONISTS HAVING A BICYCLO MOIETY<br/>[FR] ANTAGONISTES DU RÉCEPTEUR D3 DE LA DOPAMINE AYANT UN FRAGMENT BICYCLO
  申请人：INDIVIOR UK LTD

  公开号：WO2017021920A1

  公开（公告）日：2017-02-09

  The disclosure provides compounds having formula (I), wherein the substituents are as defined herein. The compounds are useful for modulating the dopamine D3 receptor and for treating conditions associated therewith, such as addictions, drug dependency, and psychiatric conditions.

  该披露提供了具有化学式（I）的化合物，其中取代基如本文所定义。这些化合物可用于调节多巴胺D3受体，并用于治疗与之相关的疾病，如成瘾、药物依赖和精神疾病。
• 1,2,4-Triazolyl octahydropyrrolo[2,3-b]pyrroles: A new series of potent and selective dopamine D3 receptor antagonists
  作者：Fabrizio Micheli、Andrea Bernardelli、Federica Bianchi、Simone Braggio、Laura Castelletti、Palmina Cavallini、Paolo Cavanni、Susanna Cremonesi、Michele Dal Cin、Aldo Feriani、Beatrice Oliosi、Teresa Semeraro、Luca Tarsi、Silvia Tomelleri、Andrea Wong、Filippo Visentini、Laura Zonzini、Christian Heidbreder

  DOI：10.1016/j.bmc.2016.02.031

  日期：2016.4

  high affinity and selectivity at the DA D3 receptor is reported here. Compounds endowed with high selectivity over the hERG channel were identified and their pharmacokinetic properties thoroughly analyzed. A few derivatives with appropriate developability characteristics were selected for further studies and progression along the screening cascade. In particular, derivative 60a, (DA D3 pKi = 8.4, DA D2

  本文报道了一系列新的1,2,4-三唑基八氢吡咯并[2,3- b ]吡咯在DA D3受体上表现出高亲和力和选择性。鉴定了在hERG通道上具有高选择性的化合物，并对其药代动力学特性进行了全面分析。选择了一些具有适当可显影性的衍生物，以进一步研究并沿着筛选级联进行。特别地，衍生物60a（DA D3 p K i  ＝ 8.4，DA D2 p K i  ＝ 6.0和hERG fp K i  ＝ 5.2）显示出平衡的分布，并且围绕该分子进行进一步的改进。
• [EN] MODULATORS OF THE INTEGRATED STRESS PATHWAY<br/>[FR] MODULATEURS DE LA VOIE DE RÉPONSE INTÉGRÉE AU STRESS
  申请人：CALICO LIFE SCIENCES

  公开号：WO2017193063A1

  公开（公告）日：2017-11-09

  Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

  本文提供了用于调节综合应激反应（ISR）并治疗相关疾病、疾患和症状的化合物、组合物和方法。
• [EN] DIPEPTIDE AND TRIPEPTIDE EPOXY KETONE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE DIPEPTIDE ET DE TRIPEPTIDE ÉPOXY CÉTONE PROTÉASES
  申请人：ONYX THERAPEUTICS INC

  公开号：WO2014152127A1

  公开（公告）日：2014-09-25

  Provided herein are dipeptide and tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of proliferative diseases including cancer and autoimmune diseases.

  本文提供了二肽和三肽环氧酮蛋白酶抑制剂，其制备方法，相关的药物组合物，以及使用它们的方法。例如，本文提供了化合物的化学式（X）：及其药用盐和包括这些化合物的组合物。本文提供的化合物和组合物可以用于治疗增生性疾病，包括癌症和自身免疫疾病。