4-甲氧基吲唑 | 351210-06-5

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 4-甲氧基吲唑
• 中文别名: 4-甲氧基-1H-吲唑
• 英文名称: 4-methoxy-1H-indazole
• 英文别名: 4-methoxyindazole
• CAS: 351210-06-5
• 化学式: C₈H₈N₂O
• mdl: MFCD09261131
• 分子量: 148.164
• InChiKey: RHXWAMSYANZWMS-UHFFFAOYSA-N

物化性质

• 熔点：
  117-120 °C
• 沸点：
  313℃
• 密度：
  1.244
• 闪点：
  115℃

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Methoxy-1h-indazole
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: 4-Methoxy-1h-indazole
CAS number: 351210-06-5

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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, 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: C8H8N2O
Molecular weight: 148.2

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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

4-甲氧基-1H-吲唑是一类含氮杂原子的杂环化合物，常用于实验室研发和化工医药合成过程中。

制备

在氮气保护下，将BINAP（5.5 mol%）、Pd(OAc)2（5 mol%）和Cs2CO3（1.4当量）以及甲苯（10毫升）加入反应器中。悬浮液加热至80°C并维持10分钟后，逐步加入二苯甲酮腙（2.1当量）。将所得混合物在100°C下搅拌并进行反应，通过TLC监控反应进度直至完成。随后，向反应液中加入水（20毫升）和二氯甲烷（20毫升）的混合物以淬灭反应，并使用硅藻土垫过滤混合物。分液后，水层用二氯甲烷萃取，合并有机层并用水（320毫升）洗涤。经MgSO4干燥后进行过滤，滤液通过减压蒸馏得到粗品4-甲氧基-1H-吲唑。

将该粗品加入含有对甲苯磺酸（2或3当量）和二氯甲烷（10毫升）的微波小瓶中密封。在100°C下加热反应物，然后将混合物倒入纯化水（20毫升）中淬灭，并用乙酸乙酯（320毫升）萃取有机层。合并有机层后，经无水MgSO4干燥、过滤并减压蒸馏。最终通过硅胶色谱进一步纯化产品。

反应信息

• 作为反应物：
  描述：

  4-甲氧基吲唑 在 碘 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以90%的产率得到3-碘-4-甲氧基-1H-吲唑
  参考文献：
  名称：

  Discovery of inhibitors of the mitotic kinase TTK based on N-(3-(3-sulfamoylphenyl)-1H-indazol-5-yl)-acetamides and carboxamides

  摘要：

  TTK kinase was identified by in-house siRNA screen and pursued as a tractable, novel target for cancer treatment. A screening campaign and systematic optimization, supported by computer modeling led to an indazole core with key sulfamoylphenyl and acetamido moieties at positions 3 and 5, respectively, establishing a novel chemical class culminating in identification of 72 (CFI-400936). This potent inhibitor of TTK (IC50=3.6nM) demonstrated good activity in cell based assay and selectivity against a panel of human kinases. A co-complex TTK X-ray crystal structure and results of a xenograft study with TTK inhibitors from this class are described.

  DOI：

  10.1016/j.bmc.2014.06.027
• 作为产物：
  描述：

  2-氟苯甲醚 在 氢氧化钾 、 2,2,6,6-tetramethylpiperidinyl-lithium 作用下， 以 乙醚 、 乙醇 、 正己烷 为溶剂， 反应 3.25h， 生成 4-甲氧基吲唑
  参考文献：
  名称：

  三甲基甲硅烷基重氮甲烷锂与苯炔的[3 + 2]环加成反应可轻松合成3-三甲基甲硅烷基吲唑

  摘要：

  由卤代苯生成的三甲基硅烷基重氮甲烷甲烷与苯炔的[3 + 2]环加成反应以良好至中等的收率得到了相应的3-三甲基硅烷基吲唑。

  DOI：

  10.1016/j.tetlet.2003.12.086

文献信息

• Solvent-Controlled, Site-Selective <i>N</i>-Alkylation Reactions of Azolo-Fused Ring Heterocycles at N1-, N2-, and N3-Positions, Including Pyrazolo[3,4-<i>d</i>]pyrimidines, Purines, [1,2,3]Triazolo[4,5]pyridines, and Related Deaza-Compounds
  作者：Brett C. Bookser、Michael I. Weinhouse、Aaron C. Burns、Andrew N. Valiere、Lino J. Valdez、Pawel Stanczak、Jim Na、Arnold L. Rheingold、Curtis E. Moore、Brian Dyck

  DOI：10.1021/acs.joc.8b00540

  日期：2018.6.15

  coordinated to sodium indicated a potential role for the latter reinforcing the N2-selectivity. Limits of selectivity were tested with 26 heterocycles which revealed that N7 was a controlling element directing alkylations to favor N2 for pyrazolo- and N3 for imidazo- and triazolo-fused ring heterocycles when conducted in THF. Use of 1H-detected pulsed field gradient-stimulated echo (PFG-STE) NMR defined

  使用NaHMDS作为碱，在THF中用碘甲烷将4-甲氧基-1 H-吡唑并[3,4- d ]嘧啶（1b）烷基化，选择性地提供了N2-甲基产物4-甲氧基-2-甲基-2 H-吡唑并[3，相对于N1-甲基产物（2b），以8/1的比例存在4- d ]嘧啶（3b）。有趣的是，在DMSO中进行反应使选择性逆转，以提供4/1的N1 / N2甲基化产物比例。产品3b的晶体结构N1和N7与钠配位表明后者可能增强N2选择性。用26个杂环测试了选择性极限，结果表明，当在THF中进行反应时，N7是控制烷基化的控制元素，对于吡唑并环而言，该环对吡唑并环反应有利于N2，对咪唑和三唑并稠合的环杂环则有利于N3。使用1个H-检测脉冲场梯度受激回波（PFG-STE）NMR确定的离子反应性复合物的分子量。该数据和DFT电荷分布计算表明，紧密离子对（CIP）或紧密离子对（TIP）控制THF中的烷基化选择性，而溶剂分离的离子对（SIPs）是DMSO中的反应性物质。
• [EN] COMPOUNDS AS INHIBITORS OF MACROPHAGE MIGRATION INHIBITORY FACTOR<br/>[FR] COMPOSÉS EN TANT QU'INHIBITEURS DU FACTEUR INHIBITEUR DE LA MIGRATION DES MACROPHAGES
  申请人：IMMUNOPHAGE BIOMEDICAL CO LTD

  公开号：WO2020186220A1

  公开（公告）日：2020-09-17

  The present invention provides compounds of Formula (I) shown above and their pharmaceutically acceptable salt, solvates, isomers, or prodrugs, as well as pharmaceutical compositions containing these compounds. Also provided by the invention is a method for treating a disorder mediated by macrophage migration inhibitory factor in a subject, comprising administering to the subject in need thereof a compound or a pharmaceutical composition of this invention.

  本发明提供了上述公式(I)所示的化合物及其药用可接受的盐、溶剂化物、异构体或前药，以及含有这些化合物的药物组合物。本发明还提供了一种用于治疗由巨噬细胞迁移抑制因子介导的疾病的方法，包括向需要治疗的对象施用本发明的化合物或药物组合物。
• New CRTh2 antagonists.
  申请人：Almirall, S.A.

  公开号：EP2548863A1

  公开（公告）日：2013-01-23

  The present invention relates to compounds of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by CRTh2 antagonist activity.

  这项发明涉及到式(I)化合物，制备这种化合物的方法以及它们在治疗病理状况或疾病中的应用，这些病理状况或疾病对CRTh2拮抗活性有改善作用。
• [EN] PIPERIDINE-DIONE DERIVATIVES<br/>[FR] DÉRIVÉS DE PIPÉRIDINE-DIONE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015140133A1

  公开（公告）日：2015-09-24

  The invention provides novel compounds having the general formula (I) and tautomers and pharmaceutically acceptable salts thereof, wherein A1, A2, A3, A4, R1, R4, R5, R6, R7 and R8 are as defined herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有通式（I）及其互变异构体和药学上可接受的盐的新化合物，其中A1、A2、A3、A4、R1、R4、R5、R6、R7和R8如本文所定义，包括这些化合物的组合物和使用这些化合物的方法。
• A general synthesis of diversely substituted indazoles and hetero-aromatic derivatives from o-halo-(het)arylaldehydes or -phenones
  作者：Emmanuelle Dubost、Silvia Stiebing、Thibault Ferrary、Thomas Cailly、Frédéric Fabis、Valérie Collot

  DOI：10.1016/j.tet.2014.07.092

  日期：2014.11

  set of variously substituted indazoles and hetero-aromatic derivatives were synthesized from o-halo-(het)arylaldehydes using a palladium catalyzed amination followed by cyclization. Starting from phenones, this process was extended to give 3-substituted indazoles. Moreover, N-1-substituted-indazoles can be reached by this strategy using an optional selective N-1-alkylation step during the process. This

  一组不同取代的吲唑和杂芳族衍生物是使用钯催化的胺化反应由邻-卤-（杂）芳基醛合成的，然后环化。从苯酮开始，该过程扩展为得到3-取代的吲唑。此外，在该方法中，使用任选的选择性N-1-烷基化步骤，可以通过该策略获得N -1-取代的吲唑。这种方法为区域选择性取代的吲唑的合成提供了一条通用而简便的途径。