5-甲氧基-1H-吲唑-3-甲醛 | 169789-37-1

• 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: 5-甲氧基-1H-吲唑-3-甲醛
• 英文名称: 5-methoxy-1H-indazole-3-carboxaldehyde
• 英文别名: 5-methoxy-1H-indazole-3-carbaldehyde；5-metoxyindazole-3-carbaldehyde；5-methoxy-2H-indazole-3-carbaldehyde
• CAS: 169789-37-1
• 化学式: C₉H₈N₂O₂
• mdl: MFCD06738288
• 分子量: 176.175
• InChiKey: MUSWNKMMIYVNJY-UHFFFAOYSA-N

物化性质

• 熔点：
  214-216 °C
• 沸点：
  391.7±22.0 °C(Predicted)
• 密度：
  1.347±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  3

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: 5-Methoxy-1H-indazole-3-carbaldehyde
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: 5-Methoxy-1H-indazole-3-carbaldehyde
CAS number: 169789-37-1

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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: C9H8N2O2
Molecular weight: 176.2

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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

简介

5-甲氧基-1H-吲唑-3-甲醛可用作有机合成试剂。其吲唑环上的氮原子可在碱性条件下与碘甲烷发生亲核取代反应，生成甲基保护的吲唑衍生物。相关文献报道该物质可用于吲唑类抗癌活性有机分子的结构修饰和合成过程中。

应用

5-甲氧基-1H-吲唑-3-甲醛具有独特的分子结构，包括一个吲唑环（含杂环氮原子）及一个醛基（CHO官能团）。这些结构单元使其能够参与多种化学反应，成为合成其他有机化合物的有效工具。该物质主要用作有机化学中的中间体，并利用其醛基单元的高化学转化性能，应用于合成具有抗癌活性的吲唑类分子。

反应信息

• 作为反应物：
  描述：

  5-甲氧基-1H-吲唑-3-甲醛 在 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 4.5h， 生成 3-(benzo[d]thiazol-2-yl)-5-methoxy-1-methyl-1H-indazole
  参考文献：
  名称：

  Synthesis and Evaluation of Anticancer Activity of Indazole Derivatives

  摘要：

  A novel series of indazole 13a-13j derivatives has been synthesized. Their structures are confirmed by H-1 and C-13 NMR, and mass spectral analysis. The compounds are tested for their anticancer activity against four human cancer cell lines including A549 (Lung), MCF7 (Breast), A375 (Melanoma), and HT-29 (Colon), using combretastatin-A4 as a positive control. Most of the synthesized compounds demonstrate potent activity against the above cell lines. Here IC50 values of target compounds range from 0.010 +/- 0.0042 to 12.8 +/- 3.77 M and the control drug from 0.11 +/- 0.02 to 0.93 +/- 0.034 M. The compounds 13a, 13b, 13e, 13g, 13h, and 13j are determined to be more potent than the positive control.

  DOI：

  10.1134/s1070363218110233
• 作为产物：
  描述：

  5-甲氧基吲哚 在 盐酸 、 水 、 sodium nitrite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以91%的产率得到5-甲氧基-1H-吲唑-3-甲醛
  参考文献：
  名称：

  通过吲哚的亚硝化直接获得 1H-吲唑-3-甲醛衍生物的优化程序†

  摘要：

  吲唑衍生物目前作为激酶抑制剂在药物化学中越来越受到关注。1 H-吲唑-3-甲醛是获得多种多官能化3-取代吲唑的关键中间体。我们在这里报告了对这个基序的一般访问，基于在微酸性环境中吲哚的亚硝化。这些非常温和的条件允许富电子和缺电子吲哚转化为 1 H-吲唑-3-甲醛。

  DOI：

  10.1039/c8ra01546e

文献信息

• Design and synthesis of a new indazole library: direct conversion of N-methoxy-N-methylamides (Weinreb amides) to 3-keto and 3-formylindazoles
  作者：François Crestey、Silvia Stiebing、Rémi Legay、Valérie Collot、Sylvain Rault

  DOI：10.1016/j.tet.2006.10.063

  日期：2007.1

  Grignard or lithiated reagents on the new Weinreb amides 3 and 4 afforded efficiently the corresponding ketones and allowed the design and synthesis of a new indazole library. These 3-ketoindazoles were obtained by a direct and original conversion of N-methoxy-N-methylamides with good yields. Furthermore, the reduction of 3 with LiAlH4 furnished the corresponding aldehydes as a versatile and efficient pathway

  在新的Weinreb酰胺3和4上亲核添加格氏试剂或锂化试剂可有效提供相应的酮，并允许设计和合成新的吲唑文库。这些3-酮吲唑是通过N-甲氧基-N-甲基酰胺的直接和原始转化以良好的收率获得的。此外，用LiAlH 4还原3可以提供相应的醛，作为通向3-甲酰基吲唑的一种通用而有效的途径。
• Discovery and Development of 1-[(2-Bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1<i>H</i>-indole Dimesylate Monohydrate (SUVN-502): A Novel, Potent, Selective and Orally Active Serotonin 6 (5-HT₆) Receptor Antagonist for Potential Treatment of Alzheimer’s Disease
  作者：Ramakrishna Nirogi、Anil Shinde、Rama Sastry Kambhampati、Abdul Rasheed Mohammed、Sangram Keshari Saraf、Rajesh kumar Badange、Thrinath Reddy Bandyala、Venugopalarao Bhatta、Kumar Bojja、Veena Reballi、Ramkumar Subramanian、Vijay Benade、Raghava Choudary Palacharla、Gopinadh Bhyrapuneni、Pradeep Jayarajan、Vinod Goyal、Venkat Jasti

  DOI：10.1021/acs.jmedchem.6b01662

  日期：2017.3.9

  04 nM) and selectivity over 100 target sites which include receptors, enzymes, peptides, growth factors, ion channels, steroids, immunological factors, second messengers, and prostaglandins. It has high selectivity over 5-HT2A receptor. It is orally bioavailable and brain penetrant with robust preclinical efficacy. The combination of 5al, donepezil, and memantine (triple combination) produces synergistic

  优化一系列新型的3-（哌嗪基甲基）吲哚衍生物作为5-羟基色胺-6受体（5-HT 6 R）拮抗剂可导致鉴定出1-[（（2-溴苯基）磺酰基] -5-甲氧基-3- [ （4-甲基-1-哌嗪基）甲基] -1 H-吲哚二甲酸酯一水合物（5al，SUVN-502）作为潜在治疗认知障碍的临床候选药物。它对人5-HT 6 R具有高亲和力（K i = 2.04 nM），对100个靶位具有选择性，这些靶位包括受体，酶，肽，生长因子，离子通道，类固醇，免疫学因子，第二信使和前列腺素。它具有超过5-HT 2A的高选择性受体。它具有口服生物利用度和脑渗透性，并具有强大的临床前功效。的组合5AL，多奈哌齐，美金刚和（三联组合）产生在腹侧海马乙酰胆碱的细胞外水平的协同效应。三联组合的临床前功效和对5-HT 2A受体的高选择性是区别特征，最终决定了5al的进一步开发。安全性和药代动力学的第一阶段评估已经完成，从而可以启动第二阶段概念验证研究。
• New practical access to 2-azatryptophans and dehydro derivatives via the Wittig–Horner reaction
  作者：François Crestey、Valérie Collot、Silvia Stiebing、Jean-François Lohier、Jana Sopkova-de Oliveira Santos、Sylvain Rault

  DOI：10.1016/j.tetlet.2007.02.042

  日期：2007.4

  Wittig–Horner reaction of protected 3-formylindazoles 1 with (±)-N-(benzyloxycarbonyl)-α-phosphonoglycine trimethyl ester 2 has been developed as a new practical synthesis of dehydro 2-azatryptophans and amino acid derivatives. The preparation of 5-bromo-3-formylindazole is discussed.

  受保护的3-甲酰基吲唑1与（±）-N-（苄氧羰基）-α-膦酰基甘氨酸三甲酯2的Wittig-Horner反应已被开发为脱氢2-氮杂色氨酸和氨基酸衍生物的新型实用合成方法。讨论了5-溴-3-甲酰基吲唑的制备。
• New indole and indazole derivatives as potential antimycobacterial agents
  作者：Violina T. Angelova、Tania Pencheva、Nikolay Vassilev、Rumyana Simeonova、Georgi Momekov、Violeta Valcheva

  DOI：10.1007/s00044-019-02293-w

  日期：2019.4

  The study reports on the synthesis and in vitro assessment of the antimycobacterial activity of a series of new indole- and indazole-based aroylhydrazones evaluated against Mycobacterium tuberculosis H37Rv. Isoniazide and ethambutol were used as reference drugs. The most active compounds 3a (MIC 0.4412 μM) and 3e (MIC 0.3969 μM) demonstrated excellent antimycobacterial activity, a very low toxicity

  该研究报道了一系列针对结核分枝杆菌H37Rv评估的新型基于吲哚和吲唑的芳酰hydr的抗分枝杆菌活性的合成和体外评估。异烟肼和乙胺丁醇用作参考药物。活性最高的化合物3a（MIC 0.4412μM）和3e（MIC 0.3969μM）具有出色的抗分枝杆菌活性，对人胚胎肾细胞系HEK-293T的毒性极低且选择性指数高（SI = 633.49和SI> 1978.83，分别）。重要的是，以2000 mg / kg bw的最高剂量口服给予化合物3e不会导致死亡或不利影响的迹象，这意味着该化合物3e无毒。具有吲哚和吲唑骨架的其他衍生物也表现出高的抗分枝杆菌活性，除了在第5位具有Br取代基的吲哚衍生物的活性弱于乙胺丁醇。在烯酰-ACP还原酶（InhA）中进行的分子对接研究显示了良好的对接分数，并且对与InhA受体可能的相互作用有很好的见解。
• INDOLES, 1H-INDAZOLES, 1,2-BENZISOXAZOLES, AND 1,2-BENZISOTHIAZOLES, AND PREPARATION AND USES THEREOF
  申请人：XIE Wenge

  公开号：US20090088437A1

  公开（公告）日：2009-04-02

  The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nAChR), activation of nAChRs, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds for example, indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, which act as ligands for the α7 nAChR subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

  本发明涉及尼古丁乙酰胆碱受体（nAChR）配体、nAChR的激活以及与缺陷或功能失调的尼古丁乙酰胆碱受体相关的疾病状态的治疗，特别是与大脑相关的疾病状态。此外，本发明涉及新型化合物，例如吲哚、1H-吲哚唑、1,2-苯并异噁唑和1,2-苯并异硫噻唑，它们作为α7 nAChR亚型的配体，制备这种化合物的方法，含有这种化合物的组合物以及使用这种化合物的方法。