6-碘-1H-吲唑 | 261953-36-0

• 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 - 苯并吡唑类
• 中文名称: 6-碘-1H-吲唑
• 中文别名: 6-碘吲唑
• 英文名称: 6-Iodo-1H-indazole
• 英文别名: 6-iodoindazole
• CAS: 261953-36-0
• 化学式: C₇H₅IN₂
• mdl: MFCD04114695
• 分子量: 244.035
• InChiKey: RSGAXJZKQDNFEP-UHFFFAOYSA-N

物化性质

• 熔点：
  207.0 to 211.0 °C
• 沸点：
  358.2±15.0 °C(Predicted)
• 密度：
  2.082±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

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
• 储存条件：
  | 室温 |

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 6-Iodo-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: 6-Iodo-1H-indazole
CAS number: 261953-36-0

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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: C7H5IN2
Molecular weight: 244.0

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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 Iodide.

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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

用途

6-碘-1H-吲唑是合成抗癌药物阿西替尼的关键中间体。阿西替尼由美国辉瑞(Pfizer)制药公司开发，是一种多靶点强效选择性酪氨酸激酶抑制剂，用于治疗其他系统治疗无效的晚期肾癌。

合成方法

在0℃下，向6-氨基吲唑（10.4g, 78mmol）溶于30mL水中得到的悬浊液中加入浓盐酸（35mL, 420mmol）和亚硝酸钠（6.64g, 96mmol）的水溶液（30mL），并在0℃下搅拌30分钟。随后，在0℃下向该溶液加入碘化钾（15.91g, 96mmol）的水溶液（30mL），在室温下搅拌30分钟后，再加入二氯甲烷（80mL），并在40℃下搅拌2小时。将反应液冷却至0℃，然后用3N氢氧化钠水溶液调节至pH＝14，滤取沉淀物。用10%硫代硫酸钠清洗得到的沉淀物，并溶解于四氢呋喃中，加入硅胶后，在室温下搅拌1小时。接着，加入己烷（600mL），进行过滤。用THF/己烷（1/3 v/v）溶液清洗残渣2次，然后在减压下馏去溶剂，最终得到橙色粉末状化合物6-碘-1H-吲唑（15.23g, 80%）。

反应信息

• 作为反应物：
  描述：

  6-碘-1H-吲唑 在 tris-(dibenzylideneacetone)dipalladium(0) 、 碘 、 palladium diacetate 、 碳酸氢钠 、 1,2-丙二胺 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 potassium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 水 为溶剂， 反应 21.5h， 生成 阿西替尼
  参考文献：
  名称：

  Development of an Efficient Pd-Catalyzed Coupling Process for Axitinib

  摘要：

  The manufacturing process of axitinib (1) involves two Pd-catalyzed coupling reactions, a Migita coupling and a Heck reaction. Optimization of both of these pivotal bond-formation steps is discussed as well as the approach to control impurities in axitinib. Essential to the control strategy was the optimization of the Heck reaction to minimize formation of impurities, in addition to the development of an efficient isolation of crude axitinib to purge impurities.

  DOI：

  10.1021/op400088k
• 作为产物：
  描述：

  6-氨基吲唑 在 盐酸 、 sodium nitrite 、 potassium iodide 作用下， 以 DMF (N,N-dimethyl-formamide) 、 水 为溶剂， 反应 17.5h， 生成 6-碘-1H-吲唑
  参考文献：
  名称：

  Heterocyclic compounds for the treatment of migraine

  摘要：

  本文描述了在治疗偏头痛中有用的化合物，其具有以下一般公式：其中：W是一个CH基团或一个N原子；Z是N或C—R4；B和D分别从CH和N中选择，但至少其中一个是CH，并进一步规定其中一个可以表示N，只有当W和Z都不是N时；A是公式II、III或IV的一个基团，使得基团A至少含有1个N原子；NR7要么是—NH—要么是—N═; 是一个单键或双键；X是一个N原子、一个CH基团或一个C(OH)基团，当 是一个单键时；或者，当 是一个双键时，是一个C原子；Y是一个NH、N-烷基、N-苄基或CH2基团；U和V分别代表一个N原子或一个CH基团，但两者不能都是N；a和b分别独立地为0或1；c是一个从0到3的整数；d是一个从1到3的整数；e是一个从1到2的整数；f是一个从0到3的整数；g是一个从3到6的整数，h是一个从2到3的整数；使得c和d的总和至少为2，e和f的总和至少为2；以及它们的盐和溶剂化合物。

  公开号：

  US06716837B1

文献信息

• Electrochemically Promoted Nickel-Catalyzed Carbon–Sulfur Bond Formation
  作者：Yang Wang、Lingling Deng、Xiaochen Wang、Zhengguang Wu、Yi Wang、Yi Pan

  DOI：10.1021/acscatal.8b04633

  日期：2019.3.1

  This work describes a nickel-catalyzed Ullmann-type thiolation of aryl iodidesunder mild electrochemical conditions. The simple undivided cell with graphene/nickel foam electrode setups offers excellent substrate tolerance, affording aryl and alkyl sulfides in good chemical yields. Furthermore, the mechanism for this electrochemical cross-coupling reaction has been investigated by cyclic voltammetry

  这项工作描述了在温和的电化学条件下镍催化的芳基碘化物的乌尔曼型硫醇化反应。具有石墨烯/镍泡沫电极设置的简单的不分隔电池可提供出色的基材耐受性，并以良好的化学收率提供芳基和烷基硫化物。此外，已经通过循环伏安法研究了这种电化学交叉偶联反应的机理。
• [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。
• Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
  申请人：Agouron Pharamaceuticals, Inc.

  公开号：US06531491B1

  公开（公告）日：2003-03-11

  Indazole compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

  描述了调节和/或抑制某些蛋白激酶活性的吲唑化合物。这些化合物及含有它们的药物组合物能够介导酪氨酸激酶信号转导，从而调节和/或抑制不需要的细胞增殖。该发明还涉及含有这些化合物的药物组合物的治疗或预防用途，以及通过给予这些化合物的有效剂量来治疗癌症和其他与不需要的血管生成和/或细胞增殖相关的疾病状态，如糖尿病视网膜病变、新生血管性青光眼、类风湿性关节炎和牛皮癣的方法。
• P38 inhibitors and methods of use thereof
  申请人：——

  公开号：US20040192653A1

  公开（公告）日：2004-09-30

  This invention relates to inhibitors of p38, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders mediated by p38.

  这项发明涉及p38的抑制剂，以及生产这些抑制剂的方法。该发明还提供了包括该发明的抑制剂的药物组合物，以及利用这些抑制剂和药物组合物在治疗和预防由p38介导的各种疾病中的方法。
• A novel <scp>d</scp>-glucosamine-derived pyridyl-triazole@palladium catalyst for solvent-free Mizoroki–Heck reactions and its application in the synthesis of Axitinib
  作者：Chao Shen、Hongyun Shen、Ming Yang、Chengcai Xia、Pengfei Zhang

  DOI：10.1039/c4gc01606h

  日期：——

  A novel d-glucosamine-derived pyridyl-triazole@palladium catalyst for solvent-free Mizoroki–Heck reactions and the synthesis of Axitinib is reported.

  报道了一种新型的D-氨基葡萄糖衍生的吡啶-三唑@钯催化剂，用于无溶剂水相的Mizoroki–Heck反应以及阿克替尼的合成。