4-溴-7-氮杂吲哚 | 348640-06-2

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 中文名称: 4-溴-7-氮杂吲哚
• 中文别名: 4-溴-1H-吡咯并[2,3-b]吡啶
• 英文名称: 4-bromo-7-azaindole
• 英文别名: 4-bromo-1H-pyrrolo[2,3-b]pyridine；4-bromo-1H-pyrrole[2,3-b]pyridine
• CAS: 348640-06-2
• 化学式: C₇H₅BrN₂
• mdl: MFCD08272233
• 分子量: 197.034
• InChiKey: LEZHTYOQWQEBLH-UHFFFAOYSA-N

物化性质

• 熔点：
  178-183 °C
• 密度：
  1.770±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 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

• 危险等级：
  6.1
• 危险等级：
  IRRITANT
• 危险品运输编号：
  UN 2811 6.1 / PGIII
• 海关编码：
  2933990090
• WGK Germany：
  3
• 危险标志：
  GHS05,GHS06
• 危险性描述：
  H301,H315,H318,H335
• 危险性防范说明：
  P261,P280,P301 + P310,P305 + P351 + P338
• 储存条件：
  室温

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
4-Bromo-1H-pyrrolo[2,3-b]pyridine
Product Name:
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H301: Toxic if swallowed
H315: Causes skin irritation
H318: Causes serious eye damage
H335: May cause respiratory irritation
Avoid breathing dust/fume/gas/mist/vapours/spray
P261:
P280: Wear protective gloves/protective clothing/eye protection/face protection
P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

---

Section 3. Composition/information on ingredients.
4-Bromo-1H-pyrrolo[2,3-b]pyridine
Ingredient name:
CAS number: 348640-06-2

---

Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

---

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.

---

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.

---

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.
Storage: Store in closed vessels, refrigerated.

---

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.

---

Section 9. Physical and chemical properties
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C7H5BrN2
Molecular weight: 197.0

---

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 bromide.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

Section 14. Transportation information
UN Number: UN2811 Class: 6.1 Packing group: III
Proper shipping name: TOXIC SOLIDS, ORGANIC, N.O.S. (4-Bromo-1H-pyrrolo[2,3-b]pyridine)

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

4-溴-7-氮杂吲哚可以作为有机合成中间体和医药中间体，它不仅适用于实验室的研发过程，还在化工生产中发挥着重要作用。

反应信息

• 作为反应物：
  描述：

  4-溴-7-氮杂吲哚 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium phosphate 、 potassium acetate 、 palladium diacetate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 47.0h， 生成 AZD6738
  参考文献：
  名称：

  开发和扩大生产至ATR抑制剂Ceralasertib的生产路线

  摘要：

  目前正在针对多种I / II期临床试验评估Ceralasertib的治疗效果。其结构包括装饰有手性吗啉，环丙基磺酰亚胺和氮杂吲哚的嘧啶核，使其难以大规模合成。药物化学的一些特征和早期开发路线使其不适用于活性药物成分的长期商业生产。我们描述了一种新的和改进的途径的研究和开发，该途径从2,4-二溴丁酸甲酯的新工艺中引入了环丙基部分。在构建嘧啶环之后，使用磷酰氯进行了大规模氯化，并进行了安全可靠的后处理。一个S ÑAr反应需要进行创新的后处理，以去除不需要的区域异构体，然后使用Baeyer-Villiger单加氧酶将硫不对称氧化为亚砜。开发了安全且可扩展的无金属亚砜亚胺形成方法，然后对Suzuki反应进行了优化，从而可制造出具有优异杂质控制能力且总收率为16％的高质量ceralasertib。

  DOI：

  10.1021/acs.oprd.0c00482
• 作为产物：
  描述：

  1H-Pyrrolo[2,3-b]pyridine 7-Oxide 在 四甲基溴化铵 、 甲基磺酸酐 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 4-溴-7-氮杂吲哚
  参考文献：
  名称：

  通过铜催化的叠氮化物-炔烃环加成反应，溶液相平行合成鲁索替尼衍生的Janus激酶抑制剂

  摘要：

  在当前的研究中开发了溶液相平行合成三唑衍生的ruxolitinib类似物。该方法利用铜催化的叠氮化物-炔烃环加成反应建立了中心三唑模板。通过沉淀和离心分离产物是直接的，并且产生适用于生物概况分析的高纯度化合物。建立了以高产率获得末端炔烃前体的简单方案，并制备了具有不同官能团的类索鲁替尼样三唑库。另外，提出了鲁索替尼与Janus激酶（JAK）2结合模式的模型。与以前的模型相比，该姿势解释了JAK1 / JAK2的化合物选择性，并且与公开的结构活性数据一致。在此基础上，推导了用于逆转鲁索替尼选择性图谱的基于结构的设计假设。该策略的应用确定了对其他JAK具有高选择性的中等效力的JAK3抑制剂（35 nM），可能利用了共价结合模式。

  DOI：

  10.1021/co500122h

文献信息

• BENZOTHIOPHENE INHIBITORS OF RHO KINASE
  申请人：Kahraman Mehmet

  公开号：US20080021026A1

  公开（公告）日：2008-01-24

  The present invention relates to compounds and methods which may be useful as inhibitors of Rho kinase for the treatment or prevention of disease.

  本发明涉及化合物和方法，这些化合物和方法可能作为Rho激酶的抑制剂在治疗或预防疾病方面有用。
• [EN] TANK-BINDING KINASE INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE KINASES SE LIANT À TANK
  申请人：GILEAD SCIENCES INC

  公开号：WO2015187684A1

  公开（公告）日：2015-12-10

  Compounds having the following formula (I) and methods of their use and preparation are disclosed:

  揭示了具有以下化学式（I）的化合物及其使用和制备方法。
• Application of Sequential Palladium Catalysis for the Discovery of Janus Kinase Inhibitors in the Benzo[<i>c</i>]pyrrolo[2,3-<i>h</i>][1,6]naphthyridin-5-one (BPN) Series
  作者：Mohamed S. A. Elsayed、Jeffery J. Nielsen、Sungtae Park、Jeongho Park、Qingyang Liu、Chang H. Kim、Yves Pommier、Keli Agama、Philip S. Low、Mark Cushman

  DOI：10.1021/acs.jmedchem.8b00510

  日期：2018.12.13

  The present account describes the discovery and development of a new benzo[c]pyrrolo[2,3-h][1,6]naphthyridin-5-one (BPN) JAK inhibitory chemotype that has produced selective JAK inhibitors. Sequential palladium chemistry was optimized for the rapid access to a focused library of derivatives to explore the structure–activity relationships of the new scaffold. Several compounds from the series displayed

  该文献描述了已经产生选择性JAK抑制剂的新型苯并[ c ]吡咯并[2，3- h ] [1，6]萘啶-5-酮（BPN）JAK抑制化学型的发现和开发。优化了顺序钯化学，可快速访问聚焦的衍生物库，以探索新支架的结构与活性之间的关系。该系列中的几种化合物对JAK家族的四个成员具有不同选择性的低纳摩尔浓度范围。具有氮杂环丁烷酰胺侧链的化合物20a显示出对JAK1激酶相对于JAK2，JAK3和TYK2的最佳选择性，且纳摩尔浓度低（IC 50 = 3.4 nM）。另一方面，BPN 17b和18对JAK家族具有良好的总体活性，并具有优异的kinome选择性特征。许多新的BPN抑制JAK3介导的STAT-5磷酸化，炎性细胞因子的产生以及原代T细胞的增殖。此外，在类风湿性关节炎动物模型中，BPN 17b的体内结果与托法替尼非常相似。
• COMPOUNDS FOR USING IN IMAGING AND PARTICULARLY FOR THE DIAGNOSIS OF NEURODEGENERATIVE DISEASES
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：US20190211011A1

  公开（公告）日：2019-07-11

  The invention relates to compounds of formula (II) for using in imaging and particularly for the diagnosis of neurodegenerative diseases

  该发明涉及公式（II）的化合物，用于影像学，特别是用于诊断神经退行性疾病。
• Discovery of 3,4-Dihydrobenzo[<i>f</i>][1,4]oxazepin-5(2<i>H</i>)-one Derivatives as a New Class of Selective TNIK Inhibitors and Evaluation of Their Anti-Colorectal Cancer Effects
  作者：Yueshan Li、Liting Zhang、Ruicheng Yang、Zeen Qiao、Ming Wu、Chong Huang、Chenyu Tian、Xinling Luo、Wei Yang、Yun Zhang、Linli Li、Shengyong Yang

  DOI：10.1021/acs.jmedchem.1c00672

  日期：2022.2.10

  colorectal cancer (CRC) that is often associated with dysregulation of Wnt/β-catenin signaling pathway. Herein, we report the discovery of a series of 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one derivatives as a new class of TNIK inhibitors. Structure–activity relationship (SAR) analyses led to the identification of a number of potent TNIK inhibitors with compound 21k being the most active one (IC50:

  Traf2 和 Nck 相互作用蛋白激酶 (TNIK) 是 Wnt/β-catenin 通路的下游信号蛋白，被认为是治疗结直肠癌 (CRC) 的潜在靶点，结直肠癌通常与Wnt/β-连环蛋白信号通路。在此，我们报告发现了一系列 3,4-二氢苯并[ f ][1,4]oxazep​​in-5(2 H )-one 衍生物作为一类新型 TNIK 抑制剂。构效关系 (SAR) 分析鉴定出许多有效的 TNIK 抑制剂，其中化合物21k是最活跃的一种 (IC 50 : 0.026 ± 0.008 μM)。该化合物还对 TNIK 对 406 种其他激酶表现出优异的选择性。在体外试验中，化合物21k可以有效抑制 CRC 细胞增殖和迁移，并在 HCT116 异种移植小鼠模型中表现出相当大的抗肿瘤活性。它还显示出良好的药代动力学特性。总体而言， 21k可能是针对 TNIK 药物发现的有前途的先导化合物，值得进一步研究。