6-溴-4-氯喹啉 | 65340-70-7

• 物质功能分类: 医药中间体 - 杂环化合物 - 喹啉类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 6-溴-4-氯喹啉
• 中文别名: 4-氯-6-溴喹啉
• 英文名称: 6-bromo-4-chloroquinoline
• 英文别名: 4-chloro-6-bromoquinoline
• CAS: 65340-70-7
• 化学式: C₉H₅BrClN
• mdl: MFCD00511001
• 分子量: 242.502
• InChiKey: KJILYZMXTLCPDQ-UHFFFAOYSA-N

物化性质

• 熔点：
  110-112℃
• 沸点：
  314.6±22.0 °C(Predicted)
• 密度：
  1.673±0.06 g/cm3(Predicted)
• 溶解度：
  溶于甲苯

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  12
• 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：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  T
• 安全说明：
  S36/37,S45
• 危险类别码：
  R25,R20/22
• WGK Germany：
  3
• 海关编码：
  2933499090
• 危险性防范说明：
  P261,P264,P271,P280,P305+P351+P338,P302+P352,P304+P340,P312,P362+P364,P403+P233,P501
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
6-Bromo-4-chloroquinoline
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
6-Bromo-4-chloroquinoline
Ingredient name:
CAS number: 65340-70-7

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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:

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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.
Storage: Store in closed vessels.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C9H5BrClN
Molecular weight: 242.5

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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 chloride, hydrogen bromide.

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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

6-溴-4-氯喹啉可用作Omipalisib的中间体，用于医药研发过程。

制备 第一步：3-(4-溴苯胺)丙烯酸乙酯的合成

将28.51g（290.66mmol）丙炔酸乙酯在氮气保护下搅拌加入到装有50g（290.66mmol）4-溴苯胺和500ml甲醇的1L三口瓶中，加热至40℃，搅拌反应48小时。通过TLC检测确认反应完成后，旋干溶剂，得到3-(4-溴苯胺)丙烯酸乙酯（78g，收率99％）作为粗品直接用于下一步。

第二步：6-溴喹啉-4(1H)-酮的合成

将78g 3-(4-溴苯胺)丙烯酸乙酯粗品溶解于150ml二苯醚中，并在200℃下慢慢滴入装有470ml二苯醚的1L三口瓶中。反应2小时后点板确认原料消失。将反应液冷却至室温，倒入1500ml石油醚中，静置过夜后过滤，滤渣用150ml乙酸乙酯打浆，过滤并干燥得到50g 6-溴喹啉-4(1H)-酮（收率77％）。

第三步：6-溴-4-氯喹啉的合成

将10g（44.63mmol）6-溴喹啉-4(1H)-酮、100ml甲苯和12.25g（89.26mmol）三氯化磷加入到250ml三口瓶中，升温回流2小时。点板确认原料消失后冷却至室温，旋干溶剂，固体用100ml乙醚打浆，过滤并干燥得到10g黄色粉末（收率92.6％）。

经检测，黄色粉末的核磁谱图如下，可以确定最终产物为6-溴-4-氯喹啉。

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  6-溴-4-氯喹啉-2-羧醛	6-bromo-4-chloroquinoline-2-carbaldehyde	904369-49-9	C10H5BrClNO	270.513
  6-溴-4-氯-2-苯基喹啉	6-bromo-4-chloro-2-phenylquinoline	860195-69-3	C15H9BrClN	318.6
  4-氯喹啉-6-甲醛	4-chloroquinoline-6-carbaldehyde	676256-25-0	C10H6ClNO	191.617
  ——	4-chloro-6-vinylquinoline	916811-99-9	C11H8ClN	189.644
  ——	4-chloro-6-phenylquinoline	5443-23-2	C15H10ClN	239.704
  6-二甲氨基-4-氯喹啉	4-chloro-6-dimethylaminoquinoline	99853-53-9	C11H11ClN2	206.675
  ——	4-chloro-6-[(1,1-dimethylethyl)thio]quinoline	1346549-09-4	C13H14ClNS	251.78
  ——	4-chloro-6-(4-methoxyphenyl)quinoline	500127-41-3	C16H12ClNO	269.73

反应信息

• 作为反应物：
  描述：

  6-溴-4-氯喹啉 在 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 sodium carbonate 、 sodium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 丙腈 为溶剂， 反应 96.5h， 生成 芸香苷
  参考文献：
  名称：

  [11C]GSK2126458 and [18F]GSK2126458, the first radiosynthesis of new potential PET agents for imaging of PI3K and mTOR in cancers

  摘要：

  GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [C-11]GSK2126458 and [F-18]GSK212 6458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 20-30% decay corrected radiochemical yield, and 370-740 and 37-222 GBq/lmol specific activity at end of bombardment (EOB), respectively. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.136
• 作为产物：
  描述：

  5-[(4-溴苯基氨基)亚甲基]-2,2-二甲基-1,3-二噁烷-4,6-二酮 在 三氯氧磷 作用下， 以 1,4-二氧六环 、 二苯醚 为溶剂， 反应 2.17h， 生成 6-溴-4-氯喹啉
  参考文献：
  名称：

  具有肿瘤富集药代动力学的 CDK8/19 介质激酶的选择性和口服生物利用度喹啉-6-腈基抑制剂

  摘要：

  Senexins 是 CDK8/19 介质激酶的强效选择性喹唑啉抑制剂。为了提高其效力和代谢稳定性，基于 Senexin A 和 Senexin B 的模拟药物-靶点对接模型，通过结构导向策略设计了基于喹啉的衍生物。合成了喹啉-Senexin 衍生物库以探索结构-活动关系（SAR）。优化的化合物20a(Senexin C) 具有高选择性的强效 CDK8/19 抑制活性。与原型抑制剂 Senexin B 相比，Senexin C 代谢更稳定，对 CDK8/19 依赖性细胞基因表达的抑制作用更持久。使用基于肿瘤的新型 PD 测定法进行体内药代动力学 (PK) 和药效学 (PD) 评估表明 Senexin C 具有良好的口服生物利用度，具有很强的肿瘤富集 PK 特征和肿瘤 PD 标志物反应。Senexin C 在全身性体内模型中抑制 MV4-11 白血病生长，具有良好的耐受性。

  DOI：

  10.1021/acs.jmedchem.1c01951

文献信息

• [EN] SMALL MOLECULE INHIBITORS OF NF-kB INDUCING KINASE<br/>[FR] INHIBITEURS À PETITE MOLÉCULE DE KINASE INDUISANT NF-KB
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2020239999A1

  公开（公告）日：2020-12-03

  The present invention relates to compounds that inhibit NIK and pharmaceutical compositions comprising such compounds and methods of using the same. These compounds and pharmaceutical compositions are envisaged to be useful for preventing or treating diseases such as cancer (such as B-cell malignancies including leukemias, lymphomas and myeloma), inflammatory disorders, autoimmune disorders, immunodermatologic disorders such as palmoplantar pustulosis and hidradenitis suppurativa, and metabolic disorders such as obesity and diabetes.

  本发明涉及抑制NIK的化合物，以及包含这些化合物的药物组合物和使用方法。这些化合物和药物组合物预期能用于预防或治疗癌症（如包括白血病、淋巴瘤和多发性骨髓瘤的B细胞恶性肿瘤）、炎症性疾病、自身免疫疾病、免疫皮肤病学疾病（如掌跖脓疱病和化脓性汗腺炎）以及代谢紊乱疾病（如肥胖和糖尿病）。
• [EN] HETEROCYCLIC COMPOUNDS USEFUL AS MODULATORS OF TNF ALPHA<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILES EN TANT QUE MODULATEURS DU TNF ALPHA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2017023905A1

  公开（公告）日：2017-02-09

  Disclosed are compounds of Formula (I) or a salt thereof, wherein: A is CR1 or N; B is CR3 or N; D is CR4 or N; L1 is -(CR7R7)m-; L2 is -(CR7R7)n-; and X, Z, R1, R2, R3, R4, R5,and R6 are define herein. Also disclosed are methods of using such compounds as modulators of TNFα, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

  披露了公式(I)化合物或其盐，其中：A是CR1或N；B是CR3或N；D是CR4或N；L1是-(CR7R7)m-；L2是-(CR7R7)n-；X，Z，R1，R2，R3，R4，R5和R6都在此定义。还披露了将此类化合物用作调节TNFα的调节剂的方法，以及包含此类化合物的药物组合物。这些化合物可用于治疗炎症和自身免疫性疾病。
• PROTOZOAN PARASITE GROWTH INHIBITORS
  申请人：Northeastern University

  公开号：US20150259331A1

  公开（公告）日：2015-09-17

  Compounds and methods for inhibiting growth of a protozoan parasite. Methods of treating a protozoan parasite infection in a subject by administering a therapeutically effective amount of a compound as disclosed herein. The compounds and methods can be used to inhibit growth of protozoan parasites such as Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., and Plasmodium spp.

  用于抑制原生动物寄生虫生长的化合物和方法。通过向主体施用如本文所述的治疗有效量的化合物来治疗原生动物寄生虫感染的方法。这些化合物和方法可用于抑制如非洲锥虫、克鲁兹锥虫、利什曼原虫属和疟原虫属等原生动物寄生虫的生长。
• [EN] COMBINATION OF KINASE INHIBITORS AND USES THEREOF<br/>[FR] COMBINAISON D'INHIBITEURS DE KINASE ET SES UTILISATIONS
  申请人：INTELLIKINE LLC

  公开号：WO2014151147A1

  公开（公告）日：2014-09-25

  The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth. The present invention also provides a pharmaceutical kit effective for treating a disease condition associated with PI3 -kinase α and/or mTOR in a subject.

  本发明提供了一种治疗与受体内PI3-激酶α和/或mTOR相关的疾病状况的方法。另一方面，该发明提供了一种治疗与受体内PI3-激酶α和/或mTOR相关的疾病状况的方法。在另一个方面，提出了一种抑制细胞内Akt（S473）和Akt（T308）磷酸化的方法。本发明还提供了一种有效治疗与受体内PI3-激酶α和/或mTOR相关的疾病状况的药物套装。
• COMBINATION OF KINASE INHIBITORS AND USES THEREOF
  申请人：INTELLIKINE, LLC

  公开号：US20150030588A1

  公开（公告）日：2015-01-29

  The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or a receptor tyrosine kinase (RTK) in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or an RTK in a subject. In yet another aspect, a method of inhibiting phosphorylation of Akt (S473) in a cell is set forth.

  本发明提供了一种治疗与PI3-激酶a和/或受体酪氨酸激酶（RTK）有关的疾病状况的方法。另一方面，该发明提供了一种治疗与PI3-激酶α和/或受体酪氨酸激酶（RTK）有关的疾病状况的方法。另一方面，提出了一种抑制细胞中Akt（S473）磷酸化的方法。

表征谱图