6,8-二溴咪唑并[1,2-a]吡嗪 | 63744-22-9

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡嗪类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡嗪类
• 中文名称: 6,8-二溴咪唑并[1,2-a]吡嗪
• 中文别名: 6,8-二溴-咪唑[1,2-A]吡嗪
• 英文名称: 6,8-dibromoimidazo[1,2-a]pyrazine
• 英文别名: 6,8-dibromoimidazo<1,2-a>pyrazine；6,8-dibromoimidazole[1,2-a]pyrazine
• CAS: 63744-22-9
• 化学式: C₆H₃Br₂N₃
• mdl: MFCD08460056
• 分子量: 276.918
• InChiKey: UQCZZGIPIMJBCL-UHFFFAOYSA-N

物化性质

• 熔点：
  165.0 to 169.0 °C
• 密度：
  2.35±0.1 g/cm3(Predicted)
• pKa：
  -0.36±0.30 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  11
• 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：
  30.2
• 氢给体数：
  0
• 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
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
6,8-Dibromoimidazo[1,2-a]pyrazine
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
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P302+P352: IF ON SKIN: Wash with soap and water
P321: Specific treatment (see on this label)
P405: Store locked up

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Section 3. Composition/information on ingredients.
6,8-Dibromoimidazo[1,2-a]pyrazine
Ingredient name:
CAS number: 63744-22-9

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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, refrigerated.

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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: C6H3Br2N3
Molecular weight: 276.9

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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 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

6,8-二溴咪唑并[1,2a]吡嗪是一种重要的药物中间体，可用于制备新型有机电致发光材料。该化合物也可通过合成具有改良效能的有机电致发光装置。

在50 mL单口圆底烧瓶中加入2-氨基-3,5-二溴吡嗪（2.53 g，10 mmol）、氯乙醛（1.96 g，10 mmol）和乙腈10 mL。将反应混合物加热至80℃并搅拌反应10小时。通过TLC和GC确认反应完全。

反应结束后，旋蒸除去溶剂得到粗产品，并使用硅胶柱层析分离获得纯度为98.30%（HPLC）、熔点在114℃-117℃的6,8-二溴咪唑并[1,2a]吡嗪。产率为61.73%。

核磁共振分析结果如下：1HNMR(400 Hz，氘代氯仿)δ: 8.288 (d, 1H)，7.887 (dd, 1H)，7.793 (dd, 1H)。

反应信息

• 作为反应物：
  描述：

  6,8-二溴咪唑并[1,2-a]吡嗪 在 聚合甲醛 、 sodium cyanoborohydride 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 6-bromo-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)imidazo[1,2-a]pyrazin-8-amine
  参考文献：
  名称：

  BICYCLIC PIPERAZINE COMPOUNDS

  摘要：

  提供了公式I的双环哌嗪化合物，包括其立体异构体、互变异构体和药学上可接受的盐，用于抑制Btk激酶，并用于治疗由Btk激酶介导的炎症等免疫紊乱。公开了使用公式I化合物进行体外、体内和体内诊断以及治疗哺乳动物细胞中的这类紊乱，或相关的病理条件的方法。

  公开号：

  US20130116262A1
• 作为产物：
  描述：

  氯乙醛 、 2-氨基-3,5-二溴吡嗪 以 水 、 异丙醇 为溶剂， 反应 24.0h， 以80%的产率得到6,8-二溴咪唑并[1,2-a]吡嗪
  参考文献：
  名称：

  取代咪唑-[1,2-a]吡嗪的旋转异构构象研究：实验和理论方法†

  摘要：

  咪唑-[1,2- a的不同旋转异构体构象]吡嗪已通过不同的实验技术，如NMR、FTIR、吸收光谱和量子化学计算进行合成和表征。不同的构象由氢键稳定，如OH⋯N、ArH⋯N和ArH⋯ArH。使用密度泛函理论 (DFT) 生成的基态优化和势能表面 (PES) 扫描曲线显示每个分子有两种稳定的旋转异构形式。构象的相对数量受氢键强度的影响。计算的吸收光谱和同位素屏蔽常数分别通过时变密度泛函理论 (TD-DFT) 和规范不变原子轨道 (GIAO)-DFT 获得。

  DOI：

  10.1039/c7ra13617j
• 作为试剂：
  描述：

  4-(4-吗啉基)苯胺 、 6,8-二溴咪唑并[1,2-a]吡嗪 在 6,8-二溴咪唑并[1,2-a]吡嗪 作用下， 生成 6-溴-N-[4-(4-吗啉基)苯基]咪唑并[1,2-a]吡嗪-8-胺
  参考文献：
  名称：

  J. Med. Chem. 2014, 57, 3856-3873

  摘要：

  DOI：

文献信息

• [EN] CONDENSED IMIDAZOLE DERIVATIVES SUBSTITUTED BY TERTIARY HYDROXY GROUPS AS PI3K-GAMMA INHIBITORS<br/>[FR] DÉRIVÉS D'IMIDAZOLE CONDENSÉS, SUBSTITUÉS PAR DES GROUPES HYDROXY TERTIAIRES, UTILISÉS COMME INHIBITEURS DE PI3K-GAMMA
  申请人：INCYTE CORP

  公开号：WO2019079469A1

  公开（公告）日：2019-04-25

  This application relates to compounds of Formula (I): or pharmaceutically acceptable salts thereof, which are inhibitors of PI3K-y which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.

  这种应用涉及到式(I)的化合物或其药用可接受的盐，这些化合物是PI3K-y的抑制剂，对于治疗自身免疫疾病、癌症、心血管疾病和神经退行性疾病等疾病是有用的。
• [EN] CERTAIN HETEROCYCLIC SUBSTITUTED IMIDAZO[1,2-A]PYRAZIN-8-YLAMINES AND METHODS OF INHIBITION OF BRUTON'S TYROSINE KINASE BY SUCH COMPOUNDS<br/>[FR] CERTAINES IMIDAZO[1,2-A]PYRAZIN-8-YLAMINES SUBSTITUEES HETEROCYCLIQUES ET METHODES D'INHIBITION DE LA TYROSINE KINASE DE BRUTON UTILISANT CES COMPOSES
  申请人：CELLULAR GENOMICS INC

  公开号：WO2005005429A1

  公开（公告）日：2005-01-20

  Compounds of formula (I) and all pharmaceutically acceptable forms thereof, are described herein. The variables R1, R2, R3, Z2, and Q, shown in Formula I are defined herein. Pharmaceutical compositions containing one or more compounds of Formula I, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and/or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and/or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases. Other embodiments include methods of treating other animals, including livestock and domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity. Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with one or more other therapeutic agent. A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.

  公式(I)的化合物及其所有药物可接受的形态在此描述。公式I中所示的变量R1、R2、R3、Z2和Q在此定义。提供含有公式I的一个或多个化合物，或此类化合物的药物可接受的形态，以及一个或多个药物可接受的载体、辅料或稀释剂的药物组合物。还提供了治疗对抑制酪氨酸激酶活性有反应的某些疾病患者的方法。在某些实施例中，这些疾病对抑制Btk活性和/或B细胞增殖有反应。这些方法包括向患者给药公式I的化合物，以减少疾病的迹象或症状。这些疾病包括癌症、自身免疫和/或炎症性疾病，或急性炎症反应。因此，治疗方法包括给药足够量的本处提供的化合物或盐，以减少这些疾病的症状或减缓这些疾病的进展。其他实施例包括治疗其他动物的方法，包括家畜和驯养的伴侣动物，这些动物患有一种对抑制激酶活性有反应的疾病。治疗方法包括将公式I的化合物作为单一活性剂给药，或将公式I的化合物与一个或多个其他治疗剂组合给药。一种用于确定样本中Btk存在的方法，包括在允许检测Btk活性的条件下将样本与公式I的化合物或其形态接触，检测样本中的Btk活性水平，并据此确定样本中Btk的存在或不存在。
• [EN] IMIDAZOPYRAZINE SYK INHIBITORS<br/>[FR] INHIBITEURS IMIDAZOPYRAZINE DE LA SYK
  申请人：GILEAD CONNECTICUT INC

  公开号：WO2013188856A1

  公开（公告）日：2013-12-19

  Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of an imidazopyrazine compound effective to reduce signs or symptoms of the disease or disorder are provided.

  本发明提供了某些咪唑并吡唑化合物及其药物组合物。还提供了治疗患有某些对Syk活性抑制有响应的疾病和障碍的患者的方法，该方法包括向这样的患者施用足以减少疾病或障碍的症状或体征的咪唑并吡唑化合物。
• [EN] THIOPENE-BASED TRICYCLIC COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS COMPRISING SAME<br/>[FR] COMPOSÉS TRICYCLIQUES À BASE DE THIOPÈNE ET COMPOSITIONS PHARMACEUTIQUES RENFERMANT LESDITS COMPOSÉS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2003084959A1

  公开（公告）日：2003-10-16

  Compounds having the formula (I), and pharmaceutically-acceptable salts, hydrates and prodrugs thereof, are useful as anti-inflammatory agents, in which R1, R2, and R3 are hydrogen, halogen, alkyl, or perfluoroalkyl; R4 is an optionally substituted alkyl or cycloalkyl group; X is a linker; A is an aryl, heteroaryl, heterocycle, cycloalkyl, or is absent; and R7 is a substituent on A as defined in the specification.

  具有公式(I)的化合物，以及其中所述化合物的药物可接受的盐、水合物和前药，作为抗炎剂是有用的，其中R1、R2和R3是氢、卤素、烷基或全氟烷基；R4是可选地取代的烷基或环烷基团；X是连接基；A是芳基、杂芳基、杂环、环烷基，或是缺失的；R7是如说明书中定义的A上的取代基。
• 一种6,8-二溴咪唑并[1,2a]吡嗪的合成方法
  申请人：山东友帮生化科技有限公司

  公开号：CN106632354A

  公开（公告）日：2017-05-10

  本发明涉及一种6,8‑二溴咪唑并[1,2a]吡嗪的合成方法，包括以下步骤：以2‑氨基‑3,5‑二溴吡嗪和氯乙醛为原料，在适当溶剂中，于25‑150℃反应4‑12小时，经提纯后得纯品6,8‑二溴咪唑并[1,2a]吡嗪。反应原料比较易得，价格合理，反应条件温和，易于操作，易于控制，后处理简单，且产品质量稳定，纯度高。