3-硝基-6-氯咪唑并[1,2-b]哒嗪 | 18087-76-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 哒嗪类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-硝基-6-氯咪唑并[1,2-b]哒嗪
• 中文别名: 6-氯-3-硝基咪唑并[1,2-B]哒嗪；6-氯-3-硝基咪唑并[1,2-b]哒嗪；6-氯-3-硝基咪唑并[1,2-b]吡嗪
• 英文名称: 6-chloro-3-nitroimidazo[1,2-b]pyridazine
• 英文别名: 6-Chlor-3-nitro-imidazo<1,2-b>pyridazin
• CAS: 18087-76-8
• 化学式: C₆H₃ClN₄O₂
• mdl: MFCD08276991
• 分子量: 198.568
• InChiKey: IJEZMDPWGDWYKJ-UHFFFAOYSA-N

物化性质

• 熔点：
  142-145 °C
• 密度：
  1.85±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 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：
  76
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S26
• 危险类别码：
  R22,R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933990090
• 危险标志：
  GHS07
• 危险性描述：
  H302,H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338
• 储存条件：
  2-8°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 6-Chloro-3-nitroimidazo[1,2-b]pyridazine
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-Chloro-3-nitroimidazo[1,2-b]pyridazine
CAS number: 18087-76-8

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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.
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: C6H3ClN4O2
Molecular weight: 198.6

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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.

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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

反应信息

• 作为反应物：
  描述：

  3-硝基-6-氯咪唑并[1,2-b]哒嗪 在 盐酸 、 potassium fluoride 、 三乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 为溶剂， 生成 ({6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl}carbamoyl)methyl acetate
  参考文献：
  名称：

  COMPOUNDS AND COMPOSITIONS AS TRK INHIBITORS

  摘要：

  该发明提供了化合物、包含该化合物的药物组合物以及使用该化合物治疗或预防与TRK激酶活性异常或失调相关的疾病或病症的方法。

  公开号：

  US20120065184A1
• 作为产物：
  描述：

  6-氯咪唑并[1,2-b]哒嗪 在 硫酸 、 硝酸 作用下， 生成 3-硝基-6-氯咪唑并[1,2-b]哒嗪
  参考文献：
  名称：

  缩合唑衍生物的合成研究。IV。ω-氨磺酰基烷基氧基咪唑并[1,2-b]哒嗪的合成及抗哮喘活性。

  摘要：

  合成了一系列新颖的（咪唑并[1,2-b]哒嗪-6-基）氧基烷基磺酰胺，并评估了其抑制血小板活化因子（PAF）诱导的豚鼠支气管收缩的能力。发现在侧链的氨磺酰基丙氧基的2位上带有宝石二烷基或亚环烷基的化合物具有有效的活性。其中，3-（咪唑并[1,2-b]哒嗪-6-基）氧基-2,2-二甲基丙烷磺酰胺（6）具有优良的抗哮喘活性，且作用时间最长。发现在咪唑并[1,2-b]哒嗪环的7或8位带有甲基的化合物具有增强的活性。其中，3-（7-甲基咪唑并[1,2-b]哒嗪-6-基）氧基-2,2-二甲基丙烷磺酰胺（25）表现出最强的抑制作用，在过敏性哮喘实验模型中的抗哮喘作用优于茶碱。讨论了这一系列化合物中的构效关系。

  DOI：

  10.1248/cpb.44.122

文献信息

• 3-硝基-6-氯咪唑并[1,2-b]哒嗪的合成方法
  申请人：山东友帮生化科技有限公司

  公开号：CN106632353A

  公开（公告）日：2017-05-10

  本发明涉及一种3‑硝基‑6‑氯咪唑并[1,2‑b]哒嗪的合成方法。以3‑氨基‑6‑氯哒嗪、氯乙醛水溶液、硝酸为原料，3‑氨基‑6‑氯哒嗪，40%氯乙醛水溶液二者物质的量之比为1:1.0‑2.3，3‑氨基‑6‑氯哒嗪与硝酸物质的量之比为1:1.2‑6.0，在适当的溶剂中，于碱的作用下，于0‑90℃连续反应6‑12个小时生成3‑硝基‑6‑氯咪唑并[1,2‑b]哒嗪粗产品，经提纯后得到3‑硝基‑6‑氯咪唑并[1,2‑b]哒嗪纯品。本发明的原料比较易得，价格合理，同时制备反应中没有使用重金属和腐蚀性气体，反应温和，对反映设备没有特殊的要求，普通的耐腐蚀设备即可生产，另外本发明反应条件适中。
• Studies on Anti-MRSA Parenteral Cephalosporins. II. Synthesis and Antibacterial Activity of 7.BETA.-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetamido]-3-(substituted imidazo [1,2-b]pyridazinium-1-yl)methyl-3-cephem-4-carboxylates and Related Compounds.
  作者：TOMOYASU ISHIKAWA、KJEIJI KAMIYAMA、NOBUYUKI MATSUNAGA、HIROYUKI TAWADA、YUJI IIZAWA、KENJI OKONOGI、AKIO MIYAKE

  DOI：10.7164/antibiotics.53.1071

  日期：——

  In an effort to discover a novel cefozopran (CZOP) derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we performed chemical modification of the alkoxyimino moiety and imidazo[1, 2-b]pyridazinium group of CZOP. Among the prepared compounds, the cyclopentyloxyimino derivative 7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(Z)-cyclopentyloxyiminoacetamido]-3-(3, 6-diaminoimidazo[1, 2-b]pyridazinium-l-yl)methyl-3-cephem-4-carboxylate (20g) showed the most potent anti-MRSA activity, reflecting its high affinity (IC50=1.6 μg/ml) for penicillin binding protein 2' (PBP2'), although its anti-MRSA activity was slightly inferior to that of vancomycin (VCM). In experimental systemic infection in mice, however, 20g showed activity comparable to that of VCM against MRSA. In addition, 20g showed activity similar or slightly inferior to that of CZOP against Pseudomonas aeruginosa both in vitro and in vivo. Considering its favorable antibacterial activity profile, 20g was considered to be the most promising CZOP derivative for further studies.

  为了发现一种对耐甲氧西林金黄色葡萄球菌（MRSA）具有出色抗菌活性、新颖的头孢唑普兰（CZOP）衍生物，我们对CZOP的烷氧亚氨基部分和咪唑并[1,2-b]哒嗪鎓基团进行了化学修饰。在制备的化合物中，环戊氧亚氨基衍生物7β-[2-(5-氨基-1,2,4-噻二唑-3-基)-2(Z)-环戊氧亚氨基乙酰胺基]-3-(3,6-二氨基咪唑并[1,2-b]哒嗪鎓-1-基)甲基-3-头孢烯-4-羧酸酯（20g）表现出最强的抗MRSA活性，反映其对青霉素结合蛋白2'（PBP2'）的高亲和力（IC50=1.6μg/ml），尽管其抗MRSA活性略逊于万古霉素（VCM）。然而，在小鼠实验性系统感染中，20g对MRSA表现出与VCM相当的活性。此外，20g无论在体外还是体内，对铜绿假单胞菌（Pseudomonas aeruginosa）的活性与CZOP相似或略逊。综合其良好的抗菌活性特征，20g被认为是最有希望的CZOP衍生物，值得进一步研究。
• Dearomatization of Electron-Deficient Nitrogen Heterocycles via Cobalt-Catalyzed Asymmetric Cyclopropanation
  作者：Amruta Joshi-Pangu、Ryan D. Cohen、Matthew T. Tudge、Yonggang Chen

  DOI：10.1021/acs.joc.6b00322

  日期：2016.4.15

  The dearomatization of a series of electron-deficient nitrogen heterocycles has been achieved through a cobalt-catalyzed asymmetric cyclopropanation reaction. This reaction proceeds with high levels of enantio- and diastereoselectivity to afford unique cyclopropanes that can be further functionalized to provide complex heterocyclic building blocks.

  通过钴催化的不对称环丙烷化反应已实现了一系列电子不足的氮杂环的脱芳香化作用。该反应以高对映体和非对映体选择性进行，得到独特的环丙烷，其可以进一步官能化以提供复杂的杂环结构单元。
• Studies on Anti-MRSA Parenteral Cephalosporins. I. Synthesis and Antibacterial Activity of 7.BETA.-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2(Z)-hydroxyiminoacetamido]-3-(substituted imidazo [1,2-b]-pyridazinium-1-yl)methyl-3-cephem-4-carboxylates and Related Compounds.
  作者：TOMOYASU ISHIKAWA、YIJJI IIZAWA、KENJI OKONOGI、AKIO MIYAKE

  DOI：10.7164/antibiotics.53.1053

  日期：——

  In order to improve the antibacterial activity of cefozopran (CZOP) against methicillin-resistant Staphylococcus aureus (MRSA), we initiated chemical modification to introduce a 2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(Z)-hydroxyimino acetyl group at the C-7 position and a 3- or 6-substituted imidazo[1, 2-b]pyridazinium or 5-substituted imidazo[1, 2-a]pyridmium group at the C-3' position. Although this approach successfully enhanced the anti-MRSA activity of CZOP two to eight times, a slight decrease in the activity against Gram-negative bacteria including Pseudomonas aeruginosa was involved. Among the novel derivatives, 3-(6-aminoimidazo[1, 2-b]pyridazinium-1-yl)methyl-7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(Z)-hydroxyiminoacetamido]-3-cephem-4-carboxylate (44a) showed an excellent balance of activity against MRSA and Gram-negative bacteria.

  为了提高cefozopran (CZOP) 对耐甲氧西林金黄色葡萄球菌 (MRSA) 的抗菌活性，我们开始了化学修饰，引入一个2-(5-氨基-1, 2, 4-噻二唑-3-基)-2(Z)-羟亚氨基乙酰基团在C-7位，以及一个3位或6位取代的咪唑[1, 2-b]吡啶鎓或5位取代的咪唑[1, 2-a]吡啶鎓基团在C-3'位。尽管这种方法成功地将CZOP对MRSA的抗性提高了两到八倍，但对包括铜绿假单胞菌在内的革兰氏阴性菌的活性略有下降。在这些新衍生物中，3-(6-氨基咪唑[1, 2-b]吡啶鎓-1-基)甲基-7β-[2-(5-氨基-1, 2, 4-噻二唑-3-基)-2(Z)-羟亚氨基乙酰氨基]-3-头孢烯-4-羧酸酯(44a)表现出了对MRSA和革兰氏阴性菌的活性之间的优良平衡。
• 一类咪唑并芳环类化合物的制备和应用
  申请人：上海轶诺药业有限公司

  公开号：CN111269233A

  公开（公告）日：2020-06-12

  本发明提供了一类芳香酰胺化合物的制备和应用，具体地，本发明提供了一种如下式I所示的化合物，其中，各基团的定义如说明书中所述。所述的化合物具有TRK激酶抑制活性，可以作为治疗TRK功能异常相关疾病的药物组合物。