6-氯咪唑[1,2A]吡嗪 | 76537-23-0

• 物质功能分类: 医药中间体 - 杂环化合物
• 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-氯咪唑[1,2A]吡嗪
• 中文别名: 6-氯咪唑并[1,2-A]吡嗪；6-氯咪唑[1,2-A]吡嗪；6-氯咪唑并[1,2-a]吡嗪
• 英文名称: 6-chloroimidazo<1,2-a>pyrazine
• 英文别名: 6-chloroimidazo[1,2-a]pyrazine
• CAS: 76537-23-0
• 化学式: C₆H₄ClN₃
• mdl: MFCD09909644
• 分子量: 153.571
• InChiKey: PTWXEVLXAHFMKK-UHFFFAOYSA-N

物化性质

• 熔点：
  137-138℃
• 密度：
  1.51

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 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：
  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

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 6-Chloroimidazo[1,2-a]pyrazine
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-Chloroimidazo[1,2-a]pyrazine
CAS number: 76537-23-0

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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.
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: C6H4ClN3
Molecular weight: 153.6

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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

制备方法与用途

用途

6-氯咪唑[1,2A]吡嗪是一种杂环衍生物，可用作医药中间体。

制备

以2-氨基吡嗪为起始原料，经过氯代反应、亚胺化反应和缩合反应，简便地合成目标产物6-氯代咪唑并[1,2-a]吡嗪。此方法具有制备方法新颖、原料廉价易得、采用结晶方式纯化、避免柱层析分离、易于放大生产以及总收率明显提高等优点。6-氯代咪唑并[1,2-a]吡嗪的合成反应式如下图所示：

反应信息

• 作为反应物：
  描述：

  6-氯咪唑[1,2A]吡嗪 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以47.2%的产率得到3-溴-6-氯咪唑并[1,2-a]吡嗪
  参考文献：
  名称：

  氮杂双环衍生物、其制法与医药上的用途

  摘要：

  本发明涉及氮杂双环衍生物、其制法与医药上的用途。具体地，本发明公开了式(I)化合物或其药学上可接受的盐、立体异构体、溶剂化合物或前药，及其制备方法，及其在EGFR抑制剂方面的应用，式中各基团的定义详见说明书。

  公开号：

  CN105524068B
• 作为产物：
  描述：

  氯乙醛 、 2-氨基-5-氯吡嗪 以 异丙醇 为溶剂， 反应 16.0h， 以33%的产率得到6-氯咪唑[1,2A]吡嗪
  参考文献：
  名称：

  [EN] COMPOUNDS AND THEIR METHODS OF USE
  [FR] COMPOSÉS ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本发明部分涉及融合的杂环化合物和组合物，用于预防和/或治疗与电压门控钠离子通道异常功能相关的疾病或病况，例如异常的晚期/持续性钠电流。本文还提供了治疗与钠离子通道异常功能相关的疾病或病况的方法，包括德拉维特综合征或癫痫。

  公开号：

  WO2018098500A1

文献信息

• Piperazinylimidazo[1,2-a]pyrazines with selective affinity for in vitro .alpha.-adrenergic receptor subtypes
  作者：William C. Lumma、William C. Randall、E. L. Cresson、Joel R. Huff、Richard D. Hartman、T. F. Lyon

  DOI：10.1021/jm00357a009

  日期：1983.3

  structure-affinity relationships for alpha 2- vs. alpha 1-adrenergic receptors are considered. Compound 2a, 8-(1-piperazinyl)imidazo[1,2-a]pyrazine, is equipotent with mianserin on the clonidine receptor (alpha 2) but ca. 70 times as selective as mianserin for this alpha 2-adrenergic receptor. Reduction of the imidazo ring (2,3-dihydro) lowers affinity for the alpha 2 receptor without affecting alpha 1-receptor

  描述了通过[（β-羟烷基）氨基]吡嗪的新型氧化脱水的烷基和卤素取代的哌嗪基咪唑并[1,2-a]吡嗪的区域选择性合成。镧系元素位移试剂的研究可以纠正咪唑并[1,2-a]吡嗪环系统（例如，J5,8大于J6,8）的NMR化学位移和偶联常数的文献指配。表中列出了参考和标题化合物从小腿大脑皮层匀浆中特异性结合的[3H]可乐定和[3H]哌唑嗪置换的平衡常数，供参考和标题化合物使用，并考虑了α2与α1肾上腺素受体的结构亲和力关系。化合物2a，8-（1-哌嗪基）咪唑并[1,2-a]吡嗪，与mianserin在可乐定受体（α2）上等效，但在 对这种α2-肾上腺素能受体的选择性是棉兰素的70倍。咪唑环（2，3-二氢）的还原降低了对α2受体的亲和力，而不影响α1受体的亲和力。计算机辅助分子建模技术被应用于估计2a及其相对于半刚性分子mianerin的5位异构体的构象能。
• Piperazinyl-imidazo[1,2-a]pyrazines
  申请人：Merck & Co., Inc.

  公开号：US04242344A1

  公开（公告）日：1980-12-30

  Piperazinyl-imidazo[1,2-a]pyrazines, derived from reactions between halo-imidazo[1,2-a]pyrazines with piperazine derivatives, are found to be active anorexic, antidepressant, antihypertensive, analgesic, antiarrhythmic, and/or anti-smoking agents.

  从卤代咪唑[1,2-a]吡嗪与哌嗪衍生物反应而得的哌嗪基咪唑[1,2-a]吡嗪，被发现具有活性，可用作厌食症、抗抑郁、降压、镇痛、抗心律失常和/或戒烟药剂。
• [EN] MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS MULTI-CYCLIQUES INHIBITEURS DE FLT3 ET IRAK ET LEURS UTILISATIONS
  申请人：CHILDRENS HOSPITAL MED CT

  公开号：WO2022140647A1

  公开（公告）日：2022-06-30

  Some embodiments of the disclosure include inventive compounds (e.g., compounds of Formula (I)) and compositions (e.g., pharmaceutical compositions) which inhibit IRAK and/or FLT3 and which can be used for treating, for example, certain diseases. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as hematopoietic cancers, myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), etc.), Additional embodiments provide disease treatment using combinations of the inventive IRAK and/or FLT3 inhibiting compounds with other therapies, such as cancer therapies.

  本发明的一些实施例包括创新化合物（例如，公式（I）化合物）和组合物（例如，制药组合物），其抑制IRAK和/或FLT3，并可用于治疗某些疾病。一些实施例包括使用创新化合物的方法（例如，用于组合物或制药组合物中）进行给药和治疗（例如，血液肿瘤、骨髓增生异常综合症（MDS）、急性髓系白血病（AML）等疾病）。另外的实施例提供使用创新的IRAK和/或FLT3抑制化合物与其他疗法（例如癌症疗法）的组合进行疾病治疗。
• Structure-Activity relationships of replacements for the triazolopyridazine of Anti-Cryptosporidium lead SLU-2633
  作者：Edmund Oboh、José E. Teixeira、Tanner J. Schubert、Adriana S. Maribona、Brylon N. Denman、Radhika Patel、Christopher D. Huston、Marvin J. Meyers

  DOI：10.1016/j.bmc.2023.117295

  日期：2023.5

  competitive binding assay. While most other heterocycles were significantly less potent than the lead, some analogs such as azabenzothiazole 31b, have promising potency in the low micromolar range, similar to the drug nitazoxanide, and represent potential new leads for optimization. Overall, this work highlights the important role of the terminal heterocyclic head group and represents a significant extension

  隐孢子虫病是一种腹泻病，对儿童和免疫功能低下的人尤其有害。感染由寄生虫隐孢子虫引起，严重时会导致脱水、营养不良甚至死亡。硝唑尼特是 FDA 唯一批准的药物，但对儿童的疗效有限，对免疫功能低下的患者无效。为了解决这一未满足的医疗需求，我们之前鉴定出三唑并哒嗪 SLU-2633 对小隐孢子虫有效，EC 50为 0.17 µM。在本研究中，我们通过探索不同的杂芳基，开发了用于取代三唑并哒嗪头基的构效关系（SAR），目的是在保持效力的同时降低对 hERG 通道的亲和力。合成了 64 种 SLU-2633 的新类似物，并分析了其相对小隐孢子虫的效力。最有效的化合物 7,8-二氢-[1,2,4]三唑并[4,3 -b ]哒嗪17a的Cp EC 50为 1.2 µM，比 SLU-2633 低 7 倍但亲脂效率 (LipE) 得分有所提高。发现17a在 hERG 膜片钳测定中相对于 10 µM 的 SLU-2633
• Calculation-assisted regioselective functionalization of the imidazo[1,2-<i>a</i>]pyrazine scaffold <i>via</i> zinc and magnesium organometallic intermediates
  作者：Agonist Kastrati、Alexander Kremsmair、Alisa S. Sunagatullina、Vasilii Korotenko、Yusuf C. Guersoy、Saroj K. Rout、Fabio Lima、Cara E. Brocklehurst、Konstantin Karaghiosoff、Hendrik Zipse、Paul Knochel

  DOI：10.1039/d3sc02893c

  日期：——

  regioselective functionalization of the underexplored fused N-heterocycle imidazo[1,2-a]pyrazine. Thus, regioselective metalations of 6-chloroimidazo[1,2-a]pyrazine using TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) such as TMPMgCl·LiCl and TMP2Zn·2MgCl2·2LiCl provided Zn- and Mg-intermediates, that after quenching with various electrophiles gave access to polyfunctionalized imidazopyrazine heterocycles. Additionally

  pKa值和N-碱度的测定等简单计算使得开发出一系列有机金属反应，用于未充分探索的稠合N-杂环咪唑并[1,2- a ]吡嗪的区域选择性功能化。因此，使用 TMP 碱（TMP = 2,2,6,6-四甲基哌啶基）（例如 TMPMgCl·LiCl 和 TMP 2 Zn·2MgCl 2 ·2LiCl ）对 6-氯咪唑并[1,2- a ]吡嗪进行区域选择性金属化，提供了 Zn-和镁中间体，用各种亲电试剂猝灭后得到多官能化咪唑并吡嗪杂环。此外，使用TMP 2 Zn·2MgCl 2 ·2LiCl作为第一次金属化的碱允许替代的区域选择性金属化。第 8 位的亲核加成以及选择性根岸交叉偶联完善了选择性修饰这种未来杂环的一套方法。