2-氨基-3-溴-6-氯吡嗪 | 212779-21-0

• 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 - 二嗪类
• 中文名称: 2-氨基-3-溴-6-氯吡嗪
• 英文名称: 3-bromo-6-chloropyrazin-2-amine
• 英文别名: 2-amino-3-bromo-6-chloropyrazine；3-bromo-6-chloropyrazine-2-amine
• CAS: 212779-21-0
• 化学式: C₄H₃BrClN₃
• 分子量: 208.445
• InChiKey: BOLCKGGORFPPJC-UHFFFAOYSA-N

物化性质

• 沸点：
  299.5±35.0 °C(Predicted)
• 密度：
  1.960

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

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：
  2-8°C

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 2-Amino-3-bromo-6-chloropyrazine
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: 2-Amino-3-bromo-6-chloropyrazine
CAS number: 212779-21-0

---

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.

---

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.
Store in closed vessels, refrigerated.
Storage:

---

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
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C4H3BrClN3
Molecular weight: 208.4

---

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.

---

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
Non-harzardous for air and ground transportation.

---

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

用途

2-氨基-3-溴-6-氯吡嗪在药物中具有重要用途，是合成抗肿瘤药物SHP2抑制剂的关键中间体。

制备方法

1. 在有机溶剂中加入2-氨基-6-氯吡嗪，体系降温后，加入催化剂。
2. 滴加液溴作为溴化试剂，并在滴加完毕后保温反应。通过TLC检测跟踪反应进程。
3. 向体系内加入亚硫酸钠溶液至红色褪去。进行氯仿萃取、水洗和无水硫酸钠干燥处理，随后浓缩并用硅胶柱粗过，最后重结晶得到黄色固体化合物2-氨基-3-溴-6-氯吡嗪。

反应信息

• 作为反应物：
  描述：

  2-氨基-3-溴-6-氯吡嗪 在 三溴化硼 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 16.0h， 生成 3-amino-5-chloro-2(1H)-pyrazinone
  参考文献：
  名称：

  [EN] DIHYDROQUINAZOLIN-2-ONE DERIVATIVES AS SELECTIVE CYTOTOXIC AGENTS USEFUL IN THE TREATMENT OF HIV
  [FR] DÉRIVÉS DE DIHYDROQUINAZOLIN-2-ONE EN TANT QU'AGENTS CYTOTOXIQUES SÉLECTIFS UTILES DANS LE TRAITEMENT DU VIH

  摘要：

  本公开涉及公式I的四氢喹噁啉衍生物及其用于选择性杀灭HIV感染的GAG-POL表达细胞，而不对HIV天然细胞产生细胞毒性，以及用于治疗或预防HIV感染，或用于治疗、预防或延缓艾滋病或艾滋病相关综合征（ARC）的发病或进展。

  公开号：

  WO2022046844A1
• 作为产物：
  描述：

  2-氨基-6-氯吡嗪 以43的产率得到2-氨基-3-溴-6-氯吡嗪
  参考文献：
  名称：

  Pyrazine compounds

  摘要：

  化合物的公式（I），其中R1是苯基，其被一个或多个卤素原子取代，萘基和其被一个或多个卤素原子取代；R2是—NH2和—NHC(═O)Ra；R3是—NRbRc，—NHC(═O)Ra或氢；R4是氢，—C1-4烷基，—CN，—CH2OH，—CH2ORd，—CH2S(O)xRd和—C1-4烷基，其被一个或多个卤素原子取代，其中Ra代表C1-4烷基或C3-7环烷基，而Rb和Rc可能相同或不同，是氢或C1-4烷基，或者与它们所连接的氮原子一起形成一个含氮的6元杂环，该杂环可以进一步被一个或多个C1-4烷基取代；Rd是C1-4烷基或C1-4烷基，其被一个或多个卤素原子取代；x是整数零，一或二；以及它们的盐，溶剂化合物和前药，但前提是当R2是—NH2时，R1不代表任何物质，而当R3和R4均为氢时，该化合物有用作镇痛剂，抗癫痫药，治疗双相障碍和神经保护剂。

  公开号：

  US06599905B2
• 作为试剂：
  描述：

  2-氨基-3-溴-6-氯吡嗪 、 2,3,5-三氯苯硼酸 在 2-氨基-3-溴-6-氯吡嗪 作用下， 以14的产率得到2-amino-6-chloro-3-(2,3,5-trichlorophenyl)pyrazine
  参考文献：
  名称：

  Pyrazine compounds

  摘要：

  化合物的公式（I），其中R1是苯基，其被一个或多个卤素原子取代，萘基和其被一个或多个卤素原子取代；R2是—NH2和—NHC(═O)Ra；R3是—NRbRc，—NHC(═O)Ra或氢；R4是氢，—C1-4烷基，—CN，—CH2OH，—CH2ORd，—CH2S(O)xRd和—C1-4烷基，其被一个或多个卤素原子取代，其中Ra代表C1-4烷基或C3-7环烷基，而Rb和Rc可能相同或不同，是氢或C1-4烷基，或者与它们所连接的氮原子一起形成一个含氮的6元杂环，该杂环可以进一步被一个或多个C1-4烷基取代；Rd是C1-4烷基或C1-4烷基，其被一个或多个卤素原子取代；x是整数零，一或二；以及它们的盐，溶剂化合物和前药，但前提是当R2是—NH2时，R1不代表任何物质，而当R3和R4均为氢时，该化合物有用作镇痛剂，抗癫痫药，治疗双相障碍和神经保护剂。

  公开号：

  US06599905B2

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF SHP2<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR INHIBER L'ACTIVITÉ DE SHP2
  申请人：NOVARTIS AG

  公开号：WO2016203404A1

  公开（公告）日：2016-12-22

  The present invention relates to compounds of formula I. The compounds are inhibitors of the Src Homolgy-2 phosphatase (SHP2) and thus useful in the treatment of Noonan Syndrome, Leopard Syndrome and cancer.

  本发明涉及式I的化合物。这些化合物是Src同源-2磷酸酶（SHP2）的抑制剂，因此在努南综合征、豹纹综合征和癌症的治疗中有用。
• [EN] NOVEL HETEROCYCLIC DERIVATIVES USEFUL AS SHP2 INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS HÉTÉROCYCLIQUES UTILES EN TANT QU'INHIBITEURS DE SHP2
  申请人：JACOBIO PHARMACEUTICALS CO LTD

  公开号：WO2017211303A1

  公开（公告）日：2017-12-14

  Provided are certain pyrazine derivatives (I) as SHP2 inhibitors which is shown as formula (I), their synthesis and their use for treating a SHP2 mediated disorder. More particularly, provided are fused heterocyclic derivatives useful as inhibitors of SHP2, methods for producing such compounds and methods for treating a SHP2-mediated disorder.

  提供了某些吡嗪衍生物（I）作为SHP2抑制剂，其化学式如下（I），以及它们的合成和用于治疗SHP2介导的疾病。更具体地，提供了有用作为SHP2抑制剂的融合杂环衍生物，生产这类化合物的方法以及治疗SHP2介导的疾病的方法。
• [EN] SUBSTITUTED TETRAHYDROQUINOLINONE COMPOUNDS AS ROR GAMMA MODULATORS<br/>[FR] COMPOSÉS TÉTRAHYDROQUINOLINONE SUBSTITUÉS EN TANT QUE MODULATEURS DE ROR GAMMA
  申请人：AURIGENE DISCOVERY TECH LTD

  公开号：WO2016185342A1

  公开（公告）日：2016-11-24

  The present invention provides substituted tetrahydroquinolinone and related compounds of formula (I), which are therapeutically useful as modulators of Retinoic acid receptor-related orphan receptors (RORs), more particularly as RORγ modulators. These compounds are useful in the treatment and prevention of diseases and/or disorder, in particular their use in diseases and/or disorder mediated by RORγ receptor. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of the substituted tetrahydroquinolinone or related compounds of formula (I), together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

  本发明提供了公式（I）的取代四氢喹啉酮及相关化合物，作为视黄酸受体相关孤儿受体（RORs）的调节剂，在RORγ调节剂方面具有治疗上的用途。这些化合物在治疗和预防疾病和/或紊乱方面具有用途，特别是它们在由RORγ受体介导的疾病和/或紊乱中的用途。本发明还提供了这些化合物的制备以及包含至少一种取代四氢喹啉酮或相关化合物的制剂和药物配方，以及其所用的药学上可接受的载体、稀释剂或赋形剂。
• Targeted Degradation of the Oncogenic Phosphatase SHP2
  作者：Vidyasiri Vemulapalli、Katherine A. Donovan、Tom C. M. Seegar、Julia M. Rogers、Munhyung Bae、Ryan J. Lumpkin、Ruili Cao、Matthew T. Henke、Soumya S. Ray、Eric S. Fischer、Gregory D. Cuny、Stephen C. Blacklow

  DOI：10.1021/acs.biochem.1c00377

  日期：2021.8.31

  development and evaluation of a SHP2 PROTAC created by conjugating RMC-4550 with pomalidomide using a PEG linker. This molecule is highly selective for SHP2, induces degradation of SHP2 in leukemic cells at submicromolar concentrations, inhibits MAPK signaling, and suppresses cancer cell growth. SHP2 PROTACs serve as an alternative strategy for targeting ERK-dependent cancers and are useful tools alongside

  SHP2 是一种蛋白质酪氨酸磷酸酶，在受体酪氨酸激酶刺激后，在 Ras-MAPK 通路的完全激活中起关键作用，受体酪氨酸激酶在人类癌症中经常被放大或突变激活。此外，SHP2 中的激活突变会导致发育障碍和血液系统恶性肿瘤。已经为 SHP2 开发了几种变构抑制剂，目前正在临床试验中。在这里，我们报告了通过使用 PEG 接头将 RMC-4550 与泊马度胺结合而创建的 SHP2 PROTAC 的开发和评估。该分子对 SHP2 具有高度选择性，在亚微摩尔浓度下诱导白血病细胞中 SHP2 的降解，抑制 MAPK 信号传导，并抑制癌细胞生长。
• [EN] BICYCLIC COMPOUNDS AS ALLOSTERIC SHP2 INHIBITORS<br/>[FR] COMPOSÉS BICYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS ALLOSTÉRIQUES DE SHP2
  申请人：REVOLUTION MEDICINES INC

  公开号：WO2018136265A1

  公开（公告）日：2018-07-26

  The present disclosure is directed to inhibitors of SHP2 and their use in the treatment of disease. Also disclosed are pharmaceutical compositions comprising the same.

  本公开涉及SHP2的抑制剂及其在治疗疾病中的应用。还公开了包含相同成分的药物组合物。