3-溴-4-氯-1H-吡唑啉并嘧啶 | 90914-41-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 3-溴-4-氯-1H-吡唑啉并嘧啶
• 中文别名: 3-溴-4-氯-1H-吡唑并[3.4-D]嘧啶；3-溴-4-氯-1H-吡唑并[3,4-d]嘧啶；3-溴-4-氯-1H-吡咯并嘧啶
• 英文名称: 3-bromo-4-chloro-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 3-bromo-4-chloro-2H-pyrazolo[3,4-d]pyrimidine
• CAS: 90914-41-3
• 化学式: C₅H₂BrClN₄
• mdl: MFCD08276165
• 分子量: 233.455
• InChiKey: MDFHFCAMBZNSLV-UHFFFAOYSA-N

物化性质

• 沸点：
  270.3±50.0 °C(Predicted)
• 密度：
  2.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  54.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  T
• 安全说明：
  S45
• 危险类别码：
  R25
• 海关编码：
  2933990090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Bromo-4-chloro-1H-pyrazolo[3,4-d]pyrimidine
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: 3-Bromo-4-chloro-1H-pyrazolo[3,4-d]pyrimidine
CAS number: 90914-41-3

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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.
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
Appearance: Not specified
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H2BrClN4
Molecular weight: 233.5

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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

简介

吡唑并[3,4-d]嘧啶衍生物是一类含氮稠环化合物，因其与嘌呤的结构类似性而具有重要的药理作用。相关报道显示这类化合物具有多种生物学效应，包括抗凝血、抗菌和抗癌等。

制备

首先，在500 mL三口瓶中加入150 mL甲酰胺和10.8 g（100.0 mmol）的3-氨基-4-氰基吡唑。将反应物加热至180℃，反应10小时后通过薄层色谱（TLC）监测确认反应完成。随后加入200 mL水稀释反应体系，观察到白色浑浊。通过减压抽滤得到白色滤饼，并用冰水洗涤。最后，在真空条件下干燥得到白色固体1H-吡唑并[3,4-d]嘧啶-4-胺，总收率为13.1 g。

其次，在250 mL三口瓶中加入6.8 g（50.0 mmol）的1H-吡唑并[3,4-d]嘧啶-4-胺、16.9 g（75.0 mmol）N-溴代丁二酰亚胺和60 mL N,N-二甲基甲酰胺。将反应体系加热至100℃，反应8小时后通过TLC监测确认反应完成。过滤得到灰白色粗品，并用冰乙醇溶液洗涤。最终，得到了化合物12.8 g，收率为98.1%。

最后，该化合物还可通过三氯氧磷氯代反应进一步制备目标化合物。

反应信息

• 作为反应物：
  描述：

  3-溴-4-氯-1H-吡唑啉并嘧啶 在 盐酸 、 sodium hydride 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 3.5h， 生成 (R)-[2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-piperazin-1-yl]-1-(4-chlorobenzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] AKT PROTEIN KINASE INHIBITORS
  [FR] INHIBITEURS DE LA PROTEINE KINASE AKT

  摘要：

  公开号：

  WO2005051304A3
• 作为产物：
  描述：

  别嘌醇 在 N-溴代丁二酰亚胺(NBS) 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 6.5h， 生成 3-溴-4-氯-1H-吡唑啉并嘧啶
  参考文献：
  名称：

  [EN] AKT PROTEIN KINASE INHIBITORS
  [FR] INHIBITEURS DE LA PROTEINE KINASE AKT

  摘要：

  公开号：

  WO2005051304A3
• 作为试剂：
  描述：

  4,4,4-Trifluoro-1-[4-methyl-3-piperazin-1-yl-5-(2-pyrrolidin-1-ylethylamino)phenyl]butan-1-one 、 3-溴-4-氯-1H-吡唑啉并嘧啶 在 3-溴-4-氯-1H-吡唑啉并嘧啶 作用下， 生成 1-[3-[4-(3-溴-1H-吡唑并[3,4-d]嘧啶-4-基)-1-哌嗪]-4-甲基-5-[[2-(1-吡咯烷)乙基]氨基]苯基]-4,4,4-三氟-1-丁酮
  参考文献：
  名称：

  Bioorg. Med. Chem. Lett. 2012, 22, 2693-2697

  摘要：

  DOI：

文献信息

• [EN] ERBB INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE ERBB ET LEURS UTILISATIONS
  申请人：UNIV CALIFORNIA

  公开号：WO2017184775A1

  公开（公告）日：2017-10-26

  Described herein, inter alia, are compositions of ErbB modulators and methods of using the same.

  本文描述了ErbB调节剂的组成和使用方法。
• Pyrazolopyrimidines as therapeutic agents
  申请人：Abbott Laboratories

  公开号：US20020156081A1

  公开（公告）日：2002-10-24

  The present invention provides compounds of Formula I, 1 including pharmaceutically acceptable salts and/or prodrugs thereof, where G, R 2 , and R 3 are defined as described herein.

  本发明提供了公式I的化合物，包括其药学上可接受的盐和/或前药，其中G、R2和R3的定义如本文所述。
• [EN] TRIAZOLONE COMPOUNDS AS PERK INHIBITORS<br/>[FR] COMPOSÉS DE TRIAZOLONE COMME INHIBITEURS DE PERK
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO 2) LTD

  公开号：WO2017046738A1

  公开（公告）日：2017-03-23

  The invention is directed to substituted triazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, X, Y, Y1, and Z are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  这项发明涉及取代三唑烷酮衍生物。具体而言，该发明涉及符合以下式(I)的化合物：其中R1、R2、R3、R4、R5、X、Y、Y1和Z如本文所定义。该发明的化合物是PERK的抑制剂，可用于治疗癌症、癌前综合征、阿尔茨海默病、神经病痛、脊髓损伤、创伤性脑损伤、缺血性中风、中风、帕金森病、糖尿病、代谢综合征、代谢紊乱、亨廷顿病、克雅氏病、致命性家族性失眠、格斯特曼-施特劳斯勒-谢因克症候群及相关朊蛋白病、肌萎缩侧索硬化、进行性核上性麻痹、心肌梗死、心血管疾病、炎症、器官纤维化、肝脏慢性和急性疾病、脂肪肝病、肝脂肪变性、肝纤维化、肺部慢性和急性疾病、肺纤维化、肾脏慢性和急性疾病、肾脏纤维化、慢性创伤性脑病（CTE）、神经退行性疾病、痴呆症、额颞叶痴呆症、tau蛋白病、皮克氏病、尼曼-皮克氏病、淀粉样变性、认知障碍、动脉粥样硬化、眼部疾病、心律失常、器官移植以及器官移植用途中的运输。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制PERK活性和治疗相关疾病的方法。
• Design, synthesis and biological evaluation of AKT inhibitors bearing a piperidin-4-yl appendant
  作者：Daoguang Zhang、Dongdong Tong、Dezhi Yang、Jing Sun、Fenghe Zhang、Guisen Zhao

  DOI：10.1039/c8md00197a

  日期：——

  Compound 10h is a potent pan-AKT inhibitor showing cellular AKT inhibition and apoptosis induction in PC-3 prostate cancer cells.

  化合物10h是一种强效的泛AKT抑制剂，在PC-3前列腺癌细胞中显示细胞AKT抑制和诱导凋亡。
• Substituted Naphthalenyl-Pyrimidine Compounds
  申请人：Ashwell Mark A.

  公开号：US20110166137A1

  公开（公告）日：2011-07-07

  The present invention relates to substituted naphthalenyl-pyrimidine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted naphthalenyl-pyrimidine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

  本发明涉及取代萘基嘧啶化合物及合成这些化合物的方法。本发明还涉及含有取代萘基嘧啶化合物的药物组合物，以及通过向需要的受试者投与这些化合物和药物组合物来治疗细胞增殖紊乱疾病，如癌症的方法。