5-氯-2-氰基-3-硝基吡啶 | 181123-11-5

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 中文名称: 5-氯-2-氰基-3-硝基吡啶
• 中文别名: 2-氰基-3-硝基-5-氯吡啶；2-氰基-5-氯-3-硝基吡啶
• 英文名称: 5-chloro-3-nitropicolinonitrile
• 英文别名: 5-chloro-2-cyano-3-nitropyridine；5-chloro-3-nitropyridine-2-carbonitrile
• CAS: 181123-11-5
• 化学式: C₆H₂ClN₃O₂
• mdl: MFCD06657552
• 分子量: 183.554
• InChiKey: UFTRTPYMNGYVGO-UHFFFAOYSA-N

物化性质

• 沸点：
  329.5±42.0 °C(Predicted)
• 密度：
  1.57

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 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：
  82.5
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26,S37
• 危险类别码：
  R36/37/38
• 海关编码：
  2933399090
• 危险类别：
  IRRITANT
• 包装等级：
  III
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P310+P330,P302+P352+P312,P304+P340+P312,P305+P351+P338+P310,P332+P313,P403+P233,P405,P501
• 危险品运输编号：
  2923
• 危险性描述：
  H301,H312+H332,H315,H318,H335
• 储存条件：
  存储条件：室温、密封保存，并保持干燥环境。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 5-Chloro-3-nitropyridine-2-carbonitrile
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: 5-Chloro-3-nitropyridine-2-carbonitrile
CAS number: 181123-11-5

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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: C6H2ClN3O2
Molecular weight: 183.6

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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：

  5-氯-2-氰基-3-硝基吡啶 在 正丁基锂 、 四丁基氟化铵 、 氢气 、 双氧水 、 sodium methylate 、 palladium(II) hydroxide 、 sodium hydride 、 二异丙胺 、 N,N-二异丙基乙胺 、 lithium chloride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 、 乙腈 为溶剂， 反应 67.58h， 生成 rac-(5aR,6S,7R,8aR)-5a-(4-bromophenyl)-3-chloro-8a-hydroxy-6-phenyl-7-(pyridin-2-ylthio)-5a,6,7,8a-tetrahydro-8H-cyclopenta[4,5]furo[3,2-b]pyridin-8-one
  参考文献：
  名称：

  EIF4A-INHIBITING COMPOUNDS AND METHODS RELATED THERETO

  摘要：

  本发明提供了根据式I合成的化合物、药用可接受的配方和用途，或其立体异构体、互变异构体或药用可接受的盐。对于式I化合物X、Y、R1、R2、R3a、R3b、R4a、R4b和R5如规范中所定义。这些创新的式I化合物是eIF4A的抑制剂，在许多治疗应用中发挥作用，包括但不限于治疗炎症和各种癌症。

  公开号：

  US20170145026A1
• 作为产物：
  描述：

  5-氯-2-溴-3-硝基吡啶 以 丙酮 为溶剂， 生成 5-氯-2-氰基-3-硝基吡啶
  参考文献：
  名称：

  Aza and aza (N-oxy) analogs of glycine/NMDA receptor antagonists

  摘要：

  治疗或预防与中风、缺血、中枢神经系统创伤、低血糖和手术相关的神经元丢失的方法，以及治疗包括阿尔茨海默病、肌萎缩侧索硬化、亨廷顿病和唐氏综合征在内的神经退行性疾病，治疗或预防兴奋性氨基酸过度活跃的不良后果，以及治疗焦虑、慢性疼痛、抽搐、诱导麻醉，以及治疗或预防阿片类药物耐受性的方法是通过向需要此类治疗或预防的动物施用取代或未取代的吡啶和吡啶（N-氧化物）类似物的4-羟基二氢喹啉酮，四氢喹啉三酮肟和喹啉酮，其互变异构体和药学上可接受的盐，这些物质对甘氨酸受体具有高结合能力。

  公开号：

  US05801183A1

文献信息

• [EN] PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE<br/>[FR] COMPOSÉS À BASE DE 1,3-OXAZIN-2-AMINE FUSIONNÉE AVEC DU CYCLOPROPYLE PERFLUORÉ UTILISABLES EN TANT QU'INHIBITEURS DE LA BÊTA-SÉCRÉTASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2014138484A1

  公开（公告）日：2014-09-12

  PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE ABSTRACT OF THE DISCLOSURE The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: INSERT STRUCTURE HERE} I wherein variables A4, A5, A6, A8, each of Ra, Rb, R1, R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

  本发明提供了一类新的化合物，用于调节β-分泌酶（BACE）活性。这些化合物具有一般的化学式I：在此插入结构} I，其中变量A4、A5、A6、A8，以及化学式I中的每个Ra、Rb、R1、R2、R3和R7，在本文中分别定义。该发明还提供了包含这些化合物的药物组合物，以及用于治疗与A-beta斑块形成和沉积相关的疾病和/或症状的化合物和组合物的用途，这些疾病和症状是由BACE的生物活性引起的。这种由BACE介导的疾病包括阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他中枢神经系统疾病。该发明还提供了化学式II和III的化合物，以及其亚式化合物、中间体和制备本发明化合物的方法。
• Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase
  作者：Justin T. Ernst、Peggy A. Thompson、Christian Nilewski、Paul A. Sprengeler、Samuel Sperry、Garrick Packard、Theodore Michels、Alan Xiang、Chinh Tran、Christopher J. Wegerski、Boreth Eam、Nathan P. Young、Sarah Fish、Joan Chen、Haleigh Howard、Jocelyn Staunton、Jolene Molter、Jeff Clarine、Andres Nevarez、Gary G. Chiang、Jim R. Appleman、Kevin R. Webster、Siegfried H. Reich

  DOI：10.1021/acs.jmedchem.0c00182

  日期：2020.6.11

  component of the eIF4F complex, which regulates cap-dependent protein synthesis. The flavagline class of natural products (i.e., rocaglamide A) has been shown to inhibit protein synthesis by stabilizing a translation–incompetent complex for select messenger RNAs (mRNAs) with eIF4A. Despite showing promising anticancer phenotypes, the development of flavagline derivatives as therapeutic agents has been hampered

  蛋白质翻译失调是许多癌症发病机理的关键驱动因素。真核生物起始因子4A（eIF4A）是ATP依赖的DEAD-box RNA解旋酶，是eIF4F复合体的重要组成部分，该复合体调节帽依赖性蛋白质的合成。天然产品的黄精油类（即，rocaglamide A）已被证明可以通过稳定带有eIF4A的特定信使RNA（mRNA）的翻译无能力复合物来抑制蛋白质合成。尽管显示出有希望的抗癌表型，但由于不良的类药物性质和合成复杂性，阻碍了黄酮衍生物作为治疗剂的开发。利用基于配体的设计策略进行了重点研究，以鉴定具有优化的理化性质的化学型。此外，进行了详细的机理研究，以进一步阐明mRNA序列的选择性，关键的调控靶基因以及相关的抗肿瘤表型。这项工作导致了eFT226的设计 （Zotatifin），具有出色的理化特性和显着的抗肿瘤活性的化合物，可支持临床发展。
• PERFLUORINATED 5,6-DIHYDRO-4H-1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE
  申请人：AMGEN INC.

  公开号：US20140249104A1

  公开（公告）日：2014-09-04

  The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A 4 , A 5 , A 6 , A 8 , each of R 1 and R 2 , R 3 and R 7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III.

  本发明提供了一类新的化合物，用于调节β-分泌酶（BACE）活性。这些化合物的通用公式为I： 其中变量A4，A5，A6，A8，公式I中的R1和R2，R3和R7各自独立定义如下。本发明还提供了包含这些化合物的药物组合物，以及使用这些化合物和组合物治疗与A-β斑块形成和沉积相关的疾病和/或状况，这些疾病和/或状况是由BACE的生物活性引起的。这样的BACE介导的疾病包括，例如，阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。本发明进一步提供了公式II和III的化合物，以及其子公式的实施例，中间体和用于制备公式I-III化合物的过程和方法。
• BRIDGED BICYCLIC AMINO THIAZINE DIOXIDE COMPOUNDS AS INHIBITORS OF BETA-SECRETASE AND METHODS OF USE THEREOF
  申请人：AMGEN INC.

  公开号：US20150038497A1

  公开（公告）日：2015-02-05

  The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A 4 , A 5 , A 6 , A 8 , R 1 , R 2 , R 3 , R 7 and n of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, compounds of Formula III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III, and sub-Formulas thereof.

  本发明提供了一类新的化合物，用于调节β-分泌酶（BACE）活性。这些化合物具有一般的化学式I： 其中化学式I中的变量A4、A5、A6、A8、R1、R2、R3、R7和n，在本文中分别定义。该发明还提供了包括这些化合物的药物组合物，以及这些化合物和组合物用于治疗与A-beta斑块形成和沉积相关的疾病和/或症状的对应用途，这些疾病和症状是由BACE的生物活性引起的。这种由BACE介导的疾病包括阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他中枢神经系统疾病。该发明还提供了化学式II和其亚式化合物、化学式III的化合物、中间体以及用于制备化学式I-III及其亚式化合物的化合物的制备的过程和方法。
• [EN] CYCLOPROPYL FUSED THIAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE<br/>[FR] COMPOSÉS THIAZIN-2-AMINE FUSIONNÉE À UN GROUPEMENT CYCLOPROPYLE UTILISÉS EN TANT QU'INHIBITEURS DE LA BÊTA-SECRÉTASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2016022724A1

  公开（公告）日：2016-02-11

  The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I): wherein variables A4, A5, A6, A8, and each of Ra, Rb, R1, R2, R3 and R7 of Formula (I), independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and 15 deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimers Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas (II) and (III), and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

  本发明提供了一类新的化合物，用于调节β-分泌酶（BACE）活性。这些化合物具有一般式（I）：其中一般式（I）中的变量A4、A5、A6、A8，以及Ra、Rb、R1、R2、R3和R7各自独立地在此定义。该发明还提供了包括这些化合物的药物组合物，以及用于治疗与A-beta斑块形成和沉积相关的疾病和/或症状的化合物和组合物的用途，这些疾病和症状是由BACE的生物活性引起的。这种由BACE介导的疾病包括，例如，阿尔茨海默病、认知缺陷、认知障碍、精神分裂症和其他中枢神经系统疾病。该发明还提供了一般式（II）和（III）的化合物，以及其亚式形式、中间体和制备本发明化合物的方法。