4-氯-6-(吡咯啉-1-基)嘧啶 | 939986-64-8

• 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 - 有机氮化合物
• 中文名称: 4-氯-6-(吡咯啉-1-基)嘧啶
• 中文别名: 4-氯-6-(吡咯烷-1-基)嘧啶
• 英文名称: 4-chloro-6-(pyrrolidin-1-yl)pyrimidine
• 英文别名: 4-chloro-6-pyrrolidin-1-ylpyrimidine
• CAS: 939986-64-8
• 化学式: C₈H₁₀ClN₃
• mdl: MFCD09475835
• 分子量: 183.64
• InChiKey: DJVYVHPCLCIYDY-UHFFFAOYSA-N

物化性质

• 熔点：
  96-98℃
• 沸点：
  327.6±27.0 °C(Predicted)
• 密度：
  1.289±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
4-Chloro-6-(pyrrolidin-1-yl)pyrimidine
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
4-Chloro-6-(pyrrolidin-1-yl)pyrimidine
Ingredient name:
CAS number: 939986-64-8

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C8H10ClN3
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：

  4-氯-6-(吡咯啉-1-基)嘧啶 在 硫酸 、 potassium tert-butylate 、 硝酸 作用下， 以 甲苯 为溶剂， 反应 36.0h， 生成 5-nitro-N⁴-pyridin-2-yl-6-pyrrolidin-1-ylpyrimidin-4-amine
  参考文献：
  名称：

  取代基结构对嘧啶亲电取代的影响

  摘要：

  在对一系列4,6-二取代的嘧啶衍生物的亲电子亚硝化反应的研究中，发现C-4和C-6取代基的电子性质与反应性之间存在微妙的相互作用，其中氯，单或双取代的氨基。尽管存在第二个活化基团，诸如在氨基部分上存在芳基或两个烷基之类的影响仍阻碍了反应的进行。

  DOI：

  10.1016/j.tet.2007.04.063
• 作为产物：
  描述：

  四氢吡咯 、 4,6-二氯嘧啶 以 异丙醇 为溶剂， 生成 4-氯-6-(吡咯啉-1-基)嘧啶
  参考文献：
  名称：

  取代基结构对嘧啶亲电取代的影响：反驳

  摘要：

  了一系列的影响激活嘧啶的电亚硝化（意外和模糊效果的报告四面体 2007年，63，5394）被证明是错误的。取代在嘧啶环的5位上进行亲电取代，在嘧啶环的4位上发生仲氨基的N-亚硝化。此外，已经表明，制备嘌呤的合成顺序也是不正确的。

  DOI：

  10.1016/j.tet.2012.01.044

文献信息

• INHIBITORS OF FLAVIVIRIDAE VIRUSES
  申请人：Canales Eda

  公开号：US20110020278A1

  公开（公告）日：2011-01-27

  Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of Flaviviridae virus infections, particularly hepatitis C infections.

  提供的是I式化合物： 及其药用可接受的盐和酯。所提供的化合物、组合物和方法对于治疗黄病毒科病毒感染，特别是丙型肝炎感染，是有用的。
• [EN] INDAZOLYL-SPIRO[2.2]PENTANE-CARBONITRILE DERIVATIVES AS LRRK2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF<br/>[FR] DÉRIVÉS D'INDAZOLYL-SPIRO [2.2] PENTANE-CARBONITRILE EN TANT QU'INHIBITEURS DE LRRK2, COMPOSITIONS PHARMACEUTIQUES ET LEURS UTILISATIONS
  申请人：MERCK SHARP & DOHME

  公开号：WO2019074809A1

  公开（公告）日：2019-04-18

  The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

  本发明涉及Formula (I)的某些取代的反转吲哚基螺[2.2]戊烷-碳腈衍生物及其药学上可接受的盐，其中R1、R2、R3、X、Y和Z如本文所定义，这些衍生物是LRRK2激酶的有效抑制剂，可能在治疗或预防LRRK2激酶参与的疾病中有用，如帕金森病和本文所述的其他疾病和疾病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗LRRK-2激酶参与的这些疾病中使用这些化合物和组合物。
• [EN] INDAZOLYL-SPIRO[2.3]HEXANE-CARBONITRILE DERIVATIVES AS LRRK2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF<br/>[FR] DÉRIVÉS D'INDAZOLYL-SPIRO [2,3] HEXANE-CARBONITRILE COMME INHIBITEURS DE LRRK2, COMPOSITIONS PHARMACEUTIQUES, ET UTILISATIONS DE CEUX-CI
  申请人：MERCK SHARP & DOHME

  公开号：WO2019074810A1

  公开（公告）日：2019-04-18

  The present invention is directed to substituted certain reversed indazole compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1A, R1B, X, Y, RZ and R2 are as defined herein, which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

  本发明涉及Formula (I)的某些取代的反向吲唑化合物及其药学上可接受的盐，其中R1A、R1B、X、Y、RZ和R2如本文所定义，这些化合物是LRRK2激酶的强效抑制剂，并且在治疗或预防LRRK2激酶参与的疾病，如帕金森病和本文所述的其他疾病和疾病中有用。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗LRRK-2激酶参与的这类疾病中使用这些化合物和组合物。
• [EN] PYRAZOLO[4,3-C]PYRIDINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] DÉRIVÉS DE PYRAZOLO [4,3-C] PYRIDINE ET LEURS COMPOSITIONS PHARMACEUTIQUES POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2021032582A1

  公开（公告）日：2021-02-25

  The present invention discloses compounds according to Formula (I) wherein R1, R2, and Cy are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of allergic diseases, inflammatory diseases, metabolic diseases, autoinflammatory diseases, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IFNα, IL12 and/or IL23 by administering the compound of the invention.

  本发明揭示了根据式（I）中R1、R2和Cy的化合物，其中R1、R2和Cy的定义如本文所述。本发明涉及化合物、其生产方法、包括这些化合物的药物组合物，以及使用这些化合物进行预防和/或治疗过敏疾病、炎症性疾病、代谢性疾病、自身炎症性疾病、自身免疫性疾病、增殖性疾病、移植排斥、涉及软骨周转受损、先天软骨畸形和/或与IFNα、IL12和/或IL23过度分泌相关的疾病的治疗方法。
• Effect of substituent structure on pyrimidine electrophilic substitution: a rebuttal
  作者：Virginija Jakubkienė、Inga Čikotienė

  DOI：10.1016/j.tet.2012.01.044

  日期：2012.3

  obscure effects influencing the electrophilic nitrosation of activated pyrimidines (Tetrahedron 2007, 63, 5394) was shown to be erroneous. Instead of electrophilic substitution at position 5 of the pyrimidine ring, N-nitrosation of the secondary amino group in the 4-position of the pyrimidine ring took place. Moreover it was shown that the synthetic sequence for the preparation of purines is also incorrect

  了一系列的影响激活嘧啶的电亚硝化（意外和模糊效果的报告四面体 2007年，63，5394）被证明是错误的。取代在嘧啶环的5位上进行亲电取代，在嘧啶环的4位上发生仲氨基的N-亚硝化。此外，已经表明，制备嘌呤的合成顺序也是不正确的。