4-氯-2-甲硫基嘧啶-5-腈 | 33089-15-5

• 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 - 有机硫化合物 - 硫醚类
• 中文名称: 4-氯-2-甲硫基嘧啶-5-腈
• 中文别名: 2-甲硫基-4-氯-5-氰基嘧啶；4-氯-2-(甲硫基)嘧啶-5-甲腈；4-氯-5-氰基-2-甲硫基嘧啶
• 英文名称: 4-chloro-5-cyano-2-methylthiopyrimidine
• 英文别名: 4-chloro-2-(methylthio)pyrimidine-5-carbonitrile；4-chloro-2-(methylsulfanyl)pyrimidine-5-carbonitrile；4-chloro-2-(methylthio)pyrimidin-5-carbonitrile；4-chloro-2-methylsulfanylpyrimidine-5-carbonitrile
• CAS: 33089-15-5
• 化学式: C₆H₄ClN₃S
• mdl: MFCD00507261
• 分子量: 185.637
• InChiKey: IGIRTCCCRNZFSQ-UHFFFAOYSA-N

物化性质

• 熔点：
  67-68 °C(Solv: benzene (71-43-2); ligroine (8032-32-4))
• 沸点：
  340.7±22.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)
• pKa：
  -3.26±0.29 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  74.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 安全说明：
  S26,S36/37,S9
• 危险类别码：
  R20/21/22,R36/37/38
• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Chloro-2-(methylthio)pyrimidine-5-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: 4-Chloro-2-(methylthio)pyrimidine-5-carbonitrile
CAS number: 33089-15-5

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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, refrigerated.
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: C6H4ClN3S
Molecular weight: 185.6

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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, sulfur oxides.

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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

嘧啶是一类非常重要的杂环化合物，在医药和农药领域有着广泛的应用。由于嘧啶化合物具有高效、低毒以及独特的药理作用方式等优点，因此其分子设计、合成与生物活性研究仍然是杂环化合物研究中的一个活跃的领域。4-氯-2-甲硫基嘧啶-5-腈作为一种衍生物，可用作受体酪氨酸激酶抑制剂，并应用于治疗癌症。此外，这种化合物还可用作医药中间体。

用途

4-氯-2-甲硫基嘧啶-5-腈是一种有机中间体。有文献报道，该化合物可用于制备甾体类抗雄激素化合物，经药理实验证明这类化合物具有良好的抗前列腺癌活性。

制备

将2克(6.6毫摩尔)原料4-氯-2-甲硫基嘧啶-5-羧酸乙酯溶于10毫升无水乙醇中，加入0.68克NaOH固体和10毫升水，升温至回流。反应1小时后，TLC显示反应完全。旋干乙醇，用6N HCl调pH值至3，会有大量白色晶体析出。抽滤可得白色晶体1.69克，收率为91.8%。

反应信息

• 作为反应物：
  描述：

  4-氯-2-甲硫基嘧啶-5-腈 在 sodium hydride 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 生成 6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-3-ylamine
  参考文献：
  名称：

  3-Amino-pyrazolo[3,4-d]pyrimidines as p38α kinase inhibitors: Design and development to a highly selective lead

  摘要：

  Learnings from previous Roche p38-selective inhibitors were applied to a new fragment hit, which was optimized to a potent, exquisitely selective preclinical lead with a good pharmacokinetic profile. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.098
• 作为产物：
  描述：

  2-甲硫基-4-羟基-5-氰基嘧啶 在 三氯氧磷 作用下， 反应 3.0h， 生成 4-氯-2-甲硫基嘧啶-5-腈
  参考文献：
  名称：

  Pyrimidinyl pyridone inhibitors of kinases

  摘要：

  该申请披露了根据式I的新型嘧啶基吡啶酮衍生物，其中A、R1、R2、R3和mare如本文所述定义，这些衍生物抑制JNK。本文披露的化合物可用于调节JNK的活性，并治疗与过度JNK活性相关的疾病。这些化合物可用于治疗自身免疫、炎症、代谢和神经系统疾病以及癌症。还披露了包含式I化合物的组合物以及包括向需要的受试者投与式I化合物的治疗方法。

  公开号：

  US20090270389A1
• 作为试剂：
  描述：

  2-甲硫基-4-羟基-5-氰基嘧啶 、 三氯氧磷 在 二氯甲烷 、 ice water 、 水 、 magnesium sulfate 、 正己烷 、 4-氯-2-甲硫基嘧啶-5-腈 作用下， 反应 3.0h， 以to afford 32 g of the title compound 4-chloro-5-cyano-2-methylsulfanyl-pyrimidine的产率得到4-氯-2-甲硫基嘧啶-5-腈
  参考文献：
  名称：

  Pyrido [2,3-D]pyrimidines for inhibiting protein tyrosine kinase

  摘要：

  6-芳基吡啶[2,3-d]嘧啶7-亚胺，7-酮和7-硫酮是蛋白酪氨酸激酶的抑制剂，因此在治疗由此介导的细胞增殖方面非常有用。这些化合物在治疗癌症、动脉粥样硬化、再狭窄和银屑病方面特别有用。

  公开号：

  US05620981A1

文献信息

• 2,4-diamino pyrimidine compounds having anti-cell proliferative activity
  申请人：AstraZeneca AB

  公开号：US06593326B1

  公开（公告）日：2003-07-15

  A pyrimidine derivative of formula (I): wherein: R1 is an optional substituent as defined within; Rx is selected from halo, hydroxy, nitro, amino, cyano, mercapto, carboxy, sulphamoyl, formamido, ureido or carbamoyl or a group of formula (Ib): A—B—C— as defined within; Q1 and Q2 are independently selected from aryl, a 5- or 6-membered monocyclic moiety; and a 9- or 10-membered bicyclic heterocyclic moiety; and one or both of Q1 and Q2 bears on any available carbon atom one substituent of formula (Ia) as defined within; and Q1 and Q2 are optionally further substituted; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof; are useful as anti-cancer agents; and processes for their manufacture and pharmaceutical compositions containing them are described.

  式（I）的嘧啶衍生物： 其中：R1是如定义的可选取代基；Rx选自卤素、羟基、硝基、氨基、氰基、巯基、羧基、磺胺基、甲酰胺基、脲基或氨基甲酰基或如定义的式（Ib）的基团：A—B—C—；Q1和Q2独立选自芳基、5-或6-成员单环基；和9-或10-成员双环杂环基；Q1和Q2中的一个或两个在任一可用碳原子上带有如定义的式（Ia）的取代基；Q1和Q2可进一步取代；或其药学上可接受的盐或体内水解酯；可用作抗癌剂；并描述了其制备方法和含有它们的药物组合物。
• N-substituted nonaryl-heterocyclic NMDA/NR2B antagonists
  申请人：——

  公开号：US20020165241A1

  公开（公告）日：2002-11-07

  Compounds represented by Formula (I): 1 or pharmaceutically acceptable salts thereof, are effective as NMDA NR2B antagonists useful for relieving pain.

  由化学式（I）表示的化合物及其药学上可接受的盐，可作为NMDA NR2B拮抗剂，用于缓解疼痛。
• Thrombin inhibitors
  申请人：——

  公开号：US20030158218A1

  公开（公告）日：2003-08-21

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1 wherein R 1 is, for example, hydrogen, Cl, or cyano, and R 2 is, for example, hydrogen, 2

  本发明的化合物在抑制凝血酶及相关血栓闭塞方面具有以下结构的有用： 1 其中R 1 例如是氢、氯或氰基，而R 2 例如是氢、 2
• Pyrido\x9b2, 3-d!pyrimidines for inhibiting protein tyrosine kinase
  申请人：Warner-Lambert Company

  公开号：US05733914A1

  公开（公告）日：1998-03-31

  6-Aryl pyrido\x9b2,3-d!pyrimidine 7-imines, 7-ones, and 7-thiones are inhibitors of protein tyrosine kinases, and are thus useful in treating cellular proliferation mediated thereby. The compounds are especially useful in treating cancer, atherosclerosis, restenosis, and psoriasis.

  6-芳基吡啶[2,3-d]嘧啶7-亚胺，7-酮和7-硫醚是蛋白酪氨酸激酶的抑制剂，因此在治疗由此介导的细胞增殖方面非常有用。这些化合物在治疗癌症、动脉粥样硬化、再狭窄和牛皮癣方面特别有用。
• SUBSTITUTED DIAMINOPYRIMIDYL COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
  申请人：Signal Pharmaceuticals, LLC

  公开号：US20150175557A1

  公开（公告）日：2015-06-25

  Provided herein are diaminopyrimidyl Compounds having the following structures: wherein X, L, R 1 , and R 2 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidyl Compound, and methods for treating or preventing PKC-theta-mediated disorders, or a condition treatable or preventable by inhibition of a kinase, for example, PKC-theta.

  本文提供具有以下结构的二氨基嘧啶化合物： 其中X、L、R1和R2如本文所定义，包含有效量二氨基嘧啶化合物的组合物，以及用于治疗或预防PKC-theta介导的疾病或通过抑制激酶（例如PKC-theta）可治疗或预防的疾病的方法。