4-氯吡啶-2-甲酰胺 | 99586-65-9

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 4-氯吡啶-2-甲酰胺
• 中文别名: 4-氯吡啶酰胺；2-甲酰胺基-4-氯吡啶；4-氯吡啶甲酰胺；4-氯吡啶-2-氨基羧酸；4-氯吡啶-2-酰胺
• 英文名称: 4-chloropicolinamide
• 英文别名: 4-chloropyridine-2-carboxamide；4-chloro-2-pyridinecarboxamide；4-Chlor-pikolinsaeure-amid
• CAS: 99586-65-9
• 化学式: C₆H₅ClN₂O
• mdl: MFCD01085339
• 分子量: 156.572
• InChiKey: XIHHOUUTBZSYJH-UHFFFAOYSA-N

物化性质

• 熔点：
  148-152
• 沸点：
  298.1±25.0 °C(Predicted)
• 密度：
  1.381±0.06 g/cm3(Predicted)
• 最大波长(λmax)：
  268nm(EtOH)(lit.)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 危险类别码：
  R22
• 危险品运输编号：
  NONH for all modes of transport
• 海关编码：
  2933399090
• 危险标志：
  GHS07
• 危险性描述：
  H302,H317
• 危险性防范说明：
  P280
• 储存条件：
  室温

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : 4-Chloro-Pyridine-2-Carboxylic Acid Amide
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Acute toxicity, Oral (Category 4), H302
Skin sensitisation (Category 1), H317
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
R43
Xn Harmful R22
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal word Warning
Hazard statement(s)
H302 Harmful if swallowed.
H317 May cause an allergic skin reaction.
Precautionary statement(s)
P280 Wear protective gloves.
Supplemental Hazard none
Statements
Other hazards
This substance/mixture contains no components considered to be either persistent, bioaccumulative and
toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher.

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SECTION 3: Composition/information on ingredients
Substances
Molecular weight : 156,57 g/mol
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
4-Chloro-Pyridine-2-Carboxylic Acid Amide
Acute Tox. 4; Skin Sens. 1; <= 100 %
H302, H317
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
4-Chloro-Pyridine-2-Carboxylic Acid Amide
Xn, R43R22 <= 100 %
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

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SECTION 4: First aid measures
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
Indication of any immediate medical attention and special treatment needed
No data available

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SECTION 5: Firefighting measures
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Nature of decomposition products not known.
Advice for firefighters
Wear self-contained breathing apparatus for firefighting if necessary.
Further information
No data available

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SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

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SECTION 7: Handling and storage
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Storage class (TRGS 510): Non Combustible Solids
Specific end use(s)
Apart from the uses mentioned in section 1.2 no other specific uses are stipulated

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SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Face shield and safety glasses Use equipment for eye protection tested and approved under
appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Do not let product enter drains.

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SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour No data available
c) Odour Threshold No data available
d) pH No data available
e) Melting point/freezing No data available
point
f) Initial boiling point and No data available
boiling range
g) Flash point No data available
h) Evaporation rate No data available
i) Flammability (solid, gas) No data available
j) Upper/lower No data available
flammability or
explosive limits
k) Vapour pressure No data available
l) Vapour density No data available
m) Relative density No data available
n) Water solubility No data available
o) Partition coefficient: n- No data available
octanol/water
p) Auto-ignition No data available
temperature
q) Decomposition No data available
temperature
r) Viscosity No data available
s) Explosive properties No data available
t) Oxidizing properties No data available
Other safety information
No data available

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SECTION 10: Stability and reactivity
Reactivity
No data available
Chemical stability
Stable under recommended storage conditions.
Possibility of hazardous reactions
No data available
Conditions to avoid
No data available
Incompatible materials
No data available
Hazardous decomposition products
In the event of fire: see section 5

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SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
No data available
Skin corrosion/irritation
No data available
Serious eye damage/eye irritation
No data available
Respiratory or skin sensitisation
No data available
Germ cell mutagenicity
No data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
No data available
Specific target organ toxicity - single exposure
No data available
Specific target organ toxicity - repeated exposure
No data available
Aspiration hazard
No data available
Additional Information
RTECS: Not available

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SECTION 12: Ecological information
Toxicity
No data available
Persistence and degradability
No data available
Bioaccumulative potential
No data available
Mobility in soil
No data available
Results of PBT and vPvB assessment
This substance/mixture contains no components considered to be either persistent, bioaccumulative and
toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher.
Other adverse effects
No data available

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SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

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SECTION 14: Transport information
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
No data available

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SECTION 15: Regulatory information
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
No data available
Chemical Safety Assessment
For this product a chemical safety assessment was not carried out

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SECTION 16: Other information
Full text of H-Statements referred to under sections 2 and 3.
Acute Tox. Acute toxicity
H302 Harmful if swallowed.
H317 May cause an allergic skin reaction.
Skin Sens. Skin sensitisation
Full text of R-phrases referred to under sections 2 and 3
Xn Harmful
R22 Harmful if swallowed.
R43 May cause sensitisation by skin contact.
Further information
Copyright 2014 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

化学性质

4-氯吡啶-2-甲酰胺具有活泼的反应性和特殊的溶解能力。除了由三个氢参与反应外，它还可以进行脱水、脱CO、引入氨基、引入酰基和环合等反应。

应用

4-氯吡啶-2-甲酰胺可用作有机合成原料、纸张处理剂、纤维工业的柔软剂、动物胶的软化剂，并且还用于测定大米中氨基酸含量的分析试剂。在有机合成中，它主要用于医药领域，在农药、染料、颜料、香料及助剂方面也有广泛的应用。此外，4-氯吡啶-2-甲酰胺还可用于分离氯硅烷和提纯油脂等。

制备 步骤1

向搅拌的无水DMF（25ml）中以控制反应温度在40-50°C的方式缓慢加入SOCl2（125ml）。30分钟内分批加入吡啶-2-羧酸（25g，0.2mol），并加热回流16小时。在此过程中沉淀出黄色固体。冷却至室温后，用甲苯（80ml）稀释混合物并浓缩。此过程重复三次。将所得干燥残余物用甲苯洗涤并减压干燥，得到4-氯吡啶-2-羰基氯，产率为79%（27.6g），无需纯化。

步骤2

以控制反应温度在40-50°C的方式向搅拌的无水DMF（25ml）中缓慢加入SOCl2（125ml）。30分钟内分批加入吡啶-2-羧酸（25g，0.2mol），并加热回流16小时。在此过程中沉淀出黄色固体。冷却至室温后，用甲苯（80ml）稀释混合物并浓缩。此过程重复三次。将所得干燥残余物用甲苯洗涤并减压干燥，得到4-氯吡啶-2-羰基氯，无需纯化。

实施例A25

按照实施例A22的程序制备4-氯吡啶-2-甲酰胺，但使用NH3代替MeNH2。

反应信息

• 作为反应物：
  描述：

  4-氯吡啶-2-甲酰胺 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 5.0h， 生成 4-吡咯烷基-1-吡啶-2-羧酸盐酸盐
  参考文献：
  名称：

  新型 N'-methyl-4-(pyrrolidin-1-yl)picolinohydrazide 和 N'-methylpyrimidine-2-carbohydrazide 衍生物的合成和抑结核活性

  摘要：

  进行N'-甲基-4-(吡咯烷-1-基)吡啶甲酰肼和N'-甲基-嘧啶-2-碳酰肼衍生物(5a和5b)的合成。这些化合物用作起始原料以获得 N'-甲基肼碳二硫代酸甲酯 6a 和 6b，在与三乙胺或肼反应后，得到相应的 1,3,4-恶二唑醇 7a 和 7b 或 1,2,4-三唑 9a 和9b 分别在 N-4 位置具有游离 NH2 基团。还获得了化合物 8a-e，特别是在 1,2,4-三唑环的 N-4 处含有环胺。合成的化合物在体外测试了它们对结核分枝杆菌的活性。对所得化合物进行构效关系分析。© 2012 Wiley Periodicals, Inc. 杂原子化学 23:223–230, 2012; 在 wileyonlinelibrary.com 上在线查看这篇文章。

  DOI：

  10.1002/hc.21008
• 作为产物：
  描述：

  2-吡啶甲酸 在 ammonium hydroxide 、 氯化亚砜 、 sodium bromide 作用下， 以 氯苯 、 甲苯 为溶剂， 反应 25.0h， 生成 4-氯吡啶-2-甲酰胺
  参考文献：
  名称：

  带有缩氨基脲部分的新型 4-(2-氟苯氧基)-2-(1H-四唑-1-基)吡啶作为有效抗肿瘤剂的合成和生物学评价

  摘要：

  合成了一系列带有缩氨基脲部分的 4-(2-氟苯氧基)-2-(1H-四唑-1-基)吡啶，并评估了它们的体外抗肿瘤效力。与索拉非尼和 PAC-1 相比，一些化合物（10b、10c、10e-10h、10m-10p、10r 和 11b）表现出中等至优异的抗肿瘤活性，以及​​对人胎肺成纤维细胞的低毒性细胞系 WI-38。最有希望的化合物 10p（IC50 = 0.08、0.36、0.97 µM）的活性是索拉非尼的 45.1-、6.1- 和 2.4 倍（IC50 = 3.61、2.19、2.32 µM），是 17、2.9 倍和 17 倍，更好PAC-1 (IC50 = 1.36, 1.17, 2.83 µM) 分别对抗三种癌细胞系（HT-29、H460 和 MKN-45）。此外，

  DOI：

  10.1002/ardp.201300188

文献信息

• Substituted benzimidazoles and methods of preparation
  申请人：Dimitroff Martin

  公开号：US20070049622A1

  公开（公告）日：2007-03-01

  Methods for preparing new substituted benzimidazole compounds having formula (I) useful for treating kinase mediated disorders are provided wherein R 1 , R 2 , R 3 , R 4 , a, b, and c are defined herein

  提供了制备新的取代苯并咪唑化合物的方法，其化学式为（I），用于治疗激酶介导的疾病，其中R1、R2、R3、R4、a、b和c在此定义。
• Discovery of a Pyrimidinedione Derivative as a Potent and Orally Bioavailable Axl Inhibitor
  作者：Hefeng Zhang、Xia Peng、Yang Dai、Jingwei Shao、Yinchun Ji、Yiming Sun、Bo Liu、Xu Cheng、Jing Ai、Wenhu Duan

  DOI：10.1021/acs.jmedchem.0c02093

  日期：2021.4.8

  therapeutics. We used molecular modeling-assisted structural optimization starting with the low micromolar potency compound 9 to discover compound 13c, a highly potent and orally bioavailable Axl inhibitor. Selectivity profiling showed that 13c could inhibit the well-known oncogenic kinase Met with equal potency to its inhibition of Axl superfamily kinases. Compound 13c significantly inhibited cellular Axl and

  受体酪氨酸激酶 Axl 在促进癌症进展、转移和耐药性中发挥重要作用，并已被确定为抗癌治疗的有希望的靶点。我们从低微摩尔效力化合物9开始，使用分子建模辅助结构优化来发现化合物13c ，这是一种高效且可口服生物利用的 Axl 抑制剂。选择性分析表明， 13c可以抑制众所周知的致癌激酶 Met，其抑制 Axl 超家族激酶的效力相同。化合物13c显着抑制细胞Axl和Met信号传导，抑制Axl和Met驱动的细胞增殖，并抑制Gas6/Axl介导的癌细胞迁移或侵袭。此外， 13c在 Axl 驱动和 Met 驱动的肿瘤异种移植模型中表现出显着的抗肿瘤功效，在耐受良好的剂量下导致肿瘤停滞或消退。所有这些有利的数据使13c成为癌症治疗的有前途的候选药物。
• INHIBITION OF P38 KINASE ACTIVITY USING SUBSTITUTED HETEROCYCLIC UREAS
  申请人：Dumas Jacques

  公开号：US20120046290A1

  公开（公告）日：2012-02-23

  This invention relates to the use of a group of aryl ureas in treating cytokine mediated diseases, other than cancer and proteolytic enzyme mediated diseases, other than cancer, and pharmaceutical compositions for use in such therapy.

  本发明涉及一组芳香脲在治疗细胞因子介导的疾病（除癌症外）和蛋白水解酶介导的疾病（除癌症外）中的用途，以及用于此类治疗的药物组合物。
• Inhibition Of Raf Kinase Using Symmetrical And Unsymmetrical Substituted Diphenyl Ureas
  申请人：Miller Scott

  公开号：US20080269265A1

  公开（公告）日：2008-10-30

  This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.

  这项发明涉及使用一组芳基脲类化合物治疗raf介导的疾病，以及用于该疗法的药物组合物。
• 一种咪唑并吡啶或嘧啶衍生物的合成方法
  申请人：中国科学院大连化学物理研究所

  公开号：CN112851677A

  公开（公告）日：2021-05-28

  本发明属于合成技术领域，具体是一种咪唑并吡啶或嘧啶衍生物的合成方法。本发明以吡啶或嘧啶甲酸为合成子，经酰胺化、霍夫曼降解及环化反应得到咪唑并吡啶或嘧啶化合物，所得咪唑并吡啶或嘧啶衍生物能够发生进一步的转化生成功能化产物。该方法原料易得、操作简便、反应效率高、后处理方便，其官能团具有多样性。