4-氯-1H-吡咯并[2,3-B]吡啶-5-甲腈 | 920966-02-5

• 物质功能分类: 有机原料 - 腈类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 中文名称: 4-氯-1H-吡咯并[2,3-B]吡啶-5-甲腈
• 中文别名: 4-氯-1H-吡咯并[2,3-b]吡啶-5-甲腈
• 英文名称: 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile
• CAS: 920966-02-5
• 化学式: C₈H₄ClN₃
• mdl: MFCD09965877
• 分子量: 177.593
• InChiKey: ULYGKPKPBWOTFQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.50

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 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：
  52.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 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：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : 4-Chloro-1H-Pyrrolo[2,3-B]Pyridine-5-Carbonitrile
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 3), H301
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
T Toxic R25
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 Danger
Hazard statement(s)
H301 Toxic if swallowed.
Precautionary statement(s)
P301 + P310 IF SWALLOWED: Immediately call a POISON CENTER or doctor/
physician.
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 : 177,59 g/mol
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
4-Chloro-1H-Pyrrolo[2,3-B]Pyridine-5-Carbonitrile
Acute Tox. 3; H301 <= 100 %
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
4-Chloro-1H-Pyrrolo[2,3-B]Pyridine-5-Carbonitrile
T, R25 <= 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. Take victim immediately to hospital. 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
Wear respiratory protection. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Prevent further leakage or spillage if safe to do so. 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, acute toxic Cat.3 / toxic hazardous materials or hazardous
materials causing chronic effects
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
Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling
the product.
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
Where risk assessment shows air-purifying respirators are appropriate use a full-face particle
respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering
controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use
respirators and components tested and approved under appropriate government standards such
as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. 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: 2811 IMDG: 2811 IATA: 2811
UN proper shipping name
ADR/RID: TOXIC SOLID, ORGANIC, N.O.S. (4-Chloro-1H-Pyrrolo[2,3-B]Pyridine-5-Carbonitrile)
IMDG: TOXIC SOLID, ORGANIC, N.O.S. (4-Chloro-1H-Pyrrolo[2,3-B]Pyridine-5-Carbonitrile)
IATA: Toxic solid, organic, n.o.s. (4-Chloro-1H-Pyrrolo[2,3-B]Pyridine-5-Carbonitrile)
Transport hazard class(es)
ADR/RID: 6.1 IMDG: 6.1 IATA: 6.1
Packaging group
ADR/RID: III IMDG: III IATA: III
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
H301 Toxic if swallowed.
Full text of R-phrases referred to under sections 2 and 3
T Toxic
R25 Toxic if swallowed.
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

用途

4-氯-1H-吡咯并[2,3-B]吡啶-5-甲腈广泛应用于生物研究领域。吡咯并吡啶骨架根据吡咯和吡啶组合形式的不同，可分为多种结构类型，包括吡咯并［3，2－b］吡啶、吡咯并［3，4－b］吡啶、吡咯并［2，3－b］吡啶等六种不同的环状化合物。这些杂环化合物因含有吡咯并吡啶结构而展现出潜在的生物活性，并且在有机合成和药物研究中扮演着重要角色。许多新的活性中间体继而成为药物合成中的关键原料，设计并创新合成具有优良生物活性、低毒副作用的新药始终是科研人员关注的重点。

这类化合物存在于多种生物碱中，例如 ASP3627、Mappicine 和 Vemurafenib，并且被用作 LRRK2 抑制剂、MPS1 抑制剂、JAK1 抑制剂和 Met 激酶抑制剂等。

制备

吡咯并[2,3-B]吡啶这种双环母体结构的合成方法已有很多报道。通常，以 2, 3-二羧酸吡啶为原料，经酯化、还原、氯化后，再通过氢化钠和对甲苯磺酰胺进行环合反应制备。该过程也可发生分子内环合，最终得到 4-氯-1H-吡咯并[2,3-B]吡啶-5-甲腈。合成流程如下图所示。

合成反应式


实验操作

以 3-乙炔基 -4- 氯吡啶-2-胺-5-甲腈为原料，在无水甲醇中溶解，并加入催化量的冰醋酸。在 N₂ 气氛下，称取 70.0 mg (1.10 mmol) 氰基硼氢化钠，混合均匀后置于烧瓶中并加热至60℃，使用薄层色谱法跟踪反应进度直至完全转化。通过 TLC 检测（甲醇展开剂），产物 Rf 值为 0.57。将反应混合物的溶剂蒸发，并用二氯甲烷重新溶解。用水洗涤两次后，有机相用无水硫酸钠干燥，进行硅胶柱层析色谱分离。最终在真空条件下干燥，得到4-氯-1H-吡咯并[2,3-B]吡啶-5-甲腈。

反应信息

• 作为反应物：
  描述：

  4-氯-1H-吡咯并[2,3-B]吡啶-5-甲腈 在 四(三苯基膦)钯 盐酸 、 水 、 sodium hydride 、 potassium carbonate 作用下， 以 氯仿 、 异丁酰胺 、 水 、 mineral oil 、 正丁醇 为溶剂， 反应 5.0h， 生成 4-(1H-pyrazol-4-yl)-5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  PIPERIDIN-4-YL AZETIDINE DERIVATIVES AS JAK1 INHIBITORS

  摘要：

  本发明提供了哌啶-4-基氮杂环丙烷衍生物，以及它们的组合物和使用方法，这些衍生物调节Janus激酶1（JAK1）的活性，并且在治疗与JAK1活性相关的疾病方面具有用处，例如炎症性疾病、自身免疫性疾病、癌症和其他疾病。

  公开号：

  US20110224190A1
• 作为产物：
  描述：

  4-氯-1H-吡咯并[2,3-b]吡啶-5-羧酸 在 三乙胺 、 N,N'-羰基二咪唑 、 三氟乙酸酐 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 4-氯-1H-吡咯并[2,3-B]吡啶-5-甲腈
  参考文献：
  名称：

  JAK激酶抑制剂及其制备方法和在医药领域的应用

  摘要：

  本申请涉及JAK激酶抑制剂及其制备方法和在医药领域的应用，属于医药化学领域。本申请提供了一类新的小分子JAK抑制剂，其具有通式II所示的结构。本申请提供的通式II所示的化合物在预防或治疗JAK相关适应症中具有更好药效和安全性。

  公开号：

  CN109535164B

文献信息

• Discovery and Optimization of Pyrrolopyrimidine Inhibitors of Interleukin-1 Receptor Associated Kinase 4 (IRAK4) for the Treatment of Mutant MYD88^L265P Diffuse Large B-Cell Lymphoma
  作者：James S. Scott、Sébastien L. Degorce、Rana Anjum、Janet Culshaw、Robert D. M. Davies、Nichola L. Davies、Keith S. Dillman、James E. Dowling、Lisa Drew、Andrew D. Ferguson、Sam D. Groombridge、Christopher T. Halsall、Julian A. Hudson、Scott Lamont、Nicola A. Lindsay、Stacey K. Marden、Michele F. Mayo、J. Elizabeth Pease、David R. Perkins、Jennifer H. Pink、Graeme R. Robb、Alan Rosen、Minhui Shen、Claire McWhirter、Dedong Wu

  DOI：10.1021/acs.jmedchem.7b01290

  日期：2017.12.28

  optimization of a series of pyrrolopyrimidine inhibitors of interleukin-1 receptor associated kinase 4 (IRAK4) using X-ray crystal structures and structure based design to identify and optimize our scaffold. Compound 28 demonstrated a favorable physicochemical and kinase selectivity profile and was identified as a promising in vivo tool with which to explore the role of IRAK4 inhibition in the treatment of mutant

  本文中，我们报告了使用X射线晶体结构和基于结构的设计来鉴定和优化我们的支架，优化了一系列白介素1受体相关激酶4（IRAK4）的吡咯并嘧啶抑制剂。化合物28表现出良好的理化和激酶选择性，并被认为是一种有前途的体内工具，可利用该工具探索IRAK4抑制作用在突变MYD88 L265P弥漫性大B细胞淋巴瘤（DLBCL）的治疗中的作用。化合物28已显示在体​​外高浓度下具有抑制NF-κB活化和ABC亚型ABC亚型生长的能力，但与低浓度下的BTK抑制剂联用则显示出更大的作用。在体内，化合物28和依鲁替尼的组合在ABC-DLBCL小鼠模型中导致肿瘤消退。
• [EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOGEN IDEC INC

  公开号：WO2011029046A1

  公开（公告）日：2011-03-10

  The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.

  本发明提供了用作Btk抑制剂的化合物、其组合物以及使用方法。
• [EN] TRICYCLIC HETEROCYLIC DERIVATIVES<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES TRICYCLIQUES
  申请人：MERCK PATENT GMBH

  公开号：WO2017202748A1

  公开（公告）日：2017-11-30

  Compounds of the formula (I) in which R1 and R2 have the meanings indicated in Claim 1,are inhibitors of ATR, and can be employed for the treatment of diseases such as cancer.

  式(I)中R1和R2具有权利要求书中指示的含义，是ATR的抑制剂，可用于治疗癌症等疾病。
• [EN] PYRROLO[2,3-B]PYRIDINE CDK9 KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PYRROLO[2,3-B]PYRIDINE CDK9 KINASE
  申请人：ABBVIE INC

  公开号：WO2014139328A1

  公开（公告）日：2014-09-18

  Disclosed are compounds of Formula (IIa), wherein R1, R2, R3A, R3B, R3C, R3D, R3E, and R4 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds may be used as agents in the treatment of diseases, including cancer. Also provided are pharmaceutical compositions comprising one or more compounds of Formula (IIa).

  公开的是Formula (IIa)的化合物，其中R1、R2、R3A、R3B、R3C、R3D、R3E和R4如规范中所定义，并且其药用盐。这些化合物可用作治疗疾病，包括癌症的药物。还提供了包含一个或多个Formula (IIa)化合物的药物组合物。
• [EN] SUBSTITUTED PYRROLOPYRIDINES AS JAK INHIBITORS<br/>[FR] PYRROLOPYRIDINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE JAK
  申请人：ACLARIS THERAPEUTICS INC

  公开号：WO2020223728A1

  公开（公告）日：2020-11-05

  The present invention relates to new pyrrolopyridine compounds having the structures of Formula (I)-(IV), wherein the R groups, A, B, C, D and n are as defined in the detailed description, and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibition of JAK kinase activity in a human or animal subject are also provided for the treatment diseases such as pruritus, alopecia, androgenetic alopecia, alopecia areata, vitiligo and psoriasis.

  本发明涉及具有化学式（I）-（IV）结构的新吡咯吡啶化合物，其中R基团，A、B、C、D和n的定义如详细说明中所述，以及这些化合物及其应用作为治疗疾病的药物。还提供了用于治疗疾病如瘙痒症、脱发、雄激素性脱发、斑秃、白癜风和牛皮癣的方法，用于抑制人类或动物主体中JAK激酶活性。