4-氯-1H-吡咯并[2,3-b]吡啶-5-羧酸 | 920966-03-6

• 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 - 吡咯并吡啶类
• 中文名称: 4-氯-1H-吡咯并[2,3-b]吡啶-5-羧酸
• 中文别名: 4-氯-1H-吡咯并[2,3-B]吡啶-5-羧酸
• 英文名称: 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid
• CAS: 920966-03-6
• 化学式: C₈H₅ClN₂O₂
• mdl: MFCD10574983
• 分子量: 196.593
• InChiKey: SJZMFAGWKZNYPX-UHFFFAOYSA-N

物化性质

• 密度：
  1.644±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• WGK Germany：
  3
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

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-Carboxylic
Acid
: ADE001004
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.

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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
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
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)
Harmful if swallowed.
Precautionary statement(s) none
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 : 196,59 g/mol
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
4-Chloro-1H-Pyrrolo[2,3-B]Pyridine-5-Carboxylic Acid
Acute Tox. 4; H302 <= 100 %
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
4-Chloro-1H-Pyrrolo[2,3-B]Pyridine-5-Carboxylic Acid
Xn, R22 <= 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
Safety glasses with side-shields conforming to EN166 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
Strong oxidizing agents
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
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

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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

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用

4-氯-1H-吡咯并[2,3-B]吡啶-5-羧酸是一种有机中间体，可通过三步反应从4-氯-7氮杂吲哚制备。该化合物可用于合成(S)-4-(3-(2,2,2-三氟乙基氨基甲酰基)哌啶-1-氨基)-1H-7-氮杂吲哚-5甲酰胺，后者是一种JAK家族抑制剂。

制备

步骤 1：4-氯-1-(三异丙基硅基)-7-氮杂吲哚的合成

在室温下，将4-氯-7氮杂吲哚（100.00g，655.39mmol）溶于DMF（1.2L）。冰浴降温至0℃时，分批加入NaH（39.47g，983.09mmol），搅拌1小时后，滴加三异丙基氯硅烷（190.80g, 983.09mmol，即TIPSCl）。随后升至室温反应2小时。将反应液倒入2L冰水中，并用石油醚萃取两次（每次1L），合并有机相后，使用饱和食盐水洗涤三次，减压浓缩至干。通过柱层析纯化（PE:EA＝1:0）得无色透明液体197.50g，收率为97%。

步骤 2：4-氯-1-(三异丙基硅基)-7-氮杂吲哚-5-甲酸乙酯的合成

在四口瓶中加入4-氯-1-(三异丙基硅基)-7-氮杂吲哚（20.00g，64.74mmol），并溶于THF（100mL）。将溶液降温至-75℃时，滴加仲丁基锂（100mL，129.48mmol，即Sec.BuLi），反应1小时后，加入氯甲酸氯乙酯（17.80g, 129.48mmol）。继续在-75℃下反应1小时。将此反应液倒入饱和氯化铵溶液中，分液并用乙酸乙酯萃取水相两次（每次100mL），合并有机相后，使用饱和食盐水洗涤，无水硫酸钠干燥，过滤浓缩，通过柱层析纯化（PE:EA＝1:0～10:1）得淡黄色液体23.15g，收率为94%。

步骤 3：4-氯-1H-吡咯并[2,3-B]吡啶-5-羧酸的合成

在单口瓶中加入4-氯-1-(三异丙基硅基)-7-氮杂吲哚-5-甲酸乙酯（12.94g，33.96mmol），并溶于乙醇（200mL）和10％的氢氧化钠溶液（100mL）。升温至60℃反应2小时。减压蒸除乙醇后，在冰浴中用1N稀盐酸将水相pH调节至4，析出大量白色固体，过滤并烘干得8.60g白色固体，收率为77%。

反应信息

• 作为反应物：
  描述：

  4-氯-1H-吡咯并[2,3-b]吡啶-5-羧酸 在 N,N-二甲基甲酰胺 草酰氯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.5h， 生成 N-Methyl-3-oxo-2-phenyl-2,3-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine-6(5H)-carboxamide
  参考文献：
  名称：

  THERAPEUTIC 5,6,5-TRICYCLIC ANALOGS

  摘要：

  这项发明提供了一种新颖的化学系列，其化学式为I，以及利用该化合物结合到GABA A 受体的苯二氮卓位点并负性调节GABA A 的α5亚型的方法，以及利用化合物I的制备药物治疗GABA A 受体相关疾病的方法。该发明还提供了一种在动物体内调节一个或多个GABA A 亚型的方法，包括向动物体内施用化合物I的有效量。

  公开号：

  US20120095016A1
• 作为产物：
  描述：

  4-氯-1-(三异丙基甲硅烷基)-1H-吡咯并[2,3-B]吡啶-5-甲酸乙酯 在 盐酸 、 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以77%的产率得到4-氯-1H-吡咯并[2,3-b]吡啶-5-羧酸
  参考文献：
  名称：

  EP3919494

  摘要：

  公开号：

文献信息

• Substituted Indoles
  申请人：AbbVie Inc.

  公开号：US20170174688A1

  公开（公告）日：2017-06-22

  The invention provides for compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by SUV420H1. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

  该发明提供了以下式（I）的化合物 其中R 1 ，R 2 ，R 3 ，R 4 ，R 5 和R 6 具有规范中定义的任何值，以及其药学上可接受的盐，这些化合物在治疗由SUV420H1介导和调节的疾病和症状中作为药剂是有用的。还提供了由一个或多个式（I）化合物组成的药物组合物。
• Monoacylglycerol Lipase Modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US20200102311A1

  公开（公告）日：2020-04-02

  Bridged compounds of Formula (I) and Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, bipolar disorder), cancers and eye conditions. wherein R 2 , R 3 R 4 , R 5 and R 6 are defined herein.

  桥接化合物，其结构式为(I)和(II)，包含它们的药物组合物，制造它们的方法，以及使用它们的方法，包括用于治疗与MGL调节相关的疾病状态、障碍和状况的方法，如与疼痛、精神障碍、神经障碍（包括但不限于重性抑郁障碍、难治性抑郁、焦虑性抑郁、双相情感障碍）、癌症和眼科疾病相关的方法。 其中R2、R3、R4、R5和R6的定义如下。
• Synthesis and Evaluation of 1&lt;i&gt;H&lt;/i&gt;-Pyrrolo[2,3-&lt;i&gt;b&lt;/i&gt;]pyridine Derivatives as Novel Immunomodulators Targeting Janus Kinase 3
  作者：Yutaka Nakajima、Takashi Tojo、Masataka Morita、Keiko Hatanaka、Shohei Shirakami、Akira Tanaka、Hiroshi Sasaki、Kazuo Nakai、Koichiro Mukoyoshi、Hisao Hamaguchi、Fumie Takahashi、Ayako Moritomo、Yasuyuki Higashi、Takayuki Inoue

  DOI：10.1248/cpb.c15-00036

  日期：——

  Here, we describe a series of 1H-pyrrolo[2,3-b]pyridine derivatives as novel immunomodulators targeting JAK3 for use in treating immune diseases such as organ transplantation. In the chemical modification of compound 6, the introduction of a carbamoyl group to the C5-position and substitution of a cyclohexylamino group at the C4-position of the 1H-pyrrolo[2,3-b]pyridine ring led to a large increase

  已知Janus激酶（JAKs）在调节多种炎症和免疫介质中起关键作用。在这里，我们描述了一系列1H-吡咯并[2,3-b]吡啶衍生物，它们是靶向JAK3的新型免疫调节剂，用于治疗免疫疾病，例如器官移植。在化合物6的化学修饰中，在1H-吡咯并[2,3-b]吡啶环的C4位上引入氨基甲酰基并在C4位上取代了环己基氨基，导致JAK3抑制活性。化合物14c被鉴定为有效的，中等选择性的JAK3抑制剂，显示了14c对白介素2刺激的T细胞增殖的免疫调节作用。1H-pyrrolo [2，]的对接计算和WaterMap分析
• JAK激酶抑制剂及其制备方法和在医药领域的应用
  申请人：上海华汇拓医药科技有限公司

  公开号：CN109535164B

  公开（公告）日：2022-01-18

  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。
• [EN] PGDH INHIBITORS AND METHODS OF MAKING AND USING<br/>[FR] INHIBITEURS PGDH ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：MYOFORTE THERAPEUTICS INC

  公开号：WO2021151014A1

  公开（公告）日：2021-07-29

  Disclosed herein are compounds that can inhibit 15-hydroxyprostaglandin dehydrogenase. Such compounds may be administered to subjects that may benefit from modulation of prostaglandin levels.

  本文披露了一些可以抑制15-羟基前列腺素脱氢酶的化合物。这些化合物可以用于给那些可能从前列腺素水平调节中受益的受试者。