4-氯-6-氟喹啉-3-甲酸乙酯 | 77779-49-8

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 4-氯-6-氟喹啉-3-甲酸乙酯
• 英文名称: 4-chloro-6-fluoroquinoline-3-carboxylic acid ethyl ester
• 英文别名: ethyl 4-chloro-6-fluoroquinoline-3-carboxylate；4-chloro-6-fluoro-quinoline-3-carboxylic acid ethyl ester；Ethyl 4-chloro-6-fluoro-quinoline-3-carboxylate；ethyl 4-chloro-6-fluoroquinolin-3-carboxylate
• CAS: 77779-49-8
• 化学式: C₁₂H₉ClFNO₂
• mdl: MFCD00173350
• 分子量: 253.66
• InChiKey: PPHSOQWURBALSQ-UHFFFAOYSA-N

物化性质

• 熔点：
  62-63℃
• 沸点：
  332.1±37.0 °C(Predicted)
• 密度：
  1.354

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933499090
• 危险性防范说明：
  P305+P351+P338
• 危险性描述：
  H319
• 储存条件：
  室温

SDS

---

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Ethyl 4-Chloro-6-Fluoroquinoline-3-Carboxylate
: VBP00044
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.

---

SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Eye irritation (Category 2), H319
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
Xi Irritant R36
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)
Causes serious eye irritation.
Precautionary statement(s)
P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
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.

---

SECTION 3: Composition/information on ingredients
Substances
Molecular weight : 253,66 g/mol
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
Ethyl 4-Chloro-6-Fluoroquinoline-3-Carboxylate
Eye Irrit. 2; H319 <= 100 %
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
Ethyl 4-Chloro-6-Fluoroquinoline-3-Carboxylate
Xi, R36 <= 100 %
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

---

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
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
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

---

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

---

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.

---

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

---

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
impervious clothing, 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.

---

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

---

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

---

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

---

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

---

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.

---

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

---

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

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  4-氯-6-氟喹啉-3-甲酸乙酯 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 2-(8-Fluoro-3-oxo-3,5-dihydro-pyrazolo[4,3-c]quinolin-2-yl)-5-methyl-thiophene-3-carboxylic acid
  参考文献：
  名称：

  噻吩并吡唑并喹啉：苯并二氮杂receptor受体的强效激动剂和反向激动剂。

  摘要：

  一系列2-（thien-3-yl）-和2-（thien-2-yl）-2,5-dihydro-3H-pyrazolo [4,3-c] quinolin-3的合成及构效关系-报告一个。与地西epa相比，许多化合物对受体的亲和力高1个数量级。平面度是与苯并二氮杂receptor受体结合的结构要求之一。激动剂和反向激动剂的活性分别基于戊烯四唑诱导的惊厥的抑制或促进进行评估。噻吩-3-基化合物表现出反向激动剂活性，而具有5'-烷基的噻吩-2-基类似物表现出激动剂活性。喹啉部分上的取代不增强体内活性。

  DOI：

  10.1021/jm00117a012
• 作为产物：
  描述：

  二甲氨亚甲基丙二酸二乙酯 在 三氯氧磷 作用下， 生成 4-氯-6-氟喹啉-3-甲酸乙酯
  参考文献：
  名称：

  Quinolin-4(1H)-imines are Potent Antiplasmodial Drugs Targeting the Liver Stage of Malaria

  摘要：

  We present a novel series of quinolin-4(1H)-imines as dual-stage antiplasmodials, several-fold more active than primaquine in vitro against Plasmodium berghei liver stage. Among those, compounds 5g and 5k presented low nanomolar IC50 values. The compounds are metabolically stable and modulate several drug targets. These results emphasize the value of quinolin-4(1H)-imines as a new chemotype and their suitable properties for further drug development.

  DOI：

  10.1021/jm400246e

文献信息

• THERAPEUTIC PYRAZOLOQUINOLINE DERIVATIVES
  申请人：Kaplan Alan P.

  公开号：US20080306049A1

  公开（公告）日：2008-12-11

  The invention provides a novel chemical series of formula I, as well as methods of use thereof for binding to the benzodiazepine site of the GABA A receptor and modulating GABA A , and use of the compound of formula I for the treatment of GABA A receptor associated disorders. The general structure of formula I is shown below and can exist in tautomeric forms: The invention further provides a method of modulation of one or more GABA A subtypes in an animal comprising administering to the animal an effective amount of a compound of formula (I).

  这项发明提供了一种新颖的化学系列，其化学式为I，以及用于结合到GABA A 受体的苯二氮卓类位点并调节GABA A 的使用方法，以及用于治疗与GABA A 受体相关疾病的化合物的使用。化学式I的一般结构如下所示，并且可以存在互变异构体形式： 该发明还提供了一种在动物中调节一个或多个GABA A 亚型的方法，包括向动物投与化学式(I)化合物的有效量。
• Synthesis and screening of triazolopyrimidine scaffold as multi-functional agents for Alzheimer's disease therapies
  作者：Jitendra Kumar、Poonam Meena、Anju Singh、Ehtesham Jameel、Mudasir Maqbool、Mohammad Mobashir、Ashutosh Shandilya、Manisha Tiwari、Nasimul Hoda、B. Jayaram

  DOI：10.1016/j.ejmech.2016.04.053

  日期：2016.8

  acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d)

  在本研究中，设计，合成和评估了一系列三唑并嘧啶-喹啉和氰基吡啶-喹啉杂化物，作为乙酰胆碱酯酶抑制剂（AChEI）。分子对接和评分用于抑制剂的设计。分子是通过容易获得的，会聚的合成途径合成的。三种基于三唑并嘧啶的化合物显示出对乙酰胆碱酯酶的纳摩尔活性。其中，乙基6-氟-4-（4-（5-甲基-[1,2,4]三唑并[1,5-a]嘧啶-7-基）哌嗪-1-基）喹啉-3-羧酸酯（10d），强烈抑制AChE，IC 50值为42 nM。此外化合物10d被认为是对丁酰胆碱酯酶（BuChE）具有12倍选择性的最有前途的化合物。该化合物显示出组成的多目标概况，并有望抑制自身诱导的和AChE诱导的Aβ聚集以及抗氧化活性。
• High affinity central benzodiazepine receptor ligands: synthesis and structure–activity relationship studies of a new series of pyrazolo[4,3- c ]quinolin-3-ones
  作者：L. Savini、P. Massarelli、C. Nencini、C. Pellerano、G. Biggio、A. Maciocco、G. Tuligi、A. Carrieri、N. Cinone、A. Carotti

  DOI：10.1016/s0968-0896(97)10039-6

  日期：1998.4

  tested as central benzodiazepine receptor ligands. Results from structure-affinity relationship studies were in full agreement with previously proposed pharmacophore models and, in addition, quantitative structure-activity analysis gave further significant insight into the main molecular determinants of high benzodiazepine receptor affinity. The intrinsic activity of some active ligands was also determined

  制备了一系列在喹啉和N2-苯环上带有适当取代基的2-芳基（杂芳基）-2,5-二氢吡唑并[4,3-c]喹啉-3-（3H）-酮，并进行了测试。中央苯并二氮杂receptor受体配体。结构亲和关系研究的结果与先前提出的药效团模型完全吻合，此外，定量结构活性分析为高苯并二氮杂receptor受体亲和力的主要分子决定因素提供了更重要的见解。还确定并初步讨论了一些活性配体的内在活性。
• Pyrazoloquinolines
  申请人：Ciba-Geigy Corporation

  公开号：US04312870A1

  公开（公告）日：1982-01-26

  2-Aryl-pyrazolo[4-3-c]quinolin-3-ones, e.g. those of the formula ##STR1## and pharmaceutically acceptable acyl derivatives or salts thereof, are psychoactive agents useful in the treatment of anxiety or depression.

  2-芳基吡唑并[4-3-c]喹啉-3-酮，例如式##STR1##及其药用可接受的酰基衍生物或盐，是用于治疗焦虑或抑郁的精神活性剂。
• Discovery of Plasmodium vivax<i>N</i>-Myristoyltransferase Inhibitors: Screening, Synthesis, and Structural Characterization of their Binding Mode
  作者：Victor Goncalves、James A. Brannigan、David Whalley、Keith H. Ansell、Barbara Saxty、Anthony A. Holder、Anthony J. Wilkinson、Edward W. Tate、Robin J. Leatherbarrow

  DOI：10.1021/jm300040p

  日期：2012.4.12

  N-Myristoyltransferase (NMT) is a prospective drug target against parasitic protozoa. Herein we report the successful discovery of a series of Plasmodium vivax NMT inhibitors by high-throughput screening. A high-resolution crystal structure of the hit compound in complex with NMT was obtained, allowing understanding of its novel binding mode. A set of analogues was designed and tested to define the

  N-肉豆蔻酰转移酶 (NMT) 是一种针对寄生原生动物的前瞻性药物靶点。在此，我们报告通过高通量筛选成功发现了一系列间日疟原虫NMT 抑制剂。获得了与 NMT 复合的命中化合物的高分辨率晶体结构，从而可以了解其新的结合模式。设计并测试了一组类似物以定义与活性和选择性相关的化学基团。