3-(2-氯-6-氟苯基)-5-甲基异恶唑-4-羧酸 | 3919-74-2

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(2-氯-6-氟苯基)-5-甲基异恶唑-4-羧酸
• 中文别名: 3-(2-氯-6-氟苯基)-5-甲基异唑-4-羧酸；3-(2-氯-6-氟苯基)-5-甲基-4-异恶唑甲酸；3-(2-氯-6-氟苯基)-5-甲基异噁唑-4-甲酸；3-(2-氯,6-氟苯基)-5-甲基-4-异噁唑酸
• 英文名称: 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid
• 英文别名: 3-(2-chloro-6-fluorophenyl)-5-methyl isoxazol-4-carbocylic acid；3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazole-4-carboxylic acid
• CAS: 3919-74-2
• 化学式: C₁₁H₇ClFNO₃
• mdl: MFCD00055659
• 分子量: 255.633
• InChiKey: REIPZLFZMOQHJT-UHFFFAOYSA-N

物化性质

• 熔点：
  202 °C
• 沸点：
  360.7±37.0 °C(Predicted)
• 密度：
  1.454±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（轻微加热）、甲醇（非常轻微）
• 稳定性/保质期：
  在常温常压下保持稳定

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36,S36/37/39,S37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2934999090
• 危险性防范说明：
  P233,P260,P261,P264,P271,P280,P302+P352,P304,P304+P340,P305+P351+P338,P312,P321,P332+P313,P337+P313,P340,P362,P403,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335
• 储存条件：
  请将药品存放在避光、通风干燥的地方，并密封保存。

SDS

Name:	3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid 97% Material Safety Data Sheet
Synonym:
CAS:	3919-74-2

Section 1 - Chemical Product MSDS Name:3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid 97% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
3919-74-2	3-(2-Chloro-6-fluorophenyl)-5-methylis	97%	223-486-8

Hazard Symbols: XI
Risk Phrases: 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 3919-74-2: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: off-white to tan
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 202 - 204 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C11H7ClFNO3
Molecular Weight: 256

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Oxidizing agents, reducing agents.
Hazardous Decomposition Products:
Hydrogen chloride, chlorine, nitrogen oxides, carbon monoxide, carbon dioxide, acrid smoke and fumes, fluorine, hydrogen fluoride gas.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 3919-74-2 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
No information available.
IMO
No information available.
RID/ADR
No information available.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 3919-74-2: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 3919-74-2 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 3919-74-2 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

3-(2-氯-6-氟苯基)-5-甲基异恶唑-4-羧酸是氟氯西林钠的关键中间体，也称为氟氯西林-杂质D，适用于实验室研发和有机合成过程。

应用

制备3-(2-氯-6-氟苯基)-5-甲基异恶唑-4-异恶唑甲酰氯：

将以下原料以摩尔比1∶0.33∶0.02的比例混合：3-(2′-氯-6′-氟苯基)-5-甲基-4-异恶唑甲酸（25.55g，100mmol）、双(三氯甲基)碳酸酯（9.80g，33mmol）和催化剂（0.232g，2mmol）。使用甲苯作为溶剂，其用量为3-(2′-氯-6′-氟苯基)-5-甲基-4-异恶唑甲酸质量的10倍。

将上述原料混合均匀后，在室温下于45分钟内滴加双(三氯甲基)碳酸酯的甲苯溶液，同时开启氯化氢吸收系统。然后升温至110℃，回流反应2小时。反应结束后，减压蒸馏回收甲苯，并在0.667KPa下收集168～170℃的馏分，在冷冻条件下固化。

反应信息

• 作为反应物：
  描述：

  3-(2-氯-6-氟苯基)-5-甲基异恶唑-4-羧酸 在 氯化亚砜 、 potassium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 0.42h， 生成
  参考文献：
  名称：

  设计，合成和生物评价取代的苯基异恶唑类似物作为除草剂安全剂。

  摘要：

  除草剂安全剂可增强农作物除草剂的解毒能力，而不会影响目标杂草的敏感性。为了提高农作物对除草剂乙草胺（ACT）引起的毒性相关胁迫的耐受性，通过中间衍生化方法设计了一类新型的取代苯基异恶唑衍生物作为除草剂安全剂。使用微波辅助合成制备苯基异恶唑类似物，并通过IR，1 H NMR，13 C NMR和HRMS确认所有结构。通过X射线衍射分析进一步表征化合物I-1。生物测定结果表明，大多数获得的化合物通过增加玉米生长恢复率，谷胱甘肽含量和谷胱甘肽提供了不同程度的抗ACT诱导伤害的安全性S-转移酶活性。特别地，化合物I-20显示出优异的抗ACT毒性的安全剂活性，可与市售安全剂贝诺沙星相比。进行了高斯计算，结果表明化合物I-20的亲核能力高于贝诺沙星，因此活性高于贝诺沙克。这些发现表明，苯基异恶唑衍生物具有在玉米田中进行保护性管理的巨大潜力。

  DOI：

  10.1021/acs.jafc.0c01867
• 作为产物：
  描述：

  2-氯-6-氟苯甲醛肟 在 水 、 氯 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.5h， 生成 3-(2-氯-6-氟苯基)-5-甲基异恶唑-4-羧酸
  参考文献：
  名称：

  铜（I）催化的环加成反应合成1,2,3-三唑取代的异恶唑

  摘要：

  据报道，从各种苯甲醛（I）开始，合成了一系列包含N-取代的1,2,3-三唑（V）的3,5-二取代的异恶唑-4-羧酸酯。苯甲醛与羟胺硫酸氢盐进行肟化反应。随后，氯化，然后与乙酰乙酸甲酯缩合，并将所得的酯水解，得到相应的羧酸（II），其在用PCl 5氯化后得到相应的酰氯（III）。炔丙基化时的钴氧酰氯（III）得到炔丙基酯（IV），点击反应这些得到标题化合物（V）。

  DOI：

  10.1002/jhet.837

文献信息

• Methods and compounds for inhibiting mrp1
  申请人：——

  公开号：US20030100576A1

  公开（公告）日：2003-05-29

  The present invention further relates to a method of inhibiting MRP1 in a mammal which comprises administering to a mammal in need thereof an effective amount of a compound of formula (I).

  本发明还涉及一种抑制哺乳动物中MRP1的方法，包括向需要的哺乳动物施用化合物(I)的有效量。
• [EN] ISOXAZOLOPYRIDINE DERIVATIVES FOR USE IN THE TREATMENT OF HIF-MEDIATED CONDITIONS<br/>[FR] DÉRIVÉS D'ISOXAZOLOPYRIDINE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT D'ÉTATS À MÉDIATION PAR HIF
  申请人：FIBROGEN INC

  公开号：WO2009073669A1

  公开（公告）日：2009-06-11

  The present invention relates to novel compounds of formula (I) capable of modulating the stability and/or activity of hypoxia inducible factor (HIF) by inhibiting the activity of at least one HIF hydroxylase enzyme.

  本发明涉及一类新的公式（I）化合物，能够通过抑制至少一种HIF羟基化酶的活性来调节低氧诱导因子（HIF）的稳定性和/或活性。
• Discovery of <i>N</i>-Aroyl Diketone/Triketone Derivatives as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibiting-Based Herbicides
  作者：Ying Fu、Dong Zhang、Shuai-Qi Zhang、Yong-Xuan Liu、You-Yuan Guo、Meng-Xia Wang、Shuang Gao、Li-Xia Zhao、Fei Ye

  DOI：10.1021/acs.jafc.9b01412

  日期：2019.10.30

  4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is an important target site for discovering new bleaching herbicides. To explore novel HPPD inhibitors with excellent herbicidal activity, a series of novel N-aroyl diketone/triketone derivatives were rationally designed by splicing active groups and bioisosterism. Bioassays revealed that most of these derivatives displayed preferable herbicidal

  4-羟基苯基丙酮酸双加氧酶（HPPD，EC 1.13.11.27）是发现新的漂白除草剂的重要靶位。为了探索具有优异除草活性的新型HPPD抑制剂，通过拼接活性基团和生物等排异构体，合理设计了一系列新型N-芳酰基二酮/三酮衍生物。生物测定法显示，这些衍生物大多数对0.045 mmol / m2的菜E（EC）和0.090 mmol / m2的芥菜（AJ）表现出较好的除草活性。特别地，与商业化的化合物甲基磺草酮相比，化合物If具有更强的效力。分子对接表明目标化合物和甲基磺草酮的相应活性分子与周围残基共享相似的相互作用，从而导致与拟南芥HPPD活性位点的完美相互作用。
• [EN] NEW COMPOUNDS 955<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：ASTRAZENECA AB

  公开号：WO2009010784A1

  公开（公告）日：2009-01-22

  Compounds of formula (I): wherein the substituents are as defined in the specification, are described and claimed. The invention further relates to pharmaceutical compositions containing said compounds and to the use of said compounds in therapy. The present invention also relates to processes for the preparation of said compounds.

  公式(I)的化合物：其中取代基如说明书中所定义，已被描述和声称。本发明进一步涉及包含所述化合物的药物组合物以及所述化合物在治疗中的用途。本发明还涉及制备所述化合物的方法。
• [EN] 1-(4-(ISOXAZOL-5-YL)-1H-PYRAZOL-1-YL)-2-METHYLPROPAN-2-OL DERIVATIVES AND RELATED COMPOUNDS AS IL-17 AND IFN-GAMMA INHIBITORS FOR TREATING AUTOIMMUNE DISEASES AND CHRONIC INFLAMMATION<br/>[FR] DÉRIVÉS DE 1-(4-(ISOXAZOL-5-YL)-1 H-PYRAZOL-1-YL)-2-MÉTHYLPROPAN-2-OL ET COMPOSÉS APPARENTÉS EN TANT QU'INHIBITEURS D'IL-17 ET D'IFN-GAMMA POUR LE TRAITEMENT DE MALADIES AUTO-IMMUNES ET D'UNE INFLAMMATION CHRONIQUE
  申请人：IMMUNIC AG

  公开号：WO2019048541A1

  公开（公告）日：2019-03-14

  The present invention relates to compounds of the general formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein Ar, Z and Y are as described herein and R1 is a group of the structure (formula (II)), wherein n is 0 or 1; R2 is H, deuterium or methyl; R3 is methyl, trilluoromethyl, ethyl, or taken with R2 together forms a cyclopropyl group, or R3 forms a methylene bridge to the carbon atom marked *, which are suitable for the treatment of autoimmune diseases and chronic inflammation.

  本发明涉及具有通用公式（I）的化合物，以及其中Ar、Z和Y如本文所述的药用可接受盐和溶剂化物，其中R1是具有结构（公式（II））的组，其中n为0或1；R2是H，氘或甲基；R3是甲基，三氟甲基，乙基，或者与R2共同形成一个环丙基组，或者R3形成一个甲基桥接到标记为*的碳原子上，这些化合物适合用于治疗自身免疫性疾病和慢性炎症。