3-氨基-5-(4-氯苯基)噻吩-2-羧酸甲酯 | 91076-93-6

• 物质功能分类: 医药中间体 - 噻吩类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 3-氨基-5-(4-氯苯基)噻吩-2-羧酸甲酯
• 中文别名: 3-氨基-5-(4-氯苯基)噻吩-2-甲酸甲酯
• 英文名称: methyl 3-amino-5-(4-chlorophenyl)-2-thiophenecarboxylate
• 英文别名: 3-amino-5-(4-chloro-phenyl)-tiophene-2-carboxylic acid methyl ester；methyl 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylate；3-amino-5-(4-chloro-phenyl)-thiophene-2-carboxylic acid methyl ester；3-amino-5-(4-chlorophenyl)thiophene-2-carboxylic acid methyl ester；methyl-3-amino-5-(4-chlorophenyl)-2-thiophene carboxylate
• CAS: 91076-93-6
• 化学式: C₁₂H₁₀ClNO₂S
• mdl: MFCD00052591
• 分子量: 267.736
• InChiKey: MELGGDOYSMRBGA-UHFFFAOYSA-N

物化性质

• 熔点：
  140-141 °C
• 沸点：
  465.9±45.0 °C(Predicted)
• 密度：
  1.363±0.06 g/cm3(Predicted)
• 溶解度：
  <0.6 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.083
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S22,S26,S36/37/39
• 危险类别码：
  R20/21/22,R36/37/38
• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P301+P312,P302+P352,P304+P340,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温且干燥环境下使用。

SDS

Name:	Methyl 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylate 97% Material Safety Data Sheet
Synonym:	None Known
CAS:	91076-93-6

Section 1 - Chemical Product MSDS Name:Methyl 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylate 97% Material Safety Data Sheet
Synonym:None Known

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
91076-93-6	Methyl 3-amino-5-(4-chlorophenyl)thiop	97%	unlisted

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated. May be harmful if swallowed.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated. May be harmful if inhaled.
Chronic:
No information found.

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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:
If swallowed, do not induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. Get medical aid.
Inhalation:
If inhaled, remove to fresh air. 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. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
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. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing.
Keep container tightly closed. Avoid ingestion and inhalation.
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# 91076-93-6: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
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: white to cream
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 141 - 143 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: C12H10ClNO2S
Molecular Weight: 268

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Dust generation.
Incompatibilities with Other Materials:
Strong oxidizing agents, acid chlorides.
Hazardous Decomposition Products:
Hydrogen chloride, chlorine, nitrogen oxides, carbon monoxide, oxides of sulfur, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 91076-93-6 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
Methyl 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylate - 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: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 91076-93-6: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 91076-93-6 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 91076-93-6 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

反应信息

• 作为反应物：
  描述：

  3-氨基-5-(4-氯苯基)噻吩-2-羧酸甲酯 在 1H-1,2,4-三唑 、 双氧水 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 苯酚 为溶剂， 反应 26.33h， 生成 BMS830216
  参考文献：
  名称：

  Identification of a Nonbasic Melanin Hormone Receptor 1 Antagonist as an Antiobesity Clinical Candidate

  摘要：

  Identification of MCHR1 antagonists with a preclinical safety profile to support clinical evaluation as antiobesity agents has been a challenge. Our finding that a basic moiety is not required for MCHR1 antagonists to achieve high affinity allowed us to explore structures less prone to off-target activities such as hERG inhibition. We report the SAR evolution of hydroxylated thienopyrimidinone ethers culminating in the identification of 27 (BMS-819881), which entered obesity clinical trials as the phosphate ester prodrug 35 (BMS-830216).

  DOI：

  10.1021/jm500026w
• 作为产物：
  描述：

  5-溴-3-(2,2,2-三氟-乙酰基氨基)-噻吩-2-羧酸甲酯 在 水 、 palladium diacetate 、 sodium carbonate 、 potassium carbonate 、 三苯基膦 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 2.0h， 生成 3-氨基-5-(4-氯苯基)噻吩-2-羧酸甲酯
  参考文献：
  名称：

  N-烷基-4-烷基氨基-6-芳基噻吩并[3,2 - d ]嘧啶-2-甲酰胺衍生物的固相合成方法

  摘要：

  在此，我们描述了一种用于合成N-烷基-4-烷基氨基-6-芳基噻吩并[3,2 - d ]嘧啶-2-甲酰胺衍生物的固相合成方法。这些衍生物由具有生物活性的 6-苯基噻吩并[3,2- d ]嘧啶支架组成。模板介导的合成策略涉及 3-氨基-5-溴噻吩-2-羧酸甲酯和芳基硼酸之间的 Suzuki 偶联反应，得到 3-氨基-5-芳基噻吩-2-羧酸甲酯。涉及 3-氨基-5-芳基噻吩-2-羧酸甲酯和氰基甲酸甲酯的环缩合反应生成酯，当进行水解反应时生成 6-芳基-4-氧代-3,4-二氢噻吩[3,2- d]嘧啶-2-羧酸（模板化合物）。这些羧酸模板与负载伯烷基胺的酸敏感甲氧基苯甲醛 (AMEBA) 树脂偶联。酰胺偶联反应之后是由苯并三唑-1-基氧基三（二甲氨基）鏻六氟磷酸盐 (BOP) 介导的直接胺化反应。随后将化合物从固体载体上裂解下来，使用反相高效液相色谱技术 (RP-HPLC) 进行纯化，然后通过用水预处理的强阴离子交换

  DOI：

  10.1016/j.tet.2021.132247

文献信息

• Heterocyclic mchr1 antagoists
  申请人：Barvian K Kevin

  公开号：US20060194871A1

  公开（公告）日：2006-08-31

  This invention relates to novel heterocycles which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), also referred to as 11 CBy, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in medicines. Compounds of the invention have the formula:

  这项发明涉及新型杂环化合物，它们是黑色素聚集激素受体1（MCHR1）的拮抗剂，也被称为11 CBy，涉及含有这些化合物的药物组合物，制备这些化合物的过程，以及它们在药物中的用途。发明的化合物具有以下公式：
• Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2-<i>d</i>]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors
  作者：Romeo Romagnoli、Filippo Prencipe、Paola Oliva、Stefania Baraldi、Pier Giovanni Baraldi、Santiago Schiaffino Ortega、Mariem Chayah、Maria Kimatrai Salvador、Luisa Carlota Lopez-Cara、Andrea Brancale、Salvatore Ferla、Ernest Hamel、Roberto Ronca、Roberta Bortolozzi、Elena Mariotto、Elena Mattiuzzo、Giampietro Viola

  DOI：10.1021/acs.jmedchem.8b01391

  日期：2019.2.14

  The clinical evidence for the success of tyrosine kinase inhibitors in combination with microtubule-targeting agents prompted us to design and develop single agents that possess both epidermal growth factor receptor (EGFR) kinase and tubulin polymerization inhibitory properties. A series of 6-aryl/heteroaryl-4-(3',4',5'-trimethoxyanilino)thieno[3,2- d]pyrimidine derivatives were discovered as novel

  酪氨酸激酶抑制剂与微管靶向剂成功结合的临床证据促使我们设计和开发具有表皮生长因子受体（EGFR）激酶和微管蛋白聚合抑制特性的单一药物。发现了一系列6-芳基/杂芳基-4-（3'，4'，5'-三甲氧基苯胺基）噻吩并[3,2-d]嘧啶衍生物，它们是新型的双微管蛋白聚合和EGFR激酶抑制剂。4-（3'，4'，5'-三甲氧基苯胺基）-6-（对甲苯基）噻吩并[3,2-d]嘧啶衍生物6g是该系列中最有效的化合物，具有抗增殖作用，其中一半最大抑制浓度（IC50）值在一位或两位数纳摩尔范围内。化合物6g与秋水仙碱位点的微管蛋白结合并抑制微管蛋白组装，IC50值为0.71μM，6g抑制EGFR活性，IC50值为30 nM。我们的数据表明，6g优异的体外和体内特性可能源于其对微管蛋白聚合和EGFR激酶的双重抑制作用。
• Synthesis and combinatorial approach of the reactivity of 6- and 7-arylthieno[3,2-d][1,3]oxazine-2,4-diones
  作者：François-Xavier Le Foulon、Emmanuelle Braud、Frédéric Fabis、Jean-Charles Lancelot、Sylvain Rault

  DOI：10.1016/j.tet.2003.10.028

  日期：2003.12

  This paper describes a general procedure for the synthesis of new substituted thiaisatoic anhydrides or 6- or 7-aryl-1H-thiéno[3,2-d][1,3]oxazine-2,4-diones 3a–j and 4a–f. They were synthesized in large scale under microwave heating conditions with high yields. The reactivity vs nucleophilic reagents of these compounds was studied and permitted to develop a simple combinatorial procedure to synthesize

  本文描述了合成新的取代硫代硫杂酸酐或6-或7-芳基-1 H-噻吩并[3,2- d ] [1,3]恶嗪-2,4-二酮3a – j和4a的一般程序。 – f。它们在微波加热条件下以高收率大规模合成。研究了这些化合物的亲核试剂的反应性与亲核试剂的关系，并允许开发一种简单的组合方法来合成新的噻吩脲酸7a – j和8a – j库。
• One-pot synthesis of 2-substituted thieno[3,2-b]indoles from 3-aminothiophene-2-carboxylates through in situ generated 3-aminothiophenes
  作者：Roman A. Irgashev、Alexander S. Steparuk、Gennady L. Rusinov

  DOI：10.1016/j.tetlet.2019.151185

  日期：2019.10

  with arylhydrazines in glacial acetic acid solution. The latter step includes in situ decarboxylation of the freed 3-aminothiophene-2-caboxylic acids to the 3-aminothiophenes and their acid promoted reaction with arylhydrazines to initially form arylhydrazones of 5-substituted thiophene-3(2H)-ones, which smoothly cause indolization to afford the desired thieno[3,2-b]indoles.

  一种方便的协议，可使用易于获得的5-取代的3-氨基噻吩-2-羧酸酯一锅合成噻吩并[3,2- b ]吲哚，在C-2位带有芳香，噻吩-2-基或苯乙烯基片段Fischer吲哚化反应是在这项研究期间开发的。该方法的两个主要步骤是用氢氧化钠对起始的3-氨基酯进行皂化，然后在冰醋酸溶液中用芳基肼对粗制的3-氨基酸钠盐进行下一步处理。后面的步骤包括将游离的3-氨基噻吩-2-羧酸原位脱羧为3-氨基噻吩，并使其与芳基肼的酸促进反应，最初形成5-取代噻吩-3（2 H的芳基hydr））-平滑地导致吲哚化以提供所需的噻吩并[3,2- b ]吲哚。
• Synthesis of aryl-substituted thieno[3,2-<i>b</i>]thiophene derivatives and their use for N,S-heterotetracene construction
  作者：Nadezhda S Demina、Nikita A Kazin、Nikolay A Rasputin、Roman A Irgashev、Gennady L Rusinov

  DOI：10.3762/bjoc.15.261

  日期：——

  Fiesselmann thiophene synthesis was applied for the convenient construction of thieno[3,2-b]thiophene derivatives. Thus, new 5- or 6-aryl-3-hydroxythieno[3,2-b]thiophene-2-carboxylates were obtained by condensation of 5- or 4-aryl-3-chlorothiophene-2-carboxylates, respectively, with methyl thioglycolate in the presence of potassium tert-butoxide. The saponification of the resulting esters, with decarboxylation

  Fiesselmann噻吩合成用于方便地构造噻吩并[3,2- b ]噻吩衍生物。因此，通过将5-或4-芳基-3-氯噻吩-2-羧酸酯分别与巯基乙酸甲酯缩合，得到新的5-或6-芳基-3-羟基噻吩并[3,2- b ]噻吩-2-羧酸酯。在叔丁醇钾存在下 所得酯的皂化以及中间酸的脱羧，得到相应的噻吩并[3,2 - b ]噻吩-3（2 H）-酮。后者的酮用于合成新的N，S-杂踪烷，即9 H -thieno [2'，3'：4,5] thieno [3,2- b吲哚是通过根据Fischer吲哚化反应用芳基肼处理而得到的。