4-氯-5,6-二甲基噻吩[2,3-D]嘧啶 | 108831-68-1

• 物质功能分类: 医药中间体 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 中文名称: 4-氯-5,6-二甲基噻吩[2,3-D]嘧啶
• 中文别名: 4-氯-5,6-二甲基噻吩并[2,3-D]嘧啶；4-氯-5,6-二甲基噻吩并[2,3-d]嘧啶
• 英文名称: 4-chloro-5,6-dimethylthieno[2,3-d]pyrimidine
• CAS: 108831-68-1
• 化学式: C₈H₇ClN₂S
• mdl: MFCD00464832
• 分子量: 198.676
• InChiKey: HYOBKTVPACQCBR-UHFFFAOYSA-N

物化性质

• 熔点：
  112 °C

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xn
• 安全说明：
  S26,S3/7,S36/37
• 危险类别码：
  R20/21/22,R26,R36,R22
• 海关编码：
  2934999090
• 危险类别：
  IRRITANT
• 储存条件：
  | 温度范围 | 存储条件 | |--------------|------------| | 2-8°C | 惰性气体 |

SDS

Name:	4-Chloro-5 6-dimethylthieno[2 3-d]pyrimidine Material Safety Data Sheet
Synonym:	None Known
CAS:	108831-68-1

Section 1 - Chemical Product MSDS Name:4-Chloro-5 6-dimethylthieno[2 3-d]pyrimidine Material Safety Data Sheet
Synonym:None Known

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
108831-68-1	4-Chloro-5,6-dimethylthieno[2,3-d]pyri	97+	unlisted

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. May cause chemical conjunctivitis.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Immediately 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. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or 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. 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 appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Clean up spills immediately, observing precautions in the Protective Equipment section. Sweep up or absorb material, then place into a suitable clean, dry, closed container for disposal. Avoid generating dusty conditions. Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Wash clothing before reuse.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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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# 108831-68-1: 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:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: brown
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 112-113 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: C8H7ClN2S
Molecular Weight: 198.68

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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:
Oxidizing agents, bases, amines.
Hazardous Decomposition Products:
Hydrogen chloride, chlorine, carbon monoxide, oxides of nitrogen, oxides of sulfur, carbon dioxide.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 108831-68-1 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
4-Chloro-5,6-dimethylthieno[2,3-d]pyrimidine - 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
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
IMO
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
RID/ADR
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing group:

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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 22 Do not breathe dust.
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 36/37/39 Wear suitable protective clothing, gloves
and eye/face protection.
WGK (Water Danger/Protection)
CAS# 108831-68-1: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 108831-68-1 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 108831-68-1 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：

  4-氯-5,6-二甲基噻吩[2,3-D]嘧啶 在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 生成 (5,6-二甲基-噻吩并[2,3-d]嘧啶-4-基)-肼
  参考文献：
  名称：

  通过在C 2和C 6位置进行结构修饰来提高潜在的FLT3抑制剂噻吩并[2,3- d ]嘧啶衍生物的溶解度的合成策略

  摘要：

  急性髓细胞性白血病（AML）是造血祖细胞的克隆性疾病。在AML中，通常会发生FLT3突变，并与不良预后相关。先前我们已经报道了噻吩并[2，3- d ]嘧啶衍生物化合物1对具有突变型FLT3的MV4-11细胞表现出比AC220更好的抗增殖活性，AC220是众所周知的FLT3抑制剂，并且具有良好的微粒体稳定性。但是，化合物1的溶解性差。然后，我们在噻吩并[2，3- d ]嘧啶骨架的C 2和C 6位置进行了进一步的结构修饰。化合物13b在化合物C 2位置具有噻唑部分的化合物，比化合物1表现出更好的抗增殖活性，并显示出更高的溶解度和适度的微粒体稳定性。这些结果表明，化合物13b可能是用于AML化学疗法的有前途的潜在FLT抑制剂。

  DOI：

  10.1016/j.bmcl.2016.12.034
• 作为产物：
  描述：

  5,6-二甲基噻吩[2,3-D]嘧啶-4(3H)-酮 在 三氯氧磷 作用下， 生成 4-氯-5,6-二甲基噻吩[2,3-D]嘧啶
  参考文献：
  名称：

  4-取代的噻吩并[2,3-d]嘧啶类作为有效的抗菌剂：合理的设计，微波辅助合成，生物学评估和分子对接研究

  摘要：

  设计，合成4-取代的噻吩并[2,3- d ]嘧啶并评估其抗菌活性。对接研究表明，强效化合物对细菌二氢蝶呤合酶具有抑制活性。因此，还确定了其与DHPS酶的结合亲和力。

  DOI：

  10.1111/cbdd.13028

文献信息

• Piperidinylamino-thieno[2,3-D] pyrimidine compounds
  申请人：Dhanoa S. Dale

  公开号：US20050222176A1

  公开（公告）日：2005-10-06

  The invention relates to 5-HT receptor modulators, particularly 5-HT 2B antagonists. Novel piperidinylamino-thieno [2,3-d] pyrimidine compounds represented by Formula I, II and III, and uses thereof for treating conditions including pulmonary arterial hypertension, congestive heart failure, and hypertension.

  这项发明涉及5-HT受体调节剂，特别是5-HT 2B 拮抗剂。公式I、II和III所代表的新型哌啶基氨基噻吩[2,3-d]嘧啶化合物，以及它们用于治疗包括肺动脉高压、充血性心力衰竭和高血压等疾病的用途。
• 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。
• Convenient and Efficient Synthesis of Some Novel Fused Thieno Pyrimidines Using Gewald's Reaction
  作者：Ramakrishna V. S. Nirogi、Rama Sastri Kambhampati、Prabhakar Kothmirkar、Sobhanadri Arepalli、Narasimha Reddy G. Pamuleti、Anil K. Shinde、P. K. Dubey

  DOI：10.1080/00397911.2010.515357

  日期：2011.10

  Abstract Several functionalized thienopyrimidines were synthesized by a facile synthetic method, which includes Gewald's reaction, and were characterized by spectral and analytical data. These functionalized thienopyrimidines were converted to various new chemical entities of biological importance, such as 2-piperazinymethyl thienopyrimidines (6, 8), 4-dimethylaminoethoxy thienopyrimidines (11), and

  摘要 通过Gewald反应等简便的合成方法合成了几种功能化的噻吩并嘧啶，并通过光谱和分析数据进行了表征。这些功能化的噻吩并嘧啶被转化为各种具有生物学重要性的新化学实体，例如 2-哌嗪甲基噻吩并嘧啶 (6, 8)、4-二甲氨基乙氧基噻吩并嘧啶 (11) 和 3-二甲氨基乙基噻吩并嘧啶 (12)。筛选由此合成的所有化合物的体外生物活性。一些化合物显示出有希望的血清素 5-HT6 受体拮抗剂活性。
• Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines
  作者：Olga V. Ostrynska、Anatoliy O. Balanda、Volodymyr G. Bdzhola、Andriy G. Golub、Igor M. Kotey、Olexander P. Kukharenko、Andrii A. Gryshchenko、Nadiia V. Briukhovetska、Sergiy M. Yarmoluk

  DOI：10.1016/j.ejmech.2016.03.004

  日期：2016.6

  research work has resulted in a number of new ATP-competitive CK2 inhibitors that have been identified among 4-aminothieno[2,3-d]pyrimidine derivatives. The most active compounds obtained in the course of the research are 3-(5-p-tolyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5e (NHTP23, IC50 = 0.01 μM), 3-(5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5g (NHTP25, IC50 = 0.065 μM) and 3

  我们先前研究工作的扩展已导致在4-氨基噻吩并[2,3-d]嘧啶衍生物中鉴定出许多新的与ATP竞争的CK2抑制剂。在研究过程中获得的活性最高的化合物是3-（5-对甲苯基-噻吩并[2,3-d]嘧啶-4-基氨基）苯甲酸5e（NHTP23，IC 50  = 0.01μM）， 3-（5-苯基-噻吩并[2,3-d]嘧啶-4-基氨基）-苯甲酸，5g（NHTP25，IC 50  = 0.065μM）和3-（6-甲基-5-苯基-噻吩并[2 ，3-d]嘧啶-4-基氨基）-苯甲酸，5n（NHTP33，IC 50 = 0.008μM）。研究了测试的4-氨基噻吩并[2,3-d]嘧啶衍生物的结构-活性关系，并提出了它们与CK2 ATP受体位点的结合方式。讨论了分子内氢键对化合物结构的负面影响。
• Computer-aided identification, synthesis and evaluation of substituted thienopyrimidines as novel inhibitors of HCV replication
  作者：Marcella Bassetto、Pieter Leyssen、Johan Neyts、Mark M. Yerukhimovich、David N. Frick、Andrea Brancale

  DOI：10.1016/j.ejmech.2016.07.035

  日期：2016.11

  technique was applied to the study of the HCV NS3 helicase, with the aim to find novel inhibitors of the HCV replication. A library of approximately 450000 commercially available compounds was analysed in silico and 21 structures were selected for biological evaluation in the HCV replicon assay. One hit characterized by a substituted thieno-pyrimidine scaffold was found to inhibit the viral replication with

  基于结构的虚拟筛选技术已应用于HCV NS3解旋酶的研究，目的是寻找HCV复制的新型抑制剂。在计算机上分析了大约450000种可商购化合物的文库，并选择了21种结构用于HCV复制子测定的生物学评估。发现一个以取代的噻吩并嘧啶骨架为特征的命中物以亚微摩尔范围的EC 50值和良好的选择性指数抑制病毒复制。设计并合成了不同系列的新型噻吩并嘧啶衍生物。几个新结构显示出在低或亚微摩尔范围内的抗病毒活性。