4-氯-2-甲基喹唑啉 | 6484-24-8

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-氯-2-甲基喹唑啉
• 英文名称: 2-methyl-4-chloroquinazoline
• 英文别名: 4-chloro-2-methylquinazoline
• CAS: 6484-24-8
• 化学式: C₉H₇ClN₂
• mdl: MFCD05666292
• 分子量: 178.621
• InChiKey: HAAZMOAXEMIBAJ-UHFFFAOYSA-N

物化性质

• 熔点：
  86-88 °C
• 沸点：
  211.2±23.0 °C(Predicted)
• 密度：
  1.292±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8°C

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 4-Chloro-2-methylquinazoline
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: 4-Chloro-2-methylquinazoline
CAS number: 6484-24-8

---

Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

---

Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

---

Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

---

Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

---

Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

---

Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C9H7ClN2
Molecular weight: 178.6

---

Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  4-氯-2-甲基喹唑啉 在 一水合肼 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-methyl-3-hydrazinothiocarbonyl-4(3H)-quinazolinone
  参考文献：
  名称：

  A definitive synthesis of 2-[(5-methyl-s-triazolo[4,3-c]quinazolin-3-yl)thio]-N-benzylacetanilide and other reactions of its precursors

  摘要：

  2-甲基-4-氯喹唑啉（2）与肼的反应生成了2-甲基-4-肼基喹唑啉（3），后者转化为5-甲基-3-巯基-s-三唑[4,3-c]喹唑啉（4），接着与氯代-N-苄基乙酰苯胺进行S-烷基化反应得到6。肼（3）与丙酮反应转化为腙（9），与乙酸酐反应转化为3,5-二甲基三唑[4,3-c]喹唑啉（10），并通过与亚硝酸的硝化中间体（11）反应转化为5-甲基-s-四唑[1,5-c]喹唑啉（12）。化合物3及其衍生物4、6、10和12与据称具有这些结构的化合物不同。由于X射线衍射研究表明共同前驱体的结构是3，因此先前报道的化合物不可能是这些结构。巯基三唑（4）被空气氧化成二硫化合物20并水解为2-甲基-3-肼基硫酰基-4(3H)-喹唑啉酮19。4与二硫化碳的反应生成了一个副产品，建议为5-甲基喹唑啉[3,4-c]-1,2,4-硫二唑-2-硫酮21。在完全芳香化合物中，喹唑啉甲基取代基的1H核磁共振化学位移接近δ 3 ppm，当杂环非芳香性时，则出现在更高的场中。

  DOI：

  10.1139/v84-439
• 作为产物：
  描述：

  2-氨基苯甲酰胺 在 sodium ethanolate 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 4-氯-2-甲基喹唑啉
  参考文献：
  名称：

  Structure–activity relationships of quinazoline derivatives: dual-acting compounds with inhibitory activities toward both TNF-α production and T Cell proliferation

  摘要：

  We synthesized 4-chlorophenethylaminoquinazoline derivatives and evaluated their inhibitory activities toward both TNF-alpha production and T cell proliferation responses; Compound 2f, containing a piperazine ring at the C(7)-position of the quinazoline ring, exhibited more potent inhibitory activities toward both than the lead compound 1a. A smaller N-substituent in the piperazine ring was required for inhibition of TNF-alpha production. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00718-6
• 作为试剂：
  描述：

  6-nitropiperonyl chloride 在 4-氯-2-甲基喹唑啉 、 四(二甲氨基)乙烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 5-甲基-6-硝基苯并[d][1,3]二氧杂环戊烯
  参考文献：
  名称：

  First SNAr reaction using TDAE-initiated carbanions in quinazoline series

  摘要：

  We report herein the first example of a SNAr reaction using TDAE-initiated carbanions in quinazoline series. The o-nitrobenzyl carbanion, formed by the action of TDAE on o-nitrobenzyl chloride, reacts with 4-chloro-2-trihalomethylquinazolines 4 and 5 via a SNAr mechanism. This enabled a new series of 4-benzyl-2-trihaloquinazoline derivatives to be synthesized in good yields under mild reaction conditions offering promising prospects for pharmacomodulation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.05.060

文献信息

• [EN] 2-METHYL-QUINAZOLINES<br/>[FR] 2-MÉTHYL-QUINAZOLINES
  申请人：BAYER PHARMA AG

  公开号：WO2018172250A1

  公开（公告）日：2018-09-27

  The present invention describes 2-methyl-quinazoline compounds of general formula (I), methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions. The 2-methyl substituted quinazoline compounds of general formula(I) effectively and selectively inhibit the Ras-Sos interaction without significantly targeting the EGFR receptor. They are therefore useful for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, such as cancer as a sole agent or in combination with other active ingredients.

  本发明描述了一般式(I)的2-甲基喹唑啉化合物，制备该化合物的方法，用于制备该化合物的中间体化合物，包含该化合物的药物组合物和组合物，以及用于制造药物组合物的该化合物的用途。一般式(I)的2-甲基取代喹唑啉化合物有效且选择性地抑制Ras-Sos相互作用，而不显著靶向EGFR受体。因此，它们对于治疗或预防疾病特别是高增殖性疾病，如癌症作为单一药剂或与其他活性成分组合使用是有用的。
• Looking for new antiplasmodial quinazolines: DMAP-catalyzed synthesis of 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines and their in vitro evaluation toward Plasmodium falciparum
  作者：Armand Gellis、Nicolas Primas、Sébastien Hutter、Gilles Lanzada、Vincent Remusat、Pierre Verhaeghe、Patrice Vanelle、Nadine Azas

  DOI：10.1016/j.ejmech.2016.04.059

  日期：2016.8

  A DMAP catalyzed synthesis of new 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines was studied, in a view to react 4-chloroquinazolines with poorly nucleophilic alcohols such as benzylic alcohols, via a simple and cheap SNAr reaction approach. A fast (1 h) general operating procedure, affording good reaction yields, was achieved under microwave irradiation. Thus, a series of 35 molecules was

  的新的4-苄氧基和4-芳氧基-2- trichloromethylquinazolines甲DMAP催化合成进行了研究，在着眼于反应4- chloroquinazolines与亲核较差醇如苄醇，通过一个简单的和廉价的小号Ñ氩反应的方法。在微波辐射下可实现快速（1小时）的常规操作程序，该程序具有良好的反应收率。因此，获得了一系列35个分子，并在K1多耐药性恶性疟原虫菌株上进行了体外评估，同时对人HepG2细胞系进行了细胞毒性评估。鉴定出5个命中分子，具有良好的抗血浆活性（1.5μM
• HISTONE DEACETYLASE INHIBITOR, AND PREPARATION METHOD AND USE THEREOF
  申请人：GUANGDONG ZHONGSHENG PHARMACEUTICAL CO., LTD

  公开号：US20180098990A1

  公开（公告）日：2018-04-12

  A compound represented by Formula I or pharmaceutically acceptable salt thereof. The present invention relates to a 4-arylamino quinazoline hydroxamic acid compound having a histone deacetylase inhibitory activity, preparation method of the compound, pharmaceutical composition comprising the compound, and use of the compound and the pharmaceutical composition in the preparation of a histone deacetylase inhibitor medicine. The present invention aims at acquiring, via a medicine design and a synthetic technology, a series of selective histone deacetylase inhibitors having good hypotype selectivity and favorable pharmacokinetic characteristics based on optimization of an enzyme surface recognition region and connection region of 4-arylamino quinazoline, thus reducing an effect on normal tissues or cells while improving an antineoplastic activity of the normal tissues or cells.

  本发明涉及一种具有组蛋白去乙酰化酶抑制活性的4-芳氨基喹唑啉羟胺酸化合物、其制备方法、包含该化合物的药物组合物，以及该化合物和药物组合物在制备组蛋白去乙酰化酶抑制剂药物中的用途。本发明的目的是通过药物设计和合成技术，基于优化4-芳氨基喹唑啉的酶表面识别区域和连接区域，获得一系列具有良好低类型选择性和有利药代动力学特性的选择性组蛋白去乙酰化酶抑制剂，从而在提高正常组织或细胞的抗肿瘤活性的同时，减少对正常组织或细胞的影响。
• Synthesis and Biological Evaluation of Selenium-Containing 4-Anilinoquinazoline Derivatives as Novel Antimitotic Agents
  作者：Baijiao An、Bo Wang、Jinhui Hu、Shaoyu Xu、Ling Huang、Xingshu Li、Albert S. C. Chan

  DOI：10.1021/acs.jmedchem.8b00128

  日期：2018.3.22

  Twenty-eight novel selenium-containing 4-anilinoquinazoline derivatives were designed, synthesized, and evaluated as antiproliferative agents. Most of them had significant in vitro activities, particularly for compounds 23a, 25a, and 25d, which also exhibited the most potent antitumor activities against cisplatin-resistant cell lines and the doxorubicin-resistant cell lines, good selectivity toward

  设计，合成并评估了28种新型的含硒的4-苯胺基喹唑啉衍生物作为抗增殖剂。它们中的大多数具有显着的体外活性，特别是对于化合物23a，25a和25d而言，它们还显示出对顺铂耐药细胞系和阿霉素耐药细胞系最有效的抗肿瘤活性，对正常细胞的良好选择性以及明显的抑制作用对A549细胞系迁移的影响。进一步的机械研究表明，23a，25a和25d诱导A549细胞G2 / M期停滞和凋亡，这与线粒体膜电位的崩溃，某些细胞周期相关蛋白和凋亡相关蛋白的表达改变以及细胞内ROS水平升高有关。最后，化合物23a，25a和25d在没有明显毒性迹象的情况下，也能有效抑制A549异种移植模型中的肿瘤生长。综上所述，这些体外和体内结果表明23a，25a和25d可能是有希望的微管稳定剂，并且可以用作开发新的抗肿瘤剂的有希望的先导。
• 一种组蛋白去乙酰化酶抑制剂及其制备方法和用途
  申请人：广东众生药业股份有限公司

  公开号：CN106045923A

  公开（公告）日：2016-10-26

  本发明提供一种式I所示化合物或其药物可接受的盐，涉及具有组蛋白去乙酰化酶抑制活性的4‑芳氨基喹唑啉异羟肟酸类的新型化合物、所述化合物的制备方法、包含所述化合物的药物组合物以及所述化合物和药物组合物在制备组蛋白去乙酰化酶抑制剂类药物中的用途；旨在通过药物设计及合成手段获取一系列基于对4‑芳氨基喹唑啉为酶表面识别区及连接区进行优化，具有亚型选择性和良好药代动力学特性的选择性组蛋白去乙酰化酶抑制剂，以提高抗肿瘤活性的同时减少对正常组织或细胞的影响。