4-氯-6-硝基喹唑啉 | 19815-16-8

• 物质功能分类: 医药中间体
• 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-6-硝基喹唑啉
• 中文别名: 4-氯-6-硝基喹啉
• 英文名称: 4-chloro-6-nitro-quinazoline
• 英文别名: 6-nitro-4-chloroquinazoline；4-Chloro-6-nitroquinazoline
• CAS: 19815-16-8
• 化学式: C₈H₄ClN₃O₂
• mdl: MFCD00464269
• 分子量: 209.592
• InChiKey: LZOSFEDULGODDH-UHFFFAOYSA-N

物化性质

• 熔点：
  128 °C
• 沸点：
  380.0±22.0 °C(Predicted)
• 密度：
  1.566±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二氯甲烷
• pKa：
  0.14±0.50 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.6
• 氢给体数：
  0
• 氢受体数：
  4

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：
  室温且干燥

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Chloro-6-nitroquinazoline
Synonyms:

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

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Section 3. Composition/information on ingredients.
Ingredient name: 4-Chloro-6-nitroquinazoline
CAS number: 19815-16-8

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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.

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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.

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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.

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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:

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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.

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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: C8H4ClN3O2
Molecular weight: 209.6

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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.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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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.

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

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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.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  4-氯-6-硝基喹唑啉 在 copper(l) iodide 、 氢气 、 caesium carbonate 、 锌 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 泛EGFR小分子抑制剂(VARLITINIB)
  参考文献：
  名称：

  一种治疗胆管癌的药物的制备方法

  摘要：

  本发明属于医药工业领域，公开了一种治疗胆管癌的药物的制备方法；胆管癌治疗药物Varlitinib的制备方法包括：由2‑氨基‑5‑硝基苯甲酸起始，经过醋酸甲咪环合、氯代合成中间体I；由2‑氯‑5‑硝基苯酚起始，经过2‑氯甲基噻唑取代，硝基还原合成中间体II；由1‑氨基‑2‑丙醇为起始，通过BTC的环合反应，氯代合成中间体III；中间体I和中间体II通过C‑N偶联、硝基还原，最后与中间体III发生C‑N偶联反应后合成Varlitinib。本发明方法合成简便，路线短，原料经济，产率高，环境友好，适合工业化生成。

  公开号：

  CN111499622B
• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 在 五氯化磷 、 硫酸 作用下， 反应 4.0h， 生成 4-氯-6-硝基喹唑啉
  参考文献：
  名称：

  一系列取代喹唑啉类抗菌剂的合成，生物学评价和QSAR研究

  摘要：

  1 - N-取代的3-（4-（5-（吡啶-3-基）-1,3,4-恶二唑-2-基硫基）喹唑啉-6-基）脲/硫脲衍生物的新系列（6a –6r）和1- N-取代的3-（7-（4-甲基哌嗪-1-基）-4-（5-（吡啶-3-基）-1,3,4-恶二唑-2-基硫基）合成了喹唑啉-6-基）脲/硫脲衍生物（14a-14s），并筛选了对金黄色葡萄球菌，枯草芽孢杆菌，铜绿假单胞菌和大肠杆菌的抗菌活性。生物学结果表明，所合成的化合物在6.25至100μg/ mL的MIC值下具有针对被测微生物的广谱活性。化合物6r表现出广谱的活性，被发现对所有受测物种均具有活性。已对合成化合物进行了定量构效关系研究，以更好地了解负责抗菌活性的药效学特征。遗传函数近似技术用于识别影响生物活性的描述符。发现疏水性（AlogP98），电子（原子极化率）和拓扑（回转半径）描述符对活性有明显影响。发现生成的模型具有统计学意义（r 2  = 0

  DOI：

  10.1007/s00044-012-0408-0
• 作为试剂：
  描述：

  4-氯-6-硝基喹唑啉 、 3-氯-4-(3-氟苄氧基)苯胺 在 4-氯-6-硝基喹唑啉 作用下， 以67的产率得到[3-氯-4-(3-氟-苄氧基)-苯基]-(6-硝基-喹唑啉-4-基)-胺
  参考文献：
  名称：

  WO2007082434A1

  摘要：

  公开号：

文献信息

• [EN] QUINOLINE AND QUINAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS QUINOLÉINE ET QUINAZOLINE
  申请人：ACERTA PHARMA BV

  公开号：WO2016055982A1

  公开（公告）日：2016-04-14

  In some embodiments, the invention relates to quinazoline and quinoline compounds of Formula I: (I) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to quinazoline and quinoline compounds, pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of Bruton's tyrosine kinase (BTK) mediated disorders.

  在某些实施例中，该发明涉及式I的喹唑啉和喹啉化合物：(I)或其药用可接受盐，或者涉及包含这些化合物的药物组合物以及它们在治疗中的应用。具体而言，在某些实施例中，本发明涉及喹唑啉和喹啉化合物、其药物组合物以及这些化合物和药物组合物在治疗布鲁顿氨基酸激酶（BTK）介导的疾病中的应用。
• Alkynyl and azido-substituted 4-anilinoquinazolines
  申请人：Pfizer Inc.

  公开号：US05747498A1

  公开（公告）日：1998-05-05

  The invention relates to compounds of the formula ##STR1## and to pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, n and m are as defined herein. The compounds of formula I are useful in the treatment of hyperproliferative diseases, such as cancer. The invention further relates to processes of making the compounds of formula I and to methods of using such compounds in the treatment of hyperproliferative diseases.

  该发明涉及公式##STR1##的化合物及其药用盐，其中R.sup.1、R.sup.2、R.sup.3、R.sup.4、n和m如本文所定义。公式I的化合物在治疗高增殖性疾病，如癌症方面是有用的。该发明还涉及制备公式I化合物的方法以及在治疗高增殖性疾病中使用这些化合物的方法。
• Aniline derivatives
  申请人：Zeneca Limited

  公开号：US05821246A1

  公开（公告）日：1998-10-13

  The invention concerns aniline derivatives of formula I ##STR1## wherein m is 1, 2 or 3, n is 0, 1, 2 or 3, Q is phenyl or naphthyl or a 5- or 6-membered heteroaryl moiety containing 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulfur, and X, R.sup.1 and R.sup.2 are defined in the claims; or pharmaceutical compositions containing them, and the methods of using the compounds as tyrosine kinase inhibitors and for the treatment of proliferative diseases such as cancer.

  本发明涉及公式I的苯胺衍生物：##STR1##，其中m为1、2或3，n为0、1、2或3，Q为苯基或萘基或含氧、氮、硫的1、2或3个杂原子的5或6元杂芳基基团，X、R1和R2的定义见权利要求；或包含它们的药物组合物，以及使用该化合物作为酪氨酸激酶抑制剂和治疗诸如癌症的增殖性疾病的方法。
• [EN] AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS D'AMINOQUINAZOLINE, LEURS SELS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2014177038A1

  公开（公告）日：2014-11-06

  Provided herein are aminoquinazoline compounds, salts and uses thereof. The compounds have Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Also provided herein are pharmaceutical compositions containing the compounds disclosed herein, and uses of the compounds or the compositions for preventing, managing, treating or lessening the severity of a proliferative disorder in a patient and for modulating the protein tyrosine kinase activity.

  本文提供了氨基喹唑啉化合物、盐及其用途。这些化合物具有式(I)，或其立体异构体、几何异构体、互变异构体、N-氧化物、水合物、溶剂合物、代谢物、药学上可接受的盐或其前药。本文还提供了含有上述化合物的药物组合物，以及利用这些化合物或组合物预防、管理、治疗或减轻患者体内增殖性疾病的严重程度，并调节蛋白酪氨酸激酶活性的用途。
• NITROGENOUS HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, COMPOSITION AND USE
  申请人：Shanghai Pharmaceuticals Holding Co., Ltd.

  公开号：EP3424928A1

  公开（公告）日：2019-01-09

  Disclosed are a nitrogenous heterocyclic compound, intermediates, a preparation method, a composition and use thereof. The nitrogenous heterocyclic compound in the present invention is as shown in formula I. The compound has a high inhibitory activity towards ErbB2 tyrosine kinase and a relatively good inhibitory activity towards human breast cancer BT-474 and human gastric cancer cell NCI-N87 which express ErbB2 at a high level, and at the same time has a relatively weak inhibitory activity towards EGFR kinase. Namely, the compound is a highly selective small-molecule inhibitor targeted at ErbB2, and hence it has a high degree of safety, and can effectively enlarge the safety window in the process of taking the drug.

  本公开揭示了一种含氮杂环化合物、中间体、制备方法、组合物及其用途。本发明中的含氮杂环化合物如公式I所示。该化合物对ErbB2酪氨酸激酶具有较高的抑制活性，并且对人类乳腺癌BT-474和人类胃癌细胞NCI-N87表达ErbB2的抑制活性相对较好，同时对EGFR激酶具有相对较弱的抑制活性。换句话说，该化合物是一种高度选择性的针对ErbB2的小分子抑制剂，因此具有很高的安全度，并且可以有效地扩大服药过程中的安全窗口。