7-氟-6-硝基-4-羟基喹唑啉 | 162012-69-3

• 物质功能分类: 医药中间体 - 原料药中间体
• 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: 7-氟-6-硝基-4-羟基喹唑啉
• 中文别名: 7-氟-6-硝基喹唑啉-4-酮；6-硝基-7-氟喹唑啉-4(3H)-酮；7-氟-6-硝基喹唑啉-4(3H)-酮；6-硝基-7-氟喹唑啉-4-酮；阿法中间体1
• 英文名称: 7-fluoro-6-nitro-3H-quinazolin-4-one
• 英文别名: 7-fluoro-6-nitroquinazolin-4(3H)-one；7-fluoro-6-nitroquinazolin-4-one；7-fluoro-6-nitroquinazoline-4(3H)-one；7-fluoro-6-nitro-4(3H)-quinazolinone；7-Fluoro-6-nitroquinazolin-4(3H)-one
• CAS: 162012-69-3
• 化学式: C₈H₄FN₃O₃
• mdl: MFCD07841697
• 分子量: 209.136
• InChiKey: VTUAEMSZEIGQRM-UHFFFAOYSA-N

物化性质

• 熔点：
  282-285 °C(Solv: acetic acid (64-19-7))
• 沸点：
  407.6±55.0 °C(Predicted)
• 密度：
  1.75±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• pKa：
  -2.69±0.20 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 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：
  87.3
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 安全说明：
  S26
• 危险类别码：
  R36
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 7-Fluoro-6-nitro-1h-quinazolin-4-one
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: 7-Fluoro-6-nitro-1h-quinazolin-4-one
CAS number: 162012-69-3

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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.
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: C8H4FN3O3
Molecular weight: 209.1

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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 fluoride.

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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

制备方法与用途

用途

7-氟-6-硝基喹唑啉-4（3H）-1 是一种重要的中间体，用于制备激酶抑制剂，例如表皮生长因子受体的酪氨酸激酶活性的ATP站点抑制剂。

7-氟-6-硝基-4-(氢)-喹唑啉酮 也是有机合成和医药研发中的关键中间体，尤其适用于抗肿瘤药物的研发，并可用于合成阿法替尼。

反应信息

• 作为反应物：
  描述：

  7-氟-6-硝基-4-羟基喹唑啉 在 盐酸 、 铁粉 、 溶剂黄146 、 三乙胺 、 potassium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N-甲基吡咯烷酮 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 9.42h， 生成 阿法替尼
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF N-[4-[(3-CHLORO-4-FLUORO PHENYL) AMINO]-7-[[(3s-TETRAHYDRO-3-FURANYL]OXY]-6-QUINAZOLINYL]-4-(DIMETHYL AMINO)-(2E)-2-BUTENAMIDE (2Z)-2-BUTENEDIOATE (1 :2) AND ITS POLYMORPHS THEREOF

  摘要：

  本发明涉及一种改进的制备N-[4-[(3-氯-4-氟苯基)氨基]-7-[[(3S)-四氢-3-呋喃基]氧基]-6-喹唑啉基]-4-(二甲氨基)-(2E)-2-丁烯酰胺(2Z)-2-丁烯二酸盐(1:2)的工艺，其结构式如下：

  公开号：

  US20180297989A1
• 作为产物：
  描述：

  2-氨基-4-氟苯甲酸 在 硫酸 、 硝酸 作用下， 以 乙醇 为溶剂， 反应 26.0h， 生成 7-氟-6-硝基-4-羟基喹唑啉
  参考文献：
  名称：

  设计，合成和对接研究带有芳基半脲酮骨架作为有效EGFR抑制剂的喹唑啉类似物。

  摘要：

  设计，合成了两个带有芳基半脲酮骨架的喹唑啉衍生物系列（9a-o和10a-o），并评估了其对四种癌细胞系（A549，HepG2，MCF-7和PC-3）的IC50值。进一步评估选择的化合物9o对EGFR激酶的抑制活性。其中四种化合物显示出优异的细胞毒性活性和选择性，IC50值在个位数μM至纳摩尔范围内。它们中的两个等于对一个或多个细胞系比阳性对照阿法替尼更具活性。最有前途的化合物9o对A549，HepG2，MCF-7和PC-3癌细胞系和EGFR激酶表现出最佳活性，IC50值为1.32±0.38μM，0.07±0.01μM，0.91±0.29μM和4.89± 0.69μM，比阿法替尼（1.40±0.83μM，1.33±1.28μM，2.63±1.06μM和3.96±0.59μM）活性更高，分别。最有前途的化合物9o（IC50 56nM）对EGFR激酶的活性略低于阳性化合物afatinib（IC50

  DOI：

  10.1016/j.bmc.2017.04.001

文献信息

• 4-(取代苯氨基)喹唑啉类化合物、其制备方法 及应用
  申请人：齐鲁制药有限公司

  公开号：CN103965175B

  公开（公告）日：2017-12-22

  本发明属于医药化工领域，具体涉及一类新的具有抗肿瘤活性的4‑(取代苯氨基)喹唑啉类化合物、其制备方法；所述4‑(取代苯氨基)喹唑啉类化合物具有有效的酪氨酸激酶不可逆抑制作用和/或具有良好的体内药物动力学行为，是有效的酪氨酸激酶不可逆抑制剂。式I。
• [EN] BICYCLIC COMPOUNDS AS KINASES INHIBITORS<br/>[FR] COMPOSÉS BICYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DES KINASES
  申请人：ZHANG DAWEI

  公开号：WO2013173254A1

  公开（公告）日：2013-11-21

  The present invention is directed to novel bicyclic compounds, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are useful for the treatment of protein kinases mediated diseases and conditions. Novel bicyclic compounds disclosed herein include quinazolines and quinolines.

  本发明涉及新颖的双环化合物，它们的衍生物，药用可接受的盐，溶剂和水合物。本发明的化合物和组合物具有蛋白激酶抑制活性，并可用于治疗蛋白激酶介导的疾病和症状。本文披露的新颖双环化合物包括喹唑啉和喹啉。
• [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。
• [EN] SUBSTITUTED AMINOQUINAZOLINES USEFUL AS KINASES INHIBITORS<br/>[FR] AMINOQUINAZOLINES SUBSTITUÉES UTILES COMME INHIBITEURS DE KINASES
  申请人：TELIGENE LTD

  公开号：WO2013166952A1

  公开（公告）日：2013-11-14

  The present invention is directed to novel quinazolines, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are expected to be useful for the treatment of protein kinases mediated diseases and conditions.

  本发明涉及新型喹唑啉类化合物及其衍生物、药用可接受的盐、溶剂合物和水合物。本发明的化合物和组合物具有蛋白激酶抑制活性，预计可用于治疗蛋白激酶介导的疾病和症状。
• [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。