6,7-二氢-5H-吡咯并[3,4-b]吡啶 | 147739-88-6

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 中文名称: 6,7-二氢-5H-吡咯并[3,4-b]吡啶
• 中文别名: 6,7-二氢-5H-吡咯基[3,4,6]吡啶；6,7-二氢-5H-吡咯[3,4-B]吡啶
• 英文名称: 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine
• 英文别名: 5H,6H,7H-pyrrolo[3,4-b]pyridine
• CAS: 147739-88-6
• 化学式: C₇H₈N₂
• mdl: MFCD06858478
• 分子量: 120.154
• InChiKey: SJMNQXLXIIXDDS-UHFFFAOYSA-N

物化性质

• 沸点：
  215.8±30.0 °C(Predicted)
• 密度：
  1.114±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 储存条件：
  储存温度应维持在2-8℃，请确保容器密封并置于干燥处。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 6,7-Dihydro-5h-pyrrolo[3,4-b]pyridine
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: 6,7-Dihydro-5h-pyrrolo[3,4-b]pyridine
CAS number: 147739-88-6

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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: C7H8N2
Molecular weight: 120.2

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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.

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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

应用

6,7-二氢-5H-吡咯并[3,4-b]吡啶，又称6,7-二氢-5H-吡咯基[3,4,6]吡啶，是一种重要的医药中间体，主要用于合成新型的氟喹诺酮药物莫西沙星（Moxifloxacin）。目前市场需求大，价格较为昂贵。各国科学家对它的合成进行了大量研究。

近年来，氟喹诺酮药物在临床上的用量已经超过了青霉素。这类药物具有低价格、吸收好等特点，既可口服也可注射，并能迅速分布到各组织中。莫西沙星作为一种新型的氟喹诺酮药物，受到了科学家们的广泛关注。

制备

以2,3-二羧酸吡啶为原料，首先进行酯化反应生成吡啶二羧酸二甲酯，然后采用硼氢化钠和无水氯化钙组成的混合试剂还原相应的甲酯。反应产物可不经提纯直接进行下一步的氯代反应，在乙腈中以无水碳酸钾为碱，于室温下反应即可得到环化产物6,7-二氢-吡咯并[3,4-b]吡啶。

本方法设计新颖、反应条件温和、处理简单，特别适合工业化生产。它丰富了吡咯并吡啶环类化合物的合成方法。6,7-二氢-5H-吡咯并[3,4-b]吡啶制备路线图如下图所示：

图1 6,7-二氢-5H-吡咯并[3,4-b]吡啶制备路线图

反应信息

• 作为反应物：
  描述：

  6,7-二氢-5H-吡咯并[3,4-b]吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 草酰氯 、 氢溴酸 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 间氯过氧苯甲酸 、 lithium hydroxide 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 76.0h， 生成 4-(3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl)isoindoline
  参考文献：
  名称：

  鉴定和分析的酪蛋白激酶1（CK1）抑制剂的体内目标占有率测量的选择性和脑渗透放射性配体。

  摘要：

  为使我们的中枢神经系统酪蛋白激酶1δ/ε（CK1δ/ε）抑制剂项目的临床开发成为可能，我们调查了开发中枢神经系统正电子发射断层显像（PET）放射性配体的可能性。为此，我们将设计和合成工作重点放在了最初的CK1δ/ε抑制剂HTS命中上，目的是鉴定出能够满足一系列推荐PET配体标准的化合物。我们确定[ 3 H] PF-5236216（9）为满足大多数关键CNS PET属性的工具配体，包括高CNS MPO PET期望值和激酶选择性，CNS渗透和低非特异性结合。我们还使用了[ 3 H] -9以确定与文献CK1δ/ε抑制剂工具化合物PF-670462的结合亲和力。最后，[ 3 H] -9用于测量小鼠中PF-670462的体内靶标占有率（TO），并将其与CK1δ/ε体内药理作用相关联（昼夜节律调节）。

  DOI：

  10.1021/acschemneuro.7b00155
• 作为产物：
  描述：

  2,3-双（氯甲基）吡啶 在 邻,对甲苯磺酰胺 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以46%的产率得到6,7-二氢-5H-吡咯并[3,4-b]吡啶
  参考文献：
  名称：

  A Robust Process for an mGluR5 Negative Allosteric Modulator: Difluoromethylation and Sonogashira Coupling on Large Scale

  摘要：

  The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in the process, which has been implemented on a multikilogram scale, include a high-temperature difluoromethylation reaction, a Sonogashira coupling, and careful control of residual Pd and Cu in the final API. Due to the relative nonpolar nature of the intermediates, water-miscible solvents were employed in all four steps to allow for direct crystallizations upon reaction completion. In addition, several crystalline morphologies of the API were discovered, and the isolation of the desired form II will be discussed.

  DOI：

  10.1021/op3002728

文献信息

• [EN] CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME<br/>[FR] COMPOSÉS CARBAMATES ET LEUR PROCÉDÉ DE FABRICATION ET D'UTILISATION
  申请人：ABIDE THERAPEUTICS

  公开号：WO2013142307A1

  公开（公告）日：2013-09-26

  Provided herein are carbamate compounds which may be useful in the treatment of, for example, pain, solid tumors and/or obesity.

  本文提供的是可能在治疗疼痛、实体肿瘤和/或肥胖等方面有用的氨基甲酸酯化合物。
• [EN] AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE<br/>[FR] DÉRIVÉS D'AMINOQUINAZOLINE ET LEURS SELS ET PROCÉDÉS D'UTILISATION
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2013071697A1

  公开（公告）日：2013-05-23

  The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter-and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明涉及医学领域。本文提供了氨基喹唑啉衍生物、其盐和药物配方，用于调节蛋白酪氨酸激酶活性，以及调节细胞间和/或细胞内信号传导。本文还提供了包含氨基喹唑啉化合物的药用可接受组合物，以及使用这些组合物治疗哺乳动物，特别是人类的增生性疾病的方法。
• AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
  申请人：SUNSHINE LAKE PHARMA CO., LTD.

  公开号：US20140228361A1

  公开（公告）日：2014-08-14

  The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明涉及医学领域。本文提供了氨基喹唑啉衍生物，其盐和药物配方在调节蛋白酪氨酸激酶活性以及调节细胞间和/或细胞内信号传导方面具有用处。本文还提供了包含氨基喹唑啉化合物的药用可接受组合物，以及在治疗哺乳动物，特别是人类的增生性疾病中使用这些组合物的方法。
• BICYCLIC HETEROARYL COMPOUNDS AND USES THEREOF
  申请人：Revolution Medicines, Inc.

  公开号：US20210139517A1

  公开（公告）日：2021-05-13

  The present disclosure is directed to modulators of SOS1 and their use in the treatment of disease. Also disclosed are pharmaceutical compositions comprising the same.

  本公开涉及SOS1的调节剂及其在治疗疾病中的应用。还公开了包含相同成分的药物组合物。
• [EN] 2-CYANOISOINDOLINE DERIVATIVES FOR TREATING CANCER<br/>[FR] DÉRIVÉS DE 2-CYANOISOINDOLINE POUR LE TRAITEMENT DU CANCER
  申请人：MISSION THERAPEUTICS LTD

  公开号：WO2017158388A1

  公开（公告）日：2017-09-21

  The invention relates to novel compounds of formula I which are inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to methods for the preparation of these compounds and to their use in the treatment of cancer.

  这项发明涉及公式I的新化合物，这些化合物是去泛素化酶（DUBs）和/或去泛素化酶的抑制剂。具体来说，该发明涉及抑制泛素C端水解酶7或泛素特异性肽酶7（USP7）。该发明还涉及这些化合物的制备方法以及它们在癌症治疗中的应用。