4-溴-2-吗啉吡啶 | 1040377-12-5

• 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 - 有机氮化合物
• 中文名称: 4-溴-2-吗啉吡啶
• 英文名称: 4-(4-bromopyridin-2-yl)morpholine
• CAS: 1040377-12-5
• 化学式: C₉H₁₁BrN₂O
• mdl: MFCD13195616
• 分子量: 243.103
• InChiKey: RHEDZKKCXNVSPI-UHFFFAOYSA-N

物化性质

• 沸点：
  368.6±42.0 °C(Predicted)
• 密度：
  1.499±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  25.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储条件：2-8°C，需使用惰性气体保护。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Bromo-2-morpholinopyridine
Synonyms: 4-(4-Bromopyridin-2-yl)morpholine

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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-Bromo-2-morpholinopyridine
CAS number: 1040377-12-5

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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: C9H11BrN2O
Molecular weight: 243.1

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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 bromide.

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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

4-(4-溴吡啶-2-基)吗啉可以作为有机合成中间体和医药中间体，主要应用于实验室研发和化工生产过程。

反应信息

• 作为反应物：
  描述：

  4-溴-2-吗啉吡啶 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 5%-palladium/activated carbon 、 氢气 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 乙醇 、 乙腈 为溶剂， 20.0~95.0 ℃ 、411.6 kPa 条件下， 反应 61.67h， 生成 2-(2-morpholinopyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-amine
  参考文献：
  名称：

  SYNTHESIS OF HETEROCYCLIC COMPOUNDS

  摘要：

  本文提供了中间体和过程，用于容易合成式子2的化合物： 其中R1是C（O）R2; R2是烷基，可选地取代1-5个卤素; G是苯基或5-6成员杂环，可选地取代1-2个R3; 每个R3都是独立的C1-C6烷基，CN，C1-C6烷基-CN，3-6成员环烷基或4-6成员杂环烷基。

  公开号：

  US20210340139A1
• 作为产物：
  描述：

  2-(4-吗啉)-4-吡啶胺 在 硫酸 、 sodium nitrite 、 氢溴酸 、 copper(I) bromide 作用下， 以 水 为溶剂， 反应 1.25h， 以56%的产率得到4-溴-2-吗啉吡啶
  参考文献：
  名称：

  WO2008/88881

  摘要：

  公开号：

文献信息

• Design and Discovery of <i>N</i>-(2-Methyl-5′-morpholino-6′-((tetrahydro-2<i>H</i>-pyran-4-yl)oxy)-[3,3′-bipyridin]-5-yl)-3-(trifluoromethyl)benzamide (RAF709): A Potent, Selective, and Efficacious RAF Inhibitor Targeting RAS Mutant Cancers
  作者：Gisele A. Nishiguchi、Alice Rico、Huw Tanner、Robert J. Aversa、Benjamin R. Taft、Sharadha Subramanian、Lina Setti、Matthew T. Burger、Lifeng Wan、Victoriano Tamez、Aaron Smith、Yan Lou、Paul A. Barsanti、Brent A. Appleton、Mulugeta Mamo、Laura Tandeske、Ina Dix、John E. Tellew、Shenlin Huang、Lesley A. Mathews Griner、Vesselina G. Cooke、Anne Van Abbema、Hanne Merritt、Sylvia Ma、Kalyani Gampa、Fei Feng、Jing Yuan、Yingyun Wang、Jacob R. Haling、Sepideh Vaziri、Mohammad Hekmat-Nejad、Johanna M. Jansen、Valery Polyakov、Richard Zang、Vijay Sethuraman、Payman Amiri、Mallika Singh、Emma Lees、Wenlin Shao、Darrin D. Stuart、Michael P. Dillon、Savithri Ramurthy

  DOI：10.1021/acs.jmedchem.6b01862

  日期：2017.6.22

  cells. To date, many small molecule approaches are under investigation to target CRAF, yet kinase-selective and cellular potent inhibitors remain challenging to identify. Herein, we describe 14 (RAF709) [Aversa, Biaryl amide compounds as kinase inhibitors and their preparation. WO 2014151616, 2014], a selective B/C RAF inhibitor, which was developed through a hypothesis-driven approach focusing on drug-like

  RAS致癌基因已涉及超过30％的人类癌症，均代表高度未满足的医疗需求。在基因工程小鼠模型和人类肿瘤细胞中已经建立了对KRAS突变肿瘤中对CRAF激酶的精确依赖性。迄今为止，许多针对CRAF的小分子方法正在研究中，但是激酶选择性抑制剂和细胞有效抑制剂的鉴定仍然具有挑战性。在此，我们描述14（RAF709）[Aversa，联芳酰胺化合物作为激酶抑制剂及其制备方法。WO 2014151616， [2014]，一种选择性的B / C RAF抑制剂，通过假设驱动的方法开发，该方法侧重于药物样特性。在药物化学研究中遇到的一个关键挑战是在KRAS突变肿瘤细胞系中保持良好的溶解度和有效的细胞活性（pMEK的抑制和增殖）之间的平衡。我们研究了铅分子7的小分子晶体结构，并假设破坏晶体堆积会提高溶解度，从而导致从N-甲基吡啶酮转变为四氢吡喃基氧基-吡啶衍生物。在KRAS突变异种移植模型中，有14种被证明是可溶的，激酶选择性的和有效的。
• Selective Inhibitors of G2019S-LRRK2 Kinase Activity
  作者：Albert W. Garofalo、Jessica Bright、Stéphane De Lombaert、Alyssa M. A. Toda、Kerry Zobel、Daniele Andreotti、Claudia Beato、Silvia Bernardi、Federica Budassi、Laura Caberlotto、Peng Gao、Cristiana Griffante、Xinying Liu、Luisa Mengatto、Marco Migliore、Fabio Maria Sabbatini、Anna Sava、Elena Serra、Paolo Vincetti、Mingliang Zhang、Holly J. Carlisle

  DOI：10.1021/acs.jmedchem.0c01243

  日期：2020.12.10

  leucine-rich repeat kinase 2 (LRRK2) gene have been identified that increase the risk for developing Parkinson’s disease in a dominantly inherited fashion. These pathogenic variants, of which G2019S is the most common, cause abnormally high kinase activity, and compounds that inhibit this activity are being pursued as potentially disease-modifying therapeutics. Because LRRK2 regulates important cellular

  富含亮氨酸的重复激酶2（LRRK2）基因中的致病性变体已被确定，这些变体以显性遗传的方式增加了发展帕金森氏病的风险。这些致病性变体（其中最常见的是G2019S）会导致异常高的激酶活性，而抑制这种活性的化合物正被视为潜在的疾病缓解疗法。由于LRRK2调节重要的细胞过程，因此开发可选择性靶向致病变体而又不影响正常LRRK2活性的抑制剂可能在杂合子携带者中提供潜在的优势。我们进行了高通量筛选，并鉴定了一种优先抑制G2019S-LRRK2的单一选择性化合物。该支架的优化产生了一系列新颖，有效和高度选择性的G2019S-LRRK2抑制剂。
• NOVEL COMPOUNDS AS NADPH OXIDASE INHIBITORS
  申请人：GenKyoTex Suisse SA

  公开号：EP3628669A1

  公开（公告）日：2020-04-01

  The present invention is related to new compounds, pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).

  这项发明涉及新化合物，其药物组成以及它们用于治疗和/或预防与烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH氧化酶）相关的疾病或症状。
• [EN] INDAZOLES AND AZAINDAZOLES AS LRRK2 INHIBITORS<br/>[FR] INDAZOLES ET AZAINDAZOLES EN TANT QU'INHIBITEURS DE LRRK2
  申请人：ESCAPE BIO INC

  公开号：WO2021178780A1

  公开（公告）日：2021-09-10

  The present invention is directed to indazole and azaindazole compounds which are inhibitors of LRRK2 and are useful in the treatment of CNS disorders.

  本发明涉及一种抑制LRRK2的吲唑和杂氮吲唑化合物，可用于治疗中枢神经系统疾病。
• [EN] FUSED TETRAZOLES AS LRRK2 INHIBITORS<br/>[FR] TÉTRAZOLES FUSIONNÉS EN TANT QU'INHIBITEURS DE LRRK2
  申请人：E SCAPE BIO INC

  公开号：WO2019222173A1

  公开（公告）日：2019-11-21

  The present invention is directed to fused tetrazoles of formula (IA) which are inhibitors of LRRK2 and are useful in the treatment of CNS disorders.

  本发明涉及式（IA）的融合四唑，它们是LRRK2的抑制剂，并且在治疗中枢神经系统疾病方面具有用途。