2-氯-5-溴吡啶-3-甲酰胺 | 75291-85-9

• 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 - 吡啶及其衍生物
• 中文名称: 2-氯-5-溴吡啶-3-甲酰胺
• 中文别名: 5-溴-2-氯吡啶-3-甲酰胺；2-氯-5-溴烟酰胺
• 英文名称: 5-bromo-2-chloronicotinamide
• 英文别名: 5-bromo-2-chloropyridine-3-carboxamide
• CAS: 75291-85-9
• 化学式: C₆H₄BrClN₂O
• mdl: MFCD13176452
• 分子量: 235.468
• InChiKey: NFUOTGWWIKJNQL-UHFFFAOYSA-N

物化性质

• 熔点：
  187-188℃ (ethanol water )
• 沸点：
  299.7±40.0 °C(Predicted)
• 密度：
  1.818±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储条件为2-8°C，并需保存在惰性气体环境中。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 5-Bromo-2-chloronicotinamide
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: 5-Bromo-2-chloronicotinamide
CAS number: 75291-85-9

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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: C6H4BrClN2O
Molecular weight: 235.5

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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, 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

反应信息

• 作为反应物：
  描述：

  2-氯-5-溴吡啶-3-甲酰胺 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium tert-butylate 、 potassium acetate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.5h， 生成 tert-butyl (3S,4R)-4-{[3-carbamoyl-5-(1-methyl-1H-imidazol-4-yl)pyridin-2-yl]oxy}-3-fluoropiperidine-1-carboxylate
  参考文献：
  名称：

  [EN] N-ACYLPIPERIDINE ETHER TROPOMYOSIN-RELATED KINASE INHIBITORS
  [FR] INHIBITEURS DE KINASE APPARENTÉS À LA N-ACYLPIPÉRIDINE ÉTHER TROPOMYOSINE

  摘要：

  本发明涉及本文所述的式(I)化合物及其药学上可接受的盐，以及它们在医学上的用途，特别是作为Trk拮抗剂。

  公开号：

  WO2015092610A1
• 作为产物：
  描述：

  5-溴-2-氯-3-吡啶羰酰氯 在 氨 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 16.0h， 生成 2-氯-5-溴吡啶-3-甲酰胺
  参考文献：
  名称：

  MET kinase inhibitors

  摘要：

  本发明涉及具有以下化学式I或II的化合物：包括其盐，并且使用它们用于治疗癌症的方法。

  公开号：

  US20070078140A1

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS FOR USE IN TREATING SKIN DISORDERS<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES CUTANÉS
  申请人：KAMARI PHARMA LTD

  公开号：WO2021154966A1

  公开（公告）日：2021-08-05

  Provided herein is a compound of formula (XXXII) or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer thereof or a physiologically functional derivative thereof, wherein R1, R2, R3, G, A, E, n, p, and q are defined herein. Also provided herein are compositions comprising a compound of formula (XXXII), and methods of using a compound of formula (XXXII), e.g., in the treatment or prevention of skin disorders.

  提供了一种公式（XXXII）的化合物或药用可接受的盐、溶剂化物、水合物、立体异构体或生理功能衍生物，其中R1、R2、R3、G、A、E、n、p和q在此定义。此外，还提供了包含公式（XXXII）化合物的组合物，以及使用公式（XXXII）化合物的方法，例如，在治疗或预防皮肤病中的应用。
• [EN] MAP4K4 INHIBITORS<br/>[FR] INHIBITEURS DE MAP4K4
  申请人：IMPERIAL COLLEGE SCI TECH & MEDICINE

  公开号：WO2020115481A1

  公开（公告）日：2020-06-11

  This invention relates to compounds that may be useful as inhibitors of Mitogen-activated Protein Kinase Kinase Kinase Kinase-4 (MAP4K4). The invention also relates to the use of these compounds, for example in a method of treatmentof cardiac conditions.In particular, the present invention relates to compounds of formula (I):

  这项发明涉及可能作为Mitogen-activated Protein Kinase Kinase Kinase Kinase-4（MAP4K4）抑制剂有用的化合物。发明还涉及这些化合物的使用，例如在治疗心脏疾病的方法中。特别是，本发明涉及公式（I）的化合物：
• Discovery of Covalent Bruton's Tyrosine Kinase Inhibitors with Decreased CYP2C8 Inhibitory Activity
  作者：Hui Qiu、Zahid Ali、Julian Bowlan、Richard Caldwell、Anna Gardberg、Nina Glaser、Andreas Goutopoulos、Jared Head、Theresa Johnson、Christine Maurer、Katrin Georgi、Roland Grenningloh、Zhizhou Fang、Federica Morandi、Felix Rohdich、Ralf. Schmidt、Ariele Viacava Follis、Brian Sherer

  DOI：10.1002/cmdc.202100453

  日期：2021.12.14

  SP series and use of a rational design approach, we successfully discovered a new nicotinamide series of potent covalent irreversible BTK inhibitors bearing acrylamide or cyanamide warheads with an improved CYP inhibition profile. One top compound, 18 A, displayed 200-fold weaker CYP2C8 inhibition (IC50=20 μM) relative to compound 1.

  在烟酰胺 SP 系列化合物1的X 射线晶体结构和合理设计方法的指导下，我们成功地发现了一种新的烟酰胺系列，该系列是有效的共价不可逆 BTK 抑制剂，带有丙烯酰胺或单氰胺弹头，具有改进的 CYP 抑制曲线。一种顶级化合物18 A显示出比化合物1弱 200 倍的 CYP2C8 抑制作用 (IC 50 =20 μM) 。
• Discovery of Potent, Selective, and Peripherally Restricted Pan-Trk Kinase Inhibitors for the Treatment of Pain
  作者：Sharan K. Bagal、Mark Andrews、Bruce M. Bechle、Jianwei Bian、James Bilsland、David C. Blakemore、John F. Braganza、Peter J. Bungay、Matthew S. Corbett、Ciaran N. Cronin、Jingrong Jean Cui、Rebecca Dias、Neil J. Flanagan、Samantha E. Greasley、Rachel Grimley、Kim James、Eric Johnson、Linda Kitching、Michelle L. Kraus、Indrawan McAlpine、Asako Nagata、Sacha Ninkovic、Kiyoyuki Omoto、Stephanie Scales、Sarah E. Skerratt、Jianmin Sun、Michelle Tran-Dubé、Gareth J. Waldron、Fen Wang、Joseph S. Warmus

  DOI：10.1021/acs.jmedchem.8b00633

  日期：2018.8.9

  inhibition of the TrkA kinase pathway in pain has been clinically validated by the NGF antibody tanezumab, leading to significant interest in the development of small molecule inhibitors of TrkA. Furthermore, Trk inhibitors having an acceptable safety profile will require minimal brain availability. Herein, we discuss the discovery of two potent, selective, peripherally restricted, efficacious, and

  已知神经营养因子家族，神经生长因子（NGF），脑源性神经营养因子（BDNF），神经营养因子3（NT3）和神经营养因子4（NT4）的激素可激活Tropomyosin受体激酶家族（TrkA，TrkB和TrkC）。此外，NGF抗体tanezumab已在临床上验证了疼痛中TrkA激酶途径的抑制作用，从而引起了对TrkA小分子抑制剂开发的极大兴趣。此外，具有可接受的安全性的Trk抑制剂将需要最小的脑可利用性。本文中，我们讨论了发现两个有效的，选择性的，周边限制性的，有效的和耐受性良好的系列pan-Trk抑制剂的发现，该系列成功递送了三种候选质量的化合物10b，13b和19。预测这三种化合物在人体内的代谢清除率较低，不会通过醛氧化酶催化的反应进行，从而解决了与我们目前的泛-Trk开发候选药物PF-06273340相关的潜在清除率预测责任。
• [EN] SUBSTITUTED PIPERAZINE COMPOUNDS AND METHODS OF USE AND USE THEREOF<br/>[FR] COMPOSÉS DE PIPÉRAZINE SUBSTITUÉS, LEURS PROCÉDÉS D'UTILISATION ET LEURS UTILISATIONS
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2016192657A1

  公开（公告）日：2016-12-08

  The invention relates to substituted piperazine compounds and methods of use and uses thereof, and further to the pharmaceutical compositions comprising the compounds and uses thereof, wherein the compound has Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. The substituted piperazine compounds and pharmaceutical compositions comprising the compounds disclosed herein can be used for inhibiting 5-hydroxytryptamine reuptake and/or stimulating 5-HT1A receptors. The invention also relates to processes for preparing these compounds and pharmaceutical compositions, and their uses in the treatment of a central nervous system dysfunction.

  本发明涉及取代哌嗪化合物及其使用方法和用途，以及包含该化合物及其用途的制药组合物，其中该化合物具有式（I）或其立体异构体、互变异构体、N-氧化物、溶剂化物、代谢物、药学上可接受的盐或其前药。本发明所披露的取代哌嗪化合物和制药组合物可用于抑制5-羟色胺的再摄取和/或刺激5-HT1A受体。本发明还涉及制备这些化合物和制药组合物的方法以及它们在治疗中枢神经系统功能障碍中的用途。