2-溴-4-三氟甲基嘧啶 | 785777-87-9

• 物质功能分类: 医药中间体 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-溴-4-三氟甲基嘧啶
• 中文别名: 2-溴-4-(三氟甲基)嘧啶；4-三氟甲基-2-溴嘧啶
• 英文名称: 2-bromo-4-(trifluoromethyl)pyrimidine
• CAS: 785777-87-9
• 化学式: C₅H₂BrF₃N₂
• mdl: MFCD09802248
• 分子量: 226.983
• InChiKey: RHCZXIKKGYOYQZ-UHFFFAOYSA-N

物化性质

• 熔点：
  21-23 °C
• 沸点：
  247℃
• 密度：
  1.807
• 闪点：
  103℃

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2-Bromo-4-(trifluoromethyl)pyrimidine
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: 2-Bromo-4-(trifluoromethyl)pyrimidine
CAS number: 785777-87-9

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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: C5H2BrF3N2
Molecular weight: 227.0

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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, 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-溴-4-三氟甲基嘧啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 羟胺 、 sodium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 甲酸 、 正庚烷 、 水 、 异丙醇 为溶剂， 反应 17.0h， 生成 (1S,2S,3S)-1-fluoro-N-hydroxy-2-phenyl-3-(4-(4-(trifluoromethyl)pyrimidin-2-yl)phenyl)cyclopropanecarboxamide
  参考文献：
  名称：

  Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class IIa Histone Deacetylase (HDAC) Inhibitors

  摘要：

  Potent and selective class Ha HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class Ha HDAC catalytic site inhibition in preclinical disease models.

  DOI：

  10.1021/acsmedchemlett.5b00302
• 作为产物：
  描述：

  2-羟基-4-三氟甲基嘧啶 在 三溴化磷 作用下， 反应 2.0h， 以81%的产率得到2-溴-4-三氟甲基嘧啶
  参考文献：
  名称：

  溴化 4-（三氟甲基）嘧啶：方便获取多功能中间体

  摘要：

  在整篇论文中，错误的试剂名称“三溴化磷”和“三氯化磷”应替换为正确的名称“三溴化磷”(POBr3) 和“三氯化磷”(POCL3)。[on SciFinder (R)]

  DOI：

  10.1002/ejoc.200400209

文献信息

• [EN] IMIDAZOTRIAZINONE COMPOUNDS<br/>[FR] COMPOSÉS D'IMIDAZOTRIAZINONE
  申请人：ENVIVO PHARMACEUTICALS INC

  公开号：WO2013142269A1

  公开（公告）日：2013-09-26

  The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.

  本发明提供了咪唑三唑酮化合物，它们是磷酸二酯酶9的抑制剂及其药用盐。本发明还提供了用于治疗哺乳动物，包括人类，PDE9相关疾病或疾病的过程、药物组成、药物制剂和化合物的药用。
• Minisci alkylations of electron-deficient pyrimidines with alkyl carboxylic acids
  作者：Daniel G.M. Shore、Kimberly A. Wasik、Joseph P. Lyssikatos、Anthony A. Estrada

  DOI：10.1016/j.tetlet.2015.04.123

  日期：2015.7

  A practical method for the Minisci reaction of electron-deficient pyrimidines with carboxylic acids is described. The one-step protocol allows for the alkylation of halo- and trifluoromethyl pyrimidines with a variety of readily available alkyl and (hetero)cycloalkyl carboxylic acids. These conditions permitted the facile synthesis of substituted pyrimidines, which are poised for further elaboration

  描述了用于缺电子的嘧啶与羧酸的Minisci反应的实用方法。一步方案允许卤代和三氟甲基嘧啶与各种容易获得的烷基和（杂）环烷基羧酸进行烷基化。这些条件允许容易地合成取代的嘧啶，其准备通过发散的方式进一步加工。
• Discovery of novel N-sulfonamide-tetrahydroisoquinolines as potent retinoic acid receptor-related orphan receptor γt agonists
  作者：Xiaojun Ma、Nannan Sun、Xinwei Li、Wei Fu

  DOI：10.1016/j.ejmech.2021.113585

  日期：2021.10

  including retinoic acid-related orphan receptor gamma t (RORγt), chemokine receptor, stimulator of interferon genes (Sting), indoleamine 2,3-dioxygenase (IDO), toll-like receptors (TLR), etc. Among them, the retinoic acid receptor-related orphan receptor γt (RORγt) has gradually attracted more attention in these years. In particular, LYC-55716 (cintirorgon), a small molecule RORγt agonist developed

  近年来，肿瘤免疫治疗成为研究热点。为小分子免疫肿瘤药物开发了多种靶标，包括视黄酸相关孤儿受体 γt (RORγt)、趋化因子受体、干扰素基因刺激物 (Sting)、吲哚胺 2,3-双加氧酶 (IDO)、toll-如受体（TLR）等，其中视黄酸受体相关孤儿受体γt（RORγt）近年来逐渐受到关注。尤其是莱赛公司开发的小分子RORγt激动剂LYC-55716（cintiorgon）已进入II期临床研究。本工作以化合物7 为起点，经过 4 轮化合物设计、合成和 SAR 研究，得到化合物28，其 EC 50在双荧光共振能量转移（双 FRET）测定中为 0.021 ± 0.002 μM，在小鼠 Th17 细胞分化测定中的 EC 50为 0.021 ± 0.002 μM。表明化合物28具有优异的RORγt激动活性，有望开发为一种新型的肿瘤免疫治疗小分子药物。分子动力学模拟表明，激动剂28形成了强大的 HYF
• [EN] BICYCLIC COMPOUNDS AND THEIR USES AS DUAL C-SRC / JAK INHIBITORS<br/>[FR] COMPOSÉS BICYCLIQUES ET UTILISATIONS ASSOCIÉES EN TANT QU'INHIBITEURS MIXTES DE C-SRC/JAK
  申请人：DEBIOPHARM SA

  公开号：WO2011101806A1

  公开（公告）日：2011-08-25

  The present invention relates to substituted aromatic bicyclic compounds containing pyrimidine and pyridine rings of formula (I) having the structure as well as pharmaceutically acceptable salts thereof. The compounds of the present invention are useful as tyrosine kinase inhibitors, preferably SRC family kinases (SFKs) inhibitors, in particular as multi SFK/JAK. kinases inhibitors and even preferably as dual c-SRC/JAK kinases inhibitors, thereby inhibiting the STAT3 activation and therefore abnormal growth of particular cell types. Notably, the compounds of the present invention are useful for the treatment or inhibition of certain diseases that are the result of deregulation of STAT3.

  本发明涉及含有嘧啶和吡啶环的取代芳香族双环化合物的化学式(I)，以及其药学上可接受的盐。本发明的化合物可用作酪氨酸激酶抑制剂，优选为SRC家族激酶（SFKs）抑制剂，特别是作为多种SFK/JAK激酶抑制剂，甚至更优选地作为双重c-SRC/JAK激酶抑制剂，从而抑制STAT3的激活，进而抑制特定细胞类型的异常生长。值得注意的是，本发明的化合物可用于治疗或抑制由于STAT3失调而导致的某些疾病。
• Metal-Bearing and Trifluoromethyl-Substituted Pyrimidines: Generation and Functionalization
  作者：Manfred Schlosser、Olivier Lefebvre、Levente Ondi

  DOI：10.1002/ejoc.200500848

  日期：2006.3

  yl)pyrimidine are deprotonated with lithium diisopropylamide before being allowed to react with dry ice. In contrast, consecutive treatment of 2-bromo-4-(trifluoromethyl)pyrimidine and 2-chloro-5-iodo-4-(trifluoromethyl)pyrimidine with butyllithium affords the expected carboxylic acids in only poor yields and not even trace amts. of acid were detected when 4-bromo-6-(trifluoromethyl)pyrimidine served

  当金属两侧有两个吸电子取代基（如三氟甲基和氯或溴）时，5-嘧啶基锂物种相当稳定。因此，在用异丙基氯化镁完成卤素/金属置换后，由 4,5-二溴-6-（三氟甲基）嘧啶和 5-溴-4-氯-6-（三氟甲基）嘧啶以高产率生产相应的 5-羧酸或丁基锂，然后羧化。当 4-氯-、2,4-二氯-和 2,4-二溴-6-（三氟甲基）嘧啶在与干冰反应之前用二异丙基氨基锂去质子化时，同样获得令人满意或优异的 5-羧酸产率. 相比之下，用丁基锂连续处理 2-bromo-4-(trifluoromethyl)pyrimidine 和 2-chloro-5-iodo-4-(trifluoromethyl)pyrimidine 得到了预期的羧酸，收率很低，甚至没有痕量的 amts。当 4-溴-6-(三氟甲基)嘧啶作为底物时，检测到酸。从两个相互竞争的机制途径中的任何一个中出现的双嘧啶的形成是一种永久性的有害副反应。[在 SciFinder