4-氯-6-三氟甲基嘧啶 | 37552-81-1

• 物质功能分类: 医药中间体 - 杂环化合物 - 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: 4-氯-6-三氟甲基嘧啶
• 中文别名: 6-氯-4-三氟甲基嘧啶；4-三氟甲基-6-氯嘧啶
• 英文名称: 4-chloro-6-(trifluoromethyl)pyrimidine
• CAS: 37552-81-1
• 化学式: C₅H₂ClF₃N₂
• mdl: MFCD04972771
• 分子量: 182.532
• InChiKey: TYSPDLZOMUDHQZ-UHFFFAOYSA-N

物化性质

• 熔点：
  -53--52 °C
• 沸点：
  35-36 °C(Press: 22 Torr)
• 密度：
  1.429 g/cm3

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

• 安全说明：
  S26,S36/37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2933599090
• 危险性防范说明：
  P305+P351+P338
• 危险性描述：
  H227,H315,H319,H335
• 储存条件：
  室温下，使用惰性气体。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
4-Chloro-6-trifluoromethylpyrimidine
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
4-Chloro-6-trifluoromethylpyrimidine
Ingredient name:
CAS number: 37552-81-1

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.
Storage: Store in closed vessels.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H2ClF3N2
Molecular weight: 182.5

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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 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

合成方法

4-氯-6-三氟甲基嘧啶类化合物的制备方法如下：以三氟乙酰基乙酸乙酯和盐酸醚为原料，使用碱催化剂，并与烃类和醇类混合物作为溶剂进行回流反应。而4-羟基-6-三氟甲基嘧啶类化合物则通过与三氯氧磷及乙腈在80～150℃下反应2～24小时来制备，反应完成后除去溶剂并加水碱化，再用有机溶剂萃取。

具体步骤如下：

1. 合成4-羟基-6-三氟甲基嘧啶类化合物

将三氟乙酰基乙酸乙酯、盐酸醚和碱催化剂与混合有机溶剂混合，在120～130℃下回流反应8～16小时。在此过程中使用分水器进行水油分离以去除水分。反应结束后，除去混合有机溶剂并用酸调整pH至中性（6.5～7.5），然后用有机溶剂（乙酸乙酯、二氯甲烷、乙二醇二甲醚等）萃取干燥得到4-羟基-6-三氟甲基嘧啶类化合物。

所述的混合有机溶剂是由烃类有机溶剂与醇类有机溶剂组成的。其中，烃类有机溶剂优选为甲苯、二甲苯或氯苯中的一种或几种；而醇类溶剂可以选择甲醇、乙醇、正丙醇和异丙醇中的任意一种或几种。这两种有机溶剂的体积比通常为1：1～3：1，更优选的方案是烃类有机溶剂使用甲苯，而醇类有机溶剂选择乙醇。

碱催化剂的选择包括氢氧化钠、氢氧化钾、甲醇钠、甲醇钾、乙醇钠和乙醇钾等。三氟乙酰基乙酸乙酯与盐酸醚及碱催化剂的摩尔比通常为1：1～3：2～10。

2. 合成4-氯-6-三氟甲基嘧啶类化合物

将步骤1中制备的4-羟基-6-三氟甲基嘧啶类化合物与三氯氧磷及乙腈混合，并用二异丙基乙基胺作为催化剂，在80～150℃下反应2～24小时。在此过程中，需要控制好各物质的比例：4-羟基-6-三氟甲基嘧啶类化合物、三氯氧磷和催化剂（二异丙基乙基胺）与乙腈的用量比为1mol：5～10mol：0.1～0.3mol：1～3L。反应完成后需除去未反应完的三氯氧磷和乙腈，然后在-2～4℃下加入水以碱化溶液至pH值达到8.5～10，并通过有机溶剂（如乙酸乙酯、二氯甲烷或乙二醇二甲醚等）进行萃取并干燥得到最终产物。

反应信息

• 作为反应物：
  描述：

  4-氯-6-三氟甲基嘧啶 在 氨 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以920 mg的产率得到4-氨基-6-三氟甲基嘧啶
  参考文献：
  名称：

  CYCLOPROPANECARBOXAMIDO-SUBSTITUTE AROMATIC COMPOUNDS AS ANTI-TUMOR AGENTS

  摘要：

  提供了一种环丙烷羧胺基取代芳香化合物，可抑制蛋白激酶，并在抗肿瘤领域中使用。具体来说，提供了酪氨酸激酶抑制剂和Raf激酶抑制剂作为抗肿瘤药物，以及它们的制备、药物组合物和在癌症治疗中的应用。

  公开号：

  US20150197511A1
• 作为产物：
  描述：

  4-羟基-6-三氟甲基嘧啶 在 三氯氧磷 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 8.5h， 生成 4-氯-6-三氟甲基嘧啶
  参考文献：
  名称：

  含三氟甲基嘧啶部分的新型 N-苯基苯甲酰胺衍生物的合成及抗真菌和杀虫活性

  摘要：

  通过四步反应合成了十七种带有三氟甲基嘧啶部分的新型N-苯基苯甲酰胺衍生物。评价了它们的抗真菌和杀虫特性。抗真菌试验结果表明，部分合成化合物在 50 μg /mL 浓度下对拟杆菌属、Botryosphaeria dothidea ( B. dothidea ) 和Botrytis cinerea ( B. cinerea ) 显示出 比嘧霉胺更好的体外生物活性。不幸的是，合成的化合物对草地贪夜蛾（S. frugiperda）和Mythimna separata 的杀虫活性较低（M. separata )比氯虫苯甲酰胺浓度为 500  μ g/mL。

  DOI：

  10.1155/2021/8370407
• 作为试剂：
  描述：

  、 4-氯-6-三氟甲基嘧啶 在 4-氯-6-三氟甲基嘧啶 作用下， 生成 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-isopropyl-3-({(1S,4S)-5-[6-(trifluoromethyl)pyrimdin-4-yl]-2,5-diazabicyclo[2,2,1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-pentaerythritol
  参考文献：
  名称：

  3-aminocyclopentanecarboxamides as chemokine receptor agonists

  摘要：

  提供一种I(a)或I(b)式的化合物：或其药学上可接受的盐，其中各种取代基在此定义。

  公开号：

  US08946413B2

文献信息

• 3-Aminocyclopentanecarboxamides as modulators of chemokine receptors
  申请人：Xue Chu-Biao

  公开号：US20060004018A1

  公开（公告）日：2006-01-05

  The present invention is directed to compounds of Formula I: which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

  本发明涉及以下式的化合物： 这些化合物是趋化因子受体的调节剂。本发明的化合物及其组合物在治疗与趋化因子受体表达和/或活性相关的疾病方面是有用的。
• DIHYDROPYRIDAZINE-3,5-DIONE DERIVATIVE AND PHARMACEUTICALS CONTAINING THE SAME
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：US20160002251A1

  公开（公告）日：2016-01-07

  The present invention provides a dihydropyridazine-3,5-dione derivative or a salt thereof, or a solvate of the compound or the salt, a pharmaceutical drug, a pharmaceutical composition, a sodium-dependent phosphate transporter inhibitor, and a preventive and/or therapeutic agent for hyperphosphatemia, secondary hyperparathyroidism, chronic renal failure, chronic kidney disease, and arteriosclerosis associated with vascular calcification comprising the compound as an active ingredient, and a method for prevention and/or treatment.

  本发明提供了一种二氢吡啶嗪-3,5-二酮衍生物或其盐，或化合物或盐的溶剂化合物，一种药物，一种药物组合物，一种钠依赖性磷酸盐转运体抑制剂，以及作为活性成分的化合物的高磷血症、继发性甲状旁腺功能亢进症、慢性肾功能衰竭、慢性肾病和与血管钙化相关的动脉硬化的预防和/或治疗剂，以及预防和/或治疗的方法。
• FLAP MODULATORS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：US20140221310A1

  公开（公告）日：2014-08-07

  The present invention relates to compounds of Formula (I), or a form thereof, wherein ring A, R 1 , L and R 2 are as defined herein, useful as FLAP modulators. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

  本发明涉及式（I）化合物，或其形式，其中环A，R1，L和R2如本文所定义，作为FLAP调节剂有用。该发明还涉及包含式（I）化合物的药物组合物。制备和使用式（I）化合物的方法也属于本发明的范围。
• BENZIMIDAZOLE-2-PIPERAZINE HETEROCYCLIC COMPOUND, PHARMACEUTICAL COMPOSITION CONTAINING THE SAME, PREPARATION METHOD AND USE THEREOF
  申请人：SHANGHAI HUILUN LIFE SCIENCE & TECHNOLOGY CO., LTD

  公开号：US20160159776A1

  公开（公告）日：2016-06-09

  The present invention relates to a class of benzimidazole-2-piperazine heterocyclic derivatives, a preparation method and medical use thereof. Specifically, the present invention relates to a new benzimidazole-2-piperazine heterocyclic derivative of general Formula (I), a preparation method, a pharmaceutical composition containing the same, and use thereof as a therapeutic agent and especially as a poly(ADP-ribose)polymerase (PARP) inhibitor.

  本发明涉及一类苯并咪唑-2-哌嗪杂环衍生物、其制备方法及其医疗用途。具体而言，本发明涉及一种通式（I）的新苯并咪唑-2-哌嗪杂环衍生物、其制备方法、含有该衍生物的药物组合物，以及作为治疗剂特别是作为聚（ADP-核糖）聚合酶（PARP）抑制剂的用途。
• [EN] PYRAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRAZOLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012168260A1

  公开（公告）日：2012-12-13

  The invention relates to compounds of formula wherein R1 is hydrogen or phenyl, optionally substitutes by halogen, CN or lower alkoxy or lower alkoxy substituted by halogen; R2 is hydrogen or lower alkyl; R3 is hydrogen or lower alkyl or is phenyl optionally substituted by one or more substituents, selected from halogen, cyano or lower alkoxy substituted by halogen, or is pyridinyl, optionally substituted by halogen or lower alkyl substituted by halogen, or is pyrimidinyl, optionally substituted by lower alkyl substituted by halogen, or is pyrazinyl, optionally substituted by halogen, cyano or lower alkyl substituted by halogen; R4 is hydrogen, lower alkyl or phenyl; Z is a bond, -CH2- or -O-; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formulas IA and IB have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  该发明涉及以下式中的化合物，其中R1是氢或苯基，可选择由卤素、CN或较低的烷氧基或由卤素取代的较低的烷氧基取代；R2是氢或较低的烷基；R3是氢或较低的烷基或是苯基，可选择由卤素、氰基或由卤素取代的较低的烷氧基取代，或是吡啶基，可选择由卤素或由卤素取代的较低的烷基取代，或是嘧啶基，可选择由较低的烷基取代的较低的烷基取代，或是吡嗪基，可选择由卤素、氰基或由卤素取代的较低的烷基取代；R4是氢、较低的烷基或苯基；Z是键，-CH2-或-O-；或其药学上适宜的酸盐。现已发现，IA和IB式的化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对TAAR1。这些化合物可用于治疗抑郁症、焦虑症、躁郁症、注意力缺陷多动障碍（ADHD）、与压力有关的疾病、如精神分裂症等精神疾病、帕金森病等神经系统疾病、阿尔茨海默病等神经退行性疾病、癫痫、偏头痛、高血压、物质滥用和代谢性疾病，如进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍、睡眠和昼夜节律障碍以及心血管疾病。