3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-a]吡嗪 | 486460-21-3

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡嗪类
• 中文名称: 3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-a]吡嗪
• 中文别名: 3-(三氟甲基)-1,2,4-三唑并[4,3-A]哌嗪盐酸盐；3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-Α]吡嗪；3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-α]吡嗪；3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-Alpha]吡嗪盐酸盐；3-(三氟甲基)-1,2,4-三唑并[4,3-A]哌嗪；3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-A]吡嗪盐酸盐(西他列汀中间体)；西他列汀-intB4；三唑哌嗪；3-三氟甲基-[1,2,4]三唑[4,3-α]哌嗪；3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-a]吡嗪盐酸盐
• 英文名称: 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine
• 英文别名: 3-(trifluoromethyl)-5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyrazine；3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-A]pyrazine
• CAS: 486460-21-3
• 化学式: C₆H₇F₃N₄
• 分子量: 192.144
• InChiKey: FMTDZGCPYKWMPT-UHFFFAOYSA-N

物化性质

• 沸点：
  266∶C
• 密度：
  1.72
• 闪点：
  115∶C

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2933990090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine
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: 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine
CAS number: 486460-21-3

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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: C6H7F3N4
Molecular weight: 192.1

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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 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

用途

3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-a]吡嗪主要用作有机合成中的重要中间体。由于引入了三氟甲基，该化合物具有优异的化学稳定性和热稳定性，在较为苛刻的反应条件下也能顺利进行。此外，它还表现出一定的生物活性和药理作用，可作为药物开发的候选化合物。因此，它可以广泛应用于有机合成、材料科学以及药物研发等领域。

合成

3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-a]吡嗪是由3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[3,3-a]吡嗪盐酸盐在碱性条件下经脱水反应合成的。

反应信息

• 作为反应物：
  描述：

  3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-a]吡嗪 在 吡啶 、 5,7-di-tert-butyl-3-phenylbenzo[d]oxazol-3-ium tetrafluoroborate 、 三甲基铝 作用下， 以 甲基叔丁基醚 为溶剂， 反应 2.08h， 生成 西他列汀
  参考文献：
  名称：

  金属光氧化还原使醇脱氧芳基化

  摘要：

  金属催化的交叉偶联是有机合成的支柱，广泛用于形成 C-C 键，特别是在不饱和支架的生产中1。然而，使用天然sp 3杂化官能团（如醇）的烷基交叉偶联仍然相对不发达2。特别是，一种稳健且通用的醇直接脱氧偶联方法将对有机合成领域产生重大影响。游离醇直接脱氧交叉偶联的一般方法必须克服几个挑战，最值得注意的是强 C-O 键的原位裂解3，但将允许使用大量可商购的、结构多样的醇作为偶联伙伴4. 我们在此报告了一种基于金属光氧化还原的交叉偶联平台，其中游离醇被 N-杂环卡宾盐原位活化，与芳基卤化物偶联伙伴形成碳-碳键。该方法温和、稳健、选择性，最重要的是，能够适应各种伯醇、仲醇和叔醇以及药学相关的芳基和杂芳基溴化物和氯化物。这种转变的力量已经在许多复杂的环境中得到证明，包括紫杉醇的后期功能化和抗糖尿病药物 Januvia 的模块化合成。该技术代表了原位醇活化与过渡金属催化相结合的一般策略。

  DOI：

  10.1038/s41586-021-03920-6
• 作为产物：
  描述：

  3-三氟甲基-5,6,7,8-四氢-1,2,4-三唑并[4,3-a]吡嗪盐酸盐 在 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 以91.2%的产率得到3-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[4,3-a]吡嗪
  参考文献：
  名称：

  喹啉类TGF-β1抑制剂的制备方法

  摘要：

  本发明属于医药化学领域，涉及喹啉类TGF‑β1抑制剂的制备方法，具体地，涉及式(I)的4‑((1‑环丙基‑3‑(四氢‑2H‑吡喃‑4‑基)‑1H‑吡唑‑4‑基)氧基)‑7‑(3‑(三氟甲基)‑5,6‑二氢‑[1,2,4]三唑并[4,3‑a]吡嗪‑7(8H)‑基)喹啉或其盐、水合物、溶剂合物或结晶的制备方法，

  公开号：

  CN113527304A

文献信息

• Design and Synthesis of Poly(ADP-ribose) Polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity
  作者：Uday Kiran Velagapudi、Marie-France Langelier、Cristina Delgado-Martin、Morgan E. Diolaiti、Sietske Bakker、Alan Ashworth、Bhargav A. Patel、Xuwei Shao、John M. Pascal、Tanaji T. Talele

  DOI：10.1021/acs.jmedchem.8b01709

  日期：2019.6.13

  Poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitors are a class of anticancer drugs that block the catalytic activity of PARP proteins. Optimization of our lead compound 1 (( Z)-2-benzylidene-3-oxo-2,3-dihydrobenzofuran-7-carboxamide; PARP-1 IC50 = 434 nM) led to a tetrazolyl analogue (51, IC50 = 35 nM) with improved inhibition. Isosteric replacement of the tetrazole ring with a carboxyl

  聚腺苷5'-二磷酸核糖）聚合酶（PARP）抑制剂是一类抗癌药物，可阻断PARP蛋白的催化活性。优化我们的先导化合物1（（Z）-2-亚苄基-3-氧代-2,3-二氢苯并呋喃-7-羧酰胺; PARP-1 IC50 = 434 nM）产生了四唑基类似物（51，IC50 = 35 nM）具有更好的抑制作用。用羧基等位取代四唑环（60，IC50 = 68 nM）产生了有希望的新先导，随后对其进行了优化，以获得具有有效PARP-1 IC50值（4-197 nM）的类似物。PARP酶谱分析显示，大多数化合物对PARP-2具有选择性，其IC50值可与临床抑制剂媲美。与PARP-1结合的关键抑制剂的X射线晶体结构说明了与向PARP-1腺苷结合袋延伸的类似附件的相互作用方式。化合物81，一种同工型选择性PARP-1 / -2（IC50 = 30 nM / 2 nM）抑制剂，与同基因BRCA1精制细胞相比，对乳腺
• [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。
• [EN] ALLOSTERIC CHROMENONE INHIBITORS OF PHOSPHOINOSITIDE 3-KINASE (PI3K) FOR THE TREATMENT OF DISEASES ASSOCIATED WITH P13K MODULATION<br/>[FR] INHIBITEURS CHROMÉNONE ALLOSTÉRIQUES DE LA PHOSPHOINOSITIDE 3-KINASE (PI3K) POUR LE TRAITEMENT DE MALADIES ASSOCIÉES À LA MODULATION DE PI3K
  申请人：PETRA PHARMA CORP

  公开号：WO2021202964A1

  公开（公告）日：2021-10-07

  The disclosure relates to compounds of Formula (I) as allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) useful in the treatment of diseases or disorders associated with PI3K modulation, Formula (I), or a prodrug, solvate, enantiomer, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, W, X, Y, s, and Ring A are as described herein.

  该披露涉及到式(I)的化合物，作为磷脂酰肌醇3-激酶（PI3K）的变构色酮抑制剂，在与PI3K调节相关的疾病或紊乱的治疗中有用，式(I)，或其前药、溶剂化合物、对映体、立体异构体、互变异构体或其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、W、X、Y、s和环A如本文所述。
• PHTHALAZINONE KETONE DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL USE THEREOF
  申请人：Tang Peng Cho

  公开号：US20130131068A1

  公开（公告）日：2013-05-23

  A phthalazinone ketone derivative as represented by formula (I), a preparation method thereof, a pharmaceutical composition containing the derivative, a use thereof as a poly (ADP-ribose) polymerase (PARP) inhibitor, and a cancer treatment method thereof are described.

  一种以化学式(I)表示的邻苯二氮酮酮衍生物，其制备方法，含有该衍生物的药物组合物，其作为聚(ADP-核糖)聚合酶（PARP）抑制剂的用途，以及其癌症治疗方法被描述。