1-(四氢吡喃-4-基)-1H-吡唑-4-硼酸频哪醇酯 | 1040377-03-4

• 物质功能分类: 化学试剂 - 有机试剂 - 磺酸/亚磺酸
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 中文名称: 1-(四氢吡喃-4-基)-1H-吡唑-4-硼酸频哪醇酯
• 中文别名: 1-(四氢吡喃-4-基)-1H-吡唑-4-硼酸频呐醇酯
• 英文名称: 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole
• 英文别名: 1-(oxan-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole；1-(tetrahydropyran-4-yl)-1H-pyrazole-4-boronic acid pinacol ester；1-(tetrahydropyran-4-yl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole；1-tetrahydropyran-4-yl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole；1‐(tetrahydro‐2H‐pyran‐4‐yl)‐4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)‐1H‐pyrazole；1-(oxan-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole
• CAS: 1040377-03-4
• 化学式: C₁₄H₂₃BN₂O₃
• 分子量: 278.159
• InChiKey: BOOVIFJKQGYEON-UHFFFAOYSA-N

物化性质

• 熔点：
  113.0 to 117.0 °C
• 沸点：
  413.8±35.0 °C(Predicted)
• 密度：
  1.16

计算性质

• 辛醇/水分配系数(LogP)：
  1.53
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  4

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

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 1-(Tetrahydro-pyran-4-yl)-1H-pyrazole-4-boronic acid pinacol ester
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: 1-(Tetrahydro-pyran-4-yl)-1H-pyrazole-4-boronic acid pinacol ester
CAS number: 1040377-03-4

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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, under −20◦C.
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: C14H23BN2O3
Molecular weight: 278.2

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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.

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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

1-(四氢吡喃-4-基)-1H-吡唑-4-硼酸频哪醇酯是一种1-取代的1H-吡唑-4-硼酸频哪醇酯。这类化合物比较新颖，且是重要的医药中间体，具有广泛的应用前景。例如，它可用作克里唑替尼中间体1-(1-叔丁氧羰基哌啶-4-基)吡唑-4-硼酸频哪醇酯的合成原料。

制备 步骤 1：四氢-2H-吡喃-4-甲基磺酸酯的合成

在0℃下，将四氢吡喃-4-醇（4 mL, 41.11 mmol）溶解于二氯甲烷（60 mL）中，并加入TEA（9 mL, 63.9 mmol），搅拌5分钟后缓慢滴加甲基磺酰氯（3.5 mL, 45 mmol）。反应继续进行1小时后恢复至室温，过夜反应。随后，向反应液中加入水（50 mL）和二氯甲烷（100 mL×3）萃取有机相，并用无水Na2SO4干燥。浓缩后得到7 g黄色固体，产率：94.5%。

MS(ESI,pos.ion)m/z: 无响应

步骤 2：1-(四氢吡喃-4-基)-1H-吡唑-4-硼酸频哪醇酯的合成

将步骤1得到的四氢-2H-吡喃-4-甲基磺酸酯（2.8 g, 16 mmol）、4-吡唑硼酸频哪醇酯（2.01 g, 10.4 mmol）和碳酸铯（5.4 g, 17 mmol）混合后加入DMF（30 mL），在100℃下反应过夜。减压浓缩除去DMF，然后加入水（20 mL）进行萃取，使用二氯甲烷（30 mL×3）三次萃取出有机相，并用无水Na2SO4干燥。经HPLC制备分离纯化后的粗产物，得到1.1 g黄色油状物，产率：38%。

MS(ESI,pos.ion)m/z: 279.3 [M+1]+

反应信息

• 作为反应物：
  描述：

  1-(四氢吡喃-4-基)-1H-吡唑-4-硼酸频哪醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 水 、 sodium hydride 、 potassium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 22.17h， 生成 ethyl (3-(benzyloxy)-4-methyl-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)picolinoyl)glycinate
  参考文献：
  名称：

  [EN] PHD INHIBITOR COMPOUNDS, COMPOSITIONS, AND METHODS OF USE
  [FR] COMPOSÉS INHIBITEURS DE PHD, COMPOSITIONS ET PROCÉDÉS D'UTILISATION

  摘要：

  本发明部分提供了PHD的新型小分子抑制剂，其结构符合公式（I），以及其子公式：或其药用可接受的盐。本文提供的化合物可用于治疗包括心脏（如缺血性心脏病、充血性心力衰竭和心瓣膜疾病）、肺（如肺部炎症、肺炎、急性肺损伤、肺动脉高压、肺纤维化和慢性阻塞性肺病）、呼吸系统（如呼吸道感染、急性呼吸窘迫综合征）、肝（如急性肝功能衰竭和肝纤维化和肝硬化）和肾（如急性肾损伤和慢性肾病）疾病、炎症性肠病（IBD）、缺血再灌注损伤（如中风）和早产儿视网膜病变（ROP）等疾病的治疗。

  公开号：

  WO2022036188A1
• 作为产物：
  描述：

  4-四氢吡喃基 甲磺酸酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 21.0h， 生成 1-(四氢吡喃-4-基)-1H-吡唑-4-硼酸频哪醇酯
  参考文献：
  名称：

  基于2-氨基-5-芳基-3-苄基硫代吡啶骨架的强效c-Met抑制剂的合成及生物学评价

  摘要：

  一系列的2-氨基Ñ -benzylpyridine -3- carboxnamides，2-氨基Ñ针对c-Met的-benzylpyridine -3-磺酰胺和2-氨基-3- benzylthiopyridines通过生物电子等排更换和对接分析来设计。对2-氨基-3-苄基硫代吡啶骨架的优化导致鉴定化合物（R）-10b，其显示出c-Met抑制，IC 50高达7.7 nM。在细胞毒性评估中，化合物（R）-10b有效抑制c-Met上瘾的人类癌细胞系的增殖（IC 50从0.19到0.71μM）和c-Met激活介导的细胞转移。在100 mg / Kg的剂量下，（R）-10b明显抑制了NIH-3T3 / TPR-Met异种移植模型中的肿瘤生长（45％）。值得注意的是，（R）-10b可以克服c-Met激活介导的吉非替尼耐药性，这表明其在药物组合中的潜在用途。综上所述，首先公开了2-氨基-3-苄基硫代吡啶

  DOI：

  10.1016/j.bmc.2013.07.032

文献信息

• [EN] [1,2,4]TRIAZOLO[1,5-C]QUINAZOLIN-5-AMINES<br/>[FR] [1,2,4]TRIAZOLO[1,5-C]QUINAZOLIN-5-AMINES
  申请人：BAYER AG

  公开号：WO2021028382A1

  公开（公告）日：2021-02-18

  The present invention covers [1,2,4]triazolo[1,5-c]quinazolin-5-amine compounds of general formula (I) in which R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients.

  本发明涵盖了通式（I）中R1、R2、R3、R4、R5、R6、R7和R8如所定义的[1,2,4]三唑并[1,5-c]喹唑啉-5-胺化合物，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包含所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是癌症或与异常AHR信号传导相关的疾病，或与失调免疫反应或其他与异常AHR信号传导相关的疾病有关的情况，作为唯一药剂或与其他活性成分组合使用。
• IMIDAZOPYRIDAZINE AND IMIDAZOPYRIDINE COMPOUNDS AND USES THEREOF
  申请人：Incyte Corporation

  公开号：US20200199131A1

  公开（公告）日：2020-06-25

  Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting ALK2 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with ALK2 activity such as cancer.

  揭示了公式（I）的化合物，使用这些化合物抑制ALK2活性的方法以及包含这些化合物的药物组合物。这些化合物在治疗、预防或改善与ALK2活性相关的疾病或障碍，如癌症方面具有用处。
• [EN] HETEROARYL COMPOUNDS AND PHARMACEUTICAL APPLICATIONS THEREOF<br/>[FR] COMPOSÉS HÉTÉROARYLES ET LEURS APPLICATIONS PHARMACEUTIQUES
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2016000615A1

  公开（公告）日：2016-01-07

  The present invention provides herein is a heteroaryl compound or a stereoisomer, a geometric isomer, a tautomer, a racemate, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, as well as a pharmaceutical composition containing the compound disclosed herein. The present invention also provides herein is use of the compound or the pharmaceutical composition thereof disclosed herein in the manufacture of a medicine for treating autoimmune diseases or proliferative diseases.

  本发明提供的是一种杂环芳基化合物或其立体异构体、几何异构体、互变异构体、消旋体、N-氧化物、水合物、溶剂合物、代谢物、药学上可接受的盐或其前药，以及含有本文所披露的化合物的药物组合物。本发明还提供的是使用本文所披露的化合物或其药物组合物制造用于治疗自身免疫疾病或增殖性疾病的药物。
• [EN] HETEROARYL COMPOUNDS AS IRAK INHIBITORS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROARYLES SERVANT D'INHIBITEURS D'IRAK, ET LEURS UTILISATIONS
  申请人：MERCK PATENT GMBH

  公开号：WO2016081679A1

  公开（公告）日：2016-05-26

  The present invention relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, useful as IRAK inhibitors.

  本发明涉及式I化合物或其药用可接受盐，用作IRAK抑制剂。
• [EN] HETEROARYL COMPOUNDS AND THEIR USE AS THERAPEUTIC DRUGS<br/>[FR] COMPOSÉS HÉTÉROARYLE ET LEUR UTILISATION COMME MÉDICAMENTS THÉRAPEUTIQUES
  申请人：DONG-A SOCIO HOLDINGS CO LTD

  公开号：WO2017039331A1

  公开（公告）日：2017-03-09

  The present invention provides heterocyclic compounds, the stereoisomer thereof, the enantiomer thereof, or the pharmaceutically acceptable salt, which are capable of modulating the activity of Mer receptor tyrosine kinase (MERTK). This invention also provides pharmaceutical compositions thereof, methods to prepare the said compounds, and the use of such compounds as a medicament. The present invention is directed to MERTK inhibitory compounds with marked potency, thereby having an outstanding potential for a pharmaceutical intervention of cancer and any other diseases related to MERTK dysregulation.

  本发明提供了一种杂环化合物、其立体异构体、对映异构体或药用可接受的盐，这些化合物能够调节Mer受体酪氨酸激酶（MERTK）的活性。本发明还提供了这些化合物的药物组合物、制备所述化合物的方法以及将这些化合物用作药物的应用。本发明针对的是具有显著活性的MERTK抑制性化合物，因此具有在癌症和任何与MERTK调控失调相关的疾病中进行药物干预的卓越潜力。