1-THP-4-吡唑硼酸频哪醇酯 | 1003846-21-6

• 物质功能分类: 化学试剂 - 有机试剂 - 硼酸
• 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-THP-4-吡唑硼酸频哪醇酯
• 中文别名: 1-(四氢-2H-吡喃-2-基)-4-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)-1H-吡唑；1-(2-四氢吡喃基)-1H-吡唑-4-硼酸频哪醇酯
• 英文名称: 1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole
• 英文别名: 1-tetrahydropyran-2-yl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole；1-(oxan-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole；1-(2-tetrahydropyranyl)-1H-pyrazole-4-boronic acid pinacol ester；1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-boronic acid pinacol ester；1-(tetrahydropyran-2-yl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole；1-(oxan-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole；1-(oxan-2-yl)-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole；1-(tetrahydropyran-2-yl)-1H-pyrazole-4-boronic acid pinacol ester；1-(tetrahydropyran-2-yl)-4-pyrazoleboronic acid pinacol ester
• CAS: 1003846-21-6
• 化学式: C₁₄H₂₃BN₂O₃
• 分子量: 278.159
• InChiKey: YYSLAWXDXHVRHU-UHFFFAOYSA-N

物化性质

• 沸点：
  413.8±35.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.88
• 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,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  2～8℃

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : 1-(Tetrahydro-2H-Pyran-2-Yl)-1H-Pyrazole-4-
Boronic Acid Pinacol Ester
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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SECTION 2: Hazards identification
Classification of the substance or mixture
Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
The product does not need to be labelled in accordance with EC directives or respective national laws.
Other hazards
This substance/mixture contains no components considered to be either persistent, bioaccumulative and
toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher.

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SECTION 3: Composition/information on ingredients
Substances
Molecular weight : 278,16 g/mol
No components need to be disclosed according to the applicable regulations.

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SECTION 4: First aid measures
Description of first aid measures
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration.
In case of skin contact
Wash off with soap and plenty of water.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
Indication of any immediate medical attention and special treatment needed
No data available

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SECTION 5: Firefighting measures
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Nature of decomposition products not known.
Advice for firefighters
Wear self-contained breathing apparatus for firefighting if necessary.
Further information
No data available

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SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Avoid dust formation. Avoid breathing vapours, mist or gas.
For personal protection see section 8.
Environmental precautions
No special environmental precautions required.
Methods and materials for containment and cleaning up
Sweep up and shovel. Keep in suitable, closed containers for disposal.
Reference to other sections
For disposal see section 13.

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SECTION 7: Handling and storage
Precautions for safe handling
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Storage class (TRGS 510): Non Combustible Solids
Specific end use(s)
Apart from the uses mentioned in section 1.2 no other specific uses are stipulated

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SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
General industrial hygiene practice.
Personal protective equipment
Eye/face protection
Use equipment for eye protection tested and approved under appropriate government standards
such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
Choose body protection in relation to its type, to the concentration and amount of dangerous
substances, and to the specific work-place., The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Respiratory protection is not required. Where protection from nuisance levels of dusts are desired,
use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and
approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
No special environmental precautions required.

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SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour No data available
c) Odour Threshold No data available
d) pH No data available
e) Melting point/freezing No data available
point
f) Initial boiling point and No data available
boiling range
g) Flash point No data available
h) Evaporation rate No data available
i) Flammability (solid, gas) No data available
j) Upper/lower No data available
flammability or
explosive limits
k) Vapour pressure No data available
l) Vapour density No data available
m) Relative density No data available
n) Water solubility No data available
o) Partition coefficient: n- No data available
octanol/water
p) Auto-ignition No data available
temperature
q) Decomposition No data available
temperature
r) Viscosity No data available
s) Explosive properties No data available
t) Oxidizing properties No data available
Other safety information
No data available

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SECTION 10: Stability and reactivity
Reactivity
No data available
Chemical stability
Stable under recommended storage conditions.
Possibility of hazardous reactions
No data available
Conditions to avoid
No data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
In the event of fire: see section 5

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SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
No data available
Skin corrosion/irritation
No data available
Serious eye damage/eye irritation
No data available
Respiratory or skin sensitisation
No data available
Germ cell mutagenicity
No data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
No data available
Specific target organ toxicity - single exposure
No data available
Specific target organ toxicity - repeated exposure
No data available
Aspiration hazard
No data available
Additional Information
RTECS: Not available
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

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SECTION 12: Ecological information
Toxicity
No data available
Persistence and degradability
No data available
Bioaccumulative potential
No data available
Mobility in soil
No data available
Results of PBT and vPvB assessment
This substance/mixture contains no components considered to be either persistent, bioaccumulative and
toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher.
Other adverse effects
No data available

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SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company.
Contaminated packaging
Dispose of as unused product.

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SECTION 14: Transport information
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
No data available

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SECTION 15: Regulatory information
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
No data available
Chemical Safety Assessment
For this product a chemical safety assessment was not carried out

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SECTION 16: Other information
Further information
Copyright 2014 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

应用 1-THP-4-吡唑硼酸频哪醇酯作为医药中间体和农药中间体具有很大的前景。

制备 关于3-氯-5-三氟甲基-1-甲基吡唑-4-硼酸的合成，在钯催化剂的作用下，以三乙胺为配体，4-碘吡唑与硼酸频哪醇发生偶联反应生成1H-吡唑-4-硼酸频哪醇酯。进一步在氧化条件下，将其转化为1-THP-4-吡唑硼酸频哪醇酯。其反应方程式如下图所示：

反应信息

• 作为反应物：
  描述：

  1-THP-4-吡唑硼酸频哪醇酯 在 四(三苯基膦)钯 、 caesium carbonate 、 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 24.0h， 以81%的产率得到4,4'-BI-1H-吡唑
  参考文献：
  名称：

  钯催化的吡唑硼酸酯的氧化均偶联剂，用于获得通用的联吡唑和柔性金属-有机骨架Co（4,4'-联吡唑酸酯）。

  摘要：

  在空气和水的存在下，通过钯催化的吡唑硼酸酯的均偶联作用，可以轻松实现通往4,4'-联吡唑（H2bpz）和其他对称联吡唑的途径，这使我们能够提供第一个晶体结构和结构证据联吡唑酸酯基金属-有机骨架Co（bpz）的相变。

  DOI：

  10.1039/c9cc08614e
• 作为产物：
  描述：

  联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 1-THP-4-吡唑硼酸频哪醇酯
  参考文献：
  名称：

  [EN] 3-(1H-PYRAZOL-4-YL)PYRIDINE ALLOSTERIC MODULATORS OF THE M4 MUSCARINIC ACETYLCHOLINE RECEPTOR
  [FR] MODULATEURS ALLOSTÉRIQUES DE TYPE 3-(1H-PYRAZOL-4-YL)PYRIDINE DU RÉCEPTEUR MUSCARINIQUE M4 DE L'ACÉTYLCHOLINE

  摘要：

  本发明涉及吡唑并[4,3-b]吡啶化合物，其为M4毒蕈碱型乙酰胆碱受体的变构调节剂。本发明还涉及在可能治疗或预防神经和精神障碍以及涉及M4毒蕈碱型乙酰胆碱受体的疾病中使用所述化合物。本发明还涉及包含这些化合物的组合物。本发明还涉及在可能预防或治疗涉及M4毒蕈碱型乙酰胆碱受体的疾病中使用这些组合物。

  公开号：

  WO2019005588A1

文献信息

• [EN] TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS<br/>[FR] AGENTS DE DÉGRADATION TRICYCLIQUES D'IKAROS ET D'AIOLOS
  申请人：C4 THERAPEUTICS INC

  公开号：WO2020210630A1

  公开（公告）日：2020-10-15

  Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.

  三环脑蛋白结合剂通过泛素蛋白酶体途径降解Ikaros或Aiolos以用于治疗应用的描述。
• Discovery and optimization of a series of 3-substituted indazole derivatives as multi-target kinase inhibitors for the treatment of lung squamous cell carcinoma
  作者：Qi Wang、Yang Dai、Yinchun Ji、Huanyu Shi、Zuhao Guo、Danqi Chen、Yuelei Chen、Xia Peng、Yinglei Gao、Xin Wang、Lin Chen、Yuchen Jiang、Meiyu Geng、Jingkang Shen、Jing Ai、Bing Xiong

  DOI：10.1016/j.ejmech.2018.12.015

  日期：2019.2

  lung squamous cell carcinoma to design multi-target inhibitors represents a potential strategy for the medical treatment. In this study, through screening an in-house focused library, we identified an interesting indazole scaffold. And following with binding analysis, we elaborated the structure-activity relationship of this hit compound by optimizing four parts guided by the DDR2 enzymatic assay, which

  尽管肺腺癌患者受益于靶向治疗的发展，但肺鳞癌（SqCC）患者由于该疾病的复杂性和异质性而无法有效治疗。因此，基于对肺鳞状细胞癌突变的遗传分析以设计多靶点抑制剂代表了一种潜在的治疗策略。在这项研究中，通过筛选内部聚焦库，我们确定了一种有趣的吲唑支架。然后进行结合分析，我们通过优化DDR2酶测定法指导的四个部分，详细阐述了这种命中化合物的结构-活性关系，从而得到了有效的先导化合物10a。。我们进一步优化了针对肺鳞状细胞癌中两个重要激酶FGFR1和DDR2的双重酶促抑制作用。最后，从细胞抗增殖活性测试和体内药代动力学测试中，发现3-取代的吲唑衍生物11k是很有前途的候选者，并通过小鼠异种移植模型进行了体内药理学研究，证明了其强大的抗肿瘤功效。额外的体外药物样评估进一步证明了化合物11k对于SqCC药物开发可能是有价值的。
• NAPHTHYRIDINES AS INHIBITORS OF HPK1
  申请人：Genentech, Inc.

  公开号：US20180282328A1

  公开（公告）日：2018-10-04

  Naphthyridine compounds and their use as inhibitors of HPK1 are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the naphthyridine compounds.

  萘啶化合物及其作为HPK1抑制剂的用途被描述。这些化合物在治疗HPK1依赖性疾病和增强免疫反应方面很有用。还描述了抑制HPK1的方法、治疗HPK1依赖性疾病的方法、增强免疫反应的方法以及制备萘啶化合物的方法。
• [EN] COMPOUNDS TARGETING RNA-BINDING PROTEINS OR RNA-MODIFYING PROTEINS<br/>[FR] COMPOSÉS CIBLANT DES PROTÉINES DE LIAISON À L'ARN OU DES PROTÉINES MODIFIANT L'ARN
  申请人：TWENTYEIGHT SEVEN INC

  公开号：WO2021178420A1

  公开（公告）日：2021-09-10

  The invention relates to a compound represented by Formula (I): or a pharmaceutically acceptable salt thereof, compositions comprising the same and methods of preparing and using the same. The variables are described herein.

  该发明涉及由化学式（I）表示的化合物，或其药用可接受盐，包括含有该化合物的组合物以及制备和使用该化合物的方法。这里描述了变量。
• Damage Incorporated: Discovery of the Potent, Highly Selective, Orally Available ATR Inhibitor BAY 1895344 with Favorable Pharmacokinetic Properties and Promising Efficacy in Monotherapy and in Combination Treatments in Preclinical Tumor Models
  作者：Ulrich Lücking、Lars Wortmann、Antje M. Wengner、Julien Lefranc、Philip Lienau、Hans Briem、Gerhard Siemeister、Ulf Bömer、Karsten Denner、Martina Schäfer、Marcus Koppitz、Knut Eis、Florian Bartels、Benjamin Bader、Wilhelm Bone、Dieter Moosmayer、Simon J. Holton、Uwe Eberspächer、Joanna Grudzinska-Goebel、Christoph Schatz、Gesa Deeg、Dominik Mumberg、Franz von Nussbaum

  DOI：10.1021/acs.jmedchem.0c00369

  日期：2020.7.9

  instability, selective ATR inhibition has been recognized as a promising new approach in cancer therapy. We now report the identification and preclinical evaluation of the novel, clinical ATR inhibitor BAY 1895344. Starting from quinoline 2 with weak ATR inhibitory activity, lead optimization efforts focusing on potency, selectivity, and oral bioavailability led to the discovery of the potent, highly selective

  ATR激酶通过激活DNA损伤修复的基本信号通路，特别是对复制压力的响应，在DNA损伤应答中起关键作用。由于DNA损伤和复制压力是基因组不稳定的主要来源，因此选择性ATR抑制已被认为是癌症治疗中一种有希望的新方法。现在，我们报告新颖的临床ATR抑制剂BAY 1895344的鉴定和临床前评估。从喹啉2开始由于ATR抑制活性较弱，针对效价，选择性和口服生物利用度的前导优化工作导致发现了有效的，高选择性的，口服的ATR抑制剂BAY 1895344，在携带某些DNA损伤的癌症异种移植模型中显示出强大的单一疗法功效维修缺陷。此外，BAY 1895344与某些诱导DNA损伤的化学疗法联合治疗可产生协同的抗肿瘤活性。BAY 1895344目前正在对晚期实体瘤和淋巴瘤（NCT03188965）的患者进行临床研究。