1-[3-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苄基]哌啶 | 859833-21-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-[3-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苄基]哌啶
• 中文别名: 3-(哌啶-1-基甲基)苯基硼酸频哪醇酯
• 英文名称: 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine
• 英文别名: 1-[[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl]piperidine
• CAS: 859833-21-9
• 化学式: C₁₈H₂₈BNO₂
• 分子量: 301.237
• InChiKey: KEKNXVTYDJCRMT-UHFFFAOYSA-N

物化性质

• 沸点：
  402.2±28.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险品标志：
  C
• 海关编码：
  2934999090
• 包装等级：
  III
• 危险类别：
  8
• 危险性防范说明：
  P305+P351+P338,P310,P280
• 危险品运输编号：
  3259
• 危险性描述：
  H314,H302

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 3-(Piperidin-1-ylmethyl)phenylboronic acid, pinacol ester
Synonyms: 1-[3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]piperidine

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: 3-(Piperidin-1-ylmethyl)phenylboronic acid, pinacol ester
CAS number: 859833-21-9

---

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.

---

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.

---

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.

---

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:

---

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.

---

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: C18H28BNO2
Molecular weight: 301.2

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  N-(3-氯-4-((3-氟苄基)氧基)苯基)-6-碘喹唑啉-4-胺盐酸盐 、 1-[3-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苄基]哌啶 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 反应 12.0h， 以66.7%的产率得到N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(3-(piperidin-1-ylmethyl)phenyl)quinazolin-4-amine
  参考文献：
  名称：

  Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis

  摘要：

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.

  DOI：

  10.1021/jm400349k
• 作为产物：
  描述：

  3-羟甲基苯硼酸 在 [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 、 sodium carbonate 、 双(2-二苯基磷苯基)醚 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 甲苯 为溶剂， 反应 26.0h， 生成 1-[3-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苄基]哌啶
  参考文献：
  名称：

  Synthesis of Amines with Pendant Boronic Esters by Borrowing Hydrogen Catalysis

  摘要：

  Amine alkylation reactions of alcohols have been performed in the presence of boronic ester groups to provide products which are known to have use as molecular sensors. The boronic ester moiety could be present in either the alcohol or amine starting material and was not compromised in the presence of a ruthenium catalyst.

  DOI：

  10.1021/ol402271a

文献信息

• Bis(het)aryl-1,2,3-triazole quinuclidines as α7 nicotinic acetylcholine receptor ligands: Synthesis, structure affinity relationships, agonism activity, [18F]-radiolabeling and PET study in rats
  作者：Aziz Ouach、Johnny Vercouillie、Emilie Bertrand、Nuno Rodrigues、Frederic Pin、Sophie Serriere、Liliana Boiaryna、Agnes Chartier、Nathalie Percina、Pakorn Tangpong、Zuhal Gulhan、Celine Mothes、Jean-Bernard Deloye、Denis Guilloteau、Guylene Page、Franck Suzenet、Frederic Buron、Sylvie Chalon、Sylvain Routier

  DOI：10.1016/j.ejmech.2019.06.049

  日期：2019.10

  and nine of them exhibited Ki values below nanomolar concentrations. The best scores were always obtained when the 5-phenyl-2-thiophenyl core was attached to the triazole. The selectivity of these compounds towards the nicotinic α4β2 and serotoninergic 5HT3 receptors was assessed and their brain penetration was quantified by the preparation and in vivo evaluation of two [18F] radiolabelled derivatives

  在本文中，我们描述了使用有效的三步序列（包括与市售的硼衍生物和自制的硼衍生物的Suzuki-Miyaura交叉偶联反应）设计和合成双（Het）芳基-1,2,3-三唑喹核苷α7R配体的方法。 。SAR的勘探需要制备罕见的硼衍生物。测试了40种最终药物结合靶标的能力，其中9种药物的Ki值低于纳摩尔浓度。当将5-苯基-2-硫代苯基核心连接到三唑上时，总会获得最高分。通过制备和体内评估两种化合物，评估了这些化合物对烟碱型α4β2和5羟色胺能5HT3受体的选择性，并定量了它们的脑渗透率[ 18F]放射性标记的衍生物。从我们的结果可以预期，这些化合物中的一些将适合进一步发展，并将对认知障碍产生影响。
• Synthesis of Biaryls Having a Piperidylmethyl Group Based on Space Integration of Lithiation, Borylation, and Suzuki-Miyaura Coupling
  作者：Yusuke Takahashi、Yosuke Ashikari、Masahiro Takumi、Yutaka Shimizu、Yiyuan Jiang、Ryosuke Higuma、Susumu Ishikawa、Hodaka Sakaue、Ibuki Shite、Kei Maekawa、Yoko Aizawa、Hiroki Yamashita、Yuya Yonekura、Marco Colella、Renzo Luisi、Toshihiro Takegawa、Chiemi Fujita、Aiichiro Nagaki

  DOI：10.1002/ejoc.201901729

  日期：2020.2.7

  enabled the generation of aryllithiums bearing a piperidylmethyl group and their selective borylation with boronic esters. Moreover, lithiation, borylation, and Suzuki–Miyaura cross‐coupling were integrated to obtain nitrogen‐containing biaryl compounds such as a synthetic intermediate of a compound with histone deacetylase (HDAC) inhibitory activity.

  流动微反应器能够生成带有哌啶基甲基的芳基锂，并使其与硼酸酯进行选择性硼化。此外，锂化，硼化和Suzuki-Miyaura交叉偶联被集成以获得含氮联芳基化合物，例如具有组蛋白脱乙酰基酶（HDAC）抑制活性的化合物的合成中间体。
• [EN] ACYLGUANIDINES AS TRYPTOPHAN HYDROXYLASE INHIBITORS<br/>[FR] ACYLGUANIDINES COMME INHIBITEURS DE LA TRYPTOPHAN HYDROXYLASE
  申请人：KAROS PHARMACEUTICALS INC

  公开号：WO2015089137A1

  公开（公告）日：2015-06-18

  The present invention is directed to acylguanidines which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPHl), that are useful in the treatment of diseases or disorders associated with peripheral serotonin including, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, and low bone mass diseases, as well as serotonin syndrome, and cancer.

  本发明涉及酰基胍，它们是色氨酸羟化酶（TPH）的抑制剂，特别是isoform 1（TPHl），在治疗与外周血清素有关的疾病或紊乱方面具有用处，例如胃肠道、心血管、肺部、炎症、代谢和骨量低等疾病，以及血清素综合征和癌症。
• Discovery of GSK251: A Highly Potent, Highly Selective, Orally Bioavailable Inhibitor of PI3Kδ with a Novel Binding Mode
  作者：Kenneth Down、Augustin Amour、Niall A. Anderson、Nick Barton、Sebastien Campos、Edward P. Cannons、Cole Clissold、Maire A. Convery、John J. Coward、Kevin Doyle、Birgit Duempelfeld、Christopher D. Edwards、Michael D. Goldsmith、Jana Krause、David N. Mallett、Grant A. McGonagle、Vipulkumar K. Patel、James Rowedder、Paul Rowland、Andrew Sharpe、Srividya Sriskantharajah、Daniel A. Thomas、Douglas W. Thomson、Sorif Uddin、J. Nicole Hamblin、Edith M. Hessel

  DOI：10.1021/acs.jmedchem.1c01102

  日期：2021.9.23

  Optimization of a previously reported lead series of PI3Kδ inhibitors with a novel binding mode led to the identification of a clinical candidate compound 31 (GSK251). Removal of an embedded Ames-positive heteroaromatic amine by reversing a sulfonamide followed by locating an interaction with Trp760 led to a highly selective compound 9. Further optimization to avoid glutathione trapping, to enhance

  通过对先前报道的 PI3Kδ 抑制剂先导系列进行优化，采用新型结合模式，确定了临床候选化合物31 (GSK251)。通过逆转磺酰胺去除嵌入的 Ames 阳性杂芳胺，然后定位与 Trp760 的相互作用，产生高度选择性的化合物9 。进一步优化以避免谷胱甘肽捕获、增强效力和选择性以及优化口服药代动力学特征，发现了化合物31 (GSK215)，其具有较低的预测日剂量（45 mg，bid）和适合于大鼠的毒性特征。进一步发展。
• Microwave-Mediated Synthesis of an Arylboronate Library
  作者：John Spencer、Christine B. Baltus、Hiren Patel、Neil J. Press、Samantha K. Callear、Louise Male、Simon J. Coles

  DOI：10.1021/co100011g

  日期：2011.1.10

  A series of arylboronates has been synthesized from the reaction of 2-(2-, (3-, or (4-(bromomethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 11-3) respectively with a range of N-, S-, and O-nucleophiles, using microwave-mediated chemistry. For the synthesis of N- and S-substituted boronates, a supported base, PS-NMM, was employed, and many reactions were complete within 15 min. With O-nucleophiles, a mixture of tetrabutylammonium bromide, potassium carbonate, and sodium hydroxide was employed. The resulting aminomethyl, mercaptomethyl, or alkoxy-/phenoxymethyl-arylboronates were subjected to microwave-mediated Suzuki Miyaura coupling reactions to afford a range of biaryls in moderate to good yields. The X-ray structures of five boronates were determined.