4-氨基-3-氟苯硼酸频那醇酯 | 819058-34-9

• 物质功能分类: 有机原料 - 有机氟化合物 - 氟苯硼酸系列
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氨基-3-氟苯硼酸频那醇酯
• 中文别名: 3-氟-4-氨基苯硼酸频哪醇酯；4-氨基-3-氟苯硼酸频哪酯
• 英文名称: 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline
• 英文别名: 4-amino-3-fluorophenylboronic acid pinacol ester；2-fluoro-4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenylamine；3-fluoro-4-aminophenylboronic acid pinacol ester
• CAS: 819058-34-9
• 化学式: C₁₂H₁₇BFNO₂
• mdl: MFCD09033884
• 分子量: 237.082
• InChiKey: AIXGNRNTXUKZLC-UHFFFAOYSA-N

物化性质

• 熔点：
  102-104°C
• 沸点：
  334℃
• 密度：
  1.11
• 闪点：
  156℃
• 溶解度：
  可溶于氯仿（少量）、DMSO（少量）、甲醇（少量）

计算性质

• 辛醇/水分配系数(LogP)：
  3.26
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22
• 海关编码：
  2931900090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  2-8°C

SDS

---

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : 4-Amino-3-Fluorophenylboronic 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

---

SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Acute toxicity, Oral (Category 4), H302
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Xn Harmful R22
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal word Warning
Hazard statement(s)
H302 Harmful if swallowed.
Precautionary statement(s) none
Supplemental Hazard none
Statements
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.

---

SECTION 3: Composition/information on ingredients
Substances
Molecular weight : 237,08 g/mol
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
4-Amino-3-Fluorophenylboronic Acid Pinacol Ester
Acute Tox. 4; H302 <= 100 %
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
4-Amino-3-Fluorophenylboronic Acid Pinacol Ester
Xn, R22 <= 100 %
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

---

SECTION 4: First aid measures
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
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. Consult a physician.
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

---

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

---

SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

---

SECTION 7: Handling and storage
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
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

---

SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 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
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Do not let product enter drains.

---

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

---

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

---

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.

---

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

---

SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

---

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

---

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

---

SECTION 16: Other information
Full text of H-Statements referred to under sections 2 and 3.
Acute Tox. Acute toxicity
H302 Harmful if swallowed.
Full text of R-phrases referred to under sections 2 and 3
Xn Harmful
R22 Harmful if swallowed.
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.

反应信息

• 作为反应物：
  描述：

  4-氨基-3-氟苯硼酸频那醇酯 在 吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 2,5-dichloro-N-[4-(6-chloro-5-formyl-pyrazin-2-yl)-2-fluoro-phenyl]benzenesulfonamide
  参考文献：
  名称：

  N- [4-（1H-吡唑并[3,4-b]吡嗪-6-基）-苯基]-磺酰胺作为高活性和选择性SGK1抑制剂的发现。

  摘要：

  从虚拟筛选的起点出发，通过结合经典药物化学和文库方法开发了血清和糖皮质激素调节激酶1抑制剂。这产生了具有纳摩尔活性并具有良好的整体体外和ADME谱的高活性小分子。此外，由于其刚性结构，这些化合物显示出异常高的激酶和脱靶选择性。

  DOI：

  10.1021/ml5003376
• 作为产物：
  描述：

  3-氟-4-硝基苯胺 在 亚硝酸特丁酯 、 5%-palladium/activated carbon 、 2-(4-联苯基)-5-苯基唑 、 氢气 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 8.0h， 生成 4-氨基-3-氟苯硼酸频那醇酯
  参考文献：
  名称：

  Sandmeyer型转化合成三甲基锡烷基芳基硼酸酯化合物及其在化学选择性交叉偶联反应中的应用

  摘要：

  描述了一种基于Sandmeyer型反应的合成方法，可从硝基苯胺衍生物中获得锡和硼取代的芳烃。该转化可用于合成一系列官能化的三甲基锡烷基芳基硼酸酯。此外，还探索了Stille和Suzuki-Miyaura交叉偶联反应的化学选择性反应，并通过进行连续的一锅法式Stille和Suzuki-Miyaura交叉偶联反应合成了一系列m-和对-三苯基衍生物。

  DOI：

  10.1021/jo402618r

文献信息

• Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 1
  作者：R. Kirk、A. Ratcliffe、G. Noonan、M. Uosis-Martin、D. Lyth、O. Bardell-Cox、J. Massam、P. Schofield、S. Hindley、D. R. Jones、J. Maclean、A. Smith、V. Savage、S. Mohmed、C. Charrier、A-M. Salisbury、E. Moyo、R. Metzger、N. Chalam-Judge、J. Cheung、N. R. Stokes、S. Best、M. Craighead、R. Armer、A. Huxley

  DOI：10.1039/d0md00174k

  日期：——

  and topoisomerase IV inhibitors that demonstrate potent activity against a range of Gram-positive and selected Gram-negative organisms, including clinically-relevant and drug-resistant strains. In part 1, we present a detailed structure activity relationship (SAR) analysis that led to the discovery of our previously disclosed compound, REDX05931, which has a minimum inhibitory concentration (MIC) of

  针对细菌感染的药物有效性令人震惊的下降，迫切需要开发新的抗菌剂来绕过细菌耐药机制。我们在此报告了一系列 DNA 促旋酶和拓扑异构酶 IV 抑制剂，它们对一系列革兰氏阳性和选定的革兰氏阴性生物体（包括临床相关和耐药菌株）表现出有效的活性。在第 1 部分中，我们提出了详细的构效关系 (SAR) 分析，导致我们发现了我们之前公开的化合物 REDX05931，该化合物对耐氟喹诺酮类金黄色葡萄球菌的最小抑制浓度 (MIC) 为 0.06 μg mL -1。虽然在体外 hERG 和 CYP 抑制阻止了进一步的发展，它验证了一种合理的设计方法来解决这一紧迫的未满足的医疗需求，并为进一步优化提供了一个支架，在第 2 部分中介绍。
• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：STEP PHARMA S A S

  公开号：WO2019106156A1

  公开（公告）日：2019-06-06

  Compounds of formula (I): (I) and related aspects.

  式(I)的化合物及相关方面。
• [EN] NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS UTILISÉS COMME INHIBITEURS DE LA KINASE RÉARRANGÉE AU COURS DE LA TRANSFECTION (RET)
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2016037578A1

  公开（公告）日：2016-03-17

  This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

  这项发明涉及一种新型化合物，这些化合物是重排转位过程中的抑制剂（RET）激酶，包含它们的药物组合物，它们的制备方法，以及它们在治疗中的使用，单独或结合使用，用于规范胃肠敏感性、蠕动和/或分泌以及/或腹部紊乱或疾病和/或与RET功能障碍相关的疾病或调节RET活性可能具有治疗益处的治疗，包括但不限于所有分类的肠易激综合征（IBS），包括以腹泻为主、以便秘为主或交替排便模式、功能性腹胀、功能性便秘、功能性腹泻、未特指的功能性肠道障碍、功能性腹痛综合征、慢性特发性便秘、功能性食管障碍、功能性胃十二指肠障碍、功能性肛门疼痛、炎症性肠病、非小细胞肺癌、肝细胞癌、结肠癌、髓样甲状腺癌、滤泡性甲状腺癌、间变性甲状腺癌、乳头状甲状腺癌、脑肿瘤、腹腔癌、实体肿瘤、其他肺癌、头颈癌、神经胶质瘤、神经母细胞瘤、冯·希普-林道氏综合征和肾肿瘤、乳腺癌、输卵管癌、卵巢癌、移行细胞癌、前列腺癌、食管和食管胃交界处癌症、胆道癌、腺癌，以及任何具有增加RET激酶活性的恶性肿瘤。
• Discovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS
  作者：Hilary Schenck Eidam、John Russell、Kaushik Raha、Michael DeMartino、Donghui Qin、Huiping Amy Guan、Zhiliu Zhang、Gong Zhen、Haiyu Yu、Chengde Wu、Yan Pan、Gerard Joberty、Nico Zinn、Sylvie Laquerre、Sharon Robinson、Angela White、Amanda Giddings、Ehsan Mohammadi、Beverly Greenwood-Van Meerveld、Allen Oliff、Sanjay Kumar、Mui Cheung

  DOI：10.1021/acsmedchemlett.8b00035

  日期：2018.7.12

  to the discovery of a first-in-class, gut-restricted RET kinase inhibitor, 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)acetamide (15, GSK3179106), as a clinical candidate for the treatment of IBS. GSK3179106 is a potent, selective, and gut-restricted pyridone hinge binder small molecule RET kinase inhibitor with a RET IC50 of

  腹痛和排便习惯异常是肠易激综合症（IBS）患者治疗不当的主要症状。尽管IBS的病因尚不完全清楚，但胃肠道（GI）的许多功能是由肠神经系统（ENS）调节的。炎症或应激诱导的生长因子或细胞因子的表达可能导致胃肠道内脏传入神经元过度神经支配，并有助于IBS的病理生理。转染（RET）期间重新排列的神经元生长因子受体酪氨酸激酶对ENS的发展至关重要，例如Hirschsprung患者携带RET功能丧失突变且缺乏正常的结肠神经支配导致结肠梗阻。相似地，成人ENS中的RET信号通过促进突触形成，信号传递和神经元可塑性来维持神经元功能。ENS中RET的抑制代表了一种新的神经元功能和IBS患者症状正常化的治疗策略。本文中，我们描述了我们的筛选工作以及随后的结构-活性关系（SAR），以优化该系列的效价，选择性和诱变性，从而发现了首屈一指的肠道限制性RET激酶抑制剂2- （4-（4-乙氧基-6-氧代-1,6-二氢
• SUBSTITUTED PYRIDOPYRAZINES AS NOVEL SYK INHIBITORS
  申请人：Su Wei-Guo

  公开号：US20140121200A1

  公开（公告）日：2014-05-01

  Provided are pyridopyrazine compounds of formula (1), pharmaceutical compositions thereof and methods of use therefore, wherein R 1 , R 2 , R 3 , R 4 and m are as defined in the specification.

  提供了式（1）的吡啶吡嗪化合物，以及其药物组合物和使用方法，其中R1、R2、R3、R4和m如规范中所定义。