BOC-(R)-3-氨基-4-(3-氟苯基)-丁酸 | 331763-66-7

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - BOC-氨基酸
• 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: BOC-(R)-3-氨基-4-(3-氟苯基)-丁酸
• 中文别名: N-叔丁氧羰基-D-3-氨基-4-(3-氟苯基)丁酸；(βr)-β-[[(1,1-二甲基乙氧基)羰基]氨基]-3-氟-苯丁酸；BOC-D-Β-3-氨基-4-(3-氟苯基)-丁酸
• 英文名称: (3R)-3-[[(tert-butoxy)carbonyl]amino]-4-(3-fluorophenyl)butanoic acid
• 英文别名: (R)-3-((tert-Butoxycarbonyl)amino)-4-(3-fluorophenyl)butanoic acid；(3R)-4-(3-fluorophenyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 331763-66-7
• 化学式: C₁₅H₂₀FNO₄
• 分子量: 297.327
• InChiKey: ZKVPDNJRPDEQCZ-GFCCVEGCSA-N

物化性质

• 沸点：
  443.3±40.0 °C(Predicted)
• 密度：
  1.192

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 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: Boc-(r)-3-amino-4-(3-fluorophenyl)-butyric acid
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: Boc-(r)-3-amino-4-(3-fluorophenyl)-butyric acid
CAS number: 331763-66-7

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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: C15H20FNO4
Molecular weight: 297.3

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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

反应信息

• 作为反应物：
  描述：

  BOC-(R)-3-氨基-4-(3-氟苯基)-丁酸 在 盐酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (3R)-2-[(3R)-3-amino-4-(3-fluorophenyl)butanoyl]-N-methyl-1H,2H,3H,4H,9H-pyrido[3,4-b]indole-3-carboxamide
  参考文献：
  名称：

  使用 DNA 编码化学发现的新型不可逆共价 BTK 抑制剂

  摘要：

  使用组合化学和合成寡核苷酸创建的 DNA 编码小分子文库正被应用于制药行业的药物发现项目。大多数报道的项目描述了可逆的，即非共价的目标调节剂的发现。我们合成了多个以亲电试剂终止的 DNA 编码化学文库，然后使用它们来发现共价不可逆抑制剂，并报告成功发现了丙烯酰胺和环氧化物终止的布鲁顿酪氨酸激酶 (BTK) 抑制剂。我们还使用一系列技术证明了它们的选择性、效力和共价半胱氨酸的参与，包括 X 射线晶体学、热转换位移分析、报告基因置换分析和完整蛋白质复合物质谱。

  DOI：

  10.1016/j.bmc.2021.116223
• 作为产物：
  描述：

  在 silver benzoate 作用下， 以 1,4-二氧六环 、 乙醚 为溶剂， 反应 6.0h， 生成 BOC-(R)-3-氨基-4-(3-氟苯基)-丁酸
  参考文献：
  名称：

  发现有效的和选择性的基于β-高苯丙氨酸的二肽基肽酶IV抑制剂。

  摘要：

  内部筛选铅β-氨基酰基脯氨酸8的修饰得到了等价的噻唑烷化物9。对9的苯环的广泛SAR研究导致发现了一系列新的有效的和选择性的DP-IV抑制剂。事实证明，在2位上引入氟对于该系列的效能至关重要。2,5-二氟（22q）和2,4,5-三氟（22t）类似物是DP-IV的有效抑制剂（分别为IC（50）= 270、119nM）。

  DOI：

  10.1016/j.bmcl.2004.06.099

文献信息

• 一种手性N-Boc-3-氨基-4-芳基-丁酸的合成 方法
  申请人：衢州学院

  公开号：CN106478460B

  公开（公告）日：2018-06-12

  本发明涉及一种手性N‑Boc‑3‑氨基‑4‑芳基‑丁酸的合成方法，第一步：以烯丙基芳香化合物与巴豆醛为起始原料，经过交叉复分解反应、不对称共轭加成反应和氧化反应连续反应一锅法合成N‑Boc‑3‑芳基甲基‑5‑氧代异噁唑中间体；或者以(E)‑4‑芳基‑2‑丁烯醛为起始原料，经不对称共轭加成反应和氧化反应连续反应一锅法合成N‑Boc‑3‑芳基甲基‑5‑氧代异噁唑中间体；第二步：(3R)‑N‑Boc‑3‑芳基甲基‑5‑氧代异噁唑中间体经高压氢化直接制得手性N‑Boc‑3‑氨基‑4‑芳基‑丁酸。本发明提供的合成方法操作简单、反应条件温和，目标产物总收率达到60‑69％，所得目标产物的ee值高达96％等优点，是一条具有工业化前景的合成路线。
• Design, synthesis and biological evaluation of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors
  作者：Xun Ji、Chunmei Xia、Jiang Wang、Mingbo Su、Lei Zhang、Tiancheng Dong、Zeng Li、Xia Wan、Jingya Li、Jia Li、Linxiang Zhao、Zhaobing Gao、Hualiang Jiang、Hong Liu

  DOI：10.1016/j.ejmech.2014.08.059

  日期：2014.10

  Based on the previous work in our group and the principle of computer-aided drug design, a series of novel beta-amino pyrrole-2-carbonitrile derivatives was designed and synthesized. Compounds 81 and 91 were efficacious and selective DPP4 inhibitors resulting in decreased blood glucose in vivo. Compound 81 had moderate DPP4 inhibitory activity (IC50 = 0.05 mu M) and good oral bioavailability (F = 53.2%). Compound 91 showed excellent DPP4 inhibitory activity (IC50 = 0.01 mu M), good selectivity (selective ratio: DPP8/DPP4 = 898.00; DPP9/DPP4 = 566.00) against related peptidases, and good efficacy in an oral glucose tolerance tests in ICR mice and moderate PR profiles (F = 22.8%, t(1/2) = 2.74 h). Moreover, compound 91 did not block hERG channel and exhibited no inhibition of liver metabolic enzymes such as CYP2C9. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Novel irreversible covalent BTK inhibitors discovered using DNA-encoded chemistry
  作者：John P. Guilinger、Archna Archna、Martin Augustin、Andreas Bergmann、Paolo A. Centrella、Matthew A. Clark、John W. Cuozzo、Maike Däther、Marie-Aude Guié、Sevan Habeshian、Reiner Kiefersauer、Stephan Krapp、Alfred Lammens、Lukas Lercher、Julie Liu、Yanbin Liu、Klaus Maskos、Michael Mrosek、Klaus Pflügler、Markus Siegert、Heather A. Thomson、Xia Tian、Ying Zhang、Debora L. Konz Makino、Anthony D. Keefe

  DOI：10.1016/j.bmc.2021.116223

  日期：2021.7

  created using combinatorial chemistry and synthetic oligonucleotides are being applied to drug discovery projects across the pharmaceutical industry. The majority of reported projects describe the discovery of reversible, i.e. non-covalent, target modulators. We synthesized multiple DNA-encoded chemical libraries terminated in electrophiles and then used them to discover covalent irreversible inhibitors

  使用组合化学和合成寡核苷酸创建的 DNA 编码小分子文库正被应用于制药行业的药物发现项目。大多数报道的项目描述了可逆的，即非共价的目标调节剂的发现。我们合成了多个以亲电试剂终止的 DNA 编码化学文库，然后使用它们来发现共价不可逆抑制剂，并报告成功发现了丙烯酰胺和环氧化物终止的布鲁顿酪氨酸激酶 (BTK) 抑制剂。我们还使用一系列技术证明了它们的选择性、效力和共价半胱氨酸的参与，包括 X 射线晶体学、热转换位移分析、报告基因置换分析和完整蛋白质复合物质谱。
• Discovery of potent and selective β-homophenylalanine based dipeptidyl peptidase IV inhibitors
  作者：Jinyou Xu、Hyun O. Ok、Edward J. Gonzalez、Lawrence F. Colwell、Bahanu Habulihaz、Huaibing He、Barbara Leiting、Kathryn A. Lyons、Frank Marsilio、Reshma A. Patel、Joseph K. Wu、Nancy A. Thornberry、Ann E. Weber、Emma R. Parmee

  DOI：10.1016/j.bmcl.2004.06.099

  日期：2004.9

  equipotent thiazolidide 9. Extensive SAR studies on the phenyl ring of 9 led to the discovery of a novel series of potent and selective DP-IV inhibitors. Introduction of a fluorine at the 2-position proved to be crucial for the potency of this series. The 2,5-difluoro (22q) and 2,4,5-trifluoro (22t) analogues were potent inhibitors of DP-IV (IC(50)=270, 119nM, respectively).

  内部筛选铅β-氨基酰基脯氨酸8的修饰得到了等价的噻唑烷化物9。对9的苯环的广泛SAR研究导致发现了一系列新的有效的和选择性的DP-IV抑制剂。事实证明，在2位上引入氟对于该系列的效能至关重要。2,5-二氟（22q）和2,4,5-三氟（22t）类似物是DP-IV的有效抑制剂（分别为IC（50）= 270、119nM）。