(S)-3-氨基-2,3,4,5-四氢-2-氧-1H-1-苯并氮杂卓-1-乙酸叔丁酯 | 109010-60-8

• 物质功能分类: 原料药 - 循环系统用药 - 抗高血压病药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (S)-3-氨基-2,3,4,5-四氢-2-氧-1H-1-苯并氮杂卓-1-乙酸叔丁酯
• 中文别名: (S)-2,3,4,5-四氢-2-氧代-3-氨基-1-叔丁基氧羰甲基-1H-1-苯并氮杂卓；(S)-3-氨基-2,3,4,5-四氢-2-氧-1H-1-苯并杂卓-1-乙酸叔丁酯；酸贝那普利；3S-氨基-2,3,4,5-四氢-1H-[1]-苯并氮杂卓-2-酮-1-乙酸叔丁酯；S-3-氨基-2,3,4,5-四氢-1H-[1]-苯并氮杂卓-2-酮-1-乙酸叔丁酯；(S)-3-氨基-2,3,4,5-四氢-2-氧-1H-1-苯并氮杂卓-1-乙酸-1,1-二甲基乙酯；(S)-2-(2-氧代-3-氨基-2,3,4,5-四氢苯并b氮杂卓-1-基)乙酸叔丁酯；(S)-3-氨基-2,3,4,5-四氢-2-氧-1H-1-苯并氮杂卓-1-乙酸-1,2-二甲基乙酯；(S)-3-氨基-2,3,4,5-四氢-2-氧-1-H-苯并氮杂卓-1-乙酸-1,1-二甲基乙酯；3-氨基-2,3,4,5-四氢-2-氧-1-H-苯并氮杂卓-1-乙酸-1,1-二甲基乙酯；贝那普利拉杂质F；(S)-2-(2-氧代-3-氨基-2,3,4,5-四氢苯并[B]氮杂卓-1-基)乙酸叔丁酯；盐酸贝那普利；S-ATBA
• 英文名称: (S)-tert-butyl 2-(3-amino-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)acetate
• 英文别名: tert-butyl (3S)-3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetate；tert-butyl 2-[(3S)-3-amino-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetate
• CAS: 109010-60-8
• 化学式: C₁₆H₂₂N₂O₃
• 分子量: 290.362
• InChiKey: QTEDVVHLTMELTB-LBPRGKRZSA-N

物化性质

• 熔点：
  115-116°C
• 比旋光度：
  -270 º (c=0.5, EtOH)
• 沸点：
  483.2±45.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶34 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 安全说明：
  S22,S24/25
• WGK Germany：
  2
• 海关编码：
  2933990090
• RTECS号：
  CX7065000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (S)-t-Butyl 2-(3-amino-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)acetate
Synonyms: (S)-3-Amino-1-(t-butoxycarbonylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine

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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: (S)-t-Butyl 2-(3-amino-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)acetate
CAS number: 109010-60-8

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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, refrigerated.
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: C16H22N2O3
Molecular weight: 290.4

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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：用于制造新型抗高血压类药物血管紧张素转化酶抑制剂（ACE-I）——苯那普利（Benazepril）。

反应信息

• 作为反应物：
  描述：

  (S)-3-氨基-2,3,4,5-四氢-2-氧-1H-1-苯并氮杂卓-1-乙酸叔丁酯 在 氯化亚砜 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 74.0h， 生成 (R)-methyl 3-(2-((S)-3-((S)-3-((5-((tertbutoxycarbonyl)(methyl)amino)pentyl)amino)-4-(4-chlorophenyl)butanamido)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)acetamido)-4-(3,4-dichlorophenyl)butanoate
  参考文献：
  名称：

  Structure Based Design of Non-Natural Peptidic Macrocyclic Mcl-1 Inhibitors

  摘要：

  Mcl-1 is a pro-apoptotic BH3 protein family member similar to Bcl-2 and Bcl-xL. Overexpression of Mcl-1 is often seen in various tumors and allows cancer cells to evade apoptosis. Here we report the discovery and optimization of a series of non-natural peptide Mcl-1 inhibitors. Screening of DNA-encoded libraries resulted in hit compound 1, a 1.5 mu M Mcl-1 inhibitor. A subsequent crystal structure demonstrated that compound 1 bound to Mcl-1 in a beta-turn conformation, such that the two ends of the peptide were close together. This proximity allowed for the linking of the two ends of the peptide to form a macrocycle. Macrocyclization resulted in an approximately 10-fold improvement in binding potency. Further exploration of a key hydrophobic interaction with Mcl-1 protein and also with the moiety that engages Arg256 led to additional potency improvements. The use of protein-ligand crystal structures and binding kinetics contributed to the design and understanding of the potency gains. Optimized compound 26 is a <3 nM Mcl-1 inhibitor, while inhibiting Bcl-2;at only 5 mu M and Bcl-xL at >99 mu M, and induces cleaved caspase-3 in MV4-11 cells with an IC50 of 3 mu M after 6 h.

  DOI：

  10.1021/acsmedchemlett.6b00464
• 作为产物：
  描述：

  在 palladium on activated charcoal 、 quinine 、 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 邻氯苯甲胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 30.0 ℃ 、200.0 kPa 条件下， 反应 26.0h， 生成 (S)-3-氨基-2,3,4,5-四氢-2-氧-1H-1-苯并氮杂卓-1-乙酸叔丁酯
  参考文献：
  名称：

  一种 (S)-氨基化合物的合成方法

  摘要：

  本发明涉及一种盐酸贝那普利中间体(S)‑氨基化合物的合成方法。本发明的技术方案是：(S)‑氨基化合物的制备方法，以2‑氨基苯甲醛15为起始原料，在碱的作用下经过Aldol缩合制备化合物16，化合物16再经Pd/C催化氢化制备化合物17，化合物17再经DCC缩合即可生成贝那普利中间体(S)‑氨基化合物的主体结构化合物18，化合物18再与氯乙酸叔丁酯发生取代反应制备化合物19，化合物19再在奎宁衍生的催化剂的催化作用下发生转胺化反应即可生成贝那普利中间体(S)‑氨基化合物1。本发明通过不对称催化直接构建手性中心的方法合成贝那普利中间体(S)‑氨基化合物，提高了反应的收率。

  公开号：

  CN113292495B

文献信息

• Cholecystokinin antagonists. Synthesis and biological evaluation of 3-substituted benzolactams
  作者：W. H. Parsons、A. A. Patchett、M. K. Holloway、G. M. Smith、J. L. Davidson、V. J. Lotti、R. S. L. Chang

  DOI：10.1021/jm00128a004

  日期：1989.8

  A series of 1,3-substituted benzolactams are reported that are potent nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK). Design considerations were based upon the natural product CCK antagonist asperlicin and the potent benzodiazepine antagonist series exemplified by L-364,718 (1). Compound 19, the most potent compound in the benzolactam series, had an IC50 = 3 nM for inhibition

  据报道，一系列的1,3-取代的苯并内酰胺类是肽激素胆囊收缩素（CCK）的有效非肽类拮抗剂。设计方面的考虑是基于天然产物CCK拮抗剂Asperlicin和有效的苯二氮卓类拮抗剂系列，例如L-364,718（1）。化合物19是苯并内酰胺系列中最有效的化合物，对于抑制125I-CCK-8与大鼠胰腺组织中CCK受体的结合，IC50 = 3 nM，发现其外消旋类似物8具有抑制CCK的口服活性。引起的小鼠胃排空，ED50 = 2.6 mg / kg po。讨论了环尺寸，位置1和3的取代以及位置3的立体化学的影响。化合物19和L-364的构象研究
• Introducing A New Class of Sulfonyl Fluoride Hubs via Radical Chloro‐Fluorosulfonylation of Alkynes
  作者：Xingliang Nie、Tianxiao Xu、Yuhao Hong、Honghai Zhang、Chenxi Mao、Saihu Liao

  DOI：10.1002/anie.202109072

  日期：2021.9.27

  Sulfonyl fluorides have widespread applications in many important fields, including ligation chemistry, chemical biology, and drug discovery. Therefore, new methods to increase the synthetic efficiency and expand the available structures of sulfonyl fluorides are highly in demand. Here, we introduce a new and powerful class of sulfonyl fluoride hubs, β-chloro alkenylsulfonyl fluorides (BCASF), which

  磺酰氟在许多重要领域有着广泛的应用，包括连接化学、化学生物学和药物发现。因此，迫切需要提高合成效率和扩展磺酰氟可用结构的新方法。在这里，我们介绍了一类新的强大的磺酰氟中心，β-氯烯基磺酰氟（BCASF），它可以在光氧化还原条件下通过炔烃的自由基氯氟磺酰基双官能化来构建。BCASF 分子表现出多种反应性，并在氯化物位点进行一系列转化，同时保持磺酰氟基团的完整性，包括还原、Suzuki 偶联、Sonogashira 偶联以及与各种氮、氧和硫亲核试剂的亲核取代。顺式烯基磺酰氟、二烯基磺酰氟和炔基磺酰氟，它们在以前用已知方法合成是具有挑战性的，甚至是不可能的。此外，还证明了 BCASF 在肽和药物的后期修饰中的进一步应用。
• Substituted azepinone dual inhibitors of angiotensin converting enzyme
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05552397A1

  公开（公告）日：1996-09-03

  Compounds of the formula ##STR1## are disclosed as possessing inhibitory activity against angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) and thus being useful as cardiovascular agents. Processes for preparing these compounds are also disclosed.

  公式##STR1##的化合物被披露具有抑制血管紧张素转换酶（ACE）和中性内肽酶（NEP）活性的特性，因此可用作心血管药物。同时也披露了制备这些化合物的方法。
• Spatial Anion Control on Palladium for Mild C–H Arylation of Arenes
  作者：Jyoti Dhankhar、Elisa González-Fernández、Chao-Chen Dong、Tufan K. Mukhopadhyay、Anthony Linden、Ilija Čorić

  DOI：10.1021/jacs.0c09611

  日期：2020.11.11

  C-H arylation of arenes without the use of directing groups is a challenge, even for simple molecules, such as benzene. We describe spatial anion control as a concept for the design of catalytic sites for C-H bond activation, thereby enabling nondirected C-H arylation of arenes at ambient temperature. The mild conditions enable late-stage structural diversification of biologically relevant small molecules

  不使用导向基团的芳烃的 CH 芳基化是一个挑战，即使对于简单的分子，如苯。我们将空间阴离子控制描述为设计用于 CH 键活化的催化位点的概念，从而在环境温度下实现芳烃的非定向 CH 芳基化。温和的条件使生物相关小分子的后期结构多样化，并且可以实现与其他芳烃功能化方法互补的位点选择性。这些结果揭示了空间阴离子控制在过渡金属催化中在温和条件下用于 CH 键功能化的潜力。
• Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines Using Aerobic Copper/Nitroxyl Catalysis
  作者：Paige E. Piszel、Aristidis Vasilopoulos、Shannon S. Stahl

  DOI：10.1002/anie.201906130

  日期：2019.8.26

  The aerobic Cu/ABNO catalyzed oxidative coupling of alcohols and amines is highlighted in the synthesis of amide bonds in diverse drug-like molecules (ABNO=9-azabicyclo[3.3.1]nonane N-oxyl). The robust method leverages the privileged reactivity of alcohols bearing electronegative hetero- atoms (O, F, N, Cl) in the β-position. The reaction tolerates over 20 unique functional groups and is demonstrated

  醇和胺的需氧Cu / ABNO催化的醇和胺的氧化偶联在不同药物样分子（ABNO = 9-氮杂双环[3.3.1]壬烷N-氧基）中酰胺键的合成中得到了强调。稳健的方法利用了在β位带有负电性杂原子（O，F，N，Cl）的醇的特权反应性。该反应可耐受20多个独特的官能团，并在空气中以15 mmol的规模进行了证明。催化剂的立体约束使得在仲胺存在下伯胺的化学选择性酰胺化成为可能。所有催化剂组分都是可商购的，并且反应在温和的条件下进行，并且在两个反应伙伴中都保留了立构中心，而仅产生副产物水。