N-(叔丁氧基羰基)-L-亮氨酸-N′-甲氧基-N′-甲酰胺 | 87694-50-6

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 亮氨酸类衍生物
• 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: N-(叔丁氧基羰基)-L-亮氨酸-N′-甲氧基-N′-甲酰胺
• 中文别名: N-(叔丁氧基羰基)-L-亮氨酸N-甲氧基-N-甲基酰胺
• 英文名称: N-(tert-butoxycarbonyl)-L-leucine-N'-methoxy-N'-methylamide
• 英文别名: tert-butyl (S)-(1-(methoxy(methyl)amino)-4-methyl-1-oxopentan-2-yl)carbamate；(S)-tert-butyl 1-(methoxy(methyl)amino)-4-methyl-1-oxopentan-2-ylcarbamate；N-(t-Butyloxycarbonyl)-L-leucine N-Methoxy-N-methylamide；(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide；tert-butyl N-[(2S)-1-[methoxy(methyl)amino]-4-methyl-1-oxopentan-2-yl]carbamate
• CAS: 87694-50-6
• 化学式: C₁₃H₂₆N₂O₄
• 分子量: 274.36
• InChiKey: IKRXSZUARJIXLZ-JTQLQIEISA-N

物化性质

• 沸点：
  235 °C(lit.)
• 密度：
  1.46 g/mL at 25 °C(lit.)
• 闪点：
  >230 °F
• 稳定性/保质期：
  避免使用强氧化剂。

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• WGK Germany：
  3
• 海关编码：
  2924199090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  请将贮藏器密封保存，并存放在阴凉干燥处。确保工作环境有良好的通风或排气设施。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Boc-L-Leu-NMe(OMe)
Synonyms: Boc-L-leucine N,O-dimethylhydroxamide

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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-L-Leu-NMe(OMe)
CAS number: 87694-50-6

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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: C13H26N2O4
Molecular weight: 274.4

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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

(S)-N-甲基-N-甲氧基-2-(叔丁氧羰基氨基)-4-甲基戊酰胺是一种亮氨酸衍生物。

反应信息

• 作为反应物：
  描述：

  N-(叔丁氧基羰基)-L-亮氨酸-N′-甲氧基-N′-甲酰胺 在 Pd-BaSO₄ lithium aluminium tetrahydride 、 正丁基锂 、 氢气 、 溶剂黄146 、 二异丙胺 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 乙酸乙酯 、 甲苯 为溶剂， -78.0~-40.0 ℃ 、344.75 kPa 条件下， 反应 9.5h， 生成 5(R)-5-<1(S)-1-(N-Boc-amino)-3-methylbutyl>dihydrofuran-2(3H)-one
  参考文献：
  名称：

  人脑Memapsin 2（β-分泌酶）有效抑制剂的设计。

  摘要：

  DOI：

  10.1021/ja000300g
• 作为产物：
  描述：

  BOC-L-亮氨酸 在 N-甲基吗啉 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 生成 N-(叔丁氧基羰基)-L-亮氨酸-N′-甲氧基-N′-甲酰胺
  参考文献：
  名称：

  卡非佐米生产中的连续过程改进，第1部分：制备环氧酮战斗部的工艺理解和商业路线的改进

  摘要：

  环氧酮4是商业蛋白酶体抑制剂卡非佐米（Kyprolis）生产过程中的分离中间体。商业流程开发和优化工作，以制备环氧酮4强调了一些改进流程的机会。在本文中，提出了三个案例研究，这些案例研究证明了对反应机理的详细了解如何导致改进，从而提高了过程的整体稳定性。在第一个案例研究中，研究了α-手性烯酮外消旋化的机理，从而开发了改进的水后处理程序。接下来，研究了用于步骤3环氧化反应的漂白剂/吡啶混合物的稳定性，从而确定了吡啶作为关键原料，并改善了反应条件和控制策略，以达到转化目标。最后，氧化的丁基化羟基甲苯（oBHT）被确定为是在氧化之前的步骤中使用BHT稳定的四氢呋喃产生的杂质。从这些调查中获得的过程理解导致了过程改进的实施，从而改进了过程的鲁棒性。第二代路线的发展4是本系列第2部分的主题（DOI：10.1021 / acs.oprd.0c00052）。

  DOI：

  10.1021/acs.oprd.0c00051

文献信息

• Synthesis and Biological Activity of Peptide α-Ketoamide Derivatives as Proteasome Inhibitors
  作者：Salvatore Pacifico、Valeria Ferretti、Valentina Albanese、Anna Fantinati、Eleonora Gallerani、Francesco Nicoli、Riccardo Gavioli、Francesco Zamberlan、Delia Preti、Mauro Marastoni

  DOI：10.1021/acsmedchemlett.9b00233

  日期：2019.7.11

  Proteasome activity affects cell cycle progression as well as the immune response, and it is largely recognized as an attractive pharmacological target for potential therapies against several diseases. Herein we present the synthesis of a series of pseudodi/tripeptides bearing at the C-terminal position different α-ketoamide moieties as pharmacophoric units for the interaction with the catalytic threonine

  蛋白酶体活性影响细胞周期进程以及免疫应答，并且它被广泛认为是针对几种疾病的潜在疗法的有吸引力的药理学靶标。在本文中，我们提出了在C末端位置带有不同α-酮酰胺部分的一系列假二/三肽的合成，作为药效学单元，用于与维持蛋白酶体蛋白水解作用的苏氨酸残基相互作用。其中，我们确定了1-萘基衍生物13c是20S蛋白酶体β5亚基的有效和选择性抑制剂，在体外表现出纳摩尔效价（β5IC 50 = 7 nM，β1IC 50 = 60μM，β2IC 50> 100μM）。此外，它显着抑制人结肠直肠癌细胞系HCT116的增殖并诱导其凋亡。
• Preparation of Weinreb Amides Using 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Chloride (DMT-MM)
  作者：Kazuhito Hioki、Hiroko Kobayashi、Rumi Ohkihara、Shohei Tani、Munetaka Kunishima

  DOI：10.1248/cpb.52.470

  日期：——

  Weinreb amides were successfully prepared from the corresponding carboxylic acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) in the solvents, methanol, isopropyl alcohol, and acetonitrile, which can solubilize DMT-MM. A variety of carboxylic acids were converted to the corresponding Weinreb amides in excellent yields by simply mixing with DMT-MM and N,O-dimethylhydroxylamine hydrochloride.

  使用溶剂甲醇、异丙醇和乙腈（这些溶剂能够溶解4-(4,6-二甲氧基-1,3,5-三嗪-2-基)-4-甲基吗啉氯化物（DMT-MM）），从相应的羧酸成功制备了Weinreb酰胺。通过简单地将各种羧酸与DMT-MM和N,O-二甲基羟胺盐酸盐混合，它们被高效地转化为相应的Weinreb酰胺。
• Preparation and biological evaluation of soluble tetrapeptide epoxyketone proteasome inhibitors
  作者：Meng Lei、Haoyang Zhang、Hang Miao、Xiao Du、Hui Zhou、Jia Wang、Xueyuan Wang、Huayun Feng、Jingmiao Shi、Zhaogang Liu、Jian Shen、Yongqiang Zhu

  DOI：10.1016/j.bmc.2019.07.044

  日期：2019.9

  in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib

  设计并合成了一系列新型的20S蛋白酶体四肽基环氧酮抑制剂。为了充分理解SAR，设计，合成和生物分析了R 1，R 2，R 3，R 4和R 5位置的各种基团，包括芳族和脂族取代基。基于酶促结果，选择了7种化合物来评估其细胞活性，可溶性化合物36对人多发性骨髓瘤（MM）细胞系显示出强大的功效。微粒体稳定性结果表明化合物36与市售的卡非佐米相比，它在小鼠，大鼠和人的微粒体中更稳定。用具有荧光素酶表达的MM细胞系ARH77和RPMI-8226的异种移植小鼠模型评价该化合物的体内活性，两个模型的T / C值分别为49.5％和37.6％。为了评估潜在的心血管毒性，化合物36和卡非佐米对HEK293细胞中的hERG离子通道进行了抑制。结果表明36对hERG离子通道没有结合亲和力，而卡非佐米可以与92.1μM的IC 50结合。
• BRAIN PERMEANT PEPTIDOMIMETIC BETA-SECRETASE 1 INHIBITORS FOR THE TREATMENT OR PROPHYLAXIS OF NEUROLOGICAL DISORDERS OR CONDITIONS
  申请人：IBET - INSTITUTO DE BIOLOGIA EXPERIMENTAL E TECNOLOGICA

  公开号：US20170296618A1

  公开（公告）日：2017-10-19

  The present application presents novel peptidomimetic substituted hydroxyethylene compounds, which are inhibitors of beta amyloid cleavage enzyme, capable to permeate the brain and to achieve therapeutic concentrations in the target organ, the brain. These compounds are incorporated in pharmaceutical compositions and applied in the treatment or prophylaxis of neurological disorders or conditions and also other disorders or conditions including Down's syndrome and diabetes.

  这项申请提出了一种新型的肽类模拟替代羟基乙烯化合物，这些化合物是β淀粉样蛋白裂解酶的抑制剂，能够渗透到大脑并在目标器官大脑中达到治疗浓度。这些化合物被纳入药物组合物中，并应用于治疗或预防神经系统疾病或症状以及其他疾病或症状，包括唐氏综合征和糖尿病。
• A One-Flask Synthesis of Weinreb Amides from Chiral and Achiral Carboxylic Acids Using the Deoxo-Fluor Fluorinating Reagent
  作者：Ashok Rao Tunoori、Jonathan M. White、Gunda I. Georg

  DOI：10.1021/ol000318w

  日期：2000.12.1

  [structure] The reagent [bis(2-methoxyethyl)amino]sulfur trifluoride (Deoxo-Fluor reagent) converts carboxylic acids to the corresponding acid fluorides, which then react with N,N-dimethylhydroxylamine to give the corresponding Weinreb amides in high yields. The reaction proceeds without racemization when optically active acids are used as the starting material. This method is operationally simple and provides

  [结构]试剂[双（2-甲氧基乙基）氨基]三氟化硫（Deoxo-Fluor试剂）将羧酸转化为相应的酰氟，然后与N，N-二甲基羟胺反应，以高收率得到相应的Weinreb酰胺。当使用光学活性酸作为起始原料时，反应在没有外消旋的情况下进行。该方法操作简单，可提供高纯度的产品。