N-Me-Val-OME盐酸盐 | 3339-44-4

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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-Me-Val-OME盐酸盐
• 中文别名: N-甲基缬氨酸甲酯盐酸盐；N-甲基L-缬氨酸甲酯盐酸盐；N-ME-VAL-OME盐酸盐
• 英文名称: methyl N-methyl-L-valinate hydrochloride
• 英文别名: methyl methyl-L-valinate hydrochloride；methyl (2S)-3-methyl-2-(methylamino)butanoate hydrochloride；methyl (2S)-3-methyl-2-(methylamino)butanoate;hydrochloride
• CAS: 3339-44-4
• 化学式: C₇H₁₆NO₂*Cl
• 分子量: 181.663
• InChiKey: DLLHGHUMLSLOID-RGMNGODLSA-N

物化性质

• 熔点：
  140-141℃

计算性质

• 辛醇/水分配系数(LogP)：
  0.83
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  42.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2922499990
• 危险性防范说明：
  P261,P305+P351+P338
• 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: N-Methyl-l-valine methyl ester, HCl
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: N-Methyl-l-valine methyl ester, HCl
CAS number: 3339-44-4

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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: C7H15NO2.ClH
Molecular weight: 181.7

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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 chloride.

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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：

  N-Me-Val-OME盐酸盐 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 2-fluoro-1-ethylpyridinium tetrafluoroborate 、 2-bromo-1-ethylpyridin-1-ium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 (S)-1-[(S)-1-((S)-2-{[(S)-2-((S)-2-Dimethylamino-3-methyl-butyrylamino)-3-methyl-butyryl]-methyl-amino}-3-methyl-butyryl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carboxylic acid benzyl ester
  参考文献：
  名称：

  1-乙基2-卤吡啶鎓盐，溶液和固相中高效阻碍肽合成的高效偶联试剂

  摘要：

  1-乙基-2-卤代吡啶鎓盐，BEP，FEP，BEPH和FEPH，合成并证明是含有受阻的肽的合成是非常有效的Ñ甲基化的或Ç α，Ç α-二烷基化的氨基酸残基。HPLC对模型反应的监测表明，与通常使用的卤化铀盐和phospho盐相比，这些吡啶鎓盐具有更高的反应活性和更低的消旋性。通过合成一系列受阻的寡肽和活性酯，具有良好的收率和方便的后处理，进一步证明了这些吡啶鎓类偶联剂的效率。使用这些吡啶鎓盐还成功合成了环孢菌素A（CsA）的8-11四肽片段和Dolastatin 15的五肽部分。这些吡啶鎓类偶联剂对SPPS的效率还通过CsA的极受阻碍的8-11肽段和CsO的线性十一肽的固相合成证明。1 H NMR，IR和HPLC。提出主要的反应性中间体是N-保护的氨基酸或肽的相应的酰卤和酰氧基吡啶鎓盐。

  DOI：

  10.1016/s0040-4020(00)00657-8
• 作为产物：
  描述：

  N-苄氧羰基-N-甲基-L-缬氨酸 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 4.0h， 生成 N-Me-Val-OME盐酸盐
  参考文献：
  名称：

  Coupling N-Methylated Amino Acids Using PyBroP and PyCloP Halogenophosphonium Salts: Mechanism and Fields of Application

  摘要：

  PyBroP (1) and PyCloP (2), two halotripyrrolidinophosphonium hexafluorophosphates, are peptide-coupling reagents highly efficient for coupling N-methylated amino esters, in contrast with PyBOP (3), the hydroxybenzotriazolyl analogue. These halogenophosphonium salts 1 and 2 are convenient (one-pot reactions) stable solids soluble in conventional solvents. Use of them gave an excellent peptide yield with essentially no epimerization. Activation with these reagents probably involves the formation of an (acyloxy)phosphonium, as shown in the case of 2,4,6-trimethylbenzoic acid activation. In the case of reagents 1 and 2, oxazolone and/or a symmetrical anhydride were intermediates which were rapidly aminolyzed. In contrast, the benzotriazolyl ester intermediate which was formed with PyBOP (3) was poorly reactive with N-methylated amino esters. PyBroP (1) and PyCloP (2) were less efficient in the coupling of some Boc-amino acids because of N-carboxyanhydride formation; this was particularly the case when Boc-Val-OH or Boc-MeVal-OH was coupled with MeVal-OMe.

  DOI：

  10.1021/jo00088a027
• 作为试剂：
  描述：

  N-Boc-L-缬氨酸 在 N-Me-Val-OME盐酸盐 、 N,N-二异丙基乙胺 、 chlorotri(pyrrolidin-1-yl)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 -N-methyl-L-valine methyl ester 、 (S)-4-异丙基恶唑-2,5-二酮
  参考文献：
  名称：

  N-methyl N-carboxyanhydride: an unexpected by-product when coupling boc-n-methyl amino acids

  摘要：

  Activation of Boc-amino acids and Boc-N-methyl amino acids leads to the corresponding NCA. This side reaction explains the low yields obtained when coupling N-methyl amino acids. It was not observed with the Z- or Fmoc-protective groups.

  DOI：

  10.1016/s0040-4039(00)78866-6

文献信息

• 2-Bromo-1-ethyl Pyridinium Tetrafluoroborate (BEP): A Powerful Coupling Reagent for<i>N</i>-Methylated Peptide Synthesis
  作者：Peng Li、Jie Cheng Xu

  DOI：10.1246/cl.2000.204

  日期：2000.3

  tetrafluoroborate (BEP) was firstly utilized to the synthesis of peptides containing N-methyl amino acid residues both in solution and solid phase, and demonstrated high reactivity, low racemization and excellent yields, which were approved by the successful synthesis of a series of oligopeptides and hindered peptide fragments, such as the 8-11 segment of Cyclosporine A and the pentapeptide moiety of Dolastatin

  2-溴-1-乙基四氟硼酸吡啶鎓（BEP）首次用于溶液和固相合成含N-甲基氨基酸残基的肽，并表现出高反应性、低外消旋化和优异的产率，并获得了国家批准。成功合成了一系列寡肽和受阻肽片段，如环孢菌素A的8-11片段和Dolastatin 15的五肽部分。
• Brop: A new reagent for coupling N-methylated amino acids
  作者：Jacques Coste、Marie-Noëlle Dufour、Antoine Pantaloni、Bertrand Castro

  DOI：10.1016/s0040-4039(00)94598-2

  日期：1990.1

  BroP (bromo tris(dimethylamino) phosphonium hexafluorophosphate) is a particularly suitable reagent for coupling N-methylated amino acids. It is stable and gives very high yields in short reaction times. Dipeptides are obtained without appreciable epimerization.

  BroP（溴化三（二甲基氨基）六氟磷酸phospho）是用于偶联N-甲基化氨基酸的特别合适的试剂。它是稳定的，并且在短的反应时间内给出了很高的产率。在没有明显差向异构的情况下获得二肽。
• [EN] METHODS FOR DELAYING, PREVENTING, AND TREATING ACQUIRED RESISTANCE TO RAS INHIBITORS<br/>[FR] MÉTHODES DE RETARDEMENT, DE PRÉVENTION ET DE TRAITEMENT DE LA RÉSISTANCE ACQUISE AUX INHIBITEURS DE RAS
  申请人：REVOLUTION MEDICINES INC

  公开号：WO2021257736A1

  公开（公告）日：2021-12-23

  The present disclosure relates to compositions and methods for the treatment of diseases or disorders (e.g., cancer) with bi-steric inhibitors of mTOR in combination with RAS inhibitors. Specifically, in some embodiments this disclosure includes compositions and methods for inducing apoptosis of tumor cells and/or for delaying, preventing, or treating acquired resistance to RAS inhibitors using bi-steric mTOR inhibitors.

  本公开涉及使用双-立体异构体mTOR抑制剂与RAS抑制剂联合治疗疾病或病状（例如，癌症）的配方和方法。具体而言，在某些实施方式中，本公开包括用于诱导肿瘤细胞凋亡和/或用于延迟、预防或治疗对RAS抑制剂获得性耐药性的双-立体异构体mTOR抑制剂的配方和方法。
• PTERIDINONE COMPOUNDS AND USES THEREOF
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20190322673A1

  公开（公告）日：2019-10-24

  The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof for treating cellular proliferative disorders (e.g., cancer).

  本发明提供了式I的化合物或其药学上可接受的盐，以及用于治疗细胞增殖性疾病（例如癌症）的药物组合物和使用方法。
• An Efficient Synthesis of N-Methylamino Acids and Some of Their Derivatives
  作者：Jan Spengler、Klaus Burger

  DOI：10.1055/s-1998-1998

  日期：1998.1

  N-Methylamino acid derivatives are obtained in high yield by a stereoselective one-pot procedure from hexafluoroacetone protected amino acids via N-chloromethylation and treatment with triethylsilane/trifluoroacetic acid.

  通过N-氯甲基化和三乙基硅烷/三氟乙酸处理，从六氟丙酮保护的氨基酸出发，通过立体选择性的一锅法步骤，可以高产率地获得N-甲基氨基酸衍生物。