N-[1-(S)-乙氧羰基-3-苄丙基]-L-丙氨酸-N-羰甲醛 | 84793-24-8

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丙氨酸类衍生物
• 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-[1-(S)-乙氧羰基-3-苄丙基]-L-丙氨酸-N-羰甲醛
• 中文别名: N-[1-(S)-乙氧羰基-3-苯丙基]-L-丙氨酸-N-羧基酸酐；N-(1-(S)-乙氧基羰基-3-苯丙基)-L-丙氨酰-N-羧酸酐；N-[1-(S)-(+)-乙氧羰基-3-苯丙基]-L-丙氨酰-N-羧酸酐；N-[1-(S)-乙氧甲酰基-3-苯丙基]-L-丙氨酸-羧酸酐；N-(1-(S)-乙氧羰基-3-苯丙基)-L-丙氨酸-N-羧基酸酐
• 英文名称: ethyl (2S)-[(4S)-methyl-2,5-dioxo-1,3-oxazolidin-3-yl]-4-phenylbutanoate
• 英文别名: (S)-ethyl 2-[(S)-4-methyl-2,5-dioxooxazolidin-3-yl]-4-phenylbutanoate；N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-N-carboxylic acid anhydride；N-(1-(S)-ethoxycarbonyl-3-phenylpropyl)-4(S)-methyloxazolidine-2,5-dione；N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-N-carboxyanhydride；(2S,4S)-2-(4-methyl-2,5-dioxo-oxazolidin-3-yl)-4-phenyl-butyric acid ethyl ester；N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-(S)-alanine-N-carboxyanhydride；N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride；N-(1-(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine.N-carboxyanhyride；N-(1-S-carbethoxy-3-phenylpropyl)-S-alanine；ethyl (2S)-2-[(4S)-4-methyl-2,5-dioxooxazolidin-3-yl]-4-phenylbutyrate；NCA；(S)-Ethyl 2-((S)-4-methyl-2,5-dioxooxazolidin-3-yl)-4-phenylbutanoate；ethyl (2S)-2-[(4S)-4-methyl-2,5-dioxo-1,3-oxazolidin-3-yl]-4-phenylbutanoate
• CAS: 84793-24-8
• 化学式: C₁₆H₁₉NO₅
• mdl: MFCD00272296
• 分子量: 305.331
• InChiKey: GFZFELCFSBCPDB-AAEUAGOBSA-N

物化性质

• 熔点：
  69-73 °C(lit.)
• 比旋光度：
  36.5 º (c=1, CHCl3)
• 沸点：
  414.8±55.0 °C(Predicted)
• 密度：
  1.223±0.06 g/cm3(Predicted)
• 稳定性/保质期：
  按规定使用和贮存的话，这些物质不会分解，并且能避开氧化物。

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.437
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S22,S24/25,S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2934999090
• 危险标志：
  GHS05,GHS07
• 危险性描述：
  H317,H318
• 危险性防范说明：
  P280,P305 + P351 + P338
• 储存条件：
  应存放在密闭、阴凉、干燥的地方。

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : N-[1-(S)-(+)-Ethoxycarbonyl-3-phenylpropyl]-L-
alanyl carboxyanhydride
CAS-No. : 84793-24-8
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP]
Serious eye damage (Category 1)
Skin sensitization (Category 1)
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Danger
Hazard statement(s)
H317 May cause an allergic skin reaction.
H318 Causes serious eye damage.
Precautionary statement(s)
P280 Wear protective gloves/ eye protection/ face protection.
P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R41 Risk of serious damage to eyes.
R43 May cause sensitization by skin contact.
S-phrase(s)
S22 Do not breathe dust.
S24 Avoid contact with skin.
S26 In case of contact with eyes, rinse immediately with plenty of water and
seek medical advice.
S37/39 Wear suitable gloves and eye/face protection.
Caution - substance not yet tested completely.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Formula : C16H19NO5
Molecular Weight : 305,33 g/mol
Component Concentration
N-[1-(S)-(+)-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl carboxyanhydride
CAS-No. 84793-24-8 -

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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
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
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
Indication of any immediate medical attention and special treatment needed
no data available

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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
Carbon oxides, nitrogen oxides (NOx)
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
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.

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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.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Specific end uses
no data available

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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
Face shield and safety glasses 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
Where risk assessment shows air-purifying respirators are appropriate use a full-face particle
respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering
controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use
respirators and components tested and approved under appropriate government standards such
as NIOSH (US) or CEN (EU).

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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 Melting point/range: 69 - 73 °C
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) Autoignition 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

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Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available

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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 sensitization
no data available
May cause sensitization by inhalation.
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
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion May be harmful if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes Causes eye burns.
Additional Information
RTECS: Not available

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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
no data available
Other adverse effects
no data available

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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.

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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

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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
no data available

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Section 16. OTHER INFORMATION
Further information
Copyright 2012 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.

制备方法与用途

用途：用于合成心血管药物如马来酸依那普利、喹那普利和雷米普利等多种普利类药物。

反应信息

• 作为反应物：
  描述：

  N-[1-(S)-乙氧羰基-3-苄丙基]-L-丙氨酸-N-羰甲醛 在 三乙胺 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.5h， 生成 群多普利
  参考文献：
  名称：

  WO2007/3947

  摘要：

  公开号：
• 作为产物：
  描述：

  ethyl 2-(S)-{N-ethoxycarbonyl-N-[1-(S)-(ethoxycarbonyloxycarbonyl)-ethyI]-amino}-4-phenylbutyrate 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以64%的产率得到N-[1-(S)-乙氧羰基-3-苄丙基]-L-丙氨酸-N-羰甲醛
  参考文献：
  名称：

  WO2007/132277

  摘要：

  公开号：

文献信息

• PREPARATION OF QUINAPRIL HYDROCHLORIDE
  申请人：——

  公开号：US20040192613A1

  公开（公告）日：2004-09-30

  Methods and materials for preparing quinapril, its pharmaceutically acceptable salts, including quinapril hydrochloride, are disclosed. The method includes reacting (2S,4S)-2-(4-methyl-2,5-dioxo-oxazolidin-3-yl)-4-phenyl-butyric acid ethyl ester with (3S)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid tert-butyl ester to yield quinapril tert-butyl ester, which is subsequently reacted with an acid to yield quinapril or an acid addition salt of quinapril.

  制备喹那普利及其可药用盐的方法和材料被公开，包括喹那普利盐酸盐。该方法包括将(2S,4S)-2-(4-甲基-2,5-二氧代恶唑烷-3-基)-4-苯基丁酸乙酯与(3S)-1,2,3,4-四氢异喹啉-3-羧酸叔丁酯反应，得到喹那普利叔丁酯，随后与酸反应，得到喹那普利或喹那普利的酸加成盐。
• Safe and Efficient Phosgenation Reactions in a Continuous Flow Reactor
  作者：Hiroaki Yasukouchi、Akira Nishiyama、Masaru Mitsuda

  DOI：10.1021/acs.oprd.7b00353

  日期：2018.2.16

  on the industrial scale is challenging owing to its toxicity. An effective method to minimize reaction volumes and mitigate the safety risks associated with hazardous chemicals is the use of flow reactors. Consequently, we have established a flow reaction system using triphosgene and tributylamine, which affords a homogeneous reaction that avoids clogging issues. In addition, we have demonstrated that

  光气因其高反应性，实用性和成本效益而被广泛用于有机合成中。然而，由于光气的毒性，在工业规模的批量生产中使用光气具有挑战性。最小化反应体积并减轻与危险化学品有关的安全风险的有效方法是使用流动反应器。因此，我们建立了使用三光气和三丁胺的流动反应系统，该系统可提供均相反应，避免发生堵塞问题。另外，我们已经证明，该方法可以良好的收率应用到各种各样的光气反应中，包括制备药物中间体。
• [EN] PROCESS FOR THE PREPARATION OF AMIDES OF N-[1-(S)-(ETHOXYCARBONYL)-3-PHENYLPROPYL]-L-ALANINE<br/>[FR] PROCÉDÉ DE PRÉPARATION D'AMIDES DE N-[1-(S)-(ÉTHOXYCARBONYL)-3-PHÉNYLPROPYL]-L-ALANINE
  申请人：SANOFI AVENTIS DEUTSCHLAND

  公开号：WO2014202659A1

  公开（公告）日：2014-12-24

  A process for the production of amides of N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine is described. The process can be used for the production of key intermediates and finally the ACE inhibitors such as Ramipril, Enalapril, Quinapril, Trandolapril, Delapril and Moexipril starting from N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine by the reaction with the appropriate amines.

  描述了一种制备N-[1-(S)-(乙氧羰基)-3-苯基丙基]-L-丙氨酸酰胺的方法。该工艺可用于从N-[1-(S)-(乙氧羰基)-3-苯基丙基]-L-丙氨酸出发，通过与适当的胺类反应，生产关键中间体，最终生产ACE抑制剂，如雷米普利、依那普利、喹那普利、群多普利、地拉普利和莫昔普利。
• 盐酸咪达普利有机杂质及其制备方法
  申请人：北京阳光诺和药物研究有限公司

  公开号：CN111253315A

  公开（公告）日：2020-06-09

  本发明公开了盐酸咪达普利3种全新的有机杂质及其制备方法。所述杂质的结构式如式I或式II所示，其中式I中R为氢或乙基。本发明提供的杂质合成路线简单，纯度高，产率高，可以获得克级的杂质对照品。该合成方法得到的盐酸咪达普利杂质可以应用于盐酸咪达普利原料及其制剂杂质的定性、定量研究和检测，对有效控制盐酸咪达普利原料及其制剂的质量控制有重要意义。
• Continuous Flow Synthesis of ACE Inhibitors From N‐Substituted <scp>l</scp> ‐Alanine Derivatives
  作者：Christopher P. Breen、Timothy F. Jamison

  DOI：10.1002/chem.201904400

  日期：2019.11.18

  angiotensin converting enzyme (ACE) inhibitors is described. An optimization effort guided by in situ IR analysis resulted in a general amide coupling approach facilitated by N-carboxyanhydride (NCA) activation that was further characterized by reaction kinetics analysis in batch. The three-step continuous process was demonstrated by synthesizing 8 different ACE inhibitors in up to 88 % yield with throughputs

  描述了一种连续流动合成血管紧张素转化酶（ACE）抑制剂的策略。通过原位IR分析进行的优化工作导致了N-羧基酐（NCA）活化促进的通用酰胺偶联方法，该方法通过分批进行反应动力学分析进一步表征。通过合成8种不同的ACE抑制剂，以高达88％的产率和在≈0.5g h-1的通量范围内生产，证明了三步连续过程，同时避免了反应性中间体的分离和过程密集的反应条件。通过在工业相关的流动平台上制备世界卫生组织（WHO）的基本药物依那普利，进一步开发了该工艺，该平台将通量提高至≈1g h-1。