1-苄基-5-氧代-3-吡咯烷甲酸 | 5733-86-8

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 1-苄基-5-氧代-3-吡咯烷甲酸
• 中文别名: 1-苯基-5-氧代吡咯烷-3-甲酸；1-苄基-5-氧代-吡咯啉-3-甲酸；1-苄基-5-氧代吡咯啉-3-甲酸；1-苯基-4-羧基-2-吡咯烷酮；1-苄基-5-氧代吡咯烷-3-甲酸
• 英文名称: 1-benzyl-5-oxopyrrolidine-3-carboxylic acid
• 英文别名: 1-benzyl-5-oxo-3-pyrrolidinecarboxylic acid；5-oxo-1-(phenylmethyl)-3-pyrrolidinecarboxylic acid
• CAS: 5733-86-8
• 化学式: C₁₂H₁₃NO₃
• mdl: MFCD00085749
• 分子量: 219.24
• InChiKey: VYKQDWPBYULGPF-UHFFFAOYSA-N

物化性质

• 熔点：
  142.0 to 146.0 °C
• 沸点：
  471.3±45.0 °C(Predicted)
• 密度：
  1.314±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933790090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温且干燥环境中保存。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 1-Benzyl-5-oxo-pyrrolidine-3-carboxylic acid
Synonyms: 1-Benzyl-2-pyrrolidinone-4-carboxylic acid

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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: 1-Benzyl-5-oxo-pyrrolidine-3-carboxylic acid
CAS number: 5733-86-8

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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.
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: C12H13NO3
Molecular weight: 219.2

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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

简介

5-氧代吡咯烷-3-羧酸是一类重要的医药中间体。其中，1-苄基-5-氧代吡咯啉-3-甲酸是制备抗老年痴呆药物奈拉西坦 (Nebracetam)的重要中间体。奈拉西坦是一种新型的吡咯烷酮类衍生物，能够改善脑能量代谢和神经传递功能，并对脑内胆碱能系统机能障碍有明显改善作用。

制备

将18克衣康酸（0.138摩尔）与14.8克苄胺（0.138摩尔）置于反应瓶中，氮气保护下升温至130℃。待其慢慢熔解后搅拌2.5小时，停止加热并冷却至100℃。在室温下，将200毫升10％的氢氧化钠溶液加入其中，并继续搅拌直至形成大量白色固体。滴加10%盐酸溶液调节pH值至1-2之间，然后过滤并用水洗涤至pH约为6。最终得到白色颗粒状固体25.1克，收率为82.9%。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  1-苄基-5-氧-3-吡咯烷羧酸甲酯	methyl 1-benzyl-5-oxo-3-pyrrolidinecarboxylate	51535-00-3	C13H15NO3	233.267
  ——	isopropyl N-benzylpyrrolidin-2-one-4-carboxylate	256451-31-7	C15H19NO3	261.321

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  (S)-1-苄基-5-氧吡咯烷-3-羧酸	(S)-(+)-1-(phenylmethyl)-5-oxo-3-pyrrolidinecarboxylic acid	428518-42-7	C12H13NO3	219.24
  1-苄基-5-氧-3-吡咯烷羧酸甲酯	methyl 1-benzyl-5-oxo-3-pyrrolidinecarboxylate	51535-00-3	C13H15NO3	233.267
  1-苄基-4-甲醇-2-吡咯烷酮	1-benzyl-4-(hydroxymethyl)-2-pyrrolidinone	96449-69-3	C12H15NO2	205.257
  ——	4-acetyl-1-benzyl-2-pyrrolidinone	107259-14-3	C13H15NO2	217.268
  ——	N-methyl-5-oxo-1-(phenylmethyl)-3-pyrrolidinecarboxamide	91189-04-7	C13H16N2O2	232.282
  ——	1-benzyl-5-oxopyrrolidine-3-carbonyl chloride	114368-05-7	C12H12ClNO2	237.686
  ——	5-oxo-1-(phenylmethyl)-N-propyl-3-pyrrolidinecarboxamide	91189-10-5	C15H20N2O2	260.336
  ——	1-benzyl-N-(2-methylpropyl)-5-oxopyrrolidine-3-carboxamide	1048886-46-9	C16H22N2O2	274.363
  ——	1-benzyl-4-propionylpyrrolidin-2-one	163554-77-6	C14H17NO2	231.294
  1-苯基-5-氧代-3-吡咯烷羰酰肼	1-benzyl-5-oxo-pyrrolidine-3-carbohydrazide	368429-72-5	C12H15N3O2	233.27

反应信息

• 作为反应物：
  描述：

  1-苄基-5-氧代-3-吡咯烷甲酸 在 palladium on activated charcoal ammonium formate 、 potassium carbonate 、 红铝 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 反应 2.75h， 生成 1-Boc-3-羟甲基吡咯烷
  参考文献：
  名称：

  Design and synthesis of potent, orally active, inhibitors of carboxypeptidase U (TAFIa)

  摘要：

  A series of 3-mercapto-propionic acid derivatives that function as reversible inhibitors of carboxypeptidase U have been prepared. We present a successful design strategy using cyclic, low basicity guanidine mimetics resulting in potent, selective and bioavailable inhibitors of carboxypeptidase U (TAFla). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.12.039
• 作为产物：
  描述：

  衣康酸二甲酯 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 1-苄基-5-氧代-3-吡咯烷甲酸
  参考文献：
  名称：

  通过β-和γ-氨基酸的自由基脱羧合成官能化氮杂环

  摘要：

  通过β-和γ-氨基酸的自由基脱羧获得碘化或氧化氮杂环。这种温和、通用的反应可用于合成生物活性产品，如 4-芳基哌啶、羟基化哌啶和新型抗真菌剂。

  DOI：

  10.1002/ejoc.200400698

文献信息

• Reductive Alkylation of Tertiary Lactams via Addition of Organocopper (RCu) Reagents to Thioiminium Ions
  作者：Pierre Mateo、Joséphine E. Cinqualbre、Melinda Meyer Mojzes、Kurt Schenk、Philippe Renaud

  DOI：10.1021/acs.joc.7b02150

  日期：2017.12.1

  A simple procedure for the conversion of tertiary lactams to 2-monoalkylated cyclic amines is described. The reaction sequence involves conversion of a lactam to a thioiminium ion followed by reaction with an organocopper (RCu) reagent and final reduction with triacetoxyborohydride. The reaction is high yielding and shows an excellent functional group tolerance. Its utility is demonstrated by a rapid

  描述了将叔内酰胺转化为2-单烷基化的环胺的简单程序。反应顺序包括将内酰胺转化为硫亚胺离子，然后与有机铜（RCu）试剂反应，最后用三乙酰氧基硼氢化物还原。该反应产率高并且显示出优异的官能团耐受性。吲哚并立定167B的快速合成证明了其实用性。仅形成单烷基化产物的该方法的优异化学选择性通过涉及形成瞬时烯胺的机理来合理化。
• 4-Heterocyclylpiperidines as Selective High-Affinity Ligands at the Human Dopamine D4 Receptor
  作者：Michael Rowley、Ian Collins、Howard B. Broughton、William B. Davey、Raymond Baker、Frances Emms、Rosemarie Marwood、Shil Patel、Smita Patel、C. Ian Ragan、Stephen B. Freedman、Richard Ball、Paul D. Leeson

  DOI：10.1021/jm970111h

  日期：1997.7.1

  5-(4-Chlorophenyl)-3-(1-(4-chlorobenzyl)piperidin-4-yl)pyrazole (3) was identified from screening of the Merck sample collection as a human dopamine D4 (hD4) receptor ligand with moderate affinity (61 nM) and 4-fold selectivity over human D2 (hD2) receptors. Four separate parts of the molecule have been examined systematically to explore structure-activity relationships with respect to hD4 affinity

  5-（4-氯苯基）-3-（1-（4-氯苄基）哌啶-4-基）吡唑（3）通过默克样品收集的筛选被鉴定为具有中等亲和力的人多巴胺D4（hD4）受体配体（61 nM）和4倍于人类D2（hD2）受体的选择性。已经系统地检查了该分子的四个独立部分，以探索与hD4亲和力和相对于其他多巴胺受体的选择性有关的构效关系。发现与吡唑连接的4-氯苯基是最佳的，与4-取代的哌啶一样。碱性氮上的亲脂基更易于改变，最佳基团是苯乙基。芳族杂环可以被改变为许多不同的基团，其中异恶唑和嘧啶显示出改善的亲和力。该杂环也可以有利地被烷基化，从而提高了化合物对D2受体的选择性。据推测，基于异恶唑（29和30）的晶体结构以及受构象约束的化合物（28），将芳族杂环与哌啶连接的键周围的构象对于D4亲和力很重要。将所有有利的变化放在一起，就发现了5-（4-氯苯基）-4-甲基-3-（1-（2-苯基乙基）哌啶-4-基）异恶唑（36）是人类的纳
• [EN] COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT DESTINÉS À TRAITER LES TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2014139882A1

  公开（公告）日：2014-09-18

  The present invention discloses compounds according to Formula I: Wherein R1a, R1b, R2, R4, R5, R6a, R6b, R7, R8, W, X, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseasesby administering the compound of the invention.

  本发明公开了根据式I的化合物：其中R1a、R1b、R2、R4、R5、R6a、R6b、R7、R8、W、X、Cy和下标a如本文所定义。本发明涉及抑制自体脂肪酶（NPP2或ENPP2）的化合物，其制备方法，包含其的药物组合物，以及使用该化合物进行预防和/或治疗涉及纤维化疾病、增生性疾病、炎症性疾病、自身免疫疾病、呼吸系统疾病、心血管疾病、神经退行性疾病、皮肤病和/或与异常血管生成相关疾病的方法。
• Synthesis of a novel and potent small-molecule antagonist of PAC1 receptor for the treatment of neuropathic pain
  作者：Ichiro Takasaki、Haruna Ogashi、Takuya Okada、Ayaka Shimodaira、Daichi Hayakawa、Ai Watanabe、Atsuro Miyata、Takashi Kurihara、Hiroaki Gouda、Naoki Toyooka

  DOI：10.1016/j.ejmech.2019.111902

  日期：2020.1

  identified novel small-molecule antagonists of the PACAP type I (PAC1) receptor using docking-based in silico screening followed by in vitro/vivo pharmacological assays. In the present study, we synthesized 18 novel derivatives based on the structure of PA-9, a recently developed antagonist of the PAC1 receptor, with a view to obtain a panel of compounds with more potent antagonistic and analgesic activities

  我们最近使用基于对接的计算机模拟筛选，然后进行体外/体内药理学鉴定，确定了PACAP I型（PAC1）受体的新型小分子拮抗剂。在本研究中，我们基于PA-9（一种最近开发的PAC1受体拮抗剂）的结构合成了18种新型衍生物，以期获得一组具有更强的拮抗和镇痛活性的化合物。其中，化合物3d显示出改善的拮抗活性。鞘内注射3d抑制垂体腺苷酸环化酶激活多肽（PACAP）和脊髓神经结扎诱导的机械性异常性疼痛。效果比PA-9更有效。口服给药后，化合物3d也显示出抗痛觉过敏作用。因此，
• [EN] ANTIVIRAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIVIRAUX
  申请人：HAPLOGEN GMBH

  公开号：WO2019068841A1

  公开（公告）日：2019-04-11

  The present invention relates to novel compounds of general formula (I) wherein R1 to R4 and n have the meanings given in the description and claims, process for preparing these compounds and their use as for treating, preventing or ameliorating viral infections and their use for treating, preventing or ameliorating diseases which are associated with PLA2G16.

  本发明涉及一般式（I）中R1至R4和n具有描述和权利要求中给定的含义的新化合物，制备这些化合物的方法以及它们作为治疗、预防或改善病毒感染的用途，以及它们用于治疗、预防或改善与PLA2G16相关的疾病的用途。