2-氨基-3-(2-氧代-1,2-二氢喹啉-4-基)丙酸盐酸盐 | 4876-14-6

• 物质功能分类: 医药中间体 - 喹啉类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 2-氨基-3-(2-氧代-1,2-二氢喹啉-4-基)丙酸盐酸盐
• 中文别名: α-氨基-1,2-二氢-2-氧-4-喹啉丙酸单水单盐酸盐；2-氨基-3-[2(1H)-喹啉酮-4-基]-丙酸盐酸盐；2-氨基-3-(1,2-二氢-2-氧喹啉-4-基)丙酸盐酸盐
• 英文名称: 2-amino-3-<2(1H)-quinolinon-4-yl>propionic acid hydrochloride
• 英文别名: 2-Amino-3-(1,2-dihydro-2-oxoquinoline-4-yl)propanoic acid hydrochloride；2-amino-3-(2-oxo-1H-quinolin-4-yl)propanoic acid;hydrochloride
• CAS: 4876-14-6
• 化学式: C₁₂H₁₂N₂O₃*ClH
• mdl: MFCD07787426
• 分子量: 268.7
• InChiKey: MPTXVJCCTVAVNL-UHFFFAOYSA-N

物化性质

• 熔点：
  220-221 °C
• 溶解度：
  可溶于DMSO（轻微）、甲醇（非常轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  -1.78
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  92.4
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• 海关编码：
  2933499090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  存储条件为：0-10°C，需置于惰性气体中，并避免潮湿和加热。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2-Amino-3-(1,2-dihydro-2-oxoquinoline-4-yl)propanoic acid, 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: 2-Amino-3-(1,2-dihydro-2-oxoquinoline-4-yl)propanoic acid, HCl
CAS number: 4876-14-6

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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.
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: C12H12N2O3.ClH
Molecular weight: 268.7

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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

制备方法与用途

2-氨基-3-(2-氧代-1,2-二氢喹啉-4-基)丙酸盐酸盐是一种丙氨酸衍生物[1]。

反应信息

• 作为反应物：
  描述：

  2-氨基-3-(2-氧代-1,2-二氢喹啉-4-基)丙酸盐酸盐 在 氯化亚砜 、 potassium carbonate 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 生成 瑞巴派特甲酯
  参考文献：
  名称：

  Studies on 2(1H)-quinolinone derivatives as gastric antiulcer active agents. 2-(4-Chlorobenzoylamino)-3-(2(1H)-quinolinon-4-yl)propionic acid and related compounds.

  摘要：

  合成了一系列N-酰基氨基酸类似物的2 (1H)-喹啉酮，并测试了它们对醋酸诱导的大鼠胃溃疡的抗溃疡活性。这些化合物是通过酰化2 (1H)-喹啉酮的氨基酸衍生物合成的，这些衍生物是通过ω-溴烷基2 (1H)-喹啉酮和乙酰胺基丙二酸酯在乙醇钠存在下反应，然后与稀盐酸水解得到的。其中，2-(4-氯苯甲酰氨基)-3-[2 (1H)-喹啉酮-4-基]丙酸(VIIIf)显示出最强的活性。讨论了结构活性关系。

  DOI：

  10.1248/cpb.33.3775
• 作为产物：
  描述：

  2-乙酰氨基-2-((2-氧代-1,2-二氢喹啉-4-基)甲基)丙二酸二乙酯 在 盐酸 作用下， 反应 9.0h， 以89%的产率得到2-氨基-3-(2-氧代-1,2-二氢喹啉-4-基)丙酸盐酸盐
  参考文献：
  名称：

  Studies on 2(1H)-quinolinone derivatives as gastric antiulcer active agents. 2-(4-Chlorobenzoylamino)-3-(2(1H)-quinolinon-4-yl)propionic acid and related compounds.

  摘要：

  合成了一系列N-酰基氨基酸类似物的2 (1H)-喹啉酮，并测试了它们对醋酸诱导的大鼠胃溃疡的抗溃疡活性。这些化合物是通过酰化2 (1H)-喹啉酮的氨基酸衍生物合成的，这些衍生物是通过ω-溴烷基2 (1H)-喹啉酮和乙酰胺基丙二酸酯在乙醇钠存在下反应，然后与稀盐酸水解得到的。其中，2-(4-氯苯甲酰氨基)-3-[2 (1H)-喹啉酮-4-基]丙酸(VIIIf)显示出最强的活性。讨论了结构活性关系。

  DOI：

  10.1248/cpb.33.3775

文献信息

• 一种瑞巴派特原料药的制备方法
  申请人：千辉药业（安徽）有限责任公司

  公开号：CN113248429A

  公开（公告）日：2021-08-13

  本发明公开了一种瑞巴派特原料药的制备方法，包括以下步骤：步骤一:瑞巴派特原料药的粗制品的制备，利用化合物三和4‑氯苯甲酰氯制备瑞巴派特原料药的粗制品；步骤二:瑞巴派特原料药的纯化。其中，化合物三由化合物二和去离子水、浓盐酸制备而成，化合物二由化合物一、冰乙酸和浓盐酸制备而成，化合物一由乙酰氨基丙二酸二乙酯和4‑溴甲基喹诺酮制备而成。且本发明利用了过程控制方法，以常用提纯方法对合成的化合物一中的杂质、合成的化合物二中的杂质、合成的化合物三中的杂质分别进行了除杂提纯，结合巴派特原料药的粗制品结晶提纯的方法，提高了瑞巴派特原料药的纯度。
• Magic Bullet! Rebamipide, a Superior Anti-ulcer and Ophthalmic Drug and Its Large-Scale Synthesis in a Single Organic Solvent via Process Intensification Using Krapcho Decarboxylation
  作者：Prashanth Kumar Babu、Mohan Reddy Bodireddy、Reshma Choudlu Puttaraju、Dnyaneshwar Vagare、Raghu Nimmakayala、Naresh Surineni、Madhusudana Rao Gajula、Pramod Kumar

  DOI：10.1021/acs.oprd.7b00382

  日期：2018.7.20

  uncontrollable frothing using Krapcho decarboxylation instead of conventional acid hydrolysis, where uncontrollable frothing became chaotic, (ii) minimizing organic waste generation by using a single organic solvent, and (iii) avoiding anti-foaming agents (n-octanol, acetophenone) and acetic acid. With these trifling modifications, the overall yield of active pharmaceutical ingredient (API) was ≥83% with

  与用于治疗消化性溃疡，胃肠道出血和消化不良的现有药物相比，瑞巴派特（1）是一种优越的药物。它还可用作治疗干眼症的眼科药物。通过（i）使用Krapcho脱羧反应代替常规的酸水解避免不可控制的起泡，从而使不可控制的起泡变得混乱；（ii）通过使用单一有机溶剂将有机废物的产生减至最少；以及（iii）避免使用发泡剂（正辛醇，苯乙酮）和乙酸。经过这些微不足道的修饰，活性药物成分（API）的总收率≥83％，纯度极佳（≥99.89％），并且该工艺符合“绿色”化学标准，并且E因子＝ 11.5。发达的无忧商业流程可用于多千克合成瑞巴派特（1）作为关键步骤，Krapcho脱羧在DMSO中在130–140°C的温度下运行是安全的，并且通过差示扫描量热法证明是有效的热筛选研究。报告了中间体，与工艺有关的杂质和API的表征数据。有效地控制了残留物和与工艺相关的杂质。目前的工作可以扩大瑞巴派特（1）的范围和在世界范围内
• Process for preparing 2-(4-chlorobenzolamino)-3[ (1h)-quinolinon-4-yl] propionic acid
  申请人：——

  公开号：US20030087930A1

  公开（公告）日：2003-05-08

  The invention relates to a novel method for preparing 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic acid, also known as Rebamipide represented by the formula I and useful for treatment of peptic ulcer from alkyl 2-(4-chlorobenzoylamino)-2-alkoxycarbonyl-3-[2(1H)-quinolinon-4-yl]propionate represented by the formula II in the presence of a base solution for hydrolysis and decarboxylation to remove a carboxyl group.

  该发明涉及一种新型制备2-(4-氯苯甲酰氨基)-3-[2(1H)-喹诺酮-4-基]丙酸，也称为利巴韦林，其化学式如下所示，并且有助于治疗消化性溃疡，方法为在碱性溶液中利用烷基2-(4-氯苯甲酰氨基)-2-烷氧羰基-3-[2(1H)-喹诺酮-4-基]丙酸酯进行水解和脱羧反应，以去除一个羧基。
• Synthesis and Antiulcer Activity of Optical Isomers of 2-(4-Chlorobenzoylamino)-3-(2(1H)-quinolinon-4-yl)propionic Acid (Rebamipide).
  作者：Kenji OTSUBO、Seiji MORITA、Minoru UCHIDA、Katsuya YAMASAKI、Toshimi KANBE、Takefumi SHIMIZU

  DOI：10.1248/cpb.39.2906

  日期：——

  enantiomers of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid [(+/-)-1, rebamipide, OPC-12759], a new antiulcer agent that enhances mucosal resistance, were synthesized from optically active alpha-amino acid derivatives of 2(1H)-quinolinone. The key intermediates, alpha-amino acid derivatives, were prepared by asymmetric synthesis and optical resolution. The (+)-1 was about 1.7 times

  2-（4-氯苯甲酰基氨基）-3- [2（1H）-喹啉酮-4-基]丙酸[（+/-）-1，瑞巴派特，OPC-12759]的对映异构体，一种增强粘膜的新型抗溃疡药由2（1H）-喹啉酮的旋光性α-氨基酸衍生物合成抗性。通过不对称合成和光学拆分制备了关键中间体α-氨基酸衍生物。（+）-1对乙醇诱导的胃溃疡的抗溃疡活性约为（-）-异构体的1.7倍。
• 瑞巴派特的合成方法
  申请人：浙江远力健药业有限责任公司

  公开号：CN103113294B

  公开（公告）日：2016-04-27

  本发明提供了一种改进的，由2-氨基-3-（1.2-二氢-2-氧代-4-喹啉基）丙酸盐酸盐（简称氨基酸盐）通过一步反应制得瑞巴派特的制备方法，能够制得高纯度的瑞巴派特，通过将氨基酸盐在碱性条件下加入活性炭吸附脱色，在碱性醇液中反应1~4小时得成品，收率80%~95%，产品纯度达到99.5%以上。本发明提高了瑞巴派特产品的得率，产生的杂质少，对环境的污染小，降低了生产成本，适合大规模、高产量地生产方式。