111911-87-6

Basic information

• Product Name: REBAMIPIDE
• Synonyms: REBAPIMIDE;(+-)-alpha-((4-chlorobenzoyl)amino)-1,2-dihydro-2-oxo-4-quinolinepropanicaci;alpha-((4-chlorobenzoyl)amino)-1,2-dihydro-2-oxo-4-quinolinepropanicaci(+;REBAMIPIDE, 99+%;RebaMipide(OPC-12759);Alpha-[(4-Chlorobenzoyl)Amino]-1,2-Dihydro-2-Oxo-4-Quinolinepropanoicacid
• CAS NO: 111911-87-6
• Molecular Formula: C19H15ClN2O4
• Molecular Weight: 370.79
• EINECS: 1806241-263-5
• Product Categories: APIs;Chiral Compound
• Mol File: 111911-87-6.mol
• Article Data: 13

Chemical Properties

• Boiling Point: 695°C at 760 mmHg
• Flash Point: 374.1°C
• Appearance: /
• Density: 1.394g/cm³
• Vapor Pressure: 2.83E-20mmHg at 25°C
• Refractive Index: 1.634
• CAS DataBase Reference: REBAMIPIDE(CAS DataBase Reference)
• NIST Chemistry Reference: REBAMIPIDE(111911-87-6)
• EPA Substance Registry System: REBAMIPIDE(111911-87-6)

Safety Data

• Hazardous Substances Data: 111911-87-6(Hazardous Substances Data)

Usage

Description

Rebamipide is a quinolinone derivative introduced as a novel antiulcer agent. It acts as a local gastric mucosa prostaglandin inducer and is reported to be effective in both the healing and prevention of recurrence of gastric ulcer.

Originator

Otsuka (Japan)

Brand name

Mucosta

InChI:InChI=1/C19H15ClN2O4/c20-13-7-5-11(6-8-13)18(24)22-16(19(25)26)9-12-10-17(23)21-15-4-2-1-3-14(12)15/h1-8,10,16H,9H2,(H,21,23)(H,22,24)(H,25,26)/t16-/m1/s1

Upstream product

• 122-01-0 4-chloro-benzoyl chloride 
• 4876-14-6 2-amino-3-<2-(1H)-quinolinon-4-yl>propionic acid hydrochloride 
• 914769-50-9 2-amino-3-[2(1H)-quinolinone-4-yl]propionic acid dihydrochloride dihydrate 
• 137433-08-0 (+)-2-amino-3-<2(1H)-quinolinon-4-yl>propionic acid hydrochloride 
• 137433-09-1 (-)-2-amino-3-<2(1H)-quinolinon-4-yl>propionic acid hydrochloride 
• 137433-07-9 (-)-2-chloro-4-<(2',5'-dimethoxy-6'-isopropyl-3',6'-dihydropyrazin-3'-yl)methyl>quinoline 
• 137354-55-3 (+)-2-chloro-4-<(2',5'-dimethoxy-6'-isopropyl-3',6'-dihydropyrazin-3'-yl)methyl>quinoline 
• 137354-57-5 methyl (-)-2-amino-3-(2-chloroquinolin-4-yl)propionate 
• 137433-11-5 methyl 2-amino-3-<2(1H)-quinolinon-4-yl>propionate, salt with D-(-)-mandelic acid 
• 4876-10-2 4-bromomethyl-2(1H)-quinolinone 
• 137354-56-4 methyl (+)-(2S)-amino-3-<2-chloroquinolin-4-yl>propionate 
• 137433-13-7 methyl 2-amino-3-<2(1H)-quinolinon-4-yl>propionate, salt with D-(-)-mandelic acid 
• 59893-99-1 N-(p-chlorobenzoyl)-glycine methyl ester 
• 62-53-3 aniline 

Downstream Products

• 90098-38-7 methyl 2-(4-chlorobenzoylamino)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionate 

Relevant articles and documents

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

Rebamipide (1) is a superior drug compared to existing drugs for use in healing of peptic ulcers, gastrointestinal bleeding, and dyspepsia. It is also useful as an ophthalmic drug for the treatment of dry eye syndrome. Process intensification for its synthesis was achieved by (i) averting 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 excellent purity (≥99.89%), and the process meets the metrics of "green" chemistry with an E-factor = 11.5. The developed hassle-free commercial process is viable for multi-kilogram synthesis of Rebamipide (1) as the key step, Krapcho decarboxylation is safe to run at 130-140 °C in DMSO, and it was proved to be effective by differential scanning calorimetry thermal screening studies. The characterization data of intermediates, process-related impurities, and API are reported. The carryover and process-related impurities were controlled efficiently. The present work can enhance the scope and worldwide adoptability of Rebamipide (1), which is currently limited to Asian countries.

New process for synthesizing rebamipide

The invention discloses a novel process for synthesizing rebamipide. The novel process comprises the following steps: adopting glycine methyl ester as a starting raw material, then performing amidation and chlorination to obtain chloroimide intermediate, enabling the chloroimide intermediate to react with bromomethylquinolone, and hydrolyzing to obtain the rebamipide. The novel process has the advantages that the starting raw material is low in price and easy to obtain, the reaction yield is high, the industrialization is easy to realize and the like.

Green and efficient preparation method of rebamipide

The invention belongs to the technical field of medical synthesis and in particular relates to a green and efficient preparation method of rebamipide. The synthesis method provided by the invention has a green and simple route and the price of raw materials is low, so that industrial production is easy to realize. The invention further discloses a novel method for preparing aniline from benzoic acid.