111911-87-6Relevant 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
Babu, Prashanth Kumar,Bodireddy, Mohan Reddy,Puttaraju, Reshma Choudlu,Vagare, Dnyaneshwar,Nimmakayala, Raghu,Surineni, Naresh,Gajula, Madhusudana Rao,Kumar, Pramod
, p. 773 - 779 (2018)
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
-
Paragraph 0013; 0029; 0036-0037; 0038; 0045-0046, (2020/12/30)
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.
A synthesis process of fluorinated
-
, (2018/07/30)
The present invention discloses a process for synthesizing a fluorinated, the specific synthetic process are as follows: ammonia added in a reaction vessel, then drip to the wherein the dripped into the 4 - chlorobenzene chloride, to obtain 4 - chlorobenzene formyl ammonia; format after the reaction will be carried out with the formic acid reaction product 1; the product 1, to carry out addition reaction product 2; then the product 2 with chloro after 4 - chlorobenzene formyl ammonia reaction to obtain the product 3; the product 3 added in a reaction vessel, then adding the mass fraction is 60% sulfuric acid solution, heating to 80 °C stirring reaction 3 h, to obtain the product 2 - (4 - chlorophenyl formamido) - 3 - [2 (1 H) - quinolinone - 4] propionic acid. In the process of synthesis of the present invention through the form reaction, nucleophilic addition and the substitution reaction preparation, the production cost is low, and a high yield of product, synthetic condition is simple, can be suitable for large-scale production.
