637027-41-9Relevant articles and documents
An Efficient Method for the Synthesis of Laquinimod
Huang, Yanyan,Feng, Ying,Gao, Wensheng,Zhang, Chao,Chen, Ligong
, p. 437 - 440 (2016/04/19)
Laquinimod, 5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N- phenyl-3-quinoline carboxamide, is an oral drug in clinical trials for the treatment of multiple sclerosis. An efficient synthetic method for laquinimod from 2-amino-6-chlorobenzoic acid via four steps was established. The overall yield of laquinimod is up to 82% as compared with 70% reported in literature. It has also been demonstrated that green reagent dimethyl carbonate is not suitable for the N-methylation of 5-chloroisatoic anhydride owing to the ring-cleavage reaction induced by the generated methanol. The ring-cleavage by-products were isolated and characterized by 1H-NMR and 13C-NMR. In addition, in the study of laquinimod derivatives, we found that 5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinoline carboxamide (laquinimod) was obtained in much higher yield than 7-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinoline carboxamide under the same reaction conditions, and it is possibly attributed to a neighboring group effect.
METHOD FOR MANUFACTURING OF QUINOLINE-3-CARBOXAMIDES
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Page/Page column 13, (2012/02/01)
A method for preparing a compound of formula (I) by reacting the appropriate alkyl ester and an aniline derivative, in a refluxing mixture containing an aliphatic solvent or a mixture of aliphatic solvents having a boiling point in the range of 68-191 °C; condensing vapors of the refluxing mixture; treating the condensed vapors with an alcohol scavenging agent or a mixture of alcohol scavenging agents; and returning the condensed vapors back to the reaction mixture.
Development of a practical and reliable synthesis of laquinimod
Wennerberg, Johan,Bjoerk, Anders,Fristedt, Tomas,Granquis, Bo,Jansson, Karl,Thuvesson, Ingela
, p. 674 - 680 (2012/12/29)
Laquinimod(5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl- 3-quinoline carboxamide) is a drug candidate for treatment of Multiple Sclerosis. A short and industrially feasible process for the preparation of laquinimod starting from 2-amino-6-chlorobenzoic acid, in essentially four steps, is discussed. The key step is a novel reaction in which a methyl ester is converted to an amide in very high yield and with excellent purity. The present article elucidates the scale-up process along with safety aspects and the impurity profiles of the intermediates and product. Initial laboratory conditions are described as well as the changes made on transfer to pilot-plant scale.