Synthesis and reactivity of laquinimod, a quinoline-3-carboxamide: intramolecular transfer of the enol proton to a nitrogen atom as a plausible mechanism for ketene …

…, A Olsson, B Svensson, S Jönsson

Index: Jansson, Karl; Fristedt, Tomas; Olsson, Arne; Svensson, Bo; Joensson, Stig Journal of Organic Chemistry, 2006 , vol. 71, # 4 p. 1658 - 1667

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Citation Number: 22

Abstract

5-Chloro-N-ethyl-1, 2-dihydro-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinolinecarboxamide (laquinimod, 2) is an oral drug in clinical trials for the treatment of multiple sclerosis. The final step in the synthesis of 2 is a high-yielding aminolysis reaction of ester 1 with N-ethylaniline. An equilibrium exists between 1 and 2, and removal of formed methanol during the reaction is a prerequisite for obtaining high yields of 2 from 1. The reactivity of 1 and 2 is explained ...