AU6789887A - Imidazo``1,2-a`` quinoline derivatives, their preparation and their application in therapy - Google Patents

Abstract

1. Claims for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE Imidazo[1,2-_a]quinoline derivatives corresponding to the formula (I) see diagramm : EP0233800,P14,F1 in which X denotes hydrogen, a halogen or a (C1-4 )alkyl, (C1-4 )-alkoxy, (C1-4 )alkylthio, methylsulphonyl, amino, (C1-4 )-alkylamino, di(C1-4 )alkylamino, nitro or trifluoroalkyl group, Y denotes hydrogen, a halogen or a methyl group at position 6, 7 or 8, and R1 and R2, taken separately, each denote hydrogen or a (C1-6 )alkyl group, or alternatively R1 and R2 together form a tetramethylene, pentamethylene, 3-methyl-3-azapentamethylene or 3-oxapentamethylene chain, as well as their addition salts which are acceptable in pharmacology. 1. Claims for the Contracting States : AT, ES, GR Process for the preparation of imidazo[1,2-_a]quinoline derivatives corresponding to the formula (I) see diagramm : EP0233800,P16,F1 in which X denotes hydrogen, a halogen or a (C1-4 )alkyl, (C1-4 )-alkoxy, (C1-4 )alkylthio, methylsulphonyl, amino, (C1-4 )-alkylamino, di(C1-4 )alkylamino, nitro or trifluoroalkyl group, Y denotes hydrogen, a halogen or a methyl group at position 6, 7 or 8, and R1 and R2, taken separately, each denote hydrogen or a (C1-6 )alkyl group, or alternatively R1 and R2 together form a tetramethylene, pentamethylene, 3-methyl-3-azapentamethylene or 3-oxapentamethylene chain, which process is characterized in that the quinoline of formula (II) see diagramm : EP0233800,P16,F2 is first subjected to the action of an alpha-bromoacetophenone bearing the substituent X defined above, in the heated state in a solvent such as methylene chloride or 1,2-dichloroethane ; an ionic compound of formula (III) see diagramm : EP0233800,P16,F3 is obtained, which is cyclized in the presence of ammonium acetate, in an acidic organic solvent such as acetic or propionic acid, at a temperature of 90 degrees C, to obtain the compound of formula (IV) see diagramm : EP0233800,P16,F4 the compound obtained (IV) is reacted with glyoxylic acid in a solvent such as acetic acid at 80 degrees C ; the alpha-hydroxy acid obtained (V) see diagramm : EP0233800,P17,F1 is acetylated using acetic anhydride in the presence of pyridine, and then converted to the alpha-acetoxyacetamide see diagramm : EP0233800,P17,F2 via the imidazolide, which is prepared in situ ; the compound (VI) is deacetylated to the alpha-hydroxyacetamide (VII) see diagramm : EP0233800,P17,F3 by treatment with potassium carbonate in ethanol ; the compound (VII) is reacted with sulphonyl chloride SOCl2 in a chlorinated solvent such as dichloromethane, to obtain the chlorinated compound (VIII) see diagramm : EP0233800,P17,F4 which is reduced using Rongalite**(r) in methylene chloride to the compound (I).