Patent GB-495783-A (GB)
Title: New therapeutically valuable quinoline derivatives
IPC: C07D215/38
Filed: 1937-05-18
Abstract: New trypanocidal agents of the general formula <FORM:0495783/IV/1> where Ar = phenylene or substituted phenylene, Alk = alkyl, Ac = an acid residue, and where one X = acylamino, and the other = <FORM:0495783/IV/2> Z1 being hydroxyalkyl and Z2 being hydrogen or alkyl, are prepared either by interacting a p - acylaminobenzaldehyde with an alkyl-6-(N - hydroxyalkylamino) - quinaldinium salt or with an alkyl-6-(N-alkyl-N-hydroxyalkylamino)-quinaldinium salt or by interacting a 6-acylaminoquinaldinium salt with a p-(N - hydroxyalkylamino) - benzaldehyde or with a p-(N-alkyl-N-hydroxyalkylamino)benzaldehyde.  Reaction is conveniently effected by refluxing the substances dissolved in a suitable solvent, e.g. methanol or ethanol, with the addition of a small proportion of a secondary amine (e.g. piperidine or diethylamine).  Examples describe the preparation of (1) Methyl 2-(41-acetylaminostyryl)-6-(N-b -hydroxyethylamino) - quinolinium chloride by treating with lime the corresponding sulphate obtained from methyl 6-(N-b -hydroxyethylamino)-quinaldinium methyl sulphate (prepared by condensing 6-aminoquinaldine with ethylene chlorhydrin and treating the product with dimethyl sulphate) and p-acetylaminobenzaldehyde; (2) methyl 2-(41-acetylaminostyryl) - 6 - (N - g  - hydroxypropylamino)-quinolinium chloride by refluxing with silver chloride the corresponding iodide, obtained by treating 6-(N-g -hydroxypropylamino)-quinaldinium iodide (prepared from 6-aminoquinaldine and trimethylene chlorhydrin, followed by methyl iodide) with p-acetylaminobenzaldehyde; (3) similar methods are employed to those of examples (1) and (2) with acetylaminobenzaldehydes which are substituted in the nucleus by methyl, methoxy or chlorine; (4) Methyl-2-(41-N-b -hydroxy-ethylaminostyryl) - 6 - acetylamino - quinolinium methyl sulphate is prepared from p-(N-b -hydroxyethylamino) - benzaldehyde and methyl - 6 - acetylamino - quinaldinium methyl sulphate.  Other aldehydes which may be employed are: 3-methyl-4-N-b -hydroxyethylaminobenzaldehyde; p - (N - g -hydroxypropylamino) - benzaldehyde; 3-methyl - 4 - N - g  - hydroxypropylaminobenzaldehyde; p-(N - methyl - N - b  - hydroxyethylamino) - benzaldehyde; p-(N-ethyl-N-b -hydroxyethylamino) - benzaldehyde.  These aldehydes may be prepared by suitable adaptation of the process described in German Specification 105,105; (5) methyl 2-(41-acetylaminostyryl) - 6 - (N - methyl - N - b  - hydroxyethylamino) - quinolinium chloride from the corresponding iodide obtained by treating 6 - (N - methyl - N - b  - hydroxyethylamino)-quinaldinium iodide (prepared by condensing 6-aminoquinaldine with ethylenechlorhydrin and treating the product with methyl iodide and sodium carbonate) with p-acetylaminobenzaldehyde; (6) methyl 2-(41-N - ethyl-N-b  - hydroxyethylaminostyryl) - 6 - n - caproylamino-quinolinium methyl sulphate is prepared from 6 - n - caproylaminoquinaldinium methyl sulphate and p-(N-ethyl-N-b -hydroxyethylamino) - benzaldehyde. Similarly methyl 2 - (31 - methyl - 41 - N - b  - hydroxyethylaminostyryl) - 6 - n - caproylaminoquinolinium methyl sulphate may be prepared; (7) methyl-2 - (41 - acetylaminostyryl) - 6 - (N - ethyl - N-g  - hydroxypropylaminoquinolinium chloride from the corresponding iodide obtained by treating methyl - 6 - (N - ethyl - N - g  - hydroxypropylamino) quinaldinium iodide (prepared by treating methyl - 6 - (N-g -hydroxypropylaminoquinaldinium iodide with ethyl iodide and sodium carbonate), with p-acetylaminobenzaldehyde. Similarly methyl 2-(41-acetylaminostyryl) - 6 - (N - methyl - N - g - hydroxypropylamino) - quinolinium iodide and chloride, and methyl 2-(41-propionylaminostyryl)-6-(N-g -hydroxypropylamino) -quinolinium iodide and chloride may be made.