Patent GB-605393-A (GB)
Title: Substituted acridines and intermediates therefor, and process of making them
IPC: C07D219/12
Filed: 1945-12-21
Abstract: 1 - Ethyl - 2 - methyl - 3 - (substituted amino) - propylamines of the general formula <FORM:0605393/IV(b)/1> wherein R and R1 represent saturated primary or secondary hydrocarbon radicals containing from 1 to 7 carbon atoms and may be the same or different, are prepared by reducing an oxime of the general formula <FORM:0605393/IV(b)/2> where R and R1 have the significance indicated above.  The substituted propylamine are condensed with 2-methoxy-6 : 9-dichloroacridine to produce a substituted acridine of the general formula <FORM:0605393/IV(b)/3> where R and R1 have the significance already indicated.  In examples: (1) 1-ethyl-2-methyl-3-(diethylamino)-propylamine is prepared by reducing 1 - ethyl - 2 - methyl - 3 - (diethylamino) propanoneoxime-1 with hydrogen in the presence of Raney nickel catalyst, and is condensed with 2-methoxy-6 : 9-dichloro-acridine to yield 2-methoxy-6-chloro-9[11-ethyl-21-methyl-31 -(diethylamino) propylamino]-acridine, which may be converted to its dihydrochloride; (2), (3), (4), (5) and (6) by a similar method 1-ethyl-2-methyl-3-(dimethylamino)-, 1-ethyl-2-methyl-3-(dicyclopentylamino)-, 1 - ethyl - 2 - methyl - 3 - (methyl - 11 - methylhexylamino)-, 1 - ethyl - 2 - methyl - 3 - (n - propyl - sec - butylamino)- and 1-ethyl - 2 - methyl - 3 - (sec. - butylisoamylamino) - propylamines, and their corresponding 9-substituted - 2 - methoxy - 6 - chloro-acridines, which are converted to the corresponding dihydrochlorides, are prepared; (8) the substituted acridines prepared in the previous examples are converted into the corresponding dihydrobromide, sulphate, nitrate, phosphate, lactate and propionate salts. 1-Ethyl-2-methyl-3-(substituted amino)-propanoneoximes-1 of the general formula <FORM:0605393/IV(b)/4> where R and R1 have the significance already indicated, are prepared by reacting a propanone of the general formula <FORM:0605393/IV(b)/5> with hydroxylamine hydrochloride.  In examples (1) to (6), the following are prepared: 1 - ethyl - 2 - methyl - 3 - (diethylamino)-, 1-ethyl-2-methyl-3-(dimethylamino)-, 1-ethyl-2-methyl - 3 - (dicyclopentylamino)-, 1 - ethyl - 2 - methyl - 3 - (methyl - 11 - methylhexylamino)-, 1-ethyl-2-methyl-3-(n-propyl-sec.-butylamino)-and 1 - ethyl - 2 - methyl - 3 - (sec. - butylisoamyl-amino)-propanoneoximes-1.  1 - Ethyl - 2 - methyl - 3 - (substituted amino)-propanones-1 of the general formula <FORM:0605393/IV(b)/6> where R and R1 have the significance already indicated, are prepared by refluxing the hydrochloride of an amine of the general formula <FORM:0605393/IV(b)/7> with diethyl ketone and paraformaldehyde in a solvent such as absolute alcohol.  In examples (1) to (6), the following are prepared: 1-ethyl-2-methyl-3-(diethylamino)-, 1-ethyl-2-methyl-3-(dimethylamino)-, 1-ethyl-2-methyl-3-(dicyclopentylamino)-, p 1-ethyl-2-methyl-3-(methyl-11-methylhexylamino)-, 1 - ethyl - 2 - methyl - 3 - (n - propyl-sec.-butylamino)- and 1-ethyl-2-methyl-3 - (sec. - butylisoamylamino) - propanones - 1. Secondary amines of the general formula <FORM:0605393/IV(b)/8> where R and R1 have the significance already indicated, are prepared by reacting a primary amine containing one of the substituents R or R1 with hydrogen and an aldehyde or ketone having the carbon skeleton of the other R or R1 substituent, in the presence of a catalyst such as Raney nickel, and may be converted to their hydrochlorides.  In example (6), sec.-butylisoamylamine is prepared by treating a mixture of methyl - ethyl - ketone, isoamylamine and Raney nickel with hydrogen under pressure.ALSO:Substituted acridine dyes of the general formula <FORM:0605393/IV (c)/1> wherein R and R1 represent saturated primary or secondary hydrocarbon radicals containing from 1 to 7 carbon atoms and may be the same or different, are prepared by condensing 2-methoxy-6 : 9-dichloroacridine with an amine of the general formula <FORM:0605393/IV (c)/2> where R and R1 have the above significance. In the examples, substituted acridines are prepared wherein R and R1 are both methyl, ethyl and cyclopentyl groups and wherein R and R1 represent methyl and 1-methylhexyl, n-propyl and see.-butyl, and sec.-butyl and isoamyl.  The substituted acridines may be converted to their dihydrochloride, dihydrobromide, sulphate, nitrate, phosphate, lactate and propionate salts.