Patent GB-600841-A (GB)
Title: Processes of producing substituted acridines
IPC: C07D219/12
Filed: 1945-06-18
Abstract: 2 - Methoxy - 6 - chloro - 9 - [21 : 21 - dimethyl-31-(unsymmetrical disubstituted amino) propylamino]-acrides of the general formula <FORM:0600841/IV(b)/1> wherein R and R1 represent different saturated non-tertiary hydrocarbon radicals and the sum of the carbon atoms in R and R1 does not exceed 10, are prepared by condensing 2 : 2-dimethyl-3-(unsymmetrical-disubstituted amino) propylamines of the general formula <FORM:0600841/IV(b)/2> where R and R1 have the above significance, with 2-methoxy-6 : 9-dichloroacridine.  The resulting substituted acridines may be reacted with an acid to form a salt.  In examples 1 to 7, substituted acridines of the above general formula are prepared and are converted to their hydrochloride, hydrobromide, sulphate, nitrate, phosphate, lactate or propionate salts.  In particular the preparation of 9-[21 : 21-dimethyl - 31 - (methyl - n - propylamino) - propylamino]-, 9-[21 : 21-dimethyl-31-(n-propylisopropylamino) propylamino]-, 9-[21 : 21-dimethyl - 31 - (sec - butylisoamylamino) - propylamino]-, 9-[21 : 21-dimethyl-31-(isobutylcyclopentylamino) propylamino]-, and 9-[21 : 21-dimethyl - 31 - (ethyl - 111 - methylhexylamino) - propylamino] - 2 - methoxy - 6 - chloro-acridines is described.  Diamines of the general formula <FORM:0600841/IV(b)/3> where R and R1 have the above significance, may be prepared for the above process by reducing 2 - dimethyl - 3 - (unsymmetrical - disubstituted amino) propionaldoximes of the general formula <FORM:0600841/IV(b)/4> In examples 1 to 6, diamines of the above general formula are prepared and in particular 2 : 2-dimethyl - 3 - (methyl - n - propylamino)-, 2 : 2-dimethyl - 3 - (n - propylisopropylamino)-, 2 : 2 - dimethyl - 3 - (sec. - butylisoamylamino)-, 2 : 2-dimethyl-3-(isobutylcyclopentylamino)-, and 2 : 2-dimethyl-3-(ethyl-11-methylhexylamino)-propylamines. Aminopropionaldoximes of the general formula <FORM:0600841/IV(b)/5> where R and R1 have the above significance, may be prepared for the above process by reacting 2 : 2-dimethyl-3-(dialkyl-amino)propionaldehydes of the general formula <FORM:0600841/IV(b)/6> with hydroxyl ammonium chloride.  In examples 1 to 6, oximes of the above general formula are prepared and in particular 2 : 2-dimethyl - 3 - (methyl - n - propylamino)-, 2 : 2 - dimethyl - 3 - (n - propyl - isopropylamino)-, 2 : 2-dimethyl-3-(sec.-butylisoamylamino)-, 2 : 2-dimethyl-3-(isobutylcyclopentylamino)-, and 2 : 2-dimethyl-3-(ethyl-11 - methylhexylamino) - propionaldoximes. Aminopropionaldehydes of the general formula <FORM:0600841/IV(b)/7> where R and R1 have the above significance, may be prepared for the above process by condensing a secondary amine of the formula <FORM:0600841/IV(b)/8> or its hydrochloride with isobutyraldehyde and paraformaldehyde. In examples 1 to 6, aminoaldehydes of the above general formula are prepared and in particular 2 : 2-dimethyl-3-(methyl - n - propylamino)-, 2 : 2-dimethyl-3-(n - propylisopropylamino)-, 2 : 2 - dimethyl-3-(sec. - butylisoamylamino)-, 2 : 2 - dimethyl-3-(isobutylcyclopentylamino)-, and 2 : 2-dimethyl - 3 - (ethyl - 11 - methylhexylamino)-propionaldehydes.  Secondary amines of the general formula <FORM:0600841/IV(b)/9> where R and R1 have the above significance, are prepared by reacting a primary amine containing one desired R or R1 substituent with hydrogen and an aldehyde or ketone containing the carbon skeleton of the other desired R or R1 substituent under pressure and in the presence of a hydrogenation catalyst such as Raney nickel.  In examples 2 to 5, n-propylisopropylamine is prepared from n-propylamine and acetone, sec-butylisoamylamine from methylethylketone and isoamylamine, isobutylcyclopentylamine from cyclopentanone and isobutylamine and ethyl-1-methylhexylamine from ethylamine and methyl-n-amyl ketone.ALSO:2-Methoxy-6-chloro-9-[21 : 21-dimethyl-31-(unsymmetrical disubstituted amino) propylamino]-acridines of the general formula <FORM:0600841/IV (c)/1> wherein R and R1 represent different saturated non-tertiary hydrocarbon radicals and the sum of the carbon atoms in R and R1 does not exceed 10, are prepared by condensing 2 : 2-dimethyl - 3 - (unsymmetrical - disubstituted amino) propylamines of the general formula <FORM:0600841/IV (c)/2> where R and R1 have the above significance, with 2-methoxy-6 : 9-dichloroacridine.  The resulting substituted acridines may be reacted with an acid to form a salt.  In examples (1) to (7), substituted acridines of the above general formula are prepared and are converted to their hydrochloride, hydrobromide, sulphate, nitrate phosphate, lactate or propionate salts.  In particular, the preparation of 9-[21 : 21-dimethyl - 31 - (methyl - n - propylamino) - propyl - amino]-, 9 - [21 : 21-dimethyl-31-(n-propyliso - propylamino) - propylamino]-, 9 - [21 : 21 - di - methyl - 31 - (sec - butylisoamylamino) - propyl - amino]-9-[21 : 21-dimethyl-31-(isobutylcyclopentylamino) - propylamino]-, and 9 - [21 : 21 - dimethyl - 31 - (ethyl - 111 - methylhexylamino) - propylamino]-2-methoxy-6-chloro-acridines is described.