Patent GB-602332-A (GB)
Title: Improvement in substituted quinolines and their intermediates, and process of makingthem
IPC: C07D215/40
Filed: 1945-03-06
Abstract: Substituted quinolines of the general formula <FORM:0602332/IV(b)/1> , wherein R represents hydrogen or an alkyl radical containing not more than two carbon atoms, R1 represents an alkyl, cycloalkyl or alkenyl radical containing from one to ten carbon atoms and R2 represents an alkyl, cycloalkyl or alkenyl radical containing from three to ten carbon atoms, are prepared by condensing 6-methoxy-8-aminoquinoline or a hydrohalide thereof with a haloamine of the general formula <FORM:0602332/IV(b)/2> , wherein R, R1 and R2 have the above significance and Ha represents chlorine or bromine, and their hydrohalides, e.g. by refluxing a solution of the reactants for a period of from one to three days.  In examples (1) to (20), substituted quinolines of the above general formula are prepared and are converted into their corresponding hydrochloride, hydrobromide, sulphate, nitrate, phosphate, lactate and propionate salts.  The preparation of the following compounds is described; 8-[21-hydroxy-31-(isobutyl - sec - butylamino) - propylamino]-, 8-[21 - hydroxy - 31 - (diisobutylamino) - propyl - amino]-, 8 - [21 - hydroxy - 31 - (methyl - n - propylamino) - propylamino]-, 8 - [21 - hydroxy - 31 - (diollylamino) - propylamino]-, 8 - [21 - hydroxy - 31 - (di - n - propylamino) - propylamino]-, 8 - [21 - hydroxy - 31 - (di - n - butylamino) - propylamino]-, 8 - [21 - hydroxy - 31 - (di - n - amylamino) - propyl - amino]-, 8 - [21 - hydroxy - 31 - (diisoamylamino) - propylamino]-, 8 - [21 - hydroxy - 31 - (ethylisopropylamino) - propylamino]-, 8 - [21 - hydroxy - 31 - (isopropyl-isobutylamino)-propylamino]-, 8-[21-hydroxy - 31 - (isobutyl - 111 - methylbutylamono)-propylamino]-, 8-[21-hydroxy-31-(n - butyl - 111-methylbutylamino) - propylamino]-, 8 - [21-hydroxy-31-(n-butyl-111-methylpropylamino) - propylamino]-, 8 - [21 - hydroxy -31 - (isobutyl - n - butylamino)-propylamino]-, 8-[21-hydroxy-31-(n-butyl-isopropylamino) -propylamino]-, 8-[21-hydroxy - 31 - (isobutyl - cyclopentylamino) - pro - pylamino]-, 8 - [21-hydroxy-21-methyl-31-(iso - butyl - sec. - butylamino) - propylamino]-, 8 - [21-hydroxy - 21 - methyl - 31 - (diisobutylamino) - propylamino]-, 8-[21-hydroxy-21-methyl-31-(ethylisopropylamino] -, 8-[21-hydroxy-21-methyl-(di-n-propylamino]-, 8-[21-hydroxy-21-methyl-31 - (isopropylisobutylamino) - propylamino]-, 8-[21-hydroxy-21-methyl-31-(di-n-butylamino) - propylamino]-, 8 - [21 - hydroxy - 21 - methyl - 31 - (n-butyl-isobutylamino)-propylamino]-, 8-[21-hydroxy-21-methyl-31-(di-n-amylamino) -propylamino]-, 8 - [21 - hydroxy - 21 - methyl - 31 - (diisooamylamino)-propylamino]-, 8-[21-hydroxy21-methyl-31-(methyl-n-propylamino) -propylamino]- and 8 - [21 - hydroxy - 21 - methyl - 31 - (diallylamino) - propylamino] - 6 - methoxyquinolines.  Haloamines of the general formula <FORM:0602332/IV(b)/3> , wherein R, R1, R2 and Ha have the above significance, may be prepared for the above reaction by reacting a secondary amine <FORM:0602332/IV(b)/4> with 1-chloro-2 : 3-epoxypropane or 1-chloro-2-methyl-2 : 3-epoxypropane or the corresponding bromo derivatives.  In examples (1) to (18), haloamines of the above general formula are prepared and in particular 3-(isobutyl-sec.-butylamino)-, 3 - (diisobutylamino)-, 3 - (methyl-n - propylamino)-, 3 - (diallylamino)-, 3 - (di - n - propylamino)-, 3 - (di - n - butylamino)-, 3 - (di - n - amylamino)-, 3 - (diisoamylamino)-, 3 - (ethylisopropylamino)-, 3 - (isopropyl - isobutylamino)-, 3-(isobutyl-11-methylbutylamino)-, 3-(n-butyl-11-methyl-butylamino)-, 3-(n-butyl-11-methylpropylamino)-, 3 - (isobutyl - n - butylamino)-, 3 - (n-butyl-isopropylamino)- and 3-(isobutylcyclopentylamino) - 2 - hydroxy - propylchlorides, 3 - (isobutyl - sec. - butylamino)-, 3 - (diisobutylamino)-, 3 - (ethyl - isopropylamino)-, 3 - (di - n - propylamino)-, 3 - (isopropyl - isobutylamino)-, 3 - (di - n - butylamino)-, 3 - (n - butyl - isobutyl - amino)-, 3 - (di - n - amylamino)-, 3 - (diisoamyl - amino)-, 3 - (methyl - n - propylamino)- and 3 - (diallylamino) - 2 - hydroxy - 2 - methyl - propyl - chlorides and their corresponding bromides.  Secondary amines of the general formula <FORM:0602332/IV(b)/5> , where R1 and R2 have the above significance, are prepared by reacting a primary amine containing one of the desired R1 or R2 substituents with hydrogen and an aldehyde or ketone having the carbon skeleton of the other desired R1 or R2 substituent in the presence of a hydrogenation catalyst such as Raney nickel or Adams' platinum oxide.  In examples (1) and (9) to (16), the following secondary amines are prepared: isobutyl-sec.-butylamine, ethylisopropylamine, isopropyl - isobutylamine, isobutyl - 1 - methylbutylamine, n - butyl - 1 - methylbutylamine, n - butyl - 1 - methylpropylamine, isobutyl-n-butylamine, n-butylisopropylamine and isobutylcyclopentylamine.