Patent GB-921315-A (GB)
Title: The manufacture of 8-aminoalkylamino quinoline derivatives
Inventor: BARRETT PAUL ANTHONY
IPC: C07D215/40
Filed: 1958-03-31
Abstract: 8-Aminoalkylaminoquinoline derivatives of the general formula <FORM:0921315/IV(a)/1> are prepared by reducing compounds of the general formula <FORM:0921315/IV(a)/2> with lithium aluminium hydride or other complex metal hydride. In the foregoing formulae X represents -CH2.Z-, -Z.CH2- or -CH2.Z.CH2-, Y represents respectively -CO.Z-, -Z.CO- or -CO.Z.CO-, Z represents a straight or branched bivalent aliphatic hydrocarbon radical, NB is the same as NB1 or is the product of the reduction of NB1 accompanying the reduction of Y, and NB1 represents a primary, secondary or tertiary amino group, and one or more carbon atoms of the quinolyl-8 residue may optionally bear a substituent.  The process is applicable particularly to the preparation of compounds of the general formula <FORM:0921315/IV(a)/3> (wherein X1 is the same as X except that it must contain 3-7 carbon atoms, R1 represents a C1-4 alkoxy group, R2 a hydrogen atom or a C1-4 alkoxy group and R3 a hydrogen atom, a methyl group or a C2-4 alkyl group in which each carbon atom other than that adjacent to the piperazine ring may carry a hydroxy group) by reduction of compounds of the general formula <FORM:0921315/IV(a)/4> (wherein Y1 is the same as Y except that it must contain 3-7 carbon atoms, and R4 is the same as R3 or may also represent an alkoxycarbonyl group in which the alkoxy portion contains 1-4 carbon atoms (reduced to methyl), a C1-4 alkanoyl group (reduced to alkyl) or an alkoxycarbonylalkyl group in which the alkoxy portion contains 1-4 carbon atoms and the alkylene portion 1-3 carbon atoms (reduced to hydroxymethylalkyl). Acid addition salts of the products are described.  Monoamides of the general formula (IV) above are prepared as follows: (a) when Y1 is -CO.Z- and R4 is other than acyl, by reaction of N-R4-piperazines with 5-R2-6-R1-8-(Halogen-Z-CONH)-quinolines, the preparation of some of which from the corresponding 8-aminoquinolines and Halogen-Z-CO-Halogen1 is also described; (b) when Y1 is -Z.CO-, by reacting the appropriate 8-aminoquinolines with N-(Halogen.Z.CO)-N1-R4-piperazines.  6 - Methoxy - 8-(3-N1-acetylpiperazino-1-oxopropylamino)-quinoline is prepared by refluxing the corresponding N1-unsubstituted compound with acetic anhydride in benzene.  Diamides of the general formula (II) above (Y = -CO.Z.CO-) are prepared by reacting the anhydride of the acid Z(COOH)2 with the amine HNB1 and reacting the product with the appropriate 8-aminoquinoline in the presence of N,N1-dicyclohexylcarbodiimide. 6-Methoxy-8-(4-N1-ethoxycarbonylpiperazino-1, 4-dioxobutylamino)-quinoline is prepared by reacting 6-methoxy-8-succinylaminoquinoline with N - ethoxycarbonylpiperazine in the presence of N,N1-dicyclohexylcarbodiimide. N-(8-Quinolyl)-succinamide is prepared by warming 8-aminoquinoline with 3-methoxycarbonylpropionyl chloride and sodium carbonate in acetone to form 8-(3-methoxycarbonylpropionamido)-quinoline, and stirring this with aqueous ammonia.  N-2-Methoxyethyl-, N-4-hydroxybutyl- and N-2-ethoxyethyl-piperazine are prepared by alkaline hydrolysis of the corresponding N1-ethoxycarbonyl compounds, obtained by condensing N-ethoxycarbonylpiperazine with the appropriate substituted alkyl chlorides. N-(2,3-Dihydroxypropyl)-piperazine is similarly prepared from N-ethoxycarbonyl-N1-(2,3-hydroxypropyl)-piperazine, obtained by reacting N-ethoxycarbonylpiperazine with glycidol. N-Ethoxycarbonylmethylpiperazine is prepared by refluxing piperazine hexahydrate with ethyl chloroacetate in ethanol containing hydrogen chloride.  Specifications 826,811, 834,300, 878,461, 921,316 and 921,318 are referred to.