Patent GB-354352-A (GB)
Title: Process for the manufacture of n-substituted 5 : 6-dialkoxy-8-amino-quinolines
Filed: 1930-05-02
Abstract: 8-Aminoalkylamino - 5 : 6 - dialkoxyquinolines are prepared by introducing an aminoalkyl group, which may be interrupted by nitrogen, oxygen or sulphur, into the amino group of 5 : 6-dialkoxy-8-aminoquinolines (see Specification 351,068) by the processes of Specifications 267,169,282,453,286,087 and 301,401, [all in Class 2 (iii), Dyes &c.].  The aminoalkylation may be effected by treatment with esters of amino- or alkylamino-alkyl alcohols or with derivatives thereof such as halogenalkylphthalimides, the latter then being decomposed.  The aminoalkyl group may also be introduced in stages, e.g. by treating first with an alkylene dihalide, alkylene oxide or halogenated alcohol and converting the products with amines etc in the usual manner.  Instead of 5 : 6-dialkoxy-8-aminoquinolines, the starting material may comprise an intermediate compound which is convertible into the desired final product.  Thus it may comprise (1) 8-aminoquinolines, or intermediate products therefor, which contain substituents in the 5- and/or 6-positions or the corresponding positions of the intermediate products, the said substituents being convertible into alkoxy groups; such substituents are hydroxy, amino and nitro groups; (2) 8-aminoquinoline or 5- or 6-alkoxy-8-aminoquinolines, the product after introduction of the aminoalkyl group being then converted into the 5 : 6-dialkoxy compounds; (3) a quinoline starting material containing in the 8-position, or an intermediate product containing in the corresponding position, a substituent convertible into the substituted amino group, e.g. a halogen or nitro group.  The products possess therapeutic properties.  Examples are given of (1) the treatment of 5 : 6-dimethoxy-8-aminoquinoline with 2-chloro-6-diethylaminohexane, a -diethylamino-a -bromopentane, the p-toluenesulphonic ester of 4-diethylamino-1-methyl-1-oxybutane followed by saponification, a - (diethylaminoethyl-ethylamino)-b -methyl-g -chlorobutane, 1 - diethylamino-2-methylbutylene-3 : 4-oxide, b -diethylamino-b 1-chlorodiethyl ether, b -diethylamino-b 1-chlorodiethyl thioether, 1-dimethylamino-2-cyclohexyl bromide, and N- (o -chloroethyl)- piperidine; (2) the interaction of 5-methoxy-6-ethoxy-8-aminoquinoline with 2-bromo-5-diethylamino-pentane; (3) the production of 5 : 6-dimethoxy-8-allylaminoquinoline from 5 : 6-dimethoxy-8-aminoquinoline and allyl bromide, treatment with hydrobromic acid to form the double bond addition product and then with diethylamine to give 5 : 6-dimethoxy-8- (diethylamino-n-propylamino)- quinoline; (4) the preparation of 5 - nitro-6-methoxy-8-(a -diethylamino-d -methyl-d -butylamino) - quinoline by interaction of 5 : 8-dinitro-6-methoxyquinoline with 2-amino-5-diethylaminopentane followed by boiling with concentrated hydrochloric acid, by interaction of 5-nitro-6-methoxy-8-aminoquinoline with 2-bromo-5-diethylamino-pentane, by interaction of 5-nitro-6-methoxy-8-bromoquinoline with 2-amino-5-diethylaminopentane, or by nitration of 6-methoxy-8- (a -diethylamino-d -methyl-d -butyl amino)- quinoline; reduction of the product yields the 5-amino compound, whose acetyl derivative is described; the same 5-amino compound is also obtained by coupling diazotized aniline with a -diethylamino-d - (6-methoxy-8-quinolylamino)- pentane and reducing; from the 5-amino compound, the corresponding 5-methoxy body is prepared by treatment with sodium nitrite to form a compound of the formula- <FORM:0354352/IV/1> converting the diazonium group into hydroxyl by boiling with sulphuric acid, methylating the product with dimethyl sulphate and splitting off the nitroso group by reduction with zinc dust; (5) the formation of 2-methyl-5-isopropyloxy-6-methoxy-8-bis-(diethylaminoethyl) - aminoquinoline from 1-isopropyloxy-2 - methoxy - 4-bis - (diethylaminoethyl)-amino-5-aminobenzene and paraldehyde; (6) the treatment of 5 : 6-dimethoxy-8-aminoquinoline with ethylene oxide and the interaction of the product first with thionyl chloride and then with diethylamine to produce 5 : 6-dimethoxy-8-diethylaminoethylaminoquinoline; (7) the combination of 4 : 5-dinitroveratrol with diethylaminoethylaminoethane, reduction of the nitro group of the resulting 1-(diethylaminoethyl-ethylamino)-2-nitro-4 : 5-dimeth - oxybenzene, and treatment of the product with glycerine, nitrobenzene and sulphuric acid to give 5 : 6-dimethoxy-8-(ethyl-diethylaminoethyl)-quinoline. 2-Amino-5-diethylaminopentane is prepared by converting a -diethylamino-d -pentanone into the oxime and reducing the latter with sodium amalgam.  5 : 8-Dinitro-6-methoxyquinoline is obtained by nitrating 6-methoxy-8-nitroquinoline. 5-Nitro-6-methoxy-8-aminoquinoline results when N-acetyl-6-methoxy-8-aminoquinoline is nitrated and the acetyl group then split off.  5-Nitro-6-methoxy-8-bromoquinoline is obtained by converting 6-methoxy-8-aminoquinoline into the 8-bromo compound by Sandmeyer's reaction and nitrating the product.  1-Isopropyloxy - 2 - methoxy - 4 - bis - (diethylaminoethyl)-amino-5-aminobenzene is prepared by treating 1-isopropyloxy-2-methoxy-4-aminobenzene (see Specification 303,093, [Class 2 (iii), Dyes &c.], with diethylaminoethyl chloride, coupling the product with diazobenzene and reducing with iron and dilute acetic acid.