Patent GB-441132-A (GB)
Title: Process for the manufacture of acridine derivatives
IPC: C07D219/12
Filed: 1934-07-05
Abstract: Acridine derivatives are prepared by (1) reacting upon acridines containing alkyl, alkoxy or alkylmercapto groups in the 2- and 7-positions and as a reactive substituent in the 9-position a halogen, alkoxy, aryloxy, mercapto, substituted mercapto or sulpho group, with a base or salt thereof which contains at least two nitrogen atoms at least one of which is in a primary or secondary amino group; (2) reacting upon acridines specified in (1) with a base or salt thereof containing at least two nitrogen atoms and wherein one of the amino groups is substituted by an acyl residue, the latter being subsequently split off by saponification; (3) reacting upon the acridines specified in (1) with an aminoalcohol or an amino substituted halogen alkyl compound and further reacting the product with ammonia or a primary or secondary amine, if necessary after esterification of the hydroxyl group; (4) reacting upon acridines which differ from those specified in (1) by containing in the 2- and/or 7-positions a hydroxyl or mercapto group according to the processes of (1), (2) or (3) followed by treatment with an alkylating agent; (5) subjecting a diphenylamine-6-carboxylic acid amide basically substituted in the amide group and containing in the 4.4<1>-positions alkoxy, alkylmercapto or alkyl groups or a mercapto or hydroxy group, to ring closure to form the acridine derivative, a mercapto or hydroxyl group in the 2- and/or 7-positions being alkylated by treatment with an alkylating agent. The basic substituents in the 9-position are those defined in Specification 363,392.  In examples: (1) 2.7-dimethoxy-9-chloracridine (obtained by ring-closure of 4.4<1>-dimethoxydiphenylamine-6-carboxylic acid and chlorination) is condensed with diethylamino-d -aminopentane, a  - diethylaminoethylthio - g  - aminopropane (cf. Specification 441,007) and dimethylaminoethoxy - b  - aminoethane; (2) 2 . 7 - dimethoxy-9-phenoxyacridine (prepared from the 9-chloro derivative and phenol) is condensed with a  - diethylamino - b  - hydroxy - g  - aminopropane; (3) 2 - isopropyloxy - 7 - methoxy - 9 - chloracridine (prepared by ring-closure of 4 - methoxy - 4<1> - isopropyloxydiphenylamine - 6 - carboxyli acid and chlorination) is condensed with a -diethylamino-d -aminopentane; (4) 2 - methylmercapto - 7 - methoxy - 9 - chloracridine (prepared by ring-closure of 4-methoxy4<1> - methylmercaptodiphenylamine - 6 - carboxylic acid and chlorination) is condensed with a  - diethylamino - d  - aminopentane; (5) 2 - methyl - 7 - methoxy - 9 - chloracridine (prepared by ring-closure of 4<1>-methyl-4-methoxydiphenylamine-6-carboxylic acid and chlorination) is condensed with a -diethylamined -aminopentane; (6) 2.7-dimethyl-9-chloracridine (prepared by ring-closure of 4.4<1>-dimethyldiphenylamine - 6 - carboxylic acid and chlorination) is condensed with a -diethylaminod  - aminopentane and a  - diethylamino - b  . b  - dimethyl - g  - aminopropane; (7) 2 - n - butyloxy - 7 - methoxy - 9 - chloracridine (prepared by ring closure of 4-methoxy-4<1>-n-butyloxydiphenylamine-6-carboxylic acid and chlorination) is condensed with a -diethylamino-d -aminopentane and a -diethylamino-b -hydroxy-g -aminopropane; 2 - n - butyloxy - 7 - ethoxy - 9 - chloracridine (prepared analogously to the 7-methoxy derivative) may be used instead; (8) 2-n-hexyloxy - 7 - methoxy - 9 - chloracridine (prepared by ring closure of 4-methoxy-4<1>-n-hexyloxydiphenylamine-6-carboxylic acid and chlorination) is condensed with a -diethylamino-d -aminopentane and a - diethylamino - b  - hydroxy - g  - aminopropane.  Samples have been furnished under Sect. 2 (5) of the following products (a) 2 - methylmercapto - 7 - methoxy - 9 - (p - aminomethylphenylamino)-acridine prepared by treating 2 - methylmercapto - 7 - methoxy - 9 - chloracridine with phenol and the resulting 9-phenoxy derivative with N-(4-aminobenzyl)-acetamide followed by saponification by means of hydrochloric acid; (b) 2.7-dimethoxy-9-(g -piperidinopropylamino)-acridine prepared by treating 4 . 4<1> - dimethoxydiphenylamine - 6 - carboxylic acid with phosphorus pentachloride and condensing the acid chloride with g -piperidinopropylamine (cf. Specification 441,007) followed by ring closure to the acridine by heating with phosphorus oxychloride; (c) 2.7-dimethoxy - 9 - (p - diethylaminoethoxyphenylamino)-acridine prepared by condensing 2.7-dimethoxy-9-phenoxyacridine with 4-aminophenyl - hydroxyethylether (cf. Specification 441,007) treating the product with thionylchloride and then with diethylamine; (d) 2-methyl - 7 - ethoxy - 9 - (a  - diethylamino - g  - butylamino - ) - acridine prepared from the corresponding 7-hydroxy derivative (which is derived by acid hydrolysis of the 7-methoxy compound) by treatment with sodium alcoholate and ethyl iodide. Most of these compounds are isolated in the form of their salts with inorganic and organic acids.  Specifications 267,169, [Class 2 (iii)], and 437,953 also are referred to.