Patent GB-766837-A (GB)
Title: Basically substituted acid amides and process for their manufacture
IPC: C07D295/15
Filed: 1954-08-20
Abstract: The invention comprises compounds of the general formula R-NH-CO-R1-N(R2)R3 where R is a phenyl group substituted in the 2 and 3 or 2 and 6 positions by an alkoxy group and a halogen atom, R1 is an alkylene group of not more than 4 carbon atoms and R2 and R3 may each be a hydrogen atom or an alkyl group of not more than 4 carbon atoms or together with the nitrogen atom may form a saturated heterocyclic ring, and salts of these compounds.  The compounds are made by acylating an aminobenzene substituted in the 2 : 6 or 2 : 3 positions by a halogen atom and an alkoxy group, with an aminoalkyl carboxylic acid or a functional derivative thereof such as the acid chloride or ester, and if required subsequently alkylating the amino group of the aminoalkyl carboxylic acid residue.  Alternatively a halogenoalkyl carboxylic acid or its functional derivative may be used in place of the aminoalkyl carboxylic acid and the resulting halogen-acylamide is condensed with ammonia or a primary or secondary amine and where ammonia or a primary amine is used the resulting compound is alkylated if desired.  Starting materials are specified in which the phenyl nucleus "R" is substituted by chlorine or bromine and a methoxy, ethoxy, propyloxy or butoxy group.  Many aminoalkyl carboxylic acids, halogenoalkyl carboxylic acids and primary and secondary amines which may be used as starting materials are specified.  The products may be converted into their salts with hydrohalic, sulphuric, phosphoric, acetic, lactic, maleic, tartaric, malic, amidosulphonic, phenol sulphonic, oxalic, succinic, hydroxyethane sulphonic or aceturic acid. Examples describe the preparation according to the invention of 1-(diethylamino-acetylamino)-2-chloro-6-ethoxybenzene; 1-(butylamino-acetylamino)-2-chloro-6-ethoxybenzene; 1-(butylamino - acetylamino) - 2 - methoxy - 3 - chlorobenzene; 1 - (diethylamino - acetylamino)-2 - butoxy - 6 - chlorobenzene; 1 - (butylamino-acetylamino) - 2 - butoxy - 6 - chlorobenzene; 1 - (diethylamino - acetylamino) - 2 - methoxy-6 - chlorobenzene; 1 - (butylamino - acetylamino) - 2 - methoxy - 6 - chlorobenzene; 1-(b  - n - butylamino - butyrylamino) - 2 - ethoxy-6 - chlorobenzene; 1 - (pyrrolidino - acetylamino) - 2 - chloro - 6 - ethoxybenzene and 1 - (butylamino - acetylamino) - 2 - chloro-6-ethoxybenzene, which are separated as their acid addition salts.  Intermediates. Halogen-acylamides of the formula R.NH.CO.R1.Halogen, where R and R1 are as above defined, are obtained as intermediate products when a halogenoalkyl carboxylic acid or its functional derivative is reacted with a substituted aminobenzene R.NH2.  In examples, 1-chloracetylamino-2-methoxy - 3 - chlorobenzene; 1 - chloroacetylamino - 2 - butoxy - 6 - chlorobenzene; 1-chloracetylamino - 2 - methoxy - 6 - chlorobenzene; 1 - chlorobutyrylamino - 2 - ethoxy-6 - chlorobenzene and 1 - chloroacetylamino-2 - chloro - 6 - ethoxybenzene are prepared. n-Butylaminoacetyl chloride is made by the action of phosphorus pentachloride on butylaminoacetic acid in acetyl chloride.