Patent GB-725745-A (GB)
Title: Pyrrolinoquinolines and processes for making same
IPC: C07D471/04
Filed: 1953-05-26
Abstract: The invention comprises pyrrolinoquinolines of general formula <FORM:0725745/IV (b)/1> wherein R is hydrogen, alkyl, dialkylaminoalkyl or aralkyl, R1 is hydrogen, alkyl, carboxy, or N-alkylcarbamyl, and R2 is one or two substituents which are hydrogen, hydroxy, alkoxy, N-alkylcarbamyl or halogen, while the two vicinal carbon atoms 8 and 9 may be part of a further heterocyclic ring.  The compounds are prepared by reacting a 3-b -haloethyl-4-haloquinoline at an elevated temperature and in a suitable solvent medium such as an alcohol or phenol with ammonia or a primary amine (e.g. an alkylamine, aralkylamine, hydroxyalkylamine or aminoalkylamine).  Using ammonia as a primary reactant compounds unsubstituted at the pyrrolino nitrogen atom are formed and these can be converted into N-metal compounds by treatment with metals such as sodium, potassium and lithium, or with Grignard compounds, and the products can then be further reacted with reactive esters (e.g. aliphatic or araliphatic halides or hydroxy- or amino-substituted aliphatic alcohols) to yield compounds substituted at the pyrrolino nitrogen atom.  The examples describe the preparation of 4-methyl-, 1-methyl-, 4-methyl-6-methoxy-, 1-methyl-4-N-methylcarbamyl-, 1-methyl-4-carboxy-, 6-methoxy-, 1-benzyl-4-methyl-6-ethoxy-, 1,4-dimethyl-, 1,4-dimethyl-6-methoxy-, 1,4 - dimethyl - 6 - ethoxy -, 1,4 - dimethyl - 7 - hydroxy-, 1,4-dimethyl-7-methoxy-, 1,4-dimethyl - 8 - hydroxy -, 1,4 - dimethyl - 8 - methoxy -, 1,4 - dimethyl - 8 - ethoxy -, 1,4 - dimethyl - 8 - N - methylcarbamyl -, 1 - b  - dimethylaminoethyl - 4 - methyl - 6 - methoxy -, 1 - b  - diethylaminoethyl - 4 - methyl -, 1 - b  - diethylaminoethyl - 4 - methyl - 6 - hydroxy -, 1 - b  - diethylaminoethyl - 4 - methyl - 6 - methoxy -, 1 - b  - diethylaminoethyl - 4 - methyl - 6 - methoxy - 9 - chloro -, 1 - b  - diethylaminoethyl - 4 - methyl - 7,8 - dimethoxy -, 1 - b  - diethylaminoethyl - 4 - methyl - 8 - chloro -, 1 - b  - diethylaminoethyl - 4 - methyl - 8 - methoxy-, 1 - b  - diethylaminoethyl - 4 - methyl - 7 - hydroxy-, 1-b -diethylaminoethyl-4-methyl-7-methoxy -, benzofurano - [9,8 - b] - 1,4 - dimethyl - 6 - methoxy -, benzopyrrolo - [9,8 - b] - 1 - b  - diethylaminoethyl - 4 - methyl -, and benzopyrrolo - [8,9 - b] - 1,4 - dimethyl - 2,3 - dihydropyrroloquinoline.  Salts of these compounds with maleic, hydrochloric, hydrobromic and naphthalene-1,5-disulphonic acid are also described.  2 - Carbethoxy - 3 - b  - chloroethyl - 4 - chloroquinoline is prepared by treating with phosphorus oxychloride, the aniline-lactone-ester condensation product formed by saturating a suspension of the sodium salt of g -butyrolactone-a -ethyloxalate in a mixture of chloroform and aniline with gaseous hydrogen chloride.  Benzopyrrolo - [5,6 - b] - 2 - methyl - 3 - b  - chloroethyl - 4 - chloro -, benzopyrrolo - [6,5 - b] - 2 - methyl - 3 - b  - chloroethyl - 4 - chloro -, and benzofurano - [5,6 - b] - 2 - methyl - 3 - b  - chloroethyl - 4 - chloro - 8 - methoxy - quinoline are prepared by condensing a -aceto-g -butyrolactone with 2-aminocarbazole, 3-aminocarbazole and 2-amino-3-methoxy-diphenylene oxide respectively under conditions usual for formation of Schiff's bases and cyclizing the resulting products with phosphorus oxychloride.  Specification 703,277 is referred to.