GB892618A - ª+-carbolines and process for their manufacture - Google Patents

Abstract

The invention comprises 1-hydroxy-g -carbolines which are 9-substituted by an alkyl or amino-substituted alkyl group having 1-5 carbon atoms or a benzyl group and quaternary compounds thereof and also pyrido-[2 : 1-b]-g -carbolinium compounds which are 11-substituted by an alkyl or amino-substituted alkyl group having 1-5 carbon atoms or a benzyl group, and 12-substituted by an alkyl group having 1-5 carbon atoms; and also a process for producing N-substituted g -carbolines in which an a -indolyl-lithium compound, which is N-substituted by an alkyl or amino alkyl group having 1-5 carbon atoms or a benzyl group and is otherwise unsubstituted or contains a tertiary aminomethyl group in b -position, is first reacted with an a -amino-aldehyde or -ketone, the nitrogen atom of which is tertiary, the indole compound so formed is reacted with formaldehyde and a secondary amine, the Mannich base produced is treated with a quaternating agent or a strong acid, and the resulting monoammonium compound is heated with the splitting off of an amine and formation of the g -carboline ring. The reaction when 1-methyl-indolyl-(2)-lithium and diethylamino acetone are used as starting materials, takes place as follows <FORM:0892618/IV (b)/1> <FORM:0892618/IV (b)/2> <FORM:0892618/IV (b)/3> <FORM:0892618/IV (b)/4> <FORM:0892618/IV (b)/5> <FORM:0892618/IV (b)/6> The reaction between the indolyl-lithium compound and the amino-aldehyde or -ketone is preferably carried out in an inert solvent, e.g. ether, dioxane or benzene. The basic nitrogen atom of the a -amino-ketones and -aldehydes may belong to a heterocyclic ring, e.g. a pyridine, piperidine, pyrrolidine, piperazine or morpholine ring. The nitrogen may alternatively carry alkyl, aralkyl or cycloalkyl groups. Suitable quaternating agents for treating the Mannich bases are, for example, alkyl halides and sulphates, and suitable acids are, for example, hydrochloric acid, sulphuric acid or toluene sulphonic acid. The mono-ammonium compound may be boiled in a solvent, such as water or tetrahydronaphthalene, to bring about the formation of the g -carboline ring. The ammonium salts may be converted by known methods into other ammonium salts. Examples are given of the preparation of (a) 1 : 9-dimethyl-1-hydroxy-3 : 3-diethyl-1 : 2 : 3 : 4-tetrahydro-g -carbolinium iodide of formula <FORM:0892618/IV (b)/7> which on heating gives 1 : 9-dimethyl-3-ethyl-g -carbolinium iodide; (b) 5 : 5-diethyl-11-methyl-11b-hydroxy-1 : 2 : 3 : 4 : 4a : 5 : 6 : 11b-octahydro-benzo(a)-g -carbolinium iodide of formula <FORM:0892618/IV (b)/8> which on heating gives 5-ethyl-11-methyl-1 : 2 : 3 : 4-tetrahydro-benzo-[a]-g -carbolinium iodide of formula <FORM:0892618/IV (b)/9> (c) 1 : 9-dimethyl-1-hydroxy-3-benzyl-3-ethyl-1 : 2 : 3 : 4-tetrahydro-g -carbolinium iodide of formula <FORM:0892618/IV (b)/100> which on heating gives 1 : 9-dimethyl-3-ethyl-g -carboliniu iodide; and (d) 11 : 12-dimethylpyrido-[2 : 1-b-]g -carbolinium iodide of formula <FORM:0892618/IV (b)/111>