Patent GB-1030623-A (GB)
Title: 3-substituted-indoles and their preparation
IPC: C07D403/04
Filed: 1962-12-21
Abstract: The invention comprises compounds of the Formulae I, V and XV, wherein R represents a C1-4 alkyl group, R1, R2, R3, and R4 represent hydrogen atoms or C1-4 alkyl groups and R5 represents a hydrogen atom or a benzyl or C1-4 alkyl group, and the preparation of compounds of the Formula XVI, wherein Z represents a 2-pyrrolidinyl group of the Formula XVII or a 2-piperidyl group of the Formula XVIII, by reacting an indole of the Formula XIX with the required 2-pyrrolidone or 2-piperidone, in the presence of phosphorus oxychloride at a temperature between about 50 DEG  and 150 DEG  C. and reducing the thus obtained products of the Formulae V and XV respectively, and, when R5 represents a hydrogen atom, if desired replacing it by an alkyl or benzyl group by reacting the product with an alkyl or benzyl halide in the presence of an alkaline condensing agent; and the preparation of compounds of the Formula VIII by reacting a compound of the Formula IX, wherein R7 and R8 represent hydrogen atoms or aryl, aralkyl or alkyl groups or when joined represent with the nitrogen atom a saturated heterocyclic amino radical, with a compound of the formula R1R2CHNO2 to produce a 3-(4-nitrobutyryl) indole of the Formula XI and reducing and concomitantly cyclizing said indole with hydrogen in the presence of Raney nickel and reducing the thus produced compound with an alkali metal complex hydride or by catalytic hydrogenation in the presence of a noble metal catalyst to produce a 3-(2-pyrrolidinyl)indole of the Formula XII and alkylating said compound, or by reducing and concomitantly cyclizing a compound of the Formula XIII, alkylating the pyrrolidinyl nitrogen atom of the resulting compound, making basic to obtain the 3-(1-alkyl-2-pyrrolidinylidene)-3H-indole and either reducing with an alkali metal complex hydride or alkylating or benzylating with an alkyl or benzyl halide to produce a 3 - (1 - alkyl - 2 - pyrrolidinylidene) - 3H - indole quaternary ammonium salt of the Formula XIV where R6 represents a benzyl or C1-4 alkyl and Y represents a halogen atom and reducing the quaternary salt with an alkali metal complex hydride. <FORM:1030623/C2/1> <FORM:1030623/C2/2> <FORM:1030623/C2/3> 3 - (1 - Formyl - 5 - methyl - 2 - pyrrolidinyl)indole is prepared by refluxing 3-(5-methyl-2-pyrrolidinyl)indole with methyl formate.  3 - (1 - Acetyl - 5,5 - dimethyl - 2 - pyrrolidinly)indole is prepared by treating 3-(5,5-dimethyl-2-pyrrolidinyl)indole with acetic anhydride.ALSO:Pharmaceutical compositions for the treatment of neuroses to psychotic conditions or oral and parenteral application comprise 3-(2-pyrrolidinyl) indoles (and 3-(2-piperidyl) indoles <FORM:1030623/A5-A6/1> <FORM:1030623/A5-A6/2> where R is an alkyl group of 1 to 4 carbon atoms, R1, R2, R3 and R4 are hydrogen atoms or alkyl groups of 1 to 4 carbon atoms and R5 is a hydrogen atom or a benzyl or alkyl group of 1 to 4 carbon atoms, or addition salts thereof, m associations with a pharmaceutical carrier.  Examples of suitable dosage forms are tablets, capsules, pills, troches, powder packets, granules, wafers, sachets, syrups, elixirs, suspensions and, for veterinary application, a food premix. Other active agents which may be present include analgetic agents, e.g. codeine, aspirin, acetophenetidine, salicylamide and N-acetyl-p-aminophenol; hypnotic agents, e.g. barbiturates and chloral hydrate; steroids, e.g. hydrocortisone, prednisolone, fluprednisolone and methylprednisolone; muscle relaxants, e.g. chlorzoxazone, carisoprodol, mephenesin; meprobamate, phenaglycodal zoxazolamine, and antihistaminics, e.g. chloropheniramine maleate, prophenpyridamine maleate and pyrilamine. Parental fluids may contain local anasthetics.