GB942548A - - Google Patents

Abstract

942,548. Indoles. SANDOZ Ltd. March 22, 1960 [April 7, 1959; July 13, 1959; Aug. 21, 1959(2); Feb. 24, 1960], No. 10166/60. Addition to 911,946. Heading C2C. The invention comprises indoles of the general formula: and their acid addition salts, wherein R 1 is a hydrogen atom or a C 7-10 aralkyl group, R 2 is a hydrogen atom or a C 1-6 alkyl group or a C 7-10 aralkyl group, each of R 3 and R 4 is a hydrogen atom or a C 1-6 alkyl group and A is a C 1-3 alkylene group with the proviso that R 1 -R 4 may be the same and with the further proviso that A and R 2 together contain at least 2 carbon atoms when R 3 and R 4 each signify an alkyl group and the preparation thereof by introducing, in known manner for such reactions, into the 3-position of an indole of the formula: (wherein R 1 <SP>1</SP> is a C 7-10 aralkyl group) an organic radical containing a nitrogen atom and capable of being converted by a method involving reduction into an amino containing group of the formula: converting the said group into the said amino group by a method involving reduction said reduction being effected under conditions such that the group R 1 <SP>1</SP> is not split off and optionally removing the group R 1 <SP>1</SP> by acid hydrolysis or reduction with hydrogen in the presence of a palladium catalyst or with an alkali metal in liquid ammonia. Compounds of the invention wherein R 2 is a hydrogen atom are prepared by reacting a 1-H-4-OR 1 <SP>1</SP>-indole with an. alkyl magnesium halide to give the indole magnesium halide, reacting this with a compound X 1 -COA-X 2 (wherein X 1 and X 2 each represent the same or different halogen atom) treating the resulting product with an amine, R 3 R 4 NH, and reducing the resulting amino-ketone. The 1- substituted compound may be prepared by reacting the 1-unsubstituted indole thus formed with an alkyl or aralkyl halide in the presence of an alkali condensation agent. Furthermore compounds of the invention are prepared either by reacting an 1-R 2 -4-OR 1 <SP>1</SP>-indole with formaldehyde and a secondary amine, quaternising the gramine so formed, reacting the salt with an alkali metal cyanide to give an indolyl-(3)- acetonitrile. saponifying this to the carboxylic acid converting this to the acid azide or halide, reacting the azide or halide with an amine R 3 R 4 NH and reducing the amide, or (when both R 3 and R 4 are hydrogen atoms) by reducing the nitrile direct to the amine, or (where R 2 R 3 and R 4 are each hydrogen atoms) by reacting an appropriate gramine with a nitroalkane H-ANO 2 in the presence of a proton acceptor and reducing the nitro indole so formed, or by heating a indolyl-(3)-aldehyde in the presence of a condensation agent favouring the splitting off of water with a nitroalkane to give an indole of the formula: (in which 'A' designates the group A less a hydrogen atom) and reducing this to the alkylamino compound. Specifications 744,773, 744,774, 781,390 and 807,876 also are referred to.