Patent GB-1109884-A (GB)
Title: Indolyl amines
Inventor: VENNER HAROLD ARTHUR LAKE
IPC: C07D209/12
Filed: 1965-06-28
Abstract: Novel compounds of the formula <FORM:1109884/C2/1> (in which R is -CHRb -CHRa -CH2-, -CHRb -CHRa - or -CHRa - wherein Ra  and Rb  are H, lower alkyl, lower haloalkyl, benzyloxy lower alkyl, hydroxy lower alkyl, lower alkenyl, lower alkynyl or phenyl, or Ra  and Rb together are methylene; R1 and R11 are H, lower alkyl, lower haloalkyl, lower alkoxy lower alkyl, aryl lower alkoxy lower alkyl, lower alkenyl, lower alkynyl, lower hydroxy alkyl, cyclopropylmethyl, cyclobutylmethyl, tetrahydrofurfuryl or cyclohexyl, or NR1R11 is piperidino, 1,2,5,6-tetrahydropyridino, morpholino, N-methyl-piperazino, piperazino, N-phenyl-piperazino, N-hydroxyethylpiperazino or pyrrolidino; R2 is H, lower alkenyl, p-alkoxyphenyl or lower alkyl; R4 and R5 are H, OH, lower alkyl, lower alkoxy, NO2, NH2 which may be mono- or di-lower alkyl substituted, C1- 6 alkanoylamino, C1- 6 alkanoyl, bis(lower hydroxyalkyl)amino, 1-pyrrolidino, 4-methyl-1-piperazinyl, morpholino, CN, CF3, halogen, di(lower alkyl)sulphamoyl, benzyloxy or benzylthio which may be lower alkyl, lower alkoxy or halogeno substituted, lower alkenyl, lower alkenyloxy, 1-azacyclopropyl, cyclopropyl lower alkoxy or cyclobutyl lower alkoxy, or R4 and R5, when ortho, can be lower alkylenedioxy; R6 is aryl or heteroaryl of one or two 5- or 6-membered rings in which any hetero atoms are O,N or S and they are at most 3 and in one ring only, which rings may be substituted by halogen, lower alkyl, lower alkylthio, lower alkoxy, CF3, phenoxy which may be lower alkyl, lower alkoxy or halogen substituted, COCF3, COCF2H, di(lower alkyl)sulphamoyl, C1- 6 alkanoyl, di(lower alkyl)carboxamido, CN, carb-lower alkoxy, CHO, CF3S, lower alkyl sulphinyl, lower alkyl sulphonyl, benzylthio or benzyloxy which may be lower alkyl, lower alkoxy or halogen substituted, SH, NO2, NH2 which may be mono- or di-lower alkyl substituted, C1- 6 alkanoylamino, OH, C1- 6 alkanoyloxy, OCOCF3, or OCOCF2H; and n is 1, 2 or 3; the word "lower" meaning of at most 5 carbon atoms) and their acid-addition salts, are prepared by (1) N-acylation; (2) when R is -CH2-, reaction of a corresponding 3-unsubstituted indole with formaldehyde and the appropriate amine which may be mono- or di-benzylated (the benzyl groups being subsequently removed); (3) when R is -CHRa -, hydrogenating a corresponding 3-C(Ra )=NR1 indole; (4) when R is -CHRb -CHRa -CH2- or -CHRb -CHRa , reducing a corresponding 3-CRb =CRa -NO2 or CHRb -CRa =CH-NO2 indole (5) when R is as in (4), by hydrogenation of a corresponding imine as in (3); or (6) when R is -CHRb -CH2- or -CHRb -CHRa -CH2, reducing a corresponding nitrile.  Resulting free amines may be alkylated or converted into cyclic amines, nitro groups reduced to amino groups, benzyloxy groups debenzylated, hydroxy groups etherified, and CONH2 groups dehydrated to CN groups. N-acylation may also precede the processes (3), (4), (5) and (6). The preparation of starting materials is illustrated in the following reaction schemes. <FORM:1109884/C2/2> <FORM:1109884/C2/3> <FORM:1109884/C2/4> <FORM:1109884/C2/5> p-Nitrophenyl p-chlorobenzoate is prepared from p-nitrophenol and p-chlorobenzoyl chloride.  The indole derivatives of the invention, which are stated to possess anti-inflammatory, anti-pyretic, anti-serotonin, analgesic, anti-depressant and psychic-stimulating action, may be made up into pharmaceutical compositions.