Patent GB-1198128-A (GB)
Title: Sulfonamidotryptamines
IPC: C07D209/12
Filed: 1967-07-20
Abstract: 1,198,128. indole derivatives. MEAD JOHNSON & CO. 20 July, 1967 [29 Aug., 1966], No. 33526/67. Heading C2C. Novel compounds I (including acid addition and metal salts thereof) wherein the group R 5 SO 2 NR 6 - is located at the 4-, 5-, 6- or 7-positions of the indole ring and Alk is a C 2-6  alkylene group such that at least 2 carbon atoms separate the ring and the N-atom, R 1  is H, benzyl or C 1-4  alkyl, R 2  is H, carboxy or C 1-4  alkyl, -NR 3 R 4  is an N-attached heterocyclic group having up to 7 carbons or an N- attached heteropolycyclic group having up to 11 carbons or an amino group wherein R 3  and R 4  may be the same or different and R 3  is H, benzyl or an alkyl or alkenyl group having up to 4 carbon atoms, R 4  is H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, polycycloalkyl, polycycloalkenyl, polycycloalkylalkyl, polycycloalkenylalkyl, aryl, aralkyl, aralkenyl, aryloxyalkyl, heterocyclic, heterocycloalkyl, heteropolycyclic or heteropolycycloalkyl group, each said group containing up to 12 carbon atoms and optionally having up to two hydroxy, carboxy, amino, C 1-4  alkoxy, C 1-4  alkyl or methylenedioxy substituents, R 5  is an alkyl, alkenyl, cycloalkyl or cycloalkenyl group each having up to 6 carbons, a polycycloalkyl orpolycycloalkenyl group each having up to 10 carbons or a phenyl, phenylalkyl, phenylalkenyl, naphthyl, substituted phenyl, substituted phenylalkyl or substituted naphthyl group wherein said substituent is alkoxy, alkyl, alkenyl, cycloalkyl or cycloalkenyl, each having up to 6 carbons, halogen or benzyloxy and R 6  is hydrogen or a C 1-4  alkyl group, are prepared by reducing or hydrolysing a compound II wherein -Alk-Y is a functional group (and also including the case where R<SP>2</SP> and -Alk-Y together comprise a lactam ring) which on reduction or hydrolysis is transformed into the group -Alk-NR 3 R 4 . 4 -, 5 - or 6 - Aminoindole - 3 - acetonitrile, obtained by reduction of the corresponding nitro compound, is reacted with methanesulphonyl chloride to yield the corresponding methanesulphonamidoindole - 3 - acetonitrile, alkylation of which affords the corresponding N- alkylmethanesulphonamidoindole - 3 - acetonitrile. N - Benzyl - N - methyl - 5 - nitroindole - 3 - oxalylamide, prepared by the interaction of benzylmethylamine and 5 - nitroindole - 3 - oxalyl chloride (obtained from 5-nitroindole and oxalyl chloride), is reduced to N-benzyl-N- methyl-5-aminoindole-3-oxalylamide. 6 - Amino - 1,2,3,4 - tetrahydro - 9H - pyrido - [3,4,b] - indol - 1 - one, prepared by reduction of the corresponding 6-nitro-compound [obtained by treating 3-(p-nitrophenylazo)-piperidone (2) with polyphosphoric acid at 110‹ C.-the azo compound being obtained from the interaction of 3 - carbethoxy - 2 - piperidone and p - nitrobenzenediazonium chloride], is treated with methanesulphonyl chloride to afford 6- methanesulphonamido - 1,2,3,4 - tetrahydro - 9H - pyrido - [3,4b] - indol - 1 - one. Methylation of the 6-nitro compound yields 6-nitro-9-methyl- 1,2,3,4 - tetrahydro - 9H - pyrido - [3,4,b] - indol - 1 - one which may be reduced to the corresponding 6 - amino - 9 - methyl - compound from which may be obtained the corresponding 6- methanesulphonamido - 9 - methyl - compound utilizing methanesulphonyl chloride. 6 - (N - Methylmethanesulphonamido)- 1,2,3,4 - tetrahydro - 9H - pyrido - [3,4b] - indol - 1 - one is obtained by methylation of the corresponding 6- methanesulphonamido-compound. 3 - Formyl - 5 - methanesulphonamidoindole, obtained by treating 5-methanesulphonamidoindole with dimethylformamide and phosphorus oxychloride, reacts with nitroethane to yield 5- methanesulphonamido - 3(2 - nitro - 1 - propenyl) - indole which is converted to 5-methanesulphonamidoindole - 3 - acetone after treatment with powdered iron, ferric chloride and concentrated hydrochloric acid.