Patent GB-1143039-A (GB)
Title: New pyrazino[1,2-a]quinolines and process for preparing same
IPC: A61K31/00
Filed: 1967-10-03
Abstract: 1,143,039. Pyrazino-quinolines. CIBA Ltd. 3 Oct., 1967 [5 Oct., 1966; 2 Feb., 1967; 11 Aug., 1967], No. 45003/67. Heading C2C. Novel 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinolines [I] in which the carbon atoms of the hetero rings are unsubstituted or alkylated and which contain in the 3-position a radical R which may be aliphatic, cycloaliphatic, cycloaliphatic - aliphatic, araliphatic or heterocyclic - aliphatic and in which the aromatic or heterocyclic rings of R may be further substituted by -CF 3 , C 1-7  alkyl, C 1-7  alkoxy or halogen atoms and their salts are prepared by (a) reacting the appropriate 3-unsubstituted compound with a compound R-X, where X is halo or an arylsulphonyloxy group, (b) reducing with lithium aluminium hydride a 3-R-2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline in which at least one of the ring carbon atoms 1, 2 or 4 or a carbon atom outside the ring, which, owing to the vicinity of a N atom is capable of forming an amidic oxo group carries an amidic oxo group, or (c) when R is a heterocyclyl-alkyl radical reacting the appropriate 3-unsubstituted compound with a heterocyclic compound which is substituted by an optionally alkylated vinyl radical and in which the double bond of the vinyl group is activated by the heterocyclic portion. Intermediates prepared are 1 - chloroacetyl - 2- (benzoylaminomethyl)- 1,2,3,4 - tetrahydro-quinoline from the chloroacetylation of the appropriate 1-unsubstituted compound; 1-oxo-3- benzoyl - 1,2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline from the former-named intermediate; 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline by debenzylation of the 3-benzyl derivative; 3-(p-methoxy-henzoyl) - 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline by reaction of the former-named intermediate with p-methoxybenzoyl chloride; 3 - (p - chlorobenzoyl) - 2,3,4,4a,5,6 - hexahydro- 1H pyrazino [1,2-a] quinoline from the 3- unsubstituted compound and p-chlorobenzoyl chloride; 3 - (p - toluoyl) - 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline from the 3-unsubstituted compound and p-toluoyl chloride; 2 - (benzoylaminomethyl)- 6 - methyl-1,2,3,4- tetrahydroquinoline from 1 - benzoyl - 2 - cyano- 6 - methyl - 1,2 - dihydroquinoline by hydrogenation; 1 - chloroacetyl - 2 - {benzoylaminomethyl) - 6 - methyl - 1,2,3,4 - tetrahydroquinoline from the previously-named intermediate and chloroacetyl chloride; 1-oxo-3-benzoyl- 8-methyl- 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline from the former intermediate; 1 - chloroacetyl - 2 - (benzoylaminomethyl) - 6 - methoxy- 1 ,2,3,4-tetrahydroquinoline from 2-(benzoylaminomethyl) - 6 - methoxy - 1,2,3,4 - tetrahydroquinoline and chloroacetyl chloride; 1 -oxo- 3 - benzoyl - 8 - methoxy - 2,3,4,4a, 5,6 - hexahydro- 1H - pyrazino [1,2-a] quinoline from the last named intermediate; 3 - phenylacetyl - 2,3,4,4a, 5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline from 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline and phenylacetyl chloride; 3 - (# phenylpropionyl) - 2,3,4,4a,5,6 - hexahydro- 1H - pyrazino [1,2-a] quinoline in a similar manner to the last-named intermediate; 3-(2- furoyl) - 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline from the appropriate 3-unsubstituted compound and furan-2-carboxylic acid chloride; 3 - (2 - thenoyl) - 2,3,4,4a,5,6 - hexahydro- 1H - pyrazino [1,2-a] quinoline in a similar manner to the last-named intermediate; 3- acetyl - 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline from the appropriate 3-unsubstituted compound and acetic anhydride; 3- butyryl - 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline in a similar manner to the lastnamed intermediate; and 3-(2-furoyl)-8-methyl- 2,3,4,4a,5,6 - hexahydro - 1H - pyrazino [1,2-a] quinoline from the 3-unsubstituted compound and furan-2-carboxylic acid chloride. Pharmaceutical compositions comprise a novel compound [I] in conjunction with a suitable excipient for oral, rectal or parenteral administration and are effective as antihypertonics and sedatives.