Patent GB-1216523-A (GB)
Title: Basically substituted dibenzoxazepines, dibenzothiazepines and dibenzodiazepines
Inventor: SCHMUTZ JEAN
IPC: C07D413/04
Filed: 1968-03-05
Abstract: 1,216,523. Dibenzoxazepines, dibenzothiazepines and dibenzodiazepines. DR. A. WANDER S.A. 5 March, 1968 [13 March, 1967; 22 March, 1967; 9 May, 1967; 14 July, 1967; 3 Nov., 1967], No. 10561/68. Heading C2C. Novel compounds of Formula (I) (in which Z represents oxygen, sulphur, sulphinyl (-SO-) or imino (-NH-); R 1  represents hydrogen, allyl, alkyl containing not more than 3 carbon atoms, hydroxyalkyl containing not more than 3 carbon atoms, alkoxyalkyl containing not more than 6 carbon atoms or alkanoyloxyalkyl containing not more than 6 carbon atoms; and R 2  represents nitro; amino; aminosulphonyl of the formula -SO 2 NR 3 R 4 , wherein R 3  and R 4  are the same or different and represent hydrogen or methyl; alkylsulphinyl of the formula -SOR 5  in which R 5  denotes alkyl with not more than 3 carbon atoms; or alkylsulphonyl of the formula -SO 2 R 5  in which R 5  denotes alkyl with not more than 3 carbon atoms) and therapeutically acceptable acid addition salts thereof, are prepared by (a) reacting a compound of Formula (II) (in which X is halogen, mercapto, alkoxy, alkylthio, p-nitrobenzylthio or tosyl) with a compound of Formula (III) or (b) intramolecularly condensing compounds of Formula (IV) (in which Y is oxygen or sulphur), or (c) for compounds I in which Z = O or S, dehydrating compounds of Formula (V) or (VI) (in which R 7  is R 1  or a removable group) and, if necessary, splitting off the removable group, or (d) for compounds I in which R 2  is not amino, reacting an amidine of Formula (VII) (in which R 2 <SP>1</SP> is the same as R 2  except for amino) with a reactive ester of an alcohol of Formula (VIII) Compounds I in which R 2  is amino are also obtained by reduction of the corresponding nitro compounds. Compounds I in which Z is sulphinyl are also obtained by oxidation of the corresponding compounds in which Z is sulphur. Compounds I in which R 2  is alkylsulphinyl or alkylsulphonyl are also obtained by oxidation of the corresponding alkylthio compounds. Compounds I in which R 2  is aminosulphonyl are also prepared by reacting a corresponding compound containing the group -SO 2 X<SP>1</SP> (in which X<SP>1</SP> is halogen) with an amine of Formula HNR 3 R 4 . Compounds I, obtained by one of the above methods, in which R 1  is hydrogen and R 2  is not amino, can be converted, e.g. by alkylation, hydroxyalkylation and alkanoylation to compounds I in which R 1  is other than hydrogen. Starting materials of Formula (II) in which X is chlorine are prepared by treating a lactam of Formula (IX) with a chlorinating agent. Lactams of Formula (IX) are prepared by ring closure of a compound of Formula (X), (XI), (XII), (XIII) or (XIV) (in which R 6  is H or C 1-3  alkyl). Compounds of Formula (VII) are prepared by treating compounds of Formula (II) with ammonia. 2 - Chlorosulphonyl - 11 (4 - methyl - 1 -piperazinyl - dibenz - [b,f] - 1,4 - oxazepine is prepared by diazotization of 2-amino-11-(4-methyl- 1 - piperazinyl) - dibenz - [b,f] - 1,4 - oxazepine, followed by the Meerwein reaction. Pharmaceutical compositions having analgesic, neuroleptic, sedative, antidepressant and antiemetic activity, comprise a compound of Formula (I) or a therapeutically acceptable acid addition thereof, together with a carrier. They may be administered enterally or parenterally.