Patent GB-1218045-A (GB)
Title: Novel 11-(piperazinyl]dibenz[b,f] [1,4] oxazepines and analogous thiazepines
Inventor: HOWELL CHARLES FREDERICK
IPC: A61K31/00
Filed: 1968-02-14
Abstract: 1,218,045. Dibenzoxazepine and dibenzothiazepine derivatives. AMERICAN CYANAMID CO. 14 Feb., 1968 [27 Feb., 1967], No. 7327/68. Heading C2C. Novel dibenzoxazepines and dibenzothiazepines of Formula I in which X is oxygen or sulphur, R 1  is hydrogen, C 1-4  alkyl or hydroxy-C 1-4  alkyl and R 2  is cyano, di-(C 1-4  alkyl)-sulphamoyl, C 2-5  alkanoyl, α- chlorovinyl or C 1-4  alkoxy-carbonyl, and non- toxic acid addition salts thereof, are prepared by (a) cyclizing a compound of Formula II in which X<SP>1</SP> is oxygen or sulphur, Z is the group of Formula III or OH, halogen, OSO 2 Ar, SH, SR, amino or substituted amino, Ar being aryl and R being alkyl, and, when required, before or after cyclization, converting Z from OH, halogen, OSO 2 Ar, SH, amino or substituted amino, to a group of Formula III, or (b) reacting a compound of Formula IV in which Q is halogen, OH, OSO 2 Ar, SH, SR, amino or substituted amino, with a compound of Formula V or (c) cyclizing a compound of Formula VI in which X<SP>1</SP> is O or S, or (d) cyclizing a compound of Formula VI A  in which one of W and Z is OH or SH and the other is H, NO 2 , halogen or diazonium, or (e) using the following reaction scheme in which R 4  is CN, sulphinic acid (-SO 2 H) or α-oximino-C 1-4  alkyl Compounds IA are prepared by treating the diazonium salt with KCN and an appropriate catalyst, with sulphur dioxide and copper powder or a ferrous salt, or with an alkanal oxime. The sulphinic compounds IA can be converted to compounds I, R 2  = dialkylsulphamoyl, by oxidation, halogenation and reaction with a dialkylamine. The oximinoalkyl compounds IA can be converted to compounds I, R 2  = C 2-5  alkanoyl, by hydrolysis. The preparation of the following intermediates is described: p - (o - nitrophenoxy) - acetophenone, p - (o - aminophenoxy)acetophenone, p - acetoxybenzenesulphonyl chloride, N,N- dimethyl - p - hydroxybenzenesulphonamide, N,N - dimethyl - p - (o - nitrophenoxy)benzenesulphonamide, o - (p - dimethylsulphamoylphenozy)aniline, o - (p - dimethylsulphamoylphenoxy)carbanilate, 2<SP>1</SP> - (p - dimethylsulphamoylphenoxy) - 4 - methyl - 1 - piperazinecarboxanilide hydrochloride, ethyl o - (p - acetylphenoxy) - carbanilate, 2<SP>1 </SP>- (p - acetylphenoxy)- 4 - methyl - 1 - piperazine carboxanilide and its hydrochloride, 4 - (N,N - dimethylsulphamoyl)- diphenyldisulphide, 4 - mercapto - N,N - dimethylbenzenesulphonamide, o.(p-dimethylsalphamoyl phenyl)aniline, p - (o - aminophenylthio)acetophenone, ethyl o - (p - dimethylsulphamoylphenylthio)carbanilate, 2<SP>1</SP>- (p - dimethylsulphamoylphenoxy) - 1 - piperazine carboxanilide, 11 - (4- methyl - 1 - piperazinyl) - 2 - (α - oximinopropyl)- dibenz[b,f][1,4]oxazepine, -ethyl o - (o - nitrophenoxy)benzoate and ethyl p - (o - amino - phenoxy)benzoate. Pharmaceutical compositions for oral or parenteral administration, comprise a compound of Formula I or an acid addition salt thereof together with a carrier. Compounds I and their salts have central nervous system and analgesic properties.