Patent GB-1433906-A (GB)
Title: 6-aza-10,11-dihydro-5h-dibenzo-b,f 1,4-diazepines
IPC: C07D213/74
Filed: 1973-09-06
Abstract: 1433906 6 - Aza - 10,11 - dihydro - 5H - dibenzo[b,f]-[1,4]-diazepines DEUTSCHE GOLDUND SILBER-SCHEIDEANSTALT 6 Sept 1973 [6 Sept 1972] 41898/73 Heading C2C Novel compounds of the Formula I wherein Alk<SP>1</SP> and Alk<SP>2</SP>, which are the same or different, each are C 1-6 alkylene groups, R<SP>1</SP> and R<SP>2</SP> are C 1-5 -alkyl groups or taken together with the N-atom to which they are attached form a 4- to 7 membered saturated ring which optionally contains an oxygen or sulphor atom or another or group, R<SP>3</SP> is hydrogen, hydroxy, C 3-6 -cycloalkyl, or halogen, Hal is halogen, Y is oxygen, sulphur or NH, Z is hydrogen, C 1-5  alkyl, halogen, hydroxy, nitro or OR, the R radicals, which may be the same or different, are C 1-5  alkyl group; and their salts may be prepared by (1) introducing the group Alk<SP>1</SP>NR<SP>1</SP>R<SP>2</SP> or the group Alk<SP>2</SP>R<SP>3</SP> or both in succession into a compound I in which Alk<SP>1</SP>NR<SP>1</SP>R<SP>2</SP> and/or Alk<SP>2</SP>R<SP>3</SP> are replaced by hydrogen; (2) cyclizing a compound I in which either a bond of the 5-nitrogen atom to one ofthe 6-membered rings is opened by this nitrogen containing a hydrogen atom and a halogen atom is situated in the corresponding position of one of the 6-membered rings, or the bond of the 10- nitrogen atom to the 11-carbon atom is opened by the 10-nitrogen containing a hydrogen atom and the 11-carbon atom is part of the group -CYOH or a reactive derivative thereof, to form the 7-membered ring; (3) introducing the halogen atom at the 7-position by direct or indirect known methods; (4) interchanging the groups at Y by known methods; (5) salt formation; or (6) converting an N-oxide group, if present, into the 3-bond pyridine nitrogen. 2 - N - Methyl - N - (o-carboxyphenylamino)- 3 - amino - 6 - chloro - pyridine is prepared by condensing 2,6-dichloro-3-nitropyridine with N-methylanthranilic acid to yield 2-N-methyl-N- (o - carboxyphenylamino)- 3 - nitro - 6 - chloropyridine which is catalytically hydrogenated to the required compound. Heating this compound yields 5 - methyl - 6 - aza - 7 - chloro - 10,11- dihydro - 5H - dibenzo - [b,f] - [1,4] - diazepin - 11- one. 4 - Chloro - N - methylanthranilic acid is prepared by reacting 2-amino-4-chlorobenzoic acid with trifluoroacetic acid anhydride to yield 2 - trifluoroacetylamino - 4 - chlorobenzoic acid which yields the required compound on reaction with methyl iodide followed by treatment with potassium hydroxide. 2 - Methylamino - 3 - # - dimethylaminoethyl amino-6-chloro-pyridine is prepared by reduction followed by acetylation of 2-methylamino - 3 - nitro - 6 - chloropyridine to yield 2 - methylamino - 3 - acetamino - 6 - chloropyridine which yields the required compound on treatment with sodium hydride followed by condensation with N,N-dimethylaminoethyl chloride. Pharmaceutical compositions of the compounds I with the usual excipients show pharmacodynamic activity, e.g. antihistaminic, antidepressive and antiulcerogenic activity when administered orally, parenterally, rectally, vaginally, perlingually or locally.