Patent GB-1180164-A (GB)
Title: Dibenzazepine Derivatives and their preparation
IPC: C07D223/22
Filed: 1968-01-18
Abstract: 1,180,164. Dibenzazepine derivatives. RHONE-POULENC S.A. 18 Jan., 1968 [18 Jan., 1967; 9 Nov., 1967], No. 2858/68. Heading C2C. Novel compounds of Formula I in which each of R and R<SP>1</SP> is hydrogen, alkyl, hydroxyalkyl, hydroxy alkoxy alkyl, phenylalkyl, or phenylalkyl substituted in the phenyl nucleus by one or more of halogen, alkyl, alkoxy, nitro, amino or trifluoromethyl, and R 1  is hydrogen, alkyl, phenylalkyl or phenylalkyl substituted in the phenyl nucleus by one or more of halogen, alkyl, alkoxy or trifluoromethyl, and acid addition salts and quaternary ammonium derivatives thereof, are prepared (a) for compounds I in which both of R and R<SP>1</SP> are hydrogen, by reducing a compound of Formula II; or (b) for compounds I in which -NRR<SP>1</SP> is -N(R 3 )CH 2 R 2 , in which R 2  is hydrogen, C 1-4  alkyl, C 1-4  hydroxyalkyl, hydroxy-C 1-4  alkoxy- C 1-4  alkyl, phenyl, phenyl-C 1-4  alkyl, or phenyl- C 1-4  alkyl in which the phenyl nucleus is substituted by one or more of halogen, alkyl, alkoxy, amino or trifluoromethyl, and R 3  is hydrogen, alkyl, phenylalkyl or phenylalkyl substituted in the phenyl nucleus by one or more of halogen, C 1-5  alkyl or trifluoromethyl, by reducing a compound of Formula III, or (c) for compounds I in which -NRR<SP>1</SP> is or -N(CH 2 -R 2 ) 2 ; in which R 4  is hydrogen, alkyl, hydroxyalkyl, hydroxyalkoxyalkyl, phenylalkyl or phenylalkyl substituted by one or more of halogen, alkyl, alkoxy, amino or trifluoromethyl, by reacting a compound of formula R 2 -CHO and hydrogen in the presence of a hydrogenation catalyst with a compound of Formula V or VI, in which Ac is an acyl radical which can be readily eliminated by acid hydrolysis, and, if necessary, eliminating the Ac radical by hydrolysis to form a compound I, in which R 1  is hydrogen; or (d) for compounds I in which -NRR<SP>1</SP> is -NRR 5  or -N(R 5 ) 2 , in which R 5  is alkyl, hydroxyalkyl, hydroxyalkoxyalkyl, phenylalkyl or phenylalkyl substituted by one or more of halogen, alkyl, alkoxy, nitro, amino or trifluoromethyl, by reacting a compound of formula R 5 -X, in which X is a reactive ester residue, with a compound of Formula VIII; or (e) for compounds I in which -NRR<SP>1</SP> is -NH-R 5 , by replacing, in a compound of Formula VIII, in which Y is cyano, alkoxycarbonyl, alkanoyl, alkane sulphonyl or arylsulphonyl, the radical Y by a hydrogen atom; or (f) for compounds I in which -NRR<SP>1</SP> is -N(R 6 )-CH 3 , in which R 6  is hydrogen or alkyl, by reducing a compound of Formula IX, in which R 7  is alkyl, and, if desired, converting a compound obtained by any of methods (a) to (f) into an acid addition salt or quaternary ammonium derivative. The alkyl and alkoxy groups referred to in the above definitions contain 1 to 5 carbon atoms unless otherwise stated. Starting materials.-5-Methyl-10-formamido-, acetylamino -, (N - acetyl - N - ethylamino) -, (N - formyl - N - ethylamino) - and (N - ethoxycarbonyl - N - ethylamino) - 10,11 - dihydrodibenzo[b,f]azepines are prepared by acylation of the corresponding amino compounds. 5- Methyl - 10 - (N - formyl - N - methylamino) - 10,11-dihydrodibenzo[b, f]azepine is prepared by methylation of 5-methyl-10-formamido-10,11- dihydrodibenzo[b,f]azepine. 5 - Methyl - 10- (N - methyl - N - tosylamino) - 10,11 - dihydrodibenzo[b,f]azepine is prepared by reacting ptoluenesulphonyl chloride with 5-methyl-10 - amino - 10,11 - dihydrodibenzo[b,f]azepine to give 5 - methyl - 10 - tosylamino - 10,11 - dihydrodibenzo[b,f]azepine and reacting this with dimothylsulphate. 5 - Methyl - 10 - (N - cyano- N - methylamino) 10,11 - dihydrodibenzo[b,f] azepine is prepared by reacting the corresponding 10-dimethylamino compound with cyanogen bromide. Pharmaceutical compositions having antidepressant, analgesic, anticonvulsant and tranquillizing activity, for oral, parenteral or rectal administration, comprise a compound I, or a pharmaceutically acceptable acid addition or quaternary ammonium derivative thereof, together with a pharmaceutically acceptable carrier or coating.