Patent GB-1017276-A (GB)
Title: Novel 1,4-benzodiazepine derivatives
IPC: C07D243/32
Filed: 1962-07-27
Abstract: The invention comprises compounds of the general formula <FORM:1017276/C2/1> (wherein R1 and R2 are the same or different and each represents a C1- 7 alkyl, C2- 7 alkenyl or C1- 7 alkanoyl group, R2 represents a C1- 7 alkyl group, R4 and R5 are the same or different and each represents a halogen atom or a trifluoromethyl, nitro, amino, C1- 7 alkanoylamino, C1- 7 alkylthio, C1- 7 alkoxy, C1- 7 alkyl, cyano, carboxy, C2- 7 alkoxycarbonyl or di(C1- 7 alkyl)amino group, and the broken lines denote optional substituents), 4,5-dehydro derivatives thereof in which R3 is absent, and acid addition salts of the basic compounds and derivatives, pharmaceutical preparations containing them, and their preparation by (a) reacting a compound of the formula <FORM:1017276/C2/2> (wherein R40 and R50 are the same or different and each represents a halogen atom or a trifluoromethyl, amino, nitro, C1- 7 alkylthio, C1- 7 alkoxy, C1- 7 alkyl or di(C1- 7 alkyl)amin group), or a 4,5-dehydro derivative thereof in which R3 is absent, with lithium aluminium hydride, (b) reacting a compound of the formula <FORM:1017276/C2/3> with a compound of the formula <FORM:1017276/C2/4> (c) treating a compound of the formula <FORM:1017276/C2/5> (wherein R10 represents a C1- 7 alkyl or C2- 7 alkenyl group, and R41 and R51 are the same or different and each represents a halogen atom or a trifluoromethyl, amino, C1- 7 alkanoylamino, C1- 7 alkoxy, C1- 7 alkyl, cyano, carboxy, C2- 7-alkoxycarbonyl or di-(C1- 7 alkyl) amino group) with Raney nickel in the presence of a solvent, or (d) hydrolysing and cyclizing a compound of the formula <FORM:1017276/C2/6> (wherein R11 represents a C1- 7 alkyl, C2- 7 alkenyl or tosyl group, R8 represents an acylamino group, and R42 and R52 are the same or different and each represents a halogen atom or a C1- 7 alkanoylamino, trifluoromethyl, nitro, C1-7 alkylthio, C1- 7 alkoxy, C1- 7 alkyl, carboxy, C2- 7 alkoxycarbonyl, cyano or di-(C1- 7 alkyl)-amino group), either by treatment with an alkaline agent or by treatment with an acid followed by treatment with a basic agent, optionally followed in each case by one or more of the steps (i) introduction of R1, R3 and/or certain of the R4, R5 substituents, (ii) replacement of certain of the R4, R5 substituents by other R4, R5 substituents, (iii) reduction of a dihydro to a tetrahydro compound, and (iv) acid addition salt formation.  In certain cases the substituents are removed or converted to other substituents during the main reaction, reduction of a dihydro to a tetrahydro compound may take place, and a mixture of products may be obtained.  The preparation of the following intermediates is described: 7-chloro-5-(2-chlorphenyl)-1 - methyl - 1,2,4,5 - tetrahydro - 1H - 1,4 - benzo-diazepinone - (2), 7 - chloro - 1,4 - dimethyl - 5 - phenyl - 1,2,4,5 - tetrahydro - 3H - 1,4 - benzo-diazepinone - (2), 2 - chloro - 21 - nitrobenzophenone, 2 - amino - 21 - chlorobenzophenone, 2 - bromo - 21 - (2 - chlorobenzoyl)acetanilide, 2 - amino - 21 - (2 - chlorobenzoyl)acetanilide, 5 - (2 - chlorophenyl - 2,3 - dihydro - 1H - 1,4 - benzodiazepinone - (2), 2 - aminoethylamino - 5 - carboxybenzophenone hydrochloride, 4-acetyl-7-chloro-5 - (2 - fluorophenyl) - 1,2,4,5 - tetrahydro - 3H - 1,4 - benzodiazepinone - (2) and 4 - acetyl - 7 - chloro - 1 - ethyl - 5 - (2 - fluorophenyl) - 1,2,4,5 - tetrahydro - 3H - 1,4 - benzodiazepinone - (2).  The compounds of the invention are muscle relaxants, sedatives and anticonvulsants and may be administered enterally or parenterally in the form of pharmaceutical preparations (e.g. tablets, dragees, suppositories, capsules, solutions, emulsions and suspensions) containing them, with or without other (unspecified) active ingredients, together with a carrier.