Patent GB-1355170-A (GB)
Title: Benzodiazepine derivatives and a process for the manufacture thereof
IPC: C07D275/02
Filed: 1972-05-12
Abstract: 1355170 Benzodiazepines F HOFFMANNLA ROCHE & CO AG 12 May 1972 [13 May 1971] 22368/72 Heading C2C Compounds of the general Formula (I) (B = CO, CH 2 ; R = H, halogen, CF 3 , NO 2 , amino, C 1-7  alkyl, 1-adamantylcarbonylamino, t-alkylcarbonylamino; R 1  = H, C 1-7  alkyl, hydroxyalkyl or aminoalkyl, C 2-7  alkenyl or alkynyl, cycloalkyl-(C 1-7  alkyl), C 1-7  alkylamino- (C 1-7  alkyl), di-(C 1-7  alkyl)amino-C 1-7  alkyl; R 2  = thiazolyl, isothiazolyl, pyrazolyl, 1-(C 1-7  alkyl)pyrazolyl, imidazolyl, 1-(C 1-7  alkyl)imidazolyl; R 3,4  = H or R 3+4  = C-N bond; R 5 =H, OH; provided that (i) when B = CO, R 3+4 = C-N bond, (ii) when B = CH 2 , R = halogen, NO 2 , amino, 1-adamantylcarbonylamino, talkylcarbonylamino, (iii) when B = CO, R 1 =H and R 2  = thiazolyl, R = amino, 1-adamantylcarbonylamino, t-alkylcarbonylamino and (iv) when R 5  = OH, B = CO and R 1  = C 1-7  alkyl) and their acid addition salts are prepared by standard methods, e.g. cyclizing an aminoacetamidophenyl ketone or reacting a 2-halo-5- nitrophenyl ketone with ethylene diamine or a derivative thereof, optionally followed by introduction of a 1-substituent, reduction of NO 2  to NH 3  and replacement of the latter by halogen and/or reduction of a 4,5-double bond. The preparation of α-(1-methyl-5-pyrazolyl)-5- chloro-2-nitrobenzyl alcohol, 5-chloro-2-nitrophenyl 1-methyl-5-pyrazolyl ketone, 2-amino-5- chlorophenyl 1-methyl-5-pyrazolyl ketone, 2-(2- bromoacetamido)-5-chlorophenyl 1-methyl-5-pyrazolyl ketone, α-(o-nitrophenyl)-2-thiazolylmethanol, o-nitrophenyl 2-thiazolyl ketone, o-aminophenyl 2-thiazolyl ketone, 2-bromoacetamidophenyl 2-thiazolyl ketone, 5-(2-thiazolyl)-1,3-dihydro-2H- 1,4-benzodiazepin-2-one, α-(2-thiazolyl)-2-chloro- 5-nitrobenzyl alcohol, 2-chloro-5-nitrophenyl 2- thiazolyl ketone, α-(1-methyl-5-pyrazolyl)-2-chloro- 5-nitrobenzyl alcohol, 2-chloro-5-nitrophenyl 1- methyl-5-pyrazolyl ketone, α-(1-methyl-2-imidazolyl)-5-chloro-2-nitrobenzyl alcohol, 5-chloro-2- nitrophenyl 1-methyl-2-imidazolyl ketone, 2-amino 5-chlorophenyl 1-methyl-2-imidazolyl ketone, 2-(2- bromoacetamido)-5-chlorophenyl 1-methyl-2-imidazolyl ketone, α-(1-methyl-2-imidazolyl)-2-chloro- 5-nitrobenzyl alcohol, 2-chloro-5-nitrophenyl 1- methyl-2-imidazolyl ketone, α-(5-chloro-2-nitrophenyl)-2-thiazolylmethanol, 5-chloro-2-nitrophenyl 2-thiazolyl ketone, 2-amino-5-chlorophenyl 2- thiazolyl ketone, 2-(2-bromoacetamido)-5-chlorophenyl 2-thiazolyl ketone, 7-chloro-5-(2-thiazolyl)- 1,3-dihydro-2H-1,4-benzodiazepin-2-one, α-(5- isothiazolyl)-5-chloro-2-nitrobenzyl alcohol, 5-chloro-2-nitrophenyl 5-isothiazolyl ketone, α-(5-isothiazolyl)-2-chloro-5-nitrobenzyl alcohol, 2-chloro- 5-nitrophenyl 5-isothiazolyl ketone, 2-amino-5- iodophenyl 2-thiazolyl ketone, 2-(2-bromoacetamido)-5-iodophenyl 2-thiazolyl ketone and 7-iodo-5- (2-thiazolyl)-1,3-dihydro-2H-1,4-benzodiazepin-2- one is described.  The compounds (I) and their salts are anticonvulsants, muscle relaxants and sedatives, and may be administered in the form of pharmaceutical preparations containing them in association with a carrier.