Patent GB-1477079-A (GB)
Title: 1-aminoalkyl-6-phenimidazo-1,2-a-1,4-benzodiazepines and their pharmaceutical compositions
IPC: C07D209/48
Filed: 1975-09-03
Abstract: 1477079 1 - Aminoalkyl - 6 - phenylimidazo- [1,2 - a][1,4]benzodiazepenes and their pharmaceutical compositions UPJOHN CO 3 Sept 1975 [12 Sept 1974] 36257/75 Heading C2C The invention comprises compounds of the general Formula XXIVA wherein R 0 , R 1  and R 2  are H, CH 3  or C 2 H 5 ; R 3  is H, Cl or F ; R 4  is H or F; R 5  is H, Cl, F, Br, CF 3  or NO 2  and R<SP>1</SP> and R<SP>11</SP> are independently H or C 1-3  alkyl, which may be prepared (a) when R<SP>1</SP> and R<SP>11</SP> are both hydrogen, by reaction of a compound of Formula III with hydrazine (b) when R<SP>1</SP> and R<SP>11</SP> are the same and are C 1-3  alkyl, by alkylation of the product of (a) with an alkyl halide or with an aldehyde, sodium cyanoborohydride and acetic acid (c) by thermal cyclization of a compound of Formula IX at 110-200 C. (d) when R<SP>1</SP> is C 1-3  alkyl and R<SP>11</SP> is hydrogen by mono dealkylation of a compound prepared by route (b) by treating with phenyl chloroformate followed by NaOH or KOH. Intermediates of Formula III (above) are prepared by reacting a compound of Formula II wherein R 1 , R 0 , R 2 , R 3 , R 4  and R 5  are as defined above, with sulphuric acid, the compounds of Formula II being prepared by reaction of a compound of Formula I with a compound of Formula XIV Phthalimidoacetone ethylene ketal is prepared by reaction of phthalimidoacetone with ethylene glycol and is then reacted with bromine to obtain (3-phthalimidoacetonyl)bromide ethylene ketal. In the same manner 1-phthalimido-3- bromo-butan-2-one, ethylene ketal is prepared by reaction of potassium phthalimide with 1- bromo-2-butanone followed by reaction of the produced 1-phthalimido-2-butanene with glycol to form the ethylene ketal which is then brominated. (3 - Phthalimidoacetonyl)azide, ethylene ketal is prepared by reaction of the corresponding bromine compound with sodium azide and is reduced with hydrogen over Pd/C to obtain (3- phthalimidoacetonyl)amine, ethylene ketal which is itself reacted with formalin to obtain (3- phthalimidoacetonyl)dimethylamine, ethylene ketal. The corresponding 3-phthalimido-butanone derivatives are prepared in the same manner from 1-phthalimido-3-bromo-2-butanone by reaction with sodium azide followed by reduction and alkylation. (3 - Bromoacetonyl)amine, ethylene ketal is prepared by reacting (3-phthalimidoacetonyl)- bromide, ethylene ketal with hydrazine and is reacted with 7-chloro-1,3-dihydro-5-phenyl-2H- 1,4-benzodiazepine-2-thione to obtain 7-chloro- 5 - phenyl - 2[3(bromoacetonyl) - amino] - 3H- 1,4 - benzodiazepine, ethylene ketal which is reacted with sodium azide to obtain the corresponding 3(azidoacetonyl) compound which is hydrogenated to form the 3-aminoacetonyl derivative and alkylated to form 7-chloro-5- phenyl - 2 - [[3 - (dimethylamino)acetonyl]amino]- 3H - 1,4 - benzodiazepine, ethylene ketal. Pharmaceutical compositions having tranquillizing and sedative activity for oral, rectal and parenteral administration comprise at least one compound of Formula XXIVA together with a pharmaceutically acceptable diluent or carrier.