Patent GB-722627-A (GB)
Title: Improvements relating to new 1-substituted-4-aminopiperazine derivatives and the preparation thereof
IPC: C07D295/32
Filed: 1952-06-18
Abstract: The invention comprises piperazine derivatives of the formula <FORM:0722627/IV (b)/1> where R is an alkyl, aralkyl, monocyclic aryl, carbalkoxy, dialkylcarbamyl or heterocyclic radical (the latter attached by a -c\s9N-group), Y1 and Y2 are hydrogen or methyl, and Z is carbalkoxy, R1-CO-, R1-SO2-, R2-NH-CO-, (R3)2N-CO- or R4-NH-CS-, R1 being alkyl, aryl or aralkyl, R2 cycloalkyl or aryl, R3 alkyl and R4 aryl, alkyl or alkenyl.  These are prepared by treating the corresponding N-aminopiperazines with the appropriate acyl halides, sulphonyl halides, haloformic esters, carbamyl halides, isocyanates or isothiocyanates; the reaction may be carried out at 0-100 DEG  C. in an inert solvent.  When R is alkyl or aralkyl the products may be converted, into salts.  Examples show the preparation of ethyl N-(4-carbethoxy-1-piperazyl)-carbamate, 1 - carbethoxy - 4 - acetyl - amino - piperazine, 1 - carbethoxy - 4 - phenylacetylamino - piper - azine, 1 - phenyl - 3 - (4 - carbethoxy - 1 - piperazyl) - urea, 1 - cyclohexyl - 3 - (4 - carbethoxy - 1 - piperazyl) - urea, 1 - phenyl - 3 - (4 - carbethoxy - 1 - piperazyl) - thiourea, 1 - allyl - 3 - (4 - carbethoxy - 1 - piperazyl) - thiourea, ethyl N - (4 - diethylcarbamyl - 1 - piperazyl) - carbamate, 1 - diethylcarbamyl - 4 - acetylaminopiperazine, 1 - diethylcarbamyl - 4 - benzoylaminopiperazine, 1 - phenyl - 3 -(4 - di - ethylcarbamyl - 1 - piperazyl) - urea, 1 - cyclo - hexyl - 3 - (4 - diethylcarbamyl - 1 - piperazyl) - urea, 1 - ethyl - 3 - (4 - diethylcarbamyl - 1 - piperazyl) - thiourea, N - (4 - diethylcarbamyl-1 - piperazyl) - 4 - chlorobenzenesulphonamide, ethyl N - (4 - methyl - 1 - piperazyl) - carbamate, 1 - cyclohexyl - 3 - (4 - methyl - 1 - piperazyl) - urea, 1 - ethyl - 3 - (4 - methyl - 1 - piperazyl) - thiourea, ethyl N - (4 - benzyl - 1 - piperazyl) - carbamate, 1 - benzyl - 4 - acetylaminopiper - azine, 1 - benzyl - 4 - phenylacetylamino - piperazine, 1 - benzyl - 4 - benzoylamino - piperazine, 1 - phenyl - 3 - (4 - benzyl - 1 - piperazyl) - urea, 1 - phenyl - 3 - (4 - benzyl - 1 - piperazyl) - thiourea, ethyl N - [4 - (p - chloro - phenyl) - 1 - piperazyl] - carbamate, 1 - (p - chlorophenyl) - 4 - acetylaminopiperazine, 1 - phenyl - 3 - [4 - (p - chlorophenyl) - 1 - piperazyl]-urea, 1 - (o - chlorophenyl) - 3 - [4 - (p - chloro - phenyl) - 1 - piperazyl] - urea, 1 : 1 - diethyl - 3 - [4 - (p - chlorophenyl) - 1 - piperazyl] - urea, 1 - allyl - 3 - [4 - (p - chlorophenyl) - 1 - piperazyl] - thiourea, ethyl N - [4 - (2 - pyridyl) - 1 - piper - azyl] - carbamate, 1 - (2 - pyridyl) - 4 - acetyl - aminopiperazine, 1 - phenyl - 3 - [4 - (2 - pyridyl) - 1 - piperazyl] - urea, 1 - allyl - 3 - [4 - (2 - pyridyl) - 1 - piperazyl] - thiourea, N - [4 - (2 - pyridyl) - 1 - piperazyl] - 4 - chloro - benzenesulphonamide, ethyl N - [4 - (2 - pyrimidyl) - 1 - piperazyl] - carbamate, 1 - (2 - pyrimidyl) - 4 - acetylaminopiperazine, 1 - cyclohexyl - 3 - [4 - (2 - pyrimidyl) - 1 - piper - azyl] - urea and 1 - ethyl - 3 - [4 - (2 - pyrimidyl)-1-piperazyl]-thiourea.