GB833474A - Piperazine derivatives - Google Patents

Abstract

The invention comprises compounds of the general formula <FORM:0833474/IV (b)/1> and their pharmaceutically acceptable acid addition salts, and the preparation thereof by condensing a compound of the general formula <FORM:0833474/IV (b)/2> with a piperazine of the formula <FORM:0833474/IV (b)/3> wherein n is 1 or 2, R1 is a hydrogen atom or a lower alkyl group or the residue of a lower aliphatic carboxylic acid (the term "lower" indicating not more than 6 carbon atoms in the group so described) and of P and Q one is hydrogen and the other is a group CH2CH2CH2X or CH2CH2COX, X being a reactive electronegative atom or radical, such as a p halogen atom or an aryl sulphonic ester radical, and if necessary reducing CH2CH2CO to propylene. The reaction is preferably carried out in the presence of a basic condensing agent. In an example, 2-trifluoromethylphenothiazine is condensed with 1-chloro-3-bromopropane in the presence of sodium amide and liquid ammonia, to form 10-(3-chloropropyl)-2-trifluoromethylphenothiazine which is heated with 1-(2hydroxyethyl)-piperazine to give 1-(2-hydroxyethyl) - 4 - [3 - (2 - trifluoromethyl - 10 - phenothiazyl)-propyl]-piperazine. Similarly, but using 1 - (3 - hydroxypropyl) - piperazine the corresponding propyl analogue is obtained. In further examples the 1-(2-hydroxyethyl) derivative is reacted with phenyl chlorocarbonate to give the corresponding phenyl carbonate ester and this in turn with ammonia yields the carbamate of 1-(2-hydroxyethyl)-4-[3-(2trifluoromethyl - 10 - phenothiazyl) - propyl]piperazine; with dimethylcarbamyl chloride to give the dimethylcarbamate ester; with ethyl chlorocarbonate to give the ethyl carbonate ester (both with the 1-(2-hydroxy)ethyl) and 1-(3-hydroxypropyl) derivatives); and with acetic or propionic anhydrides to give the acetate or propionate esters. Condensing 10gives 1 - (2 - ethoxyethyl) - 4 - [3 - 2 - trifluoromethyl - 10 - phenothiazyl) - propyl] - piperazine. The dihydrochlorides and dimaleates of the esters above are also described.