Provided herein is a process and intermediates for the preparation of a compound of formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof, using cyanamide in the reaction.

The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxysulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives.

The new method of preparing 1-(2-(2,4-di-methylphenylsulphanyl)phenyl)piperazine of formula (I) or its salt comprises a reaction of 2-(2,4-dimethylphenyl-sulphanyl)benzeneamine of formula (XI), wherein Me is methyl, with a suitable precursor of formation of piperazine ring of formula (XII), wherein LG is a leaving group and R is hydrogen or a protective group, in a suitable organic solvent, wherein the reaction is carried out without presence of a base in a neutral or acidic environment. (Formulae (I), (XI), (XII)) ##STR00001##

The new method of preparing 1-(2-(2,4-di-methylphenylsulphanyl)phenyl)piperazine of formula (I) or its salt comprises a reaction of 2-(2,4-dimethylphenyl-sulphanyl)benzeneamine of formula (XI), wherein Me is methyl, with a suitable precursor of formation of piperazine ring of formula (XII), wherein LG is a leaving group and R is hydrogen or a protective group, in a suitable organic solvent, wherein the reaction is carried out without presence of a base in a neutral or acidic environment. (Formulae (I), (XI), (XII)) ##STR00001##

A method for treating in an industrial water treatment system for at least two of metal corrosion inhibition, scale inhibition, suspended matter dispersion, biocide efficacy, or biofilm removal/biofilm dispersion is taught by the use of at least one compound which is a salt derived from a thioamine or an oxyamine and an acid.

The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxysulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives.

The new method of preparing 1-(2-(2,4-di-methylphenylsulphanyl)pheny!)piperazine of formula (I) or its salt comprises a reaction of 2-(2,4-dimethylphenyl-sulphanyl)benzeneamine of formula (XI), wherein Me is methyl, with a suitable precursor of formation of piperazine ring of formula (X11), wherein LG is a leaving group and R is hydrogen or a protective group, in a suitable organic solvent, wherein the reaction is carried out without presence of a base in a neutral or acidic environment.

##STR00001##

The new method of preparing 1-(2-(2,4-di-methylphenylsulphanyl)pheny!)piperazine of formula (I) or its salt comprises a reaction of 2-(2,4-dimethylphenyl-sulphanyl)benzeneamine of formula (XI), wherein Me is methyl, with a suitable precursor of formation of piperazine ring of formula (X11), wherein LG is a leaving group and R is hydrogen or a protective group, in a suitable organic solvent, wherein the reaction is carried out without presence of a base in a neutral or acidic environment.

##STR00001##