The present invention provides a process for preparing the compound 5-fluoro-4-imine-3-methyl-1-(phenyl-4-sulfonyl)-3,4-dihydro-1H-pyrimidin-2-one having the formula (I):

##STR00001##

comprising (a) reacting 5-fluorocytosine with compound having the formula (III):

##STR00002##

in the presence of at least one polar solvent and at least one base to obtain the compound having the formula (II)

##STR00003##

and (b) reacting compound having the formula (II) with dimethylsulphate (DMS), wherein R is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, alkoxycarbonyl, alkyl carbonyl, hydroxyalkyl, ester, acid halogen, —SH, —OH, —NH.sub.2, —NO.sub.2, —CN or CF.sub.3, and X is a halogen or —OSO.sub.2PhR.

The present invention provides a process for preparing the compound 5-fluoro-4-imine-3-methyl-1-(phenyl-4-sulfonyl)-3,4-dihydro-1H-pyrimidin-2-one having the formula (I):

##STR00001##

comprising (a) reacting 5-fluorocytosine with compound having the formula (III):

##STR00002##

in the presence of at least one polar solvent and at least one base to obtain the compound having the formula (II)

##STR00003##

and (b) reacting compound having the formula (II) with dimethylsulphate (DMS), wherein R is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, alkoxycarbonyl, alkyl carbonyl, hydroxyalkyl, ester, acid halogen, —SH, —OH, —NH.sub.2, —NO.sub.2, —CN or CF.sub.3, and X is a halogen or —OSO.sub.2PhR.

Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for the inhibition of Signal Transducer and Activator of Transcription 5a and 5b (STAT5). Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as, for example, breast cancer and pancreatic cancer.

Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for the inhibition of Signal Transducer and Activator of Transcription 5a and 5b (STAT5). Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as, for example, breast cancer and pancreatic cancer.

The present invention relates to technical field of chemical synthesis of drugs, and provides a preparation method of Macitentan and intermediate compound thereof. Adding THF solution containing compound II and 5-bromo-2-chloropyrimidine slowly into THF solution containing base to react, or adding THF solution containing compound II and THF solution containing 5-bromo-2-chloropyrimidine slowly at the same time into THF solution containing base to react and obtain Macitentan (shown as compound I), wherein the base is selected from sodium hydride, potassium hydride, lithium hydride or lithium bis(trimethylsilyl)amide. The selectivity of the preparation method is very good, which is suitable for industrial production. The obtained product Macitentan has good quality and high yield. And the product compound II also has good quality and high yield, its HPLC purity is up to 99.0%, the content of impurity A is less than 0.20%, the content of impurity B is less than 0.25%. ##STR00001##

The present invention relates to technical field of chemical synthesis of drugs, and provides a preparation method of Macitentan and intermediate compound thereof. Adding THF solution containing compound II and 5-bromo-2-chloropyrimidine slowly into THF solution containing base to react, or adding THF solution containing compound II and THF solution containing 5-bromo-2-chloropyrimidine slowly at the same time into THF solution containing base to react and obtain Macitentan (shown as compound I), wherein the base is selected from sodium hydride, potassium hydride, lithium hydride or lithium bis(trimethylsilyl)amide. The selectivity of the preparation method is very good, which is suitable for industrial production. The obtained product Macitentan has good quality and high yield. And the product compound II also has good quality and high yield, its HPLC purity is up to 99.0%, the content of impurity A is less than 0.20%, the content of impurity B is less than 0.25%. ##STR00001##

The present invention provides a process for preparing a compound having the formula (I):

##STR00001## wherein R is alkyl or alkylaryl; each of X.sub.1, X.sub.2, X.sub.3, X.sub.4 and X.sub.5 is, independently, H, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, alkoxycarbonyl, alkyl carbonyl, hydroxyalkyl, ester, acid halogen, —SH, —OH, —NH.sub.2, —NO.sub.2, —CN or CF.sub.3; Y is O or S; and and Z is a halogen.

The present invention provides a process for preparing a compound having the formula (I):

##STR00001## wherein R is alkyl or alkylaryl; each of X.sub.1, X.sub.2, X.sub.3, X.sub.4 and X.sub.5 is, independently, H, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, amino, alkylamino, dialkylamino, alkoxycarbonyl, alkyl carbonyl, hydroxyalkyl, ester, acid halogen, —SH, —OH, —NH.sub.2, —NO.sub.2, —CN or CF.sub.3; Y is O or S; and and Z is a halogen.

Compounds of formula (I), wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides.

##STR00001##

Compounds of formula (I), wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides.

##STR00001##