PROCESS FOR THE MANUFACTURE OF SUBSTITUTED MALEIMIDES

The invention provides a process for the manufacture of substituted maleimides of the formula (see formula I) wherein R1 represents alkyl, aryl or heteroaryl and R2 represents hydrogen, alkyl, alkoxycarbonyl, aryl or heteroaryl, by reacting an activated glyoxylate of the formula (see formula II) wherein R1 has the above significance and X represents a leaving atom or group, with an imidate of the formula (see formula III) wherein R2 has the above significance, R3 represents alkyl, aryl or trialkylsilyl and Y represents oxygen or sulphur, in the presence of a base and, after treating a reaction product obtained in which R2 represents hydrogen or alkyl with a strong base, hydrolyzing and dehydrating the resulting hydroxypyrrolinone of the formula (see formula IV) wherein R1, R2, R3 and Y have the above significance. The substituted maleimides of formula I are pharmacologoically active, for example as protein kinase C inhibitors useful e.g. in the treatment and prophylaxis of inflammatory, immunological, bronchopulmonary and cardiovascular disorders, or as antiproliferative agents useful e.g. in the treatment of immune diseases and allergic disorders.