PROCESS FOR MAKING 1,3-DISUBSTITUTED-4-OXOCYCLIC UREAS

摘要

A process for making 1,3-disubstituted-4-oxocyclic ureas of general formula (I) wherein R1, R2, and R3 are independently selected from the group consisting of nil, C1, F, Br, NH2, NO2, COOH, CH3SO2, NH, SO3H, OH, alkoxy, alkyl, alkoxycarbonyl, hydroxyalkyl, carboxyalkyl, and acyloxy; R4 is selected from the group consisting of a substituted or unsubstituted alkyl, alkenyl, alkynyl, alkylacyl, and heteroalkyl; and A is a substituted or unsubstituted, saturated or unsaturated, straight-chain or branched alkyl or alkenyl amino group comprised of 1-7 carbon atoms; or A is a substituted or unsubstituted, saturated or unsaturated heterocycle having 5, 6, or 7 members containing at least one nitrogen, and R4 is attached to this nitrogen; wherein said 1,3-disubstituted-4-oxocyclic urea is made without isolation of intermediates and comprising the steps: Ia) reacting a 1-substituted-4-oxocyclic urea with a carbon chain containing at least two leaving groups in the presence of a mild base and a solvent to form an adduct containing at least one leaving group, and; Ib) condensing the adduct with an amine to form a 1,3-disubstituted-4-oxocyclic urea, and; II) recovering said 1,3-disubstituted-4-oxocyclic urea, are disclosed. This method is particularly preferred for making 1[[[5-(4-Chlorophenyl)-2-furanyl]methylene]amino]-3-[4-(4-methyl-1-piperazinyl)butyl)-2,4-imidazolidinedione.