Three-component Reaction of Cycloheptanone, 6-Amino-1,3-Dimethyluracil and Aromatic Aldehydes; X-Ray Structure, and Anti-inflammatory Evaluation of the Products

Abstract

1,3-Dimethyl-5-aryl-1,6,7,8,9,10-hexahydrocyclohepta[5,6]pyrido[2,3-d]pyrimidine-2,4-diones 4a, b (the linear regioisomers) and the Schiff bases, 6-N-benzylidenamino-1,3-dimethyluracil derivatives 5a, b, were isolated from a three-component reaction of cycloheptanone, 6-amino-1,3- dimethyluracil, and 4-chloro- or 4-bromobenzaldehyde. Surprisingly, 1,3-dimethyl-10-aryl-1,5,6,7, 8,9-hexahydrocyclohepta[4,5]pyrido-[2,3-d]pyrimidine-2,4-diones 6f, g (the angular regioisomers which are described for the first time in the literature under the given reaction conditions) and the Schiff bases, 6-N-benzylidenamino-1,3-dimethyluracil derivatives 5f, g, were isolated and characterized from the reaction with 4-methoxybenzaldehyde and 4-cyanobenzaldehyde. However, the three-component reaction of 6-amino-1,3-dimethyluracil, cycloheptanone, and 2-methoxybenzaldehyde afforded 1,3-dimethylbenzo[4,5]pyrido[3,2-d]pyrimidine-3,4-dione (7). Single crystal X-ray diffraction and 13C NMR studies of 4a and 6f provided support for the established structures. Some of the new products were tested for antiinflammatory activity comparable to indomethacin.