A series of new hexahydropyrido [2,3-d]pyrimidine derivatives 3 were synthesized by the cyclocondensation reaction of (arylmethylidene)pyruvic acids (¼ (3E)-4-aryl-2-oxobut-3-enoic acids) 1 and 6-aminouracils (¼ 6-aminopyrimidine-2,4(1H,3H)-diones) 2 in H 2 O under reflux conditions (Scheme 1, Table). This novel protocol has the advantages of facility, of easy workup, of high yields, and of an environmentally benign procedure. The structures of compounds 3a -3f were corroborated spectroscopically (IR, 1 H-and 13 C-NMR, and EI-MS). A plausible mechanism for the reaction is proposed (Scheme 2).Introduction. -The compounds which possess a dihydropyridopyridine framework in their structure have been recognized both in medicinal [1] and in synthetic chemistry [2 -4] With the aim of developing more efficient synthetic methods, improving the bondforming efficiency (BFE), and in continuation of our previous work on the cyclocondensation reactions, which were performed in H 2 O successfully [18], we now report our study about the reaction of (arylimethylidene)pyruvic acids (¼ (3E)-4-aryl-2-oxobut-3-enoic acids) 1 with 6-aminouracils (¼ 6-aminopyrimidine-2,4(1H,3H)-diones) 2 as highly reactive heterocyclic C-nucleophiles. This approach allowed us to prepare the previously unknown hexahydropyrido [2,3-d]pyrimidine derivatives 3 (Scheme 1). Besides their potential biologic activities, the produced target compounds 3, as heterocyclic a-amino-a,b-unsaturated carboxylic acids, can be of interest for the synthesis of novel peptides containing a heterocyclic moiety in their skeleton, which could lead to some biologically active compounds. On the other hand, compounds 3 can be used as efficient starting materials for further multicomponent reactions due to the presence of both an amine and a carboxylic acid functional group.Because of the toxic and volatile nature of many organic solvents, the use of H 2 O as a solvent medium is of interest. Compared with organic solvents, H 2 O has advantages

A simple and fastthree-component synthesis of new and biologically active hexahydro-2-quinolinecarboxylic acid scaffold 4 was carried out using cyclocondensation reaction of arylmethylidenepyruvic acids 1, 1,3-cyclohexandiones 2 and ammonium acetate 3 under solvent-free conditions and at room temperature. This protocol has the advantages of facility, easy work-up, high yields, short reaction time and environmentally friendly character.