Fused heterocyclic systems, incorporating a uracil ring in their structures, play important roles in biological and pharmaceutical processes [1] [2] [3]. Uracil and its derivatives, such as pyrido[2,3-d]pyrimidines, have received considerable attention over the past years because of their biological activities, such as dihydrofolate reductase inhibiting, antibacterial, antiallergic, antitumor, antimicrobial, tyrosine kinase inhibiting, anti-inflammatory, analgesic, calcium channel antagonists, antihypertensive, antitubercular, antileishmanial, potassium sparing, anti-aggressive and antifungal activities [4] - [13]. In addition, uracil fused compounds have also been found to display interesting luminescent properties [14].

Environmentally friendly methodologies for the preparation of heterocyclic compounds offer several important advantages. Multicomponent reactions (MCRs) have gained significant interest from modern medicinal and combinatorial chemists due to the powerful bond forming efficiency, diversity-oriented synthesis, simple reaction design, atom-economy, and response to environmental concerns [15] [16]. In recent years, most of the procedures of the synthesis of pyrido[2,3-d]pyrimidine derivatives have been reported using different catalysts, such as DMAP [17] [18], L-proline [19], BiCl₃ [20], KF-alumina [21], ionic liquids [22] [23] [24] [25] [26], magnetic metal nanoparticles (γ-Fe₂O₃@HAp-SO₃H) [3] [27], Al-HSM-20 [28], DBA (dibutylamine) [29], organo catalyst (DABCO) [30], nano crystalline MgO [31] and ZrO₂ [32].

Bismuth derivatives are attracting the attention of an increasing number of organic chemists. As a result, bismuth (III) triflate was used as the Lewis-acidic catalyst due to its high catalytic activity, low toxicity and stability. Catalytic quantities of Bi(III) compounds are effective in promoting allylations and cyanations, etherification, Diels-Alder reactions, and protection/deprotection, Mannich reactions. The moisture-stable metal triflates, Bi(OTf)₃ (Tf = SO₂CF₃) have been reported as efficient catalysts for various types of organic reactions [33] - [39].

Pyrimidine and its derivatives have been synthesized using various approaches, including multi-component reactions (MCRs). However, most of the procedures which use organic solvents are better than other methods which are toxic and, expensive with non-recoverability of the catalyst.

According to the literature research, it was observed that pyrimidine and its derivatives were obtained by using different catalysts via one-pot method [40] [41]. We describe here an efficient and rapid method for the synthesis of novel pyrido[2,3-d]pyrimidines using triflate as the catalyst.

In this study, we have devised convenient one-pot, three-component reaction for the synthesis of the annulated derivatives of the pyrimidines (4a-h) Scheme 1. To study the effect of the amount of catalyst, the reactions were carried out using different amounts of Bi(OTf)₃ ranging from 10 to 30 mol%. The use of 10 mol% Bi(OTf)₃ in EtOH had optimum results. Using more triflate did not improve the reaction yields.

In our initial study, the preparation of pyrido[2,3-d]pyrimidines (4) was carried out by condensation of 6-amino-1,3-dimethyluracil (1), malononitrile (2) and various substituted aromatic aldehydes (3) in EtOH as the solvent (Table 1). Bi(OTf)₃ catalyst was used for the first time in this type of compound synthesis.

To optimize the loading of the catalyst, the reaction of benzaldehyde (1 mmol), malononitrile (1 mmol), and 6-amino-1,3-dimethyluracil (1 mmol) as a model was investigated. The results are presented in Table 2. According to the data, 20 mol% and 30 mol% of the catalyst was used and the most suitable amount of catalyst was 10 mol%.

Based on with these results, 7-amino-5-(substitued-phenyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-carbonitrile compounds (4a-h) were synthesized in the presence of mol 10% catalyst in ethanol at 80˚C (Table 1).