Solid-Phase Synthesis of 4,6-Diaryl-3,4-dihydropyrimidine-2(1H)-one- 5-carboxylic Acid Amide Derivatives:  A Biginelli Three-Component Condensation Protocol Based on Immobilized β-Ketoamides

Development of Novel Thiazolopyrimidines as CDC25B Phosphatase Inhibitors

“…[27] Here, compounds 2-18 were synthesized by reacting a substituted benzaldehyde, a thio-or selenourea (X = S or Se), and a b-keto ester in dioxane at reflux; para-toluenesulfonic acid (TsOH) was used as the catalyst (Table 1). [28] Preparation of homologue 6, which bears a free carboxylic group at position 5, was achieved through the mild saponification of the corresponding 2-cyanoethyl ester Biginelli product 5. [29,30] Condensation of DHPMs with chloroacetyl chloride and the appropriate benzaldehydes in the presence of sodium acetate in acetic acid/acetic anhydride medium at reflux provided the final thiazolopyrimidines 35-59 and 67-74 as Z isomers, as previously described (Scheme 1).…”

Synthesis of 3,4-dihydropyrimidin-2(1H)-ones catalyzed by nafion-H under ultrasound irradiation and solvent-free conditions

“…However, when the aliphatic aldehydes were used as the starting materials, the yield dropped because of the lower activity of carbonyl group in aliphatic aldehydes (entry 10). 3,4-Dihydropyrimidin-2(1H)-thiones (entries [17][18][19][20][21], which were also of considerable interest with regard to biological activity, were successfully synthesized under similar conditions. 3, 4-Dihydropyrimidin-2-(1H)-ones were achieved in excellent yields without the In summary, we have developed a simple and efficient procedure for the synthesis of dihydropyrimidinones or thiones, using nafion-H as catalyst.…”

“…Basically, these methods are all similar, using different Lewis acid catalysts such as BF 3 [10], FeCl 3 [11], InCl 3 [12], BiCl 3 [13], LaCl 3 [14], LiClO 4 [15], in a solvent such as CH 3 CN, CH 2 Cl 2 , or THF. In addition, several ionic liquids [16], microwave irradiation [17], and combinatorial approaches [18] to 3,4-dihydropyrimidin-2-(1H)-ones have also been employed. Obviously, many of these catalysts and solvents are not at all acceptable in the context of green synthesis.…”

N‐acyliminium intermediates in solid‐phase synthesis

“…Products were in both cases released from the solid support by treatment with TFA, giving the desired dihydropyrimidines 111 (purities: >95%, yields: 30-86%). Recently, Gross et al 47 reported a modification of the Biginelli procedure using b-ketoamides instead of the b-ketoesters (Scheme 21). The b-ketoamides were attached to a Rink-functionalized polystyrene resin via the amide nitrogen and then condensed with urea (or thiourea) and an aldehyde under p-toluenesulfonic acid catalysis.…”