Dihydropyrimidones, synthesis

P rez, R., Beryozkina, T., Zbruyev, O.I., Haas, W. and Kappe, C.O., Traceless solid phase synthesis of bi-cyclic dihydropyrimidones using multidirectional cyclization cleavage, /. Comb. Chem., 2002,4, 501-510 and references cited therein. 

Dondoni and Massi9 executed a Bignelli synthesis to prepare dihydro-pyrimidinones starting from aldehydes, 1,3-dicarbonyl compounds, and urea with ytterbium(III) supported on Amberlyst 15 resin as a Lewis acid (entry 5). After condensation, the reaction mixture is treated with both strongly basic and acid resins to sequester reaction by-products. For more than 30 reported examples, dihydropyrimidones obtained directly from concentration of the filtrates are produced in high yields and in excellent purities. 

As an alternative to the chemical resolution methods described by Atwal et al. (Scheme 4.13), a biocatalytic strategy towards the preparation of enantiopure (R) and (S)-SQ 32,926 was developed (Scheme 4.15). The key step in the synthesis is the enzymatic resolution of an N3-acetoxymethyl-activated dihydropyrimidone precursor by Thermomyces lanuginosus lipase [189]. The readily available racemic DHPM 43 was hydroxymethylated at N3 with formaldehyde, followed by standard acetylation with acetyl chloride. The resulting N3-acetoxymethyl-activated DHPM... 

This acid-catalyzed, three-component reaction between an aldehyde, a i-ketoester and urea constitutes a rapid and facile synthesis of dihydropyrimidones, which are interesting compounds with a potential for pharmaceutical application. 

The ytterbium triflate catalyzed Biginelli reaction of aldehydes, ethyl acetoacetate and urea to give in a one-pot synthesis dihydropyrimidones was performed again in higher yields without any solvent (Scheme 13) [38]. 

Very recently, Maiti and coworkers150 developed a new methodology for the synthesis of dihydropyrimidones, 246, by a one-pot three-component condensation using a catalytic amount of LiBr, under very mild reaction conditions (Scheme 76). 

Scheme 2.3-8 Solid-phase synthesis of dihydropyrimidones by Wipf and Cunningham.

Rafiee, E., Shahbazi, F. 2006. One-pot synthesis of dihydropyrimidones using silica-supported heteropoly acid as an efficient and reusable catalyst Improved protocol conditions for the Biginelli reaction. Journal of Molecular Catalysis A Chemical 250(l-2) 57-61. 

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