DBU-Mediated Cyclization of Acylcyclopropanecarboxylates with Amidines: Access to Polysubstituted Pyrimidines

Abstract

DBU-mediated cyclization of 2-acyl-1-cyanocyclopropanecarboxylates with amidines for the synthesis of multisubstituted pyrimidine derivatives is described. This reaction gives a practical method for producing a diverse set of pyrimidines, having simple experimentation, readily available starting materials, a wide substrate scope, and very good yields.

Stereoselective Synthesis of 4,5‐Dihydroisoxazole Derivatives from 1,1‐Dicyanocyclopropanes and Hydroxylamine Hydrochloride

“…Thin layer chromatography (TLC) was used to monitor all reactions. These reported methods were used for the preparation of substituted cyclopropane‐1,1‐dicarbonitriles 7a – 7e , [97–112] other reagents and solvents were purchased from commercial suppliers and purified by standard techniques.…”

“…to construct various carbo‐ and heterocyclic compounds, containing many natural compounds and their analogs. As easily available multifunctional D‐A cyclopropanes, 2‐acyl‐3‐aryl‐cyclo‐propane‐1,1‐dicarbonitriles and 2‐acyl‐3‐aryl‐1‐cyanocyclopropane‐1‐carboxylates [84–96] have attracted wide attention in the classical heterocycle syntheses [97–112] . Considering the driving forces for the development of these new routes, and in continuation of using multifunctional D‐A cyclopropanes in the synthesis of diverse and complex compounds, we envisioned an approach to access functionalized isoxazoline derivatives through a cyclization reaction of substituted 1,1‐dicyanocyclopropane derivatives and hydroxylamine hydrochloride.…”

Synthesis of 1,2,4,5‐tetrasubstituted imidazoles and 2,4,5,6‐tetrasubstituted pyrimidines: three‐component, the one‐pot reaction of arylamidines, malononitrile, and arylglyoxals or aryl aldehydes

“…[17] Besides, many imidazole and pyrimidine-based agents have been extensively studied as drug candidates and some of them are used clinically such as nilotinib, [18] metronidazole, [19] voriconazole, [20] eprosartan, and losartan. [21] Due to the wide range of applications of imidazole and pyrimidine cores, a variety of methods have been reported to the synthesis of them including various multi-component methods, [22][23][24][25][26] cyclization reaction, [22,[27][28][29] metal-catalyzed, [30][31][32][33] multistep approaches, [34,35] Diels-Alder reaction, [36] and various other methods. [37,38] However, the above-mentioned methods for synthesis of imidazole and pyrimidine derivatives suffer from one or more disadvantages, for example difficult reaction conditions, low yields, complex work-up and purification, multiple synthetic steps, and usage of expensive catalysts and reagents.…”

Annulation of α-bromocinnamaldehydes to access 3-formyl-imidazo[1,2-α]pyridines and pyrimidines under transition metal-free conditions

“…3 For example, imidazo[1,2- α ]pyridines can be used as the synthetic precursors of soraprazan, 4 alpidem 5 and zolpidem. 6 Pyrimidine derivatives can be applied to antibacterial, 7 anticancer, 8 antiviral 9 and antitumor drugs. 10 Therefore, many efforts have been made to construct these important nitrogen-containing heterocyclic skeletons.…”