Synthesis of fused pyrimidone derivatives of 4-pyrones from the acetates of Baylis–Hillman adducts

Abstract

A series of fused pyrimidone derivatives of 4-pyrones was synthesized by conversion of the acetates of Baylis−Hillman adducts obtained from 2-formyl-4-pyrones with 2-aminopyridine and 2-aminothiazole.The fused pyrimidine derivatives are of interest not only for their rich and varied synthetic chemistry but also for their important medicinal and physiological properties [1][2][3]. Therefore the synthesis of such derivatives has been an attractive area of a focus for synthetic organic and bioorganic chemists as well as numerous methods for the preparation of these heterocyclic compounds have been developed [4][5][6][7][8][9].The Baylis-Hillman reaction, a powerful tool for construction of a variety of cyclic and heterocyclic frameworks, has been used for the synthesis of various fused heterocyclic systems [10,11] such as fused pyrimidines. The reaction of 2-aminopyridine with acetates of Baylis-Hillman adducts leading to the formation of substituted fused pyrimidones has been reported [12]. Later the Baylis-Hillman products of acrylonitrile were used for the synthesis of annelated pyrimidine derivatives [13]. The allyl amine derivatives generated from acetates of Baylis-Hillman adducts have been also used as viable precursors for several fused pyrimidine derivatives [14][15][16][17].Heterocyclic substituted 4-pyrones have also been found in a variety of natural and synthetic biologically active compounds. Some of them are anticoagulants [18] or anti-HIV [19] agents. In continuation of our attempts in preparing various N-hetaryl-substituted 4-pyrones [20], we turned our attention to the synthesis of 4-pyrone derivatives containing a fused pyrimidone moiety. Since the Baylis-Hillman derivatives originating from substituted heterocyclic aldehydes have been known as excellent synthons for the synthesis of polycyclic ring systems, we first examined the Baylis-Hillman reactions of 2-formyl-4-pyrones that had not yet been reported. We describe in this report the results of these reactions and the reaction of acetates of these new adducts with 2-aminopyridine and 2-aminothiazole to afford fused pyrimidone derivatives in 4-pyrone structures.

Synthesis of Imidazopyridines from the Morita–Baylis–Hillman Acetates of Nitroalkenes and Convenient Access to Alpidem and Zolpidem

“…But, since the reaction was still incomplete, we turned to protic solvents (entries 5–7). However, the reaction in MeOH/H 2 O (1:1) at room temperature and elevated temperature (60 °C) provided the product in low yield, again due to incomplete conversion (entries 5–6) . Surprisingly, the reaction was complete in just 5 min in MeOH alone as solvent to afford the product in nearly quantitative yield (94%, entry 7).…”

Kojic acid in organic synthesis

“…Shahrisa et al 150 synthesized fused pyrimidone derivatives containing KA skeleton 260 and 261. The Baylis-Hillman reaction of comenic aldehyde 84, derived from KA, with methyl acrylate using DABCO in THF followed by the reaction with AcCl and pyridine in CH 2 Cl 2 at room temperature produced 259 in 67% yield.…”

Synthesis of Some New 1,2,3,4-Tetrahydropyrimidine-2-thione and Their Thiazolo[3,2-a]pyrimidine, Thiazino and Benzothiazepine Derivatives

“…In addition to the aforementioned activities, pyrimidine derivatives possessing antitumor , antimicrobial , antibacterial , antifungal and anti‐infective activities have also been reported in the literature. Several synthetic approaches have been reported for the synthesis of fused heterocyclic pyrimidine derivatives .…”