An efficient synthesis of thiazolo[3,2-a]pyrimidinones

Synthesis of mesoionic 1,2,4-triazolo[4,3-a]pyrimidin-5-ones and subsituted formamidines from diethyl (5-1-r-1h-1,2,4-triazol -3-yl)aminomethylenemalonates

“…However, cyclization of hetaryl-substituted aminomethylenemalonates to give azolopyrimidines often proceeds only at high temperature or under upon microwave activation [1] or by using special reagents [2]. In the present work, we found that brief heating of diethyl aminomethylenemalonates 1a and 1b in ethanol in the presence of sodium ethylate leads to the formation of mesoionic 1,2,4-triazolo[4,3-a]pyrimidin-5-ones 2a or 2b in high yield.…”

“…

Hetaryl-substituted aminomethylenemalonates obtained by the condensation of aminoazoles with 2-alkoxymethylenemalonates are commonly used for the synthesis of biologically active azolopyrimidines [1,2]. However, cyclization of hetaryl-substituted aminomethylenemalonates to give azolopyrimidines often proceeds only at high temperature or under upon microwave activation [1] or by using special reagents [2].

…”

Synthesis of substituted methylidenepyrimidobenzothiazolones as potential cytotoxic agents

“…The gauche The unexpected formation of pyrimidobenzothiazol-2-ones 9 can be rationalized assuming that the addition of 2-aminobenzothiazoles 3 to chloroacrylate 7 proceeds via the imine nitrogen atom and, after the elimination of chloride, substitution products 8 are formed, which undergo spontaneous intramolecular cyclization to yield 9. It is worth mentioning, that previously reported additions of 2-aminobenzothiazoles to 2-alkoxyalkylidenemalonates [5][6][7][8] or ethyl 2-cyano-3,3-bis(methylthio)acrylate 9,10 proceeded always via the amine nitrogen, yielding 3-alkoxycarbonyl or 3-cyanopyrimidobenzothiazol-4-ones, respectively. In turn, addition of 2-aminobenzothiazole 3a to alkyl 2-arylidenemalonates proceeds via the imine nitrogen atom.…”

“…One of such characteristic structural motifs are pyrimidobenzothiazolones, in which a pyrimidine ring is fused with another pharmacophorically active nucleus, benzothiazole, through a nitrogen atom. Synthesis and biological activity of both possible structural arrangements, 4H-pyrimido [ Pyrimidobenzothiazol-4-ones 1 substituted at positions 2, 3 or in benzothiazole moiety were synthesized by condensation of 2-aminobenzothiazoles with diethyl malonates 2 or ethyl acetoacetate 3,4 or in the reaction of 2-aminobenzothiazoles with various Michael acceptors, such as diethyl alkoxymethylidenemalonates, [5][6][7][8] ethyl 2-cyano-3,3-bismethylthioacrylate, 9,10 2-cyano-3-dimethylaminoacrylohydrazides 11 or dimethyl aminofumarate. 6 Pyrimidobenzothiazol-4-ones 1 display interesting biological properties, for example anticancer, [9][10][11] antimicrobial, 2,4,9 antiallergic 6 or antifungal.…”

A Simple and Efficient One‐Pot Synthesis of Multifunctional 5‐Aryl‐5H‐thiazolo[3,2‐a]pyrimidines

“…The protocols for the synthesis of these molecules, reported so far, suffer the drawbacks of heating at high temperatures, prolonged reaction times and low yields. Very recently a two‐step high‐yield process involving the condensation of 2‐aminothiazole and diethylmalonate followed by intramolecular cyclization with Eaton's reagent (a mixture of 7.7 wt % phosphorus pentoxide solution in methanesulfonic acid) at low temperature has been disclosed . Reactions of 1,4‐dihydropyrimidine‐thiones with haloketones have also been reported to give various thiazolo[3,2‐ a ]pyrimidine derivatives .…”