The reaction of 1,1,1-trifluoro-4-(sulfonyl)-but-3-ene-2,2-dioles 1a,b with corresponding aminoazoles was investigated. A new simple and efficient way for the regioselective synthesis of 5-CF 3 or 7-CF 3 triazolo-and tetrazolopyrimidines is described.Fluorine containing heterocyclic compounds are a subject of continuous interest 1,2 due to their potent pharmacological properties. Some fluorinated pyrimidines were clinically evaluated as valuable anticancer agents. 3 It is known that incorporation of a fluorine atom or CF 3 -group into bioactive molecule leads to increased lipid solubility and thereby enhances the rate of absorption and transport of that substance in vivo. 1 Also, many triazolopyrimidines have shown significant herbicidal, 4 fungicidal 5 activity and are well-known as new cardiovascular agents 6 . The reported methods for the synthesis of substituted azolopyrimidines usually involves cyclocondensation of aminotriazoles 5-12 or aminoterazoles 8,13 with three carbon 1,3-electrophilic fragments. 14 A drawback of these approaches is the formation of the mixture of isomers from the reaction of non-symmetrical systems with aminoazoles. 4,12 Paudler at al. obtained mixtures when treating triazolopyrimidine with phenyllithium. 15 Novel methods for the construction of the triazolopyrimidines nucleus involving reactions of vinylogous iminium salts and related analogs with 3-amino-1,2,4-triazoles have been reported last year. 16 An alternative synthetic route to different triazolopyrimidines is the reaction of 2-hydrazinopyrimidine with acylating agents and also the Dimroth-like rearrangement of triazolo[4,3-a]pyrimidines to triazolo[1,5-a]pyrimidines in acid or alkali. 5,17 Thus, there is a limited amount of the regiospecific synthesis of 7-and 5-substituted azolopyrimidines. 7,16 There is a definite need to develop new methods for the regiospecific synthesis of this class of compounds.In recent work, we have prepared some b-trifluoroacetylvinylsulfones. 18 We have found that alkenes 1a,b are very reactive electrophiles, reacting with heteroarenes such as pyrrole, indole and furan. 19 Also, we have recently described a new simple and efficient way for the regiospecific formation of CF 3 -containing imidazo[1,2-a]pyridines, 20 pyrazolo[1,5-a]pyrimidines, 21 6,7-dihydro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidines, 22 and 6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines 23 by the reaction of sulfones 1a,b with various aminoheterocycles. It was therefore considered that the reaction of diols 1a,b with 3-amino-1,2,4-triazoles and 5-aminotetrazole might result in improved regioselectivity yielding only one regioisomer under a particular reaction condition.Treatment of 1a,b with different 3-amino-1,2,4-triazoles and 5-aminotetrazole in acetic acid at reflux gave a mixture of cycloadducts 2a-k and 3a-k in 70-90% isolated yields (Scheme 1, Table 1). It is worth mentioning, that in water, under reflux, no significant difference of the ratio of regioisomer was observed. The reaction of 1a,b with aminotriazoles at room temperature...
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A new simple and efficient way to CF 3 -containing pyrimido[1,2-a]benzimidazole and pyrazolo[1,5-a]pyrimidines, by the reaction of 1,1,1-trifluoro-4-sulfonyl-but-3-ene-2,2-dioles 1a,b with aminoheterocycles is described. The influence of reaction conditions and nature of the aminoheterocycles on regiochemistry was investigated.
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