2,4,6-trisubstituted pyrimidines, synthesis

Fig. 19 Synthesis and cyclative cleavage of 2,4,6-trisubstituted pyrimidines using microwave-assisted solid-phase protocol. Reagents and conditions a DMF, camphorsul-phonic acid, MW 80 °C, 30 min, open vessel b EtONa, EtOH/THF (4/1), MW 130 °C, to min, closed vessel. Y = O, NEt2 R = Me, i-Pr R = Et R" = H, alkyl, cycloalkyl, aryl, benzyl R" = H, Me, Et...

Scheme 6.247 Synthesis of2,4,6-trisubstituted pyrimidines from amidine and alkyne building blocks.

Scheme 48 Cl-cyclocondensation three-component synthesis of 2,4,6-trisubstituted pyrimidines 89...

In a standard method, 1,3-diketones are cyclocondensed with amidines, ureas, thioureas and guanidines giving 4,6-di- and 2,4,6-trisubstituted pyrimidines 4, 2-pyrimidones 5, 2-thiopyrimidones 6 and 2-aminopyrimidines 7 respectively Pinner synthesis) [140] ... 

A convenient method for the synthesis of substituted pyrimidines involves the reaction of amidine or guanidine derivatives with a 1,3-dielectrophilic, three-carbon unit. Synthesis of 2,4,5-trisubstituted pyrimidines from Baylis-Hillman adducts and amidines is a good example. The ester group in the reactant can be replaced with acetyl and cyano groups, and the corresponding products are isolated in moderate to excellent yields. 

The high selectivity in sequential nucleophilic substitution in perfluorodiazines made them attractive scaffolds for the synthesis of a diverse array of polysubstituted diazines. These approaches were recently developed by Stanford group. Thus, tetra-fluoropyritnidine may be used as a scaffold for the synthesis of a range of 2,4,6-trisubstituted pyrimidine derivatives upon sequential displacement of the fluorine atoms attached to the strongly activated 4-, 6- and 2-positions (Table 9) [158]. The first two substitutions proceed in very mild conditioned (0 °C or room temperature). The last nucleophilic substitution of fluorine at 2-position proceeds in harsh conditions and needs MW heating. 

A rapid synthesis of trisubstituted l,2,4-triazolo[4,3-b]pyridazines has been devised to give selective variation of the three substituents through combinations of silicon-directed anion formation, palladium-catalyzed couplings and SnAt displacements <00TL781>. The synthesis of new l,2,4-triazolo[l,5-a]pyrimidines <00M1435>, 1,2,3-triazolo[4,5-(f]... 

The synthesis of 3-dimethyl-2-benzoyl propenenitriles l(a-b) is the vital key intermediate for the synthesis of various nitrogen heterocycles, such as pyrazole and pyrimidine derivatives. The literature reports suggest that 1,3,4-trisubstituted pyrazole derivatives are important compounds in the preparation of 1,5-diphenylpyrazole nonnudeoside derivatives, which are used as HIV-1 normucleoside reverse transcriptose inhibitors [15]. Similarly, 4-cyano pyrazole... 

Cottam HB, Mackernan PA, Robins PA, Revanker RK (1985) Synthesis and biological activity of 6-azacadeguomycin and certain 3,4,6-trisubstituted pyrazolo[3,4-ri pyrimidine ribo-nucleosides. J Med Chem 28 1010-1016... 

Solid-Phase Synthesis of 2,4,6-Trisubstituted Thiazolo[4,5-(/]pyrimidine-5,7-diones... 

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