Pyrimidines from 1,3-dicarbonyl compound

The synthesis of 2-substituted pyrimidines from 1,3-dicarbonyl compounds and urea derivatives was first described by Evans2 and was later improved by Hunt, McOmie, and Sayer3 for the preparation of 2-mercapto-4,6-dimethylpyrimidine. Burness4 employed 3-ketobutyraldehyde acetal in this procedure to give 2-mercapto-4-methylpyrimidine. 2-Mercaptopyrimidine has been prepared from 1,1,3,3-tetraethoxypropane and thiourea by variations of this basic method 3 6 6 as well as by the reaction of 2-chloropyrimidine with thiourea 1 or sodium hydrosulfide.8... 

How to make pyrimidines from 1,3-dicarbonyl compounds and amidines... 

Reactions of heterocycles ch29 How to make pyridazines and pyrazoles How to make pyrimidines from 1,3-dicarbonyl compounds and amidines How to make thiazoles How to make isoxazoles and tetrazoles by 1,3-dipolar cycloadditions The Fischer indole synthesis Making drugs Viagra, sumatriptan, ondansetron, indomethacin How to make quinolines and isoquinolines ... 

Ghosh et al reported a modified procedure for the preparation of highly substituted pyrimidines by condensation of a 1,3-dicarbonyl compound 22 with tri-(trimethylsilyl)amidine (23) in good yield as compared to the lesser yield obtained from employing a classical Pinner procedure. ... 

This preparation describes a convenient and general method of synthesis of substituted pyrimidines from compounds containing a /3-dicarbonyl group, either intact or as the corresponding ketal. The usefulness of the 2-mercaptopyrimidines is enhanced by the ease of removal of the mercapto group by desulfurization 9 or oxidation 10 and its replacement by other functional groups.1 ... 

Pteridine syntheses from pyrimidine intermediates Traube synthesis and can be condensed with 1,2-dicarbonyl compounds and ketones and aldehydes, respectively, in a very effective manner. There is also a series of regioselective approaches leading towards 6- and 7-substituted pteridine derivatives carrying a broad variety of substituents in these positions. 

Cycloaddition of diphenylketene to some Schiff bases (192) derived from 2-amino-5-phenyl-l,3,4-selenadiazole (185 R = Ph) affords 7-(4-substituted phenyl)-2,6,6-triphenyl- 6,7-dihydro-5if- l,3,4-selenadiazolo[3,2-a]pyrimidin-5-one (193 Scheme 84) (76CPB2532). The selenadiazolopyrimidinium perchlorates of type (194) are prepared by the reaction of (185 R = Ph) and dicarbonyl compounds (74KGS1435). 

Azole approach. 2-Amino-l,3,4-thiadiazoles react with appropriately substituted a,/3-unsaturated carbonyl compounds to form fused pyrimidines (729). The orientation of the substituents in the fusion products suggests that the reaction is initiated by Michael addition of the amino group. 1,3-Dicarbonyl compounds will condense in the same manner to yield the salt (729) from a /3-keto ester the 5-oxo derivative (730) is formed (73ABC1197). 

Pyrimidines can be made from 1,3-dicarbonyl compounds andamidines... 

Each of the diazines can be constructed from an appropriate source of two nitrogens and a dicarbonyl compound. In the case of pyridazines, the nitrogen source is, of course, hydrazine and this in combination with 1,4-dicarbonyl compounds readily produces dihydro-pyridazines, which are very easily dehydrogenated to the aromatic heterocycle. Pyrimidines result from the interaction of a 1,3-dicarbonyl component and an amidine (as shown) or a urea (giving 2-pyrimidones) or a guanidine (giving 2-amino-pyrimidines), without the requirement for an oxidation step. 

Other synthons for 1,3-dicarbonyl compounds that have been successfully applied include p-chloro-a,P-unsaturated ketones and aldehydes, P-dimethylamino-a,P-unsaturated ketones (easily obtained from ketones by reaction with DMFDMA), P-alkoxy-enones"" and vinyl-amidinium salts."" Alkynyl-ketones react with 5-alkyl-isothioureas, giving 2-alkylthio-pyrimidines" and propiolic acid reacts with urea to give uracil directly in about 50% yield. "" 1,3-Keto-esters with formamidine produce 4-pyrimidinones"" and C-substituted formamidines with ethyl cyanoacetate give 2-substituted-6-amino -pyrimidinones. In analogy, pyrimidines fused to other rings, for example as in quinazolines, can be made from ortho-aminonitriles " and in general, from P-enamino esters. ... 

The synthesis of the pteridine ring system has been approached by two obvious routes one is the fusion of the pyrazine ring onto a pre-formed 4,5-diamino-pyrimidine, and the second, the elaboration of the pyrimidine ring on a pre-formed pyrazine. The first of these, the Isay synthesis, suffers from the disadvantage that condensation of the heterocyclic 1,2-diamine with an unsymmetrical 1,2-dicarbonyl compound... 

With different substituents in the /f-dicarbonyl compounds, the substitution pattern of the products is compatible with the 6-amino nitrogen condensing with the carbonyl group which is least tautomerized in the enol form. The orientation in condensations with ix,/l-unsaturated carbonyl compounds results from the addition of C5 of the pyrimidin-6-amine to the Michael system.254... 

Formation of Pyrimidines from beta-Dicarbonyl and 1,1-Diamino Compounds. Yet another application of the amine-carbonyl reaction is viewed in the constmction of the pyrimidine ring. Here a 1,1-diamino compound reacts with a beta-dicarbonyl compound, as is outlined in Scheme 4.12. 

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