4 -Pyrimidinones, 6-chloro- from

Cyclocondensation routes also provide access to pyrimidines. 2,3-Disubstituted pyrido[2,3-/i]-quinazolin-4(3//)-ones are obtained via cyclocondensation of 5-aminoquinoline-6-caiboxylic acid with acid chlorides <02SC235>. 5,6,8-Trialkyl-7-methoxy-2-aminoquinazolines are obtained from 1,3-dimethoxybenzenes via cyclocondensation of intermediate dihydrobenzenes with guanidine carbonate <02TL3295>. Diastereoselective intramolecular hetero Diels-Alder cyclization of a pyrazole carboxaldehyde condensed onto 1,3-dimethylbarbituric acid (101) gave polycyclic heterocycle 102 <02T531>. An efficient one-step synthesis of cyclobutene-annelated pyrimidinones 103 from methyl 2-chloro-2-cyclopropylideneacetate and amidines has been... 

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. ... 

Ring contraction occurs also on irradiation of pyridazine-3(2//)-ones to give a mixture of pyrrolines 278 and 279 (minor product).576 Similarly, 3-methyl-l-phenyl-hexahydropyridazine-6-one gives 280.577 However, photolysis of 5-amino-4-chloro-2-phenylpyridazine-3(2H)-one, a selective herbicide, in sunlight gives a mixture of 281 and 282, the last compound originating from 281.578 The first photoisomerization of 3-hydroxypyrid-azinium betaines into pyrimidinones converts 283 into 284 the mechanism proposed involves valence isomerization.579... 

The bisulfite adducts of electrophilic pyrimidines are relatively stable, and several have been isolated. Thus, iV-substituted 5-chloro-2(l/7)-pyrimidinones readily form bisulfite adducts in aqueous solution. Both the 3,4- (329) and the 3,6-bisulfite (330) adducts are formed, with the former as the predominant isomer. In water, the 3,4-isomer was significantly less soluble and was precipitated selectively from concentrated solutions. Solubilization in more dilute aqueous solution, and addition of TFA, precipitates the parent heterocycle <87ACS(B)448,91ACS177). 

Compound (VIII.98), a folic acid analogue with a y-fluoro substituent in the side-chain was described first by Alekseeva e/ al. [281] and several years later by Bergmann and Chun-Hsu [282]. The synthesis of (VIII.98), as mixture of threo and erythro isomers, was achieved via the Waller method from V-(4-ami-nobenzoyl)-y-fluoroglutamic acid, 2,4,5-triamino-6(lif)-pyrimidinone, and 2,3-dibromopropionaldehyde, but the yield was low (5.6%). y-Fluoroglutamic acid, as a mixture of D- and L-enantiomers, was prepared from diethyl 2-fluoromalonate by condensation with ethyl 2-acetamidoacrylate followed by hydrolysis and decarboxylation in refluxing 12 M HCl, or from ethyl 3-chloro-2-hydroxypropanoate by a sequence consisting of (i) 0-t-butylation with CH2 = C(CH3)2, (ii) condensation with diethyl 2-acetamidomalonate, (hi)... 

Aryl-6-phenyl-2-methylthio/secondary amino substituted-4(3//)-pyrimidinones were derived from a reaction of N-arylamino substituted 1,3-diaza-1,3-butadienes with substituted ketenes that was analyzed by computational methods <97T13829>. 1,3-Diazines related to 6-amino-4-chloro-5-cyano-2-(dimethylamino)pyrimidine were prepared in one-pot fashion from 1,1-diamino-2,2-dicyanoethylene and phosgeniminium chloride <97SC1223>. Pyrazolo[3,4- /]pyrimidines were derived from 4-substituted 5-aminopyrazole-l-carbothioamides <97JCR(S)352>. Amino-5-(trifluoromethyl)-l,2,4-triazole gave polysubstituted 2-... 

Hydrogen peroxide acetic acid 5-Chloro>4(3H)-pyrimidinones from 4>chloropyrimidines Position shift of chlorine... 

Hydrogen chloride 6-Chloro-4(3H)-pyrimidinones from 2 nitrile molecules... 

Thiazolo[5,4-d]p3rriinidine-l-N-oxides, ready to obtain from 6-chloro-l,3-dimethyl-5-nitro-pyrimidinone by reaction with mercapto compounds, monitored by base catalyzed dehydra-tive cyclization, can be simply deoxygenated to produce thiazolop5n imidines. Reductive deoxygenation by treatment of the thiazolopyrimidine oxides with sodium dithionite or oxidative deoxygenation with dimethylformamide at reflux temperature can produce the anticipated thiazolopyrimidines [137]. 

---