Pyrimidines chromones

H-l-Benzopyran-4-ones — see Chromones 4H-l-Benzopyran-4-ones, 2-phenyl — see Flavones Benzopyranopyrazoles synthesis, S, 317, 341 Benzopyrano[4,3-c]pytazol-4-one synthesis, 3, 712 Benzopyrano[4,3-6]pyridine synthesis, 3, 712 Benzopyrano[4,3-ii]pyrimidine synthesis, 3, 712 Benzopyrans nomenclature, 1, 23 pyrylium salt synthesis from, 3, 873 reactions... 

This was later extended to the synthesis of novel pyrimido-[l,3-a]-pyrimidines under solvent-free conditions ethyl-2-armno-4-aryl-l,4-dihydro-6-phenylpyrimidine-5-car-boxylates react regioselectively with 3-formyl chromone or diethyl (ethoxymethylene) malonate, without solvent, to afford pyrimido-[l,3-a]-pyrimidines [92] (Scheme 8.66). 

There are few cases in which free /3-aldehydo esters have been condensed successfully with ureas. Commonly, alkoxymethylene esters are used. The initial reaction leads to an acyclic intermediate that may require a separate treatment to induce ring closure. The reaction of a /3-keto ester with urea may be a two-step process in which case acid catalysis can be used in the formation of an acyclic intermediate, with ring closure effected by strong alkali. When the ester component is a lactone or chromone, the product contains a hydroxyalkyl <2000JME3837> or 2-hydroxyphenyl substituent <2004S942>, as shown by the synthesis of the 5-(2-hydroxyethyl)-4-pyrimidinone 657 and the 6-(2-hydroxyphenyl)-pyrimidine 659. 

Pyran-4-ones, chromones and flavones are converted into pyrimidines, usually under base catalysis, by reaction with compounds which contain the grouping N—C—N urea, thiourea, guanidine, aminoguanidine, acetamidine and dicyandiamide are examples of this type. Scheme 24 shows some typical examples (77BSF369, 81JHC619). 

Other ring transformations giving isoxazoles (or isoxazolines capable of conversion into isoxazoles) are as follows ring expansion of oxirans41 and oxetanones42 ring contraction of pyrimidines, pyrimidinium salts, pyrimidine JV-oxides,43 pyrylium salts,44 ketonylidenepyrans,45 chromones, thiochromones, chromylium salts,46-51 and oxazinones 52 photoisomeriza-... 

Chloroperoxidase catalysis by, 58, 302 in chlorination of pyrazoles, 57, 337 Chlorophyll, thioaldehyde synthetic intermediate to, 55, 3 Chlorosulfonyl isocyanate, reaction with 2-arylhydrazono-3-oxobutanoate, 59, 148 Chromatography, of [l,2,4]triazolo[l,5-a]-pyrimidines, 57, 106 Chrom-3-enes, see 2//-l-Benzopyrans Chromium tricarbonyl complexes of 3,5-diphenyl-l-(alkyl- or oxido-)-thiabenzenes, 59, 206, 227 indoles, lithiation of, 56, 181, 184 of pyridine, 58, 160 pyridines, lithiation of, 56, 230, 239 of 2f/-thiopyrans, 59, 227 Chromones, see l-Benzopyran-4-ones Cinnamonitrile, a-cyano-, condensations with thio-, seleno-amides, 59, 184, 186 Cinnoline, nitration, MO calculation, 59, 302... 

Pyrimidin 5-(2-Hydroxy-benzoyl)-2-methyl- E9b/2, 170f. (3-CHO 4H-chromon + Acetamidin) Quinazolin 2-(2-Furyl)-4-methyl- -3-oxid E9b/2, 18 [2-(NH-CO-Het) —Ar— 1-CR = N —OH/H+] Quinolin 3-Amino-4-hydroxy-2-oxo-1 -(2-propinyl)-l, 2-dihydro-E15/2, 1251 (1,3-Oxazol-Spalt.)... 

Anthranilamide and many other aminocarboxamides are converted into the fused pyrimidin-4-one analogues in a base-catalysed reaction with diethyl oxalate [182]. When this reaction was applied to the chromone analogues (46.5), the expected product was obtained when R = COOEt, but the diazepinetrione was the only product isolated from the chromone (46.5, R = H). 

Lodoxamide (0.1 mg via aerosol) protected against grass pollen antigen in asthmatics. The chromone derivative (28) (FPL 58668) given via aerosol inhibited Ascarls-lnduced bronchoconstriction and the concomitant increase in plasma histamine levels in laboratory-bred monkeys. The pyrimidine (29) (BL 5255) inhibited mediator release... 

Chromones and Coumarins Anwii species (Umbettiferae) Corfandrum sativum DNA, RNA viruses and Bacteriophages HIV Cross linking viral DNA Adds to viral pyrimidines (in DNA) and uridines (in RNA), forming cycloadduct [11] [21]... 

Another conversion of a chromone to a coumarin proceeds through chromone-2-carbonyl azide and either the amide (94, R = CCI3) or the urea (95) hydrolysis of either of these gives 4-hydroxycoumarin (9(S) [157]. The amide (94, R = CCI3 or OEt) reacts with a primary alkylamine and a twofold molar quantity of formaldehyde to form a reduced chromono [3,2-c]pyrimidine (97) [176]. 

The formation of a pyrimidine and an imidazolidone by the reaction of ethyl chromone-2-carboxylate with guanidine has been mentioned earlier (p. 100). 

Even more complex pyrimidine derivatives such as thienopy-rimidines can be zincated. Interestingly, they display a similar re-gioselectivity switch, as already seen with the chromones. Thus, the treatment with TMPZnCl LiCl (1.2 equiv, 25 °C, 12 h) leads to a smooth deprotonation of the most acidic proton in position 6 (eq 16). Complementarily, addition of BF3-OEt2 (1.1 equiv, 0°C, 15 min) to thienopyrimidines followed by TMPZnCl-LiCI (1.5 equiv, 0°C, 2 h) leads to a regioselective zincation at position 2. ... 

Substituted 2-R -chromones are effective in the reaction with amidines to create R -containing pyrimidine derivatives. Reflux of chromones 13 with benzamidine hydrochloride or guanidinium nitrate in the presence of KOH yielded the pyrimidines 173 in moderate to high yields [87] (Scheme 55). 

The reaction is applicable to the 8-aza-5,7-dimethyl-2-(trifluoromethyl)chromone (133a) to afford the corresponding pyrimidines with 2-pyridone substituent [87]. 

When 3-cyano-2-(polyfluoroalkyl)chromones 229, prepared from 3-(polyfluoro-acyl)chromones 230 (see Sect. 3.4.1), were treated with H2SO4, amides 231 were obtained in high yields. Heterocyclization of 229 with hydrazines, hydroxylamine and acetamidine resulted in pyrazoles 232, 5-aminoisoxazole oxime 233, and pyrimidin-5-ones 234 in variable yields [117] (Scheme 75). 

Kotljarov A, Irgashev RA, Iaroshenko VO, Sevenard DV, Sosnovskikh VY (2009) 3-(Polyfluoroacyl)chromones and their hetero analogues as valirable substrates for syntheses of 4-(polyfluoroalkyl)pyrimidines. Synthesis 2009 3233-3242... 

Fluoroalkyl-substituted enones represent another important class of CCC bis-eletrophiles widely used for the preparation of pyrimidines with fluorinated alkyl at C-4. Their chemistry has been reviewed recently [435, 436], therefore, preparation of these bis-electrophiles is not discussed herein. Several subtypes of p-enones are amendable for the synthesis of chain-fluorinated pyrimidines. The most common group include compounds with a leaving group at p position (700-702 and 706). (Fig. 24). A special case of these bis-electrophiles is chromone derivatives and their hetero-analogues (704, 705). Other p-enones 703 i.e. non-functionalized) and 712 (P-sulfonyl, hydrates) are also used. 

Chromone derivatives and their analogues 704 and 705 were used for synthesis of 4-fluoroalkylpyrimidines. In both cases, reaction with NCN binucleophiles was accompanied with recyclization of the y-(thia)pyrone ring to give (2-(thio) hydroxyphenyl)-substituted pyrimidines or their analogues (Table 37). 

Table 37 Synthesis of pyrimidines with fluorinated chromones and their hetero-analogues...

An efficient synthesis of pyrrlo[2,3-d]pyrimidine annulated pyrano[5,6-c]cou-marin/[6,5-c]chromone derivatives was achieved by intramolecular hetero-Diels-Alder reaction by microwave irradiation under solvent-free and solid supported conditions (Ramesh and Raghunathan, 2008). 

Pyimido(l,2,a)pyrimidines were prepared from dihydroaminopyrimidines and chromone-3-aldehydes (Eynde et al., 2001). The conventional reaction proceeds with refluxing in ethanol for 4 h with 60-70% yield where as much faster reactions (20 min) and better yields (95%) have been obtained with microwaves and it is solvent-free also. 

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