Pyrazolo pyrimidine-4,6-diones

Applications of MCR-Derived Heterocycles in Drug Discovery Table 6 Antibacterial activities of select pyrazolo-pyrido-pyrimidine-diones... 

Bazgir A, Khanaposhtani MM, Soorki AA (2008) One-pot synthesis and antibacterial activities of pyrazolo[4, 3 5, 6]pyrido[2, 3-] d pyrimidine-dione derivatives. Bioorg Med Chem Lett 18 5800-5803... 

The addition of organometaiiics to unactivated pyrimidines normally produces unstable dihydro derivatives which readily oxidize back to the pyrimidine oxidation level, although successful conjugate addition to pyrimidinone derivatives can occur. Thus, the addition of lithium trimethylsilyldiazomethane [TMSC(Li)N2] to 1,3-dimethyluracil 418 occurred at the 6-position to produce a mixture of the two pyrazolo[4,3-rf]pyrimidine-5,7-diones 419 and 420, where the initial addition had been accompanied by cyclization <1997T7045>. 

Benzyl-4,6-dimethyl-2//-pyrazolo [3,4-d ] pyrimidine-2,4-( 1 f/,3ff)dione 1-oxide (273) affords the pyrimido[4,3-d]pyrimidine derivative 276 upon... 

The UV spectra of isomeric pairs of pyrazolo[3,4-d]pyrimidine-4,6-diones and pyrazolo[4,3-type ring fusion absorbs at longer wavelength (red shift) compared to its [3,4-d] isomer (82IJC(B)585). 

One final interesting preparation of pyrimido[5,4-ring transformation of pyrazolo[4,3-d]pyrimidines. Reaction of the A-oxides (272) with sodium ethoxide in.refluxing ethanol leads to the isolation of l,3-dimethyl-6-substituted pyrimido[5,4-[Pg.365]

Ring opening of 3-(phenylsulfonyloxy)pyrido[3,4-d]pyrimidine-2,4-dione (587) with sodium methoxide, followed by a Lossen rearrangement gave the hydrazinopyridine ester (588) which in refluxing acid yielded 1 //-pyrazolo[3,4-c]pyridin-3-one (589) (Scheme 75) <74JHC163>. 

Using the general method described in Section 7.08.10.2 <74JHC163> 3-(phenylsulfonyloxy) pyrido[4,3-fi ]pyrimidine-2,4-dione (590) ring opens with sodium methoxide and rearranges to a hydrazinopyridine ester, which in refluxing acid yields l//-pyrazolo[4,3-c]pyridin-3-one (591) (Equation (59)). 

The four most important tautomers of pyrazolo[4,3-<7]pyrimidine-5,7(477,677)-dione (52a-d) were studied using ab initio LCAO-MO methods <91CPL(181)123>. Calculation indicates that structure (52a) is the predominant form both in nonpolar and polar environments. The second most stable species, the oxo hydroxy tautomers (52b) and (52c), have relative energies of 38.7 kJ mol . For the dioxo to oxo-hydroxy transition, the calculated energy gap corresponds to an equilibrium constant... 

The UV spectra of isomeric pairs of pyrazolo[3,4-d]pyrimidine-4,6-diones and pyrazolo[4,3-<7]pyrimidine-5,7 diones show that the isomers with a [4,3-d] ring fusion absorb at longer wavelengths (red shift) compared to the [3,4-d] isomers <82IJC(B)585>. The />-quinonoid structure of the pyrimidine moiety in compounds (74) and (75) causes a bathochromic shift of 20-25 nm, relative to compounds (53) and (76). The close values of 2max for 7-methyl (77 R = Me) and 2,7-dimethyl allopurinol (74) suggest that the former is present in aqueous solutions as the A(2)-H tautomer <79JCS(Pl)2795>. 

Benzyl-4,6-dimethyl-2//-pyrazolo[3,4-(f pyrimidine-2,4-(l H,3H) dione-l-oxide (188) affords the pyrimidopyrimidine derivative (191), most likely via the intermediates (189) and (190) (Scheme 11)... 

Azido-6-formyl-l,3-dimethyluracil (473) is cyclized with hydrazines to form l-substituted-5,7-dimethyl-1 //-pyrazolo[3,4-. 

An interesting approach for the synthesis of some fused pyrimidines has been reported by Shaaban [102] via reaction of 4,4,4-trifluoro-l-(thien-2-yl)butane-1,3-dione in the presence of triethylorthoformate with 5-aminopyrazole or 1,2,4-aminotriazole or 2-aminobenzimidazole under microwave irradiation. The resulting trifluoromethyl derivatives of pyrazolo[l,5-a]pyrimidine 56, l,2,4-triazolo[l,5-a] pyrimidine 57 and pyrimido[l,2-a]benzimidazoles 58 were obtained in excellent yields and purity (Scheme 42). 

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