Pyrimidine V-oxide

In the Reissert-Henze reaction, quinoline 1-oxide reacts with benzoyl chloride and potassium cyanide to give 2-cyanoquinoline in good yield (Scheme 30). Pyridine 1-oxides undergo the Reissert-Henze reaction readily when the reaction is carried out in non-aqueous medium using PhCOCl-Me3SiCN (Scheme 31). Pyrimidine /V-oxides and pyrazine /V-oxides also undergo Reissert-Henze reactions. 

These two syntheses have one theme in common — they all involve modification of a pre-existing pyrimidine V-oxide. However, the third Upjohn synthesis of minoxidil (3), on the other hand, entails the cyclization of a linear intermediate 33 as the key... 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

Mbhrle and Mayer " ° oxidized the 3-piperidinopropylamine (182) with mercuric acetate-EDTA reagent to obtain the pyrido[l,2-a]pyrimidine (184), Oxidation of the N-monomethyl and (V,iV-dimethyl derivatives of 182 resulted in the (V-methyl and A,A-dimethypiperidone derivatives of 185. If the reactions were carried out without the addition of EDTA, the perhydropyrido[l,2-o]pyrimidine(183) and its A-methyl derivative also could be isolated from the reaction mixture. " The pyrido[l,2-a]pyrimidine (184) was also prepared from the piperidone (186). " The oxidative cyclization was successfully when applied to the piperidinopropionamides (187) to prepare the pyrido [1,2-a]pyrimidines (188) in addition to 2-oxopiperidino-propionamides. " ... 

Certain heteroaromatic compounds that have acidic methyl groups are effective in the Knoevenagel condensation. 6-Methyl-1,3,5-triazine (156), 2-methylpyridine V-oxides (157), quinolines and pyrimidines all condense with aromatic aldehydes in the presence of the usual catalysts. An example of a doubly activated methylene compound in which one activation group is a heterocycle is the 2-oxopro-pylthiazole (158), which condenses with a number of aldehydes. " ... 

There are generally two methods to obtain the (V-oxides of pyrido[2,3-r/]pyrimidines (i) the use of nitrogen substituents already containing the necessary oxygen, i.e. oxime functions,14 309 for cyclization or (ii) oxidation of the already established ring system. 

The introduction of carbon side chains in low yield at the expense of the (V-oxide oxygen have been observed with pyrido[2,3-t/]pyrimidine 3-oxide (18). By treatment with pentane-2,4-dione at 140 °C, l-(pyrido[2,3-d]pyrimidin-2-yl)acetone (19) is obtained, whereas with 1-phenylbu-tanc-1,3-dione the reaction proceeds in a different way and results in the production of 2-phenyl-l,8-naphthyridine (20).309 342... 

Pyrazines,/V-oxides 176,196 Pyrazoles 189 Pyridine complexes 314 Pyridines 8, 28, 43. 125, /6S Pyridines, A -oxides 28, 41, 169, 196 Pyridinium salts 171 Pyridols 172 Pyridones 151 Pyridthione.s 31, 172 Pyrimidines 43, 174 Pyrimidines, iV-oxides 174,196 Pyrones /78... 

In contrast with the Schiff base salen, salicylaldehyde oxime (79) (salox) complexes of Co have received comparatively little attention, but a series of bis-bidentate divalent complexes of the form iraiis-Co(sa 1 ox)2( D M SO)2 have been reported.343 The heterocyclic bidentate oxime violurate (lH,3H-pyrimidine-2,4,5,6-tetrone 5-oximate, Hvi) (80) and its /V-methyl (mvi) and /V,/V -dimethyl (dmvi) derivatives form high-spin divalent [Co(vi)]+ and Co(vi)2 complexes, whereas [Co(vi)3] is low spin.344 The mixed-ligand Co(dmvi)2(phen) complex is also low spin. The crystal structure of m-Co(pxo)2Br2 (pxo = 2-acetylpyridine-l-oxide oxime) is isostructural with the Ni11 relative.345 The dichloro complex also adopts a cis configuration. The tridentate dioximes 2,6-diformyl-4-methylphenol dioxime and 2,6-diacetyl-4-methylphenol dioxime (Hdampo) form binuclear complexes of the type (81a) and (81b) respectively.346 Cobalt oxide nanoparticles were prepared by... 

Fig. 6. Difference spectra between xanthine oxidase inactivated with various pyra-zolo [3, 4-d] pyrimidines and the native enzyme. The spectra are believed to represent the increase in absorption occurring when Mo(VI) of native enzyme is converted to Mo(IV) complexed with the inhibitors. Spectra were obtained by treating the enzyme with inhibitors in the presence of xanthine, then admitting air, so as to re-oxidize the iron and flavin chromophores. The extinction coefficients, de, are expressed per mole of enzyme flavin. Since some inactivated enzyme was present, extinction coefficients per atom of molybdenum of active enzyme will be about 30% higher than these values. (Reproduced from Ref. 33, with the permission of Dr. V. Massey.)...

Although demethylation, which occurs in the liver, is normally considered to be a catabolic process, it may result in conversion of an inactive form of a drug to the active form. Thus 6-(methylthio)purine (XXXIX) is demethylated by the rat to 6-mercaptopurine [205]. This demethylation occurs in the liver micro-somes and is an oxidative process which converts the methyl group to formaldehyde [204, 207]. The 1-methyl derivative of 4-aminopyrazolo[3,4-d] pyrimidine (XLI) is demethylated slowly, but 6-mercapto-9-methylpurine (XLII) not at all [208]. The A -demethylation of puromycin (XLlIl) [209, 210], its aminonucleoside (XLIV) [211], and a number of related compounds, including V-methyladenine and V,V-dimethyladenine, occurs in the liver microsomes of rodents [212]. In the guinea-pig the rate-limiting step in the metabolism of the aminonucleoside appears to be the demethylation of the monomethyl compound, which is the major urinary metabolite [213]. The relationship of lipid solubility to microsomal metabolism [214], and the induction of these demethylases in rats by pre-treatment with various drugs have been studied [215]. 

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