Pyrimidin-dione

Pyrido[3,4-d]pyrimidine-2,4-dione synthesis, 3, 215 Pyridopyrimidines, 3, 201 iV-alkylations, 3, 206 biological activity, 3, 260-261 1-electron reductions, 3, 207 IR spectra, 3, 204 mass spectra, 3, 204 MO calculations, 3, 204 NMR, 3, 202, 203 nucleophilic substitution, 3, 213 8-nucleosides synthesis, 3, 206 physical properties, 3, 201-205 protonation, 3, 206 radical reactions, 3, 215 reactions with water, 3, 207 reduced... 

Pyrimido[4,5-d]pyrimidine-2,4-dione, 5-amino-7-methylthio-synthesis, 3, 364... 

These compounds have been extensively investigated because they are important nucleic acid constituents. Uracil has been shown conclusively to exist predominantly as pyrimidine-2,4-dione (99) both by a refined X-ray crystallographic technique in which the positions... 

The replacement of a heterocyclic hydroxyl group (generally in the 0X0 form, Section II,E, 2,e) with thioxo or chloro groups by phosphorus pentasulfide or phosphorus oxychloride presumably proceeds through nucleophilic substitution (frequently acid-catalyzed, 21 and 86) of thiophosphoryloxy and dichlorophosphoryloxy intermediates. The 4-position in pyrimidine is more reactive than the 2-position and, at low temperature, this type of thionation of pyrimidine-2,4-diones is specific for the 4-position. In as-triazine... 

Photocyclization of A -(4-phenyl-4-pentenyl)monothiobarbiturate (327) afforded a mixture of l,2,3-trimethyl-9-phenyl-l,2,3,6,7,8-hexahydro-4//-pyrido[l,2-u]pyrimidine-2,4-dione and tricyclic nitrogen bridgehead compound 328 (96H(42)117). 

Reaction of 2-aminopyridine and 6-chloro-1,3-dipropyl-l//,3//-pyrimi-dine-2,4-dione in THE in the presence of NaH at room temperature overnight gave a mixture of 4-[A-(propylaminocarbonyl)-A-propylamino]-2//-pyrido[l,2-n]pyrimidin-2-one (349) and 6-(2-pyridylamine)-l,3-dipropyl-l//,3//-pyrimidine-2,4-dione (350, R = H) (94JHC81). Only the non-cyclized product 350 (R = Cl) was obtained from 5-chloro-2-aminopyridine. 

The one-pot MCR of methylene active nitriles 47 has been used in the synthesis of both pyrano- and pyrido[2,3-d]pyrimidine-2,4-diones in a single-mode microwave reactor [90]. Microwave irradiation of either barbituric acids 61 or 6-amino- or 6-(hydroxyamino)uracils 62 with triethyl-orthoformate and nitriles 47 (Z = CN, C02Et) with acetic anhydride at 75 °C for 2-8 min gave pyrano- and pyrido[2,3-d]pyrimidines in excellent yield and also provided a direct route to pyrido[2,3-d]pyrimidine N-oxides (Scheme 27). 

Scheme27 Synthesis of pyrano- and pyrido[2,3-d]pyrimidin-2,4-diones...

SN]-Labeled 4,6-dimethyl-47/-[l,2,5]oxadiazolo[3,4-rf pyrimidine-5,7-dione 1-oxide 290 is conveniently prepared by nitration of commercially available 6-amino-l,3-dimethyl-l//-pyrimidine-2,4-dione using 15N-enriched nitric acid followed by an intramolecular oxidative cyclization with iodosylbenzene diacetate under mild conditions <2000JOC6670>. 

In a similar manner, 47/-[l,2,5]oxadiazolo[3,4- /]pyrimidine-5,7-dione 1-oxides 344 are conveniently prepared in high yields by the oxidative intramolecular cyclization of 6-amino-5-nitro-l/7-pyrimidine-2,4-diones 343 employing iodosylbenzene diacetate as an oxidant in the presence of lithium hydride (Equation 80) <1998JOG6947>. 

The thieno[3,2-d]pyrimidine-2,4-diones were prepared as shown in Scheme 237, and their silyl derivatives were coupled with various acetoxy-methyl ethers in the presence of stannic chloride to give diseco (type 2.1), triseco (type 3.1), and pentaseco benzyl derivatives of type 5.1 nucleosides (94JHC305). 

Ring closure at the uracil 6-position also occurred with brominated aromatic derivatives 444 linked to the 6-position, to give benzopyrano[4,3-rf pyrimidine-2,4-dione spiro derivatives 445 <2004S1864>. 

Methyl 5-(3-fluorophenyl)-7-methyl-l,2,3,4,5,8-hexahydropyrido[2,3-tetrahydro derivative 137 by the action of sodium nitrite in acetic acid <1994T8085>. Oxidation of 2,7-disubstituted-5-trifluoromethyl-l,2-dihydropyrido[2,3-r/]pyrimidin (3//)-ones using active Mn02 in CH2CI2 gave the corresponding pyridopyrimidin-4(3//)-ones 138 <1995IJB587>. 

A series of pyrido[2,3-rf pyrimidine-2,4-diones bearing substituents at C-5 and/or C-6 were synthesized using palladium-catalyzed coupling of uracil derivative 417 with vinyl substrates or allyl ethers to give the regioisomeric mixtures of 418/419 and 420/421, respectively. The ratio of the isomeric structures was dependent on the substituent R. In the case of the reaction with -butyl vinyl ether, only the product 419 was obtained. However, the reactions with acrylonitrile, ethyl acrylate, 2-trifluoromethylstyrene, and 3-nitrostyrene afforded only 418. Also, reaction with allyl phenyl ether gave only 420. The key intermediate 417 was prepared by the reaction of 6-amino-l-methyluracil with DMF-DMA (DMA = dimethylacetamide), followed by N-benzylation with benzyl chloride and vinyl iodination with iV-iodosuccinimide (NIS) (Scheme 15) <2001BML611>. 

The synthesis of pyrido[4,3-rf]pyrimidine-2,4-diones was carried out by thermal fusion of enamine 601 with A-methylurea at 180 °C to give the pyridopyrimidines 156 and 607 in addition to the unexpected a,/3-unsaturated esters 608, which were separated chromatographically in very poor yield (Equation 51). Alternatively, 156 was obtained in 59% yield by treatment of 601 with methyl isocyanate and EtsN to give the corresponding uriedo intermediate which was cyclized in situ with NaOH <1994JHC1569>. 

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