Pyrimidinediones synthesis

Furo[2,3-amino-synthesis, 4, 986 Furo[3,4-d]pyrimidinedione synthesis, 4, 987 Furopyrimidines, 4, 986 Furo[2,3-d]pyrimidines synthesis, 4, 986 Furo[3,2-d]pyrimidines synthesis, 4, 987 Furo[3,2- 6]pyrone synthesis, 4, 994 Furo[3,2-c]pyrone synthesis, 4, 993 Furo[3,2-6]pyrrole, hexahydro-biological activity, 6, 1024 1 H-Furo[3,4-6]pyrrole-2,3-dione, 4,6a-diphenyl-6-(phenylimino)-6,6a-dihydro-synthesis, 6, 1004 Furopyrroles... 

Alkyl halides can also be used to generate the radical center, and N -substituted uracil and thymine derivatives have been used to prepare octahydropyrrolo[l,2-f]pyrimidinedione derivatives <2001TL6637, 2006CC844> as demonstrated by diasteroeoselective synthesis of the azabicycle 447 <2006CG844>. 

The reaction with /3-keto esters 660 has also been performed where the amidine component 661 was attached to a solid support, as shown by the synthesis of 2,4-pyrimidinediones 663 where oxidation of the thio linker of 662 was followed by hydrolytic cleavage from the solid support <2004ARK(v)349>. 

While the usual method for preparing a fused pyrimidinedione involves cyclization of ortho amino and carboethoxy groups (see Equation 12), an unusual synthesis of a fused pyrimidinedithione 46 has been obtained by treating the ortho amino and cyano compound 45 with CS2 (Equation 17) <2003BKC1181>. 

An interesting synthesis of furo[3,4-d]pyrimidinedione (149) is afforded by the reaction of 3,4-furandicarboxamide (148) with hypobromite (60JOC956). By this method, other pyrimidinediones have also been prepared (45JCS229, 69AHC(10)149, 67HC(24-l)l23, 7iHC(24-2)9l). The chemistry of the furo[3,4-[Pg.987]

Ring closure by reaction between an amino and a fluoro function is a frequently used method (see Chapter 9) it is sometimes convenient to use a heterocyclic carbonyl group as a precursor of the amine, and thus reduce the number of compounds that have to be isolated and purified in a multistep synthesis. Pyrimidinediones are susceptible to this type of conversion as is demonstrated in the synthesis of a diaza-acridinone. 

Hie cyclic anhydride (80.4) reacts with trimethylsilyi azide under anhydrous conditions to give a mixture of I,3-oxazine-2,6-dione isomers, which was used without further purification to synthesis several extended purines. Reaction with formamidine acetate in DMF in effect replaced the furandione ring by a pyrimidinone. Cyanamide produced a new fiued 2-aminopyrimidin-4-one [in (80.5, R = NH )], while urea led to a pyrimidinedione. Isatoic anhydride similarly yields 2-aminoquinazolin-4-one on treatment with cyanamide-DMF. 

Compounds with a peri-fused imidazole ring to the purine ring 257 were only little studied. Their synthesis involved an intramolecular alkylation of 8-alkyl- or 8-aryl-9-(2-mesyloxyethyl)-l-methyl-purinediones 260b. The necessary intermediates 260b were achieved by hydrogenation of the 6-[2-(hydroxyethyl)-amino]-3-methyl-5-nitroso-pyrimidinedione 258 to 5-amino-6-[2-(hydroxyethyl)amino] compound 259 further reactions with the respective ortho-carboxylates and mesyl chloride gave 8-alkyl- or 8-aryl-9-(2-hydroxyethyl)-purinediones 260 or 261 (98CCC407) (Scheme 76). 

Most N - and A3-aminopyrimidines have been made by primary synthesis. In this way 1-benzylideneamino-2,4(l//,3/ -pyrimidinedione (499) and its 3-benzylidenamino isomer have been... 

Guanosine triphosphate and ribulose-5-phosphate are recruited in a 1 2 stoichiometric ratio by GTP cyclohydrolase II and DHBP synthase, respectively, for riboflavin biosynthesis. Since at substrate saturation the activity of B. subtilis DHBP is twice the activity of B. suhtilis cyclohydrolase II (DSM, unpublished observations) and since both enzymatic activities are associated with the same bifunctional protein encoded by rihA, the balanced formation of the pyrimidinedione and the dihydroxybutanone intermediates is ensured. However, the ifg.s constant of DHBP synthase ( 1 mmol is about 100-fold higher than the ifg.s constant of GTP cyclohydrolase II imposing the risk of excessive synthesis of the pyrimidinone and pyrimidinedione intermediates in case of reduced intracellular concentrations of pentose phosphate pathway intermediates. This can be expected, for instance, in glucose-limited fed-batch fermentations, which are frequentiy used in industrial applications. The pyrimidinone and pyrimidinedione intermediates are highly reactive, oxidative compounds, which can do serious damage on the bacteria. 

The synthesis of pyrimidinediones by the several reagents dealt with under this heading constitutes the principal current use of the o-amino esters. The less frequently used reagents are dealt with first, leading up to the organic isocyanates, which hold pride of place. 

Methylazines are still further activated by the presence of nitro substituents, and there are many heterocyclic syntheses that involve condensation of the methyl group as the first step. Most of them require a subsequent reduction step (cf. Section VI), and not many can be regarded as even potentially one-pot processes. However, the reaction sequence from 1,3,6-trimethyl-5-nitrouracil (159) depicted in Scheme 37 provides a genuine one-pot synthesis of pyrrolo[3,2-(f]pyrimidinediones (160). The initial condensation is catalyzed by piperidine, and it is also postulated that piperidine participates in addition-elimination and redox sequences along the lines shown (82CPB3187). 

Recent progress in the synthesis of heterocycles (pyridines, p3ridones, pyrans, pyrimidinediones, etc.) using [2 + 2 + 2] cycloaddition reactions catalyzed by transition metal complexes 06ASC2307. 

Design, synthesis, and SAR of pyrazolo[3,4-d]pyrimidinediones as highly potent and selective inhibitors of /fe/Zcobacter py/orr glutamate racemase (Murl)... 

InouyeY, Yokozawa T, Ishikawa N (1985) 2-Hydryl-2-(F-methyl)-F-propanoyl fluoride as a useful building block for the synthesis of trifluoromethylated heterocyclic compounds. Synthesis of l,3-dimethyl-2,3-dihydro-5-(F-methyl)-6-fluoro-2-thioxo-4(lH)-pyrimidinone and l,3-dimethyl-5-(F-methyl)-6-fluoro-2,4(lH, 3H)-pyrimidinedione. J Fluor Chem 27 379-384... 

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