5-R-l,3-Dimethyluracil

This replacement reaction has been reported to take place on treatment of 5-R-l,3-dimethyluracil derivatives (R = H, Me, CN, F, Br, Cl,) with of-substituted (R ) acetamides (R =C0NH2, CN, COMe, Ph) in basic medium. The reaction provides an easy entry to the synthesis of 3-R-5-R -2,6-dihydroxypyridines (Scheme 22). 

As mentioned above (Section 2.13.2.1.3), bipyrimidine photoproducts can arise, probably by reaction between two radicals. Thus, irradiation of an aqueous solution of 5-bromouracil (ill R=Br) in the absence of oxygen produces a variety of products including uracil, barbituric acid, 5-carboxyuracil (111 R = CO2H), several non-pyrimidine compounds and, as a stable end-product, the biuracil (114 R = H). A similar product (114 R = Me) is formed from 5-bromo-l,3-dimethyluracil (ilS). When two such related uracil derivatives are irradiated together, a mixed bipyrimidine product is formed, inter alia (B-76MI21302). 

Heating 5-(benzylideneamino)-l,3-dimethyluracil-6-amine, which is readily available by the condensation of l,3-dimethyluracil-5,6-diamine with benzaldehyde in ethanol, °° with thionyl chloride affords 8-phenyltheophyllinc (7, R = Ph) in good yield. This reaction is applicable to other 5-(arylideneamino)-l,3-dimethyluracil-5,6-diamines to give the corresponding 8-substi-tuted theophyllines 7. ... 

MI1 74MI7). The acetates of these acydo C-nucleosides (539, R = Ac) were obtained by oxidative cyclization of the Schiff bases 540, derived from aldehydo-sugar acetates 180 and 4,5-diimino-l,3-dimethyluracil, with mercury(II) chloride in dimethyl sulfoxide [79CPB1094, 79H(12)359] (Scheme 144). 

The aminomethylenemalonate derived from 5-amino-pyrimidin-4(3H)-one was unchanged after a similar period of heating. The cyclization of the corresponding cyanoacetates (e.g., 119, R = CN) was more difficult, and only that derived from 5-amino-l,3-dimethyluracil (110) yielded a pure product (122, R = CN). 

Removal of the 2 -sulfonyloxy group of 859 in a basic medium, followed by reaction with metal halides (LiBr and Nal) or hydrogen halides (HCl-1,4-dioxane, HBr-acetone, or0.1% HFin l,4-dioxane-AlF3)gave, byway of the 2,2 -anhydro intermediate 861, the 2 -halo derivatives 862-865. The 2 -deoxy analog 866 and l-(6-deoxy-6-fluoro- ff-D-mannopyranosyl)thy-mine were also prepared from 864 (R = H) and 861 (R = H), respectively. l-(4-Deoxy-4-fluoro-y -D-glucopyranosyl)thymine was obtained by the condensation method. A different kind of nucleoside, 5-(5-deoxy-5-fluoro-2,3-0-isopropylidene-a-D-ribofuranosyl)-l,3-dimethyluracil has also been prepared. ... 

A novel approach to purine synthesis involves the use of ADC compounds as a source of one nitrogen atom in the five-membered ring.148 150 Treatment of 6-amino-l,3-dimethyluracil (94, R = H) with DEAZD gives the 5-substitution product (95, R = H). The N—N bond is cleaved by Raney nickel or formic acid, and ring closure to 1,3-dimethyluric acid is simply effected by heating.148 Whether the initial adduct is formed by a substitution... 

Dicyano-l,3-dimethyluracil (156) undergoes substitution reactions with amines or sodium methoxide to yield 157 (R = NHR or OCH3). Compounds 157 reacted with hydrazines to yield the hydrazino derivative 158, which readily cyclized to the pyrazolo[3,4-[Pg.343]

Azido-l,3-dimethyluracil is converted into l,2,3-triazolo[4,5-pyri-midine (R = H) in a reaction with potassium carbonate in DMF, and the presence of alkyl halides affords 1-alkylated products [77H(6) 1915]. Another study reports that the reaction with methyl iodide gives two... 

Whereas from benzylmalonic acid and 6-amino-l,3-dimethyluracil with phosphoryl chloride a yield of only 15% is obtained,218 in the presence of acetic anhydride/acetic acid at 100 °C, malonic acids condense with 6-amino-l,3-dimethyluraeils to give 5-hydroxypyrido[2,3-r/]-pyrimidinc-2,4,7(l//,3//,8//)-triones 9 in moderate to fair yields.220... 

Treatment of 6-[(dimethylamino)]methylene]amino-l,3-dimethyluracil 242 with 662 under MWI for 5-45 min in an MW reactor gave pyrimido[4,5-r/]pyrimidines 663 in 90-98% yields (Scheme 129). Thermal heating in dry DMF required 3.5-4h to give 70-75% yields (04SL1179). 

Diamino-l,3-dimethyluracil stirred 2 hrs. under Ng at 150-160° with n-butyl phenylboronate in anhydrous xylene with azeotropic distillation of the resulting n-butanol -> 7,8-dihydro-8-phenylboratheophylline. Y 89%. F. e. s. R. Caujolle and Dang-Quoc-Quan, C. r. 271 (C), 754 (1970). 

The n.m.r. spectra and rates of periodate oxidation of anomeric l-A -o-gluco-pyranosylnicotinamide cations have been measured, and they indicate that the anti-anomeric effect stabilizes the conformations in which the aglycone is equatorially oriented. The conformations of jV-hexopyranosylimidazoles are discussed in Chapter 23. Modified nucleoside derivatives [e.g. (156)] have been synthesized by condensation of 2,3,4,6-tetra-O-acetyl-jS-D-glucopyranosyl isothiocyanate with either 5,6-diamino-l,3-dimethyluracil or o-phenylenediamine. ... 

Most unusual is the synthesis of y/c-triazolo[4,5-i/]pyrimidine (262) by heating 6-azido-l,3-dimethyluracil with potassium carbonate in DMF. Whereas intramolecular cyclization of an azide function onto C=N to give tetrazoles is well known, the corresponding formation of triazoles by addition to C=C is extremely rare. Also noteworthy are the 5-diazo-6-amino-uracils (263 R = Me, Et, or Ph), which, although table in boiling acetic acid, cyclize (with loss of nitrogen) in hot DMF to indolo[2,3-d]pyrimidines (264). Far superior are the photodecompositions of (263) which furnish the indolo-pyrimidines in quantitative yield. 

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