6-amino-l,3-dimethyluracil

In a similar way, 6-amino-l,3-dimethyluraciles (63) undergo easy conversion to the corresponding thiazolopyrimidines (64) upon treatment with thionyl chloride in pyridine solution (except with R = CF3, where SO2CI2 is more effective in the absence of pyridine) (Scheme 29) (654), with R = H, CO2H, C02Et, Ph, or CF3. 

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... 

Heating 6-amino-l,3-dimethyluracil with PhC(0)N=C(CF3)C02Et and Et3N in DMF gives compound 112 in 98% yield <2001IZV1113>. 

The 7-aryl-5-cyanomethyl-l,3-dimethyl-2,4-dioxopyrido[2,3- pyrimidines 458 have been regioselectively synthesized through the nucleophilic attack of the amino groups in 6-amino-l,3-dimethyluracil 452 on the highly electrophilic center at C-6 in 6-aryl-3-cyano-4-methylthio-2//-pyran-2-ones 457. Ring opening of 457 followed by decarboxylation and recyclization with the elimination of methylmercaptan gave 458 with no detection of the 5-aryl-7-cyanomethyl isomers 459 (Equation 38) <20008541 >. 

Reaction of 6-amino-l,3-dimethyluracil with the Mannich base 524 under nitrogen in boiling H2O gave 5,6-dihydropyrido[2,3- pyrimidine-(17/,37/)-2,4-diones 531 rather than their oxidized analogues 530. The latter could be obtained by boiling the reactants in AcOH (Scheme 22) <2004T11511>. 

Reactions of substituted a-ketoalkynes (RC=CCOR ) with 6-amino-l,3-dimethyluracil and a water-soluble nickel catalytic system [Ni(CN)2-CO-KCN-NaOH] afforded 2,4-dioxopyrido[2,3- pyrimidine derivatives 532 under very mild conditions (room temperature and atmospheric pressure). The mechanism involved a nucleophilic attack by Ni(0), formed in situ, onto the triple bond of the substrate. The reaction terminates within 30 min, giving 98% of 532, while in the absence of this catalytic system the reaction took a longer time (lOh) to reach a maximum yield of 30% <2001J(P1)2341>. A regioselective interaction of 6-aminouracil derivatives with GF3COCH2COR in boiling AcOH afforded the cyclized 5-trifluoromethylpyrido[2,3-, pyrimidines 533 <200381531 >. 

The pyrimidine ester (323) was amidated with ethylamine and cyclocondensed with DMF to give compound (324) (Equation (47)) <86EUP 188094). 5-Acetyl-6-amino-l,3-dimethyluracil was cyclized using POCI3-DMF to give compound (325) <87EUP24331l>. 

Benzoquinone, reaction with 6-amino-l,3-dimethyluracil, 55, 200 aryl isocyanides, 57, 5... 

Amino-l,3-dimethyluracil reacts with ethoxymethylene-malonodini-trile in a complex reaction pathway to give 1,3,7,9-tetramethylpyridol[2,3-d 6,5-fif dipyrimidine-2,4,6,8(l//,3//,7//,9//)-tetraone as well as a 7-aminopyrido[2,3-fif pyrimidine-6-carbonitrile (78H197) (cf. Scheme 48) (Scheme 112). 

The pyrido(2,3-d)pyrimidinediones (244a, b)34 are formed from 6-amino-l,3-dimethyluracil (243)9 which contains a stable enamine moiety with a free amino group. If in (243) the condensation with vinamidinium salts (7) takes place exclusively at the amino group or at the j3-enamine carbon also may be questionable. 

The enaminones 44 (R1 = Me, H) react with oxazolidines 27/28g, f to form partially reduced quinolinones 58a-c. 6-Amino-l,3-dimethyluracil reacts with oxazolidines 27/28f, e to form pyridopyrimidine derivatives 59a, b respectively in over 80% yields as against reported low-yield methodologies. Similarly, 27/28g, i, c react with 6-amino-1,3-dimethyluracil to give 59c, d, e, but in the case of 27/28d, b the un-cyclized products 60a,b are isolated exclusively (98T935). 

The amino group of 6-amino-l,3-dimethyluracil added onto penta-O-acetyl-D-gluconoyl isothiocyanate (603) to form the thiourea derivative 604, which eliminated a molecule of water to yield the 2-(penta-0-acetyl-D-g/Mco-pentitol-l-yl)pyrimido[4,5-d]pyrimidine 605 (76MI3 81CPB1832) (Scheme 161). 

Reactions of 6-amino-l,3-dimethyluracil with substituted a-ketoalkynes using homogeneous nickel catalysts in an aqueous alkaline medium afford substituted 2,4-dioxopyrido[2,3-d]pyrimidine derivatives in quantitative yields under very mild conditions. A mechanism has been proposed for the reaction involving the nucleophilic attack by a Ni(0) anion, formed in situ, on the triple bond of the substrate [27]. 

The Vilsmeier complex prepared from dimethylformamide and phosphoryl chloride has been used as a C, unit to cyclize 5-acetyl-6-amino-l,3-dimethyluracil. Subsequently, the resulting 5-hydroxy group is converted into achloro substituent by the same reagent. Thus, after 2 hours at 60°C, 5-chloro-l,3-dimethylpyrido[2,3-c/]pyrimidine-2,4(l//,3A)-dione (26) is obtained.183... 

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... 

It is, however, possible to obtain either pyrido[2,3-rf]pyrimidine-2,4,7(1/7,377,8//)-triones or, to a lesser extent, py rido[2,3-acetic acid 99 affords ethyl 1,3-dimethyl-2,4,7-trioxo-l,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-6-carboxylate. Further examples of this pathway are the reaction of diethyl (ethoxymethylene)malonate with 6-amino-165 or 6-(methylamino)-l,3-dimethyluracil 222 neat at 220-230 °C, or with 6-amino-2-methoxypyrimidin-4(3/7)-one223 in acetic acid to yield the corresponding ethyl 2,4,7-trioxo-l, 2,3,4,7,8-hexahydropyrido[2,3-[Pg.118]

Contrary to the above regioselectivity, diketene reacts with 6-amino-l,3-dimethyluracils at 60 -80°C by acylation at C5, giving after cyclization the 5-oxo compounds 17.142... 

Instead of a,/ -unsaturated ketones, the products of Mannich reactions, such as the hydrochloride resulting from the condensation of acetophenone, formaldehyde, and dimethylamine, may be used in a one-pot reaction together with 6-amino-l,3-dimethyluracil in refluxing acetic acid.266... 

With 6-amino-l,3-dimethyluracil (32), both possible orientations of annulation have been observed.270... 

Heating 6-amino-l,3-dimethyluracil together with 2-chlorobenzaldehyde and a 4-substituted benzoylacetic ester in refluxing ethanol directly leads to the corresponding 5,8-dihydropyrido-[2,3-(7]pyrimidine.273 Similarly, other uracils react with aromatic aldehydes and various alkyl acetoacetates in propan-2-ol.235... 

An efficient approach to fused pyrimidine derivatives 154 was developed by Singh and coworkers [85]. This multicomponent reaction was performed with 69, 6-amino-l,3-dimethyluracil 153, and 33a, and promoted by p-TsOH in water (Scheme 12.61). The protocol avoided the use of expensive catalysts, toxic solvents, and chromatographic separation. Both aromatic and aliphatic aldehydes could be utilized for this reaction. 

Theophylline is used as a cardiac stimulant Preparation of 8-(ferrocenylmethyl)-theophylline 6, was carried out by condensation of 5,6-amino-l,3-dimethyluracil with ferrocenylacetic acid 5 in N,N -dimethylaniline at reflux, followed by cyclization in a basic medium (Scheme 8.4) [28]. 

A one-pot Hantzsch reaction in aqueous medium without any solvent or catalyst is known for the synthesis of 1,4-dihydropyridines. Tamaddon and coworkers have reported the synthesis of 1,4-dihydropyridines 107 by the reaction of aldehydes 51 and methyl/ethyl acetoacetates 106 in aqueous ammonium carbonate at 55-60 °C (Scheme 35) [88]. Recently, a similar study has also been carried out by Yang and coworkers to obtain dihydro-pyridines [89]. Another example of dihydro pyridine ring formation in water employs methyl/ethyl acetoacetates and aromatic aldehydes with 6-amino-l,3-dimethyluracil in the presence of thiourea dioxide as the catalyst [90]. The utilization of water as a solvent and indium(III) chloride as a promoter for the formation of dihydropyridine ring is reported by Khurana and coworkers in the reaction of with 6-amino-l,3-dimethyluracil, aldehydes, and 1,3-diketones [91]. 

An analogous reaction as described in the preceding procedure a) was performed with 0.208 g (1 mmole) of 5 at -1.8 V for 24 h. The reaction solution in the cathode compartment was evaporated to dryness, the residue extracted with hot EtOH and then again evaporated. This mixture was separated by column chromatography on silica gel in CHCl3/MeOH (19/1) to give 0.088 g (45%) of 10 of m.p. 330 C and 0.014 g (6%) of 5-acetamino-6-amino-l,3-dimethyluracil (15) as a crystalline powder of m.p. 280 C ... 

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