Pyrimidine-2,4-diones, addition

Chloro-l,3-dimethyluracil undergoes 1,2-Addition to benzene on irradiation. A 1,3-addition path has been discounted. Other studies by the same group have demonstrated that the irradiation of the pyrimidine dione derivative (140) in acidic media (a large excess of trifluoroacetic acid) brings about its conversion into the tricyclic product (141). ... 

The addition of organometaiiics to unactivated pyrimidines normally produces unstable dihydro derivatives which readily oxidize back to the pyrimidine oxidation level, although successful conjugate addition to pyrimidinone derivatives can occur. Thus, the addition of lithium trimethylsilyldiazomethane [TMSC(Li)N2] to 1,3-dimethyluracil 418 occurred at the 6-position to produce a mixture of the two pyrazolo[4,3-rf]pyrimidine-5,7-diones 419 and 420, where the initial addition had been accompanied by cyclization <1997T7045>. 

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>. 

The course of this reaction could be explained by nucleophilic attack of the isothiocyanato group on C-5 (hard site) of enamine 61, with the formation of 199 by way of intermediate 198. However, this occurs only in N,N-dimethylformamide or acetonitrile solution. The formation of the additional products 2-glycosyliminothiazolo[4,5-d]pyrimidine-4,6-dione (201) by way of intermediate 200, by attack of the isothiocyanato group on the 6-amino group (soft site), was observed when the reaction was performed in oxolane solution. On the other hand, treatment of isothiocyanates 2, 30,... 

A strong oxidant, mixtures with both organic and inorganic compounds are potentially explosive. It is recommended that the synthesis be not scaled up and be performed with due safety precautions [1], Addition to olefins can prove explosive, especially those bearing hydrogen. It was actually enones reported, 5-substituted pyrimidine-2,4-diones, on which a 6 alkoxy substituent was to be placed by the oxide and corresponding alkanol under base catalysis [2]. 

A major problem, that of reproducibility, soon became evident. Preparation of a class I blue , to which this discussion is restricted, typically involved incubation of an aqueous solution of CD -[Pt(NH3)2(H20)2](N03)2 (prepared from cisplatin and AgN03) with a pyrimidine-2,4-dione or a cyclic amide over a period of 3 - 5 days in air, 37 °C, with the pH kept constant (at 7) by repeated addition of NaOH. Various fractions of products were then obtained upon cooling the solution and/or after addition of ethanol. Consequently, these fractions differed in color (dark blue, light blue, green, purple), as did elemental analysis data. If the pH was not kept at 7 but rather allowed to drop, products were likewise different. In particular,... 

However, treatment with dimethyl acetylenedicarboxylate gives only, in one example, the expected pyrido[2,3-rf]pyrimidine in all other cases the previously mentioned Michael-addition-ring cleavage-cyclization-condensation sequence is observed to afford pyrrolo[3,4-cJpyridine-diones (cf. Scheme 128) (88TL4401 89CB1673) (Scheme 163). 

Photolysis (10 h) of l,3-dimethyl-5-nitro-6-(l-methyl-2-acetophenyli-denehydrazino)pyrimidine-2,4-dione (71b) in acetonitrile gave an excellent yield of 2,6-dioxo-l,3,9-trimethyl-8-azapurine 7-JV-oxide (72). This product was apparently formed by the addition of a photoexcited NO2 group across the exocyclic double bond, followed by rearrangement of the tricyclic (dioxatriaza) product. ... 

Many ring-fused imidazole derivatives have been synthesized by various methods. Domino Michael addition retro-ene reaction of 2-alkoxyiminoimidazolidines and acetylene carboxylates provided a synthesis of 2,3-dihydroimidazo[l,2-a]pyrimidin-5-(l//)-ones <05T5303>. A single step synthesis of 3,5-dialkyl-9-nitroimidazo[l,2-c]quinazolin-2(3//)-ones from simple carbonyl compounds, primary amines or amino acid methyl esters and 2-azido-5-nitrobenzonitrile has been published <05TL5778>. Diels-Alder reaction of azadienes and benzimidazole-4,7-diones afforded imidazo[4,5-g ]quinoline-4,9-dione derivatives <05EJ01903>. Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 4,5-diphenyl-l,3-dihydro-2//-imidazol-2-one provided a one-pot synthesis of 5//-imidazo[2,l-ft][l,3]oxazine derivatives <05T2645>. Microwave irradiation was employed in the synthesis of 1-ary 1-3-acetyl-1,4,5,6-... 

For the preparation of pyrido[2,3-d]pvrimidinc-2,4(l//,3//)-diones 28, an adaption of the Doebner-Miller quinaldine synthesis (cf. Houben-Weyl, Vol. E7a, p 363), can be used. The orientation of addition of oc,/5-unsaturated carbonyl compounds to pyrimidin-6-amines is governed by the attack of C5 of the pyrimidinamine at the carbon /5 to the carbonyl function.219 Besides pyrimidine-2,4,6-triamine,149 263 aminouracils are used as partners for the base-catalyzed reaction with a,/5-unsaturated ketones.148,219 264,570,571 Without the final oxidation step, which occurs mostly by air, the dihydro compounds are produced.265 Examples are the Michael additions of 4,4-dimethyl-l-phenylpent-l-en-3-one266 or of 1,3-diphenylprop-2-en-l-one264 to 6-amino-l,3-dimethylpyrimidine-2,4(l//,37T)-dione, which are followed by ring closure to give the corresponding pyrido[2,3-d]pyrimidme-2,4(l//,3//)-diones or their dihydro derivatives. 

The transformation of 5-nitropyrimidine into pyridine derivatives by the reaction of carbanions bearing, in addition to the cyano group, a suitable function R which is cyclizable with the 2-amino substituent of the new pyridine leads to pyrido[2,3-[Pg.132]

To a stirred solution of pyrido[2,3-small amounts over a period of 15 min. The addition caused slight warming of the mixture after which it was heated at reflux for 3 h. After cooling and removal of dioxane in vacuo, the syrupy mixture was subjected to successive extraction with toluene/petroleum ether (40 - 60 °C 1 1) such that a major part of the white crystalline Ph sP was left behind. Column chromatography (MeOH/CH2Cl2 1 99) was used for separation, recrystallization (CHCI,) gave colorless plates yield 0.179 g (25%) mp 160—162°C. 

Ar-[(Ar,Ar-Dimethylamino)methylene]pyrido[2,3-c/]pyrimidin-4-amine 3-oxide (6) plays a central role as an educt for 3-(3-pyridyl)-l,2,4-oxadiazoles. Thus, it has been treated with carbon nucleophiles such as the anions of diethyl malonate, ethyl cyanoacetate, or pentanc-2,4-dione.417 After addition across the 2,3-bond, ring opening of the pyrimidine moiety with simultaneous 1,2,4-oxadiazole ring formation occurs. Evidently, the five-membered ring is formed easily through participation of the [(dimethylamino)methylene]amino and TV-oxide functions. 

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