A Pyrimidine Rearrangement

6-Substituted uracils 1 are of much interest due to their possible use as anti-cancer and anti-AIDS drugs, and both 2,4-dimethoxy-6-iodopyrimidine and l,3-dimethyl-6-iodouracil (1, R = Me, X = I) were required as starting materials for the synthesis of a variety of uracils 1 by palladium-catalysed C-C bond formation. It was reported in 1961 that treatment of 6-chloro-2,4-dimethoxypyrimidine with sodium iodide in refluxing DMF gave a 42% yield of the corresponding 2,4-dimethoxy-6-iodopyrimidine, but repetition of the reaction recently clearly established that the product was in fact the isomeric l,3-dimethyl-6-iodouracil (1, R = Me, X = I). 

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Pyrimido[ 1,2-a]pyrimidine-1,4,6,9-tetrones rearrangement, 3, 341 Pyrimido[4,5-d]pyrimidine-2,4,5,7-tetrones synthesis, 3, 364... 

Amino-l,2,4-triazole undergoes a cyclocondensation with 3-etlioxyacrolein (7) to form 1,2,4-triazolo[l,5-a]pyrimidine (3) or its [4,3-u] isomer (5), according to whether it reacts as IH or 4H tautomer 2 or 4. Moreover, the pyrimidines 3 and 5 can interconvert by a Dimroth rearrangement. Since the H NMR spectrum 30a does not enable a clear distinction to be made AMX systems for... 

Attempts to get more information on this interesting meta-rearrangement by choosing derivatives of 2-bromopyridine containing various substituents in the 6-position for the starting material led to a remarkable result. Whereas 2-bromo-6-picoline gave a mixture of 2-and 4-amino-6-picoline (in a ratio of 60 1) in 25% total yield together with a resinous mass, 2,6-dibromopyridine (79) was converted into a pyrimidine, i.e. 4-amino-2-methylpyrimidine (80), in 20% yield. The same pyrimidine was obtained from 2,6-dichloropyridine and, in small amount, also from 2,4-dibromopyridine (81). The course of the... 

In attempts to formylate the bicyclic compound 5-methyl-9-phenylhy-drazono-6,7,8,9-tetrahydro-4-oxo-4//-pyrido[l,2- z]pyrimidine 3-carboxy-late (129) with dimethylformamide-phosphoroxychloride at 90-100°C, a degenerate ring rearrangement took place, resulting in the formation of 7-(o -chloroethyl)-8-chloro-9-(A,A-dimethylaminomethylene)amino-6,7,8,9-tetrahydro-4-oxo-4H-pyrido[l,2-a]pyrimidine-3-carboxylate (131)... 

Another interesting rearrangement, involving a pyrimidine-pyridine ring transformation combined with a Dimroth rearrangement, is observed when 6-nitro[l,2,4-triazolo][l,5- ]pyrimidine (74) reacts with ethyl cyanoacetate. 

Scheme 2.4. Process for preparing a pyrimidine by Dimroth "rearrangement."...

Regioselective chlorination at C-5 of 3-pivaloyloxymethylpyrido[4,3- pyrimidine A -oxide 198 with POCI3 (100°C/2h) gave 199 via a Meisenheimer A -oxide rearrangement (Equation 15)<2004TL3737>. 

The second important reaction path similar to AT synthesis starts with aminoguanidine derivatives (in this case part of a HP) and proceeds via condensation with a synthon Z (see principle in Scheme 8). In a first step l,2,4-triazolo-[4,3-a]pyrimidines (15) are formed these are often isolable and nearly always transformable into the more stable TPs by Dimroth rearrangement. 

The Dimroth rearrangement (69ZC241) including l,2,4-triazolo[4,3-a] pyrimidines generally proceeds rather easily therefore these compounds, when prepared, are often not isolable (or only by very carefully handling). The extremely fast rearrangement, compared, for example, with that of 1,2,4-triazolo[4,3-a]pyridines, is attributed to the increase in electron de-... 

Type B syntheses starting from HPs require a Dimroth rearrangement. By contrast, in the following reaction paths, the 1,3 orientation of two nitrogen atoms needed to form the triazole ring of the TP is preformed in the pyrimidine precursor. 

Reaction of 104 with ethyl orthoformate affords 105, which gives a mixture of 57% 106 and 36% 107 upon treatment with ammonia in methanol. When alkylamines are used, 6-alkylaminopyrazolo[3,4-d] pyrimidines are produced they are formed via a Dimroth rearrangement of 5-aIkyl-4-iminopyrazolo[3,4-d]pyrimidine (80JA3897). Reaction of 104 with ethyl orthoformate, followed by HjS, gives 3-cyano-4-mercaptopyrazolo[3,4-d]-pyrimidine (84KGS253). 

Pyrazolo[l,5-a]pyrimidin-7-ones 220 rearrange on treatment with sodium hydroxide into the pyrazolo[3,4-fc]pyridines 221 (77USP4048184). 

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