Pyrrolo pyrimidine-2,4-diones

Pyrrolo[2,3-d]pyrimidine, 5-cyano-bromination, 4, 506 Pyrrolo[2,3-d]pyrimidine, 5-nitroso-nucleophilic reactions, 4, 507 Pyrrolo[l, 2- c]pyrimidine-3-carboxylic acids methyl ester synthesis, 4, 293 Pyrrolopyrimidine-2,4-diones Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolopyrimidines synthesis, 4, 514, 517, 524, 527 Pyrrolopyrimidines, chloro-nucleophilic attack, S, 312 Pyrrolo[2,3-d]pyrimidines NMR, 4, 500... 

Alternatively, pyrrolo[3,4-d]pyrimidine-2,5-diones were synthesized using the same pyrimidine resin precursor, which was first treated with a representative set of primary amines to substitute the chlorine. Subsequent cyclative cleavage was carried out as described previously, leading to the corresponding pyrrolopyrimidine-2,5-dione products in high purity but moderate yield. 

Finally, ortho aminoesters have been used to produce 7-deazaxanthines. For example ethyl 2-amino-5-phenyl-l//-pyrrole-3-carboxylate is first treated with 2-chloroethyl isocyanate in refluxing toluene. The resulting urea derivative is then allowed to react with l-(2-methoxyphenyl)piperazine and cyclized to the expected pyrrolo[2,3-,7 pyrimidin-2,4(177,377)-dione <2006BMCL150>. 

The use of pyrimidines as precursors for pyrrolo[3,4-rf]pyrimidines is the most common synthetic approach. 6-Phenyl-7-(substituted)amino-pyrrolo[3,4-ii]pyrimidine-2,4(l//,3//)-diones (164) are readily obtained from the reaction of 5-formylpyrimidines (163) with arylamines (Equation (54)) <89BCJ3043>. Formation of the Schiff base, followed by cyclization, is the proposed pathway. A more traditional approach is found in the conversion of the cyanoester (165), via the amide, to the corresponding pyrrolopyrimidine (166) (Equation (55)) (88LA643). 

The syntheses of 1,3-dipropyl-l//,3//-pyrazino-, pyrid0 5 pynmido-, and pyrrolo[2,1 /]purine-2,4-diones starting from 5,6-diamino-l,3-dipropylpyrimidine-2,4-dione and 6-chloro-l,3-dipropyl-pyrimidine-2,4-dione have been described (Scheme 15) <94JHC8l>. A new route to 1,3-dipropyl-1H, 3/f-pyrido- (or pyrazino-) [T,2 -l,2]pyrimidino[4,5-d]pyrimidino-2,4,5-triones has also been developed (Scheme 16). 

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). 

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