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Issue 10, 1995
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Some pyrrolopyrimidine chemistry directed to the synthesis of tricyclic purine analogues


Chemistry directed to the synthesis of the tricyclic ring system 3, a purine analogue with degenerate hydrogen-bonding potential, has been investigated and has resulted in the synthesis of several novel pyrrolo[2,3-d]pyrimidine derivatives as potential precursors. The known analogue 2-amino-7H-pyrrolo[2,3-d]pyrimidin-4-one (7-deazaguanine) is converted by the Vilsmeier reagent into 4-chloro-2-dimethylaminomethyleneamino-6-formyl-7H-pyrrolo[2,3-d]pyrimidine 10. Formylation at the α-position of the pyrrole ring was determined by the comparison of 13C NMR data of the corresponding alcohol and the unsubstituted derivative and is in agreement with the regiospecificity reported for the Mannich reaction of this compound. In contrast, base-catalysed hydroxymethylation of 4-chloro-2-methylsulfanyl-7H-pyrrolo[2,3-d]pyrimidine with formaldehyde in aqueous THF occurs at the desired β-position to afford the 5-hydroxymethyl product 17. 7-Methylation of the ButMe2Si-protected alcohol 17 led to several potential precursors of the desired tricyclic structure. The 5-phthalimidooxymethyl derivatives of either 2-methylsulfanyl- or 4-chloro-7-methyl-2-methylsulfonyl-7H-pyrrolo[2,3-d]pyrimidine with ammonia gave the aminooxymethyl derivatives but these subsequently failed to cyclise. Several approaches to cyclise 4-hydroxyamino-5-hydroxymethyl-7-methyl-2-methylsulfonyl-7H-pyrrolo[2,3-d]pyrimidine 27 afforded the corresponding 4-amino compound as the major component. Both the experimental and modelling results show that considerable strain is associated with the formation of 3.

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Article type: Paper
DOI: 10.1039/P19950001225
J. Chem. Soc., Perkin Trans. 1, 1995, 1225-1231

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    Some pyrrolopyrimidine chemistry directed to the synthesis of tricyclic purine analogues

    D. M. Williams and D. M. Brown, J. Chem. Soc., Perkin Trans. 1, 1995, 1225
    DOI: 10.1039/P19950001225

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