Deazapurine solid-phase synthesis: construction of 3-substituted pyrrolo[3,2-d]pyrimidine-6-carboxylates on cross-linked polystyrene bearing a cysteamine linker.
The first solid-phase methodology for the preparation of pyrrolo[3,2-d]pyrimidines is presented. Merrifield resin bearing a cysteamine "traceless" linker was treated with 4-oxo-N-(PhF)proline benzyl ester (10; PhF = 9-(9-phenylfluorenyl)) to provide resin-bound aminopyrrole 20, which was treated with ethyl, phenyl, 4-phenoxyphenyl, and 2,4-dimethoxyphenyl isocyanates to furnish resin-bound ureidopyrroles 21a-d. Resin-bound pyrrolo[3,2-d]pyrimidines 22a-d were then obtained by acylation of 21 using trichloroacetyl chloride in dioxane followed by treatment with Cs2CO3 in DMF. Cleavage of pyrrolo[3,2-d]pyrimidines 22a-d from the resin was achieved in two steps, by oxidation of the sulfur to the sulfone followed by beta-elimination in the presence of t-BuONa. Four pyrrolo[3,2-d]pyrimidines, 24a-d, with different alkyl and aryl substituents at the N3 pyrimidine nitrogen, were thus obtained in overall yields of 42-50% and purities of 90-100%.
Rombouts
Frederik J R
FJ
Département de chimie, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec, Canada H3C 3J7.
Fridkin
Gil
G
Lubell
William D
WD
D000215:Acylation; D020650:Combinatorial Chemistry Techniques; D003543:Cysteamine / Q000737:chemistry*; D015394:Molecular Structure; D011137:Polystyrenes / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry*
D011137:Polystyrenes; D011743:Pyrimidines; D003543:Cysteamine