Diversity-oriented synthesis of functionalized pyrrolo[3,2-d]pyrimidines with variation of the pyrimidine ring nitrogen substituents.
Nine 2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidine-6-carboxylic acid benzyl esters 12 were synthesized in four steps from 4-oxo-N-(PhF)proline benzyl ester 7 by a general method in which elements of molecular diversity were readily added onto the pyrimidine nitrogens. Conversion of 4-oxoproline 7 into the corresponding aminopyrrole 8 using benzyl-, allyl-, and isopropylamine followed by treatment with phenyl, allyl, and ethyl isocyanate gave nine different ureas 9. 4-Ureido-1H-pyrrole-2-carboxylic acid benzyl esters 9 were then converted into the respective pyrrolo[3,2-d]pyrimidines 12 using trichloroacetyl chloride in acetonitrile followed by treatment with Cs(2)CO(3). Crystallization from toluene gave the desired deazapurines in 37-55% overall yield from proline 7.
Marcotte
Félix-Antoine
FA
Département de chimie, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec, Canada H3C 3J7.
Rombouts
Frederik J R
FJ
Lubell
William D
WD