Synthesis of several isotopically labeled pyrrolo[1,3-d]pyrimidine analogs

Four members of a novel class of pyrrolo[2,3-d]pyrimidines that show potential for the treatment of asthma and neurodegenerative disorders, have been prepared with radioisotope labels and in one case with multiple stable isotope labels for ADME studies as part of the drug development process. The syntheses utilize an isotopically labeled 2,4,6-trisubstituted pyrimidine as a common building block, readily prepared from isotopically labeled urea. Cyclizations of the pyrimidine with bromo-ketones generate the ring fused pyrrolo[2,3-d]-pyrimidines with elegant efficiency as demonstrated by the preparation of structures 4, 5, 8 and 12. Copyright © 2001 John Wiley & Sons, Ltd.