We report herein a facile, solid-phase synthesis of 5-amino- 1-β-D-ribofuranosylimidazole-4-carboxamide-5􏰀-monophos- phate (ZMP), a biosynthetic precursor of purine nucleotides, as well as a small collection of its 4-N-alkyl derivatives. The very difficult, direct, chemical phosphorylation of 5-amino-1- β-D-ribofuranosylimidazole-4-carboxamide (AICAR) was cir- cumvented by installing a suitable, fully protected, phosphate group on the 5􏰀-position of N-1-(2,4-dinitrophenyl)- inosine, connected to the solid support through the 2􏰀,3􏰀-posi- tions, prior to the purine degradation, which led to the 5- amino-imidazole-4-carboxamide moiety. A plausible reaction mechanism for the formation of the ZMP imidazole was also reported.