SYNTHESIS OF LY288601, A 5,6-DIHYDROPYRROLO[2,3-D]PYRIMIDINE BASED ANTIFOLATE COMPOUND RELATED TO LY231514

An expeditious synthesis of LY288601 (2), the 5,6-dihydro analog of th e pyrrolo[2,3-d]pyrimidine-based antifolate compound LY231514 (1a), is described. The synthesis proceeds in eight steps from tert-butyl 4-io dobenzoate and involves the elaboration of a 2-amino-4-hydroxypyrimidi ne ring onto an activated 3-carboalkoxy-2-pyrrolidinone via reaction w ith guanidine as a key step.