A practical synthesis of multitargeted antifolate LY231514

A concise and scalable synthesis of LY231514 (1), a new pyrrolo[2,3-d]pyrim idine-based antitumor agent, is presented. Reaction of 2-bromo-4-arylbutana l 9 with 2,4-diamino-6-hydroxypyrimidine (10) regioselectively provided pyr rolo[2,3-d] pyrimidine 11, representing the core structure of the drug, in good yield. Assimilation of the glutamic acid residue by conventional means completed the synthesis. Development of the optimized synthetic route emph asized avoiding isolation of the relatively unstable aldehyde and bromoalde hyde intermediates.