Antifolate alimta (1) derived from pyrrolo[2,3-d]pyrimidine is a multitargeted antitumor agent and a novel synthetic route to it was established. Ethyl 4-(4-ethoxy-4-oxobutyl)benzoate (5) was prepared via Friedel-Crafts acylation and Huang reduction in 36.6% yield, then alimta was synthesized through selective reduction with KBH₄/LiBr, oxidation, ring-closing and etc. in overall yield of 4.8%.

Key words: antifolate, Huang reduction., alimta, Friedel-Crafts, pyrrolo[2,3-d]pyrimidine