A Concise Synthesis of a Novel Insulin-Like Growth Factor I Receptor (IGF-IR) Inhibitor^†

An efficient synthesis of a potent insulin-like growth factor I receptor (IGF-IR) hihibitor AEW541 (1) is described. The key step in the synthesis is the cis-selective reductive amination of cyclobutanone, which sets up the desired 1,3-stereochemistry of the cyclobutane ring. The amino group thus generated is used as a handle to build the pyrrolopyrimidine ring. The final step resulting in 1 is accomplished by alkylation of in situ generated mesylate with azetidine.