Development of an Efficient, Scalable Route for the Preparation of a Novel Insulin-Like Growth Factor‑1 Receptor Modulator

A chromatography-free and efficient synthesis of insulin-like growth factor-1 receptor (IGF-1R) modulator is reported. Herein we describe an improved synthesis for the target compound, which features facile introduction of a novel pyrrolidinyl-pyrimidyl isoxazole 8, via in situ sulfone displacement by fluorine. The overall process consists of six chemical steps and five isolations, with introduction of the expensive triheterocyclic unit 8 towards the end of the synthesis.