The prodrug  BIIB028, an Hsp90 oncology candidate, was chosen for development based on its improved solubility, safety profile and efficacy relative to a predecessor, BIIB021. An improved multi-kilogram process was developed that featured a simplified Sonogashira coupling of BIM-362, a heteroaryl iodide, with 3-propyn-1-ol, an improved phosphorylation protocol using POCl3 and a reprecipitation procedure that improved the HPLC impurity profile of the API. Using these improvements a scale up campaign was completed to afford 12.5 kg (70% yield over 3 steps) of high purity, GMP quality BIIB028.

Process improvements to the synthesis of BIIB028, a potent Hsp90 inhibitor

244th National Meeting (2012)

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