Multi-Kilo Delivery of AMG 925 Featuring a Buchwald-Hartwig Amination and Processing with Insoluble Synthetic Intermediates

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Amgen describes the development of a synthetic route to manufacture the drug candidate AMG 925 on kilogram scale. The synthetic route features a Buchwald-Hartwig amination using BrettPhos as ligand and conducted to afford 12 kg of product in a single batch (scheme).

Yet, the target levels of heavy metal in the drug substance AMG 925 were < 100 ppm, much lower than that found in the crude Buchwald-Hartwig product (700 - 800 ppm).

After the screening of potential scavengers, SiliaMetS Thiourea was selected as the scavenger of choice since it was the most effective. At 100 wt % relative to crude product, in 80 % (v/v) toluene/MeOH and a total of 15 volumes of solvent, it afforded product in 90 % with less than 2 ppm of residual Pd.

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• SiliaMetS Thiourea
• SiliaMetS Metal Scavengers