Green Chemistry Challenge: 2022 Greener Reaction Conditions Award
Amgen is being recognized for creating an improved manufacturing process to enable a greener synthesis process for LUMAKRAS™ (sotorasib), a novel drug for treatment of certain non-small cell lung cancers. The improved manufacturing process substantially reduced waste and decreased manufacturing time by cutting the number of steps involved and eliminating a purification step that created large quantities of solvent waste. Amgen also implemented a recycling process for a harmful substance which improved efficiency and reduced the amount of waste generated. Amgen estimates these improvements will reduce waste by up to 31.7 million pounds per year while also improving the yield, cost, throughput and overall sustainability of sotorasib production.
Summary of Technology:
LUMAKRAS™ (sotorasib) is an atropisomeric molecule, or a molecule where rotation of one or more chemical bonds is limited because of limitations on the speed of chemical reactions due to the spatial arrangement of atoms in a molecule, known as steric hindrances. Amgen improved the commercial manufacturing process for sotorasib by implementing improved telescoped syntheses for two isolated intermediates, reducing the number of reaction steps. A telescoped synthesis, also called a one-pot synthesis, occurs by adding reagents to a reaction vessel one at a time to cause multiple sequential reactions in one vessel, instead of performing one reaction in the vessel and separating and purifying intermediates before performing the next step. This can minimize chemical waste and save time. Further, implementing a recycling process allowed for the recovery of the undesirable P-atropisomer back into the reaction. Amgen made many changes to improve the process and increase efficiency. Previously, solvent-intensive and slow processes (chiral chromatography and recrystallization) were used to separate the M and P atropisomers; Amgen replaced these steps with resolution with the inexpensive chiral-pool derived reagent (+)-DBTA. Combined, Amgen estimates these improvements will reduce waste by up to 31.7 million pounds per year while also improving the yield, cost, throughput and overall sustainability of sotorasib production.