A Continuous Flow Process for LSN647712 via Double Organometallic Additions to Dimethylcarbamyl Chloride
The ketone intermediate, LSN647712, is a key synthetic intermediate for Eli Lilly’s drug substance lasmiditan during its manufacturing process. In this article, we explain how our team at Snapdragon Chemistry helped them develop a three-step connected continuous flow process to deliver the ketone intermediate in a high chemical yield (>85%). The team was able to achieve this utilizing a Turbo Grignard reagent, N-methylpiperidin-4-ylmagnesium chloride, and lithiated 2,6-dibromopyridine sequentially added to double electrophile (O═C(++) synthon dimethylcarbamyl chloride (DMCC).
Our results show this highly productive (>100 g/h lab system) and intensified process (τ ∼ 3 min) yielded the product in high purity upon batch reactive crystallization to form a corresponding hydrobromide salt. In addition to the connected plug flow reactor system, the Grignard reagent, N-methylpiperidin-4-ylmagnesium chloride, was also prepared continuously in CSTR as a more soluble LiCl adduct in THF (Turbo Grignard).
Read the entire article, “A Continuous Flow Process for LSN647712 via Double Organometallic Additions to Dimethylcarbamyl Chloride,” to learn more.