A Continuous Flow Process for LSN647712 via Double Organometallic Additions to Dimethylcarbamyl Chloride

Article
Continuous flow
Drug substance
Process development

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.

View the full article (via ACS)