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Updated: Oct 25, 2025

Accessing Valuable Ligand Supports for Transition Metals: A Modified, Intermediate Scale Preparation of 1,2,3,4,5-Pentamethylcyclopentadiene
Published on: March 20, 2017
A Continuous Flow Process for LSN647712 via Double Organometallic Additions to Dimethylcarbamyl Chloride
Hui Li1, Jillian W Sheeran1, David Kouvchinov1
1Snapdragon Chemistry Inc., 300 Second Ave, Waltham, Massachusetts 02451, United States.
Abstract:
The ketone intermediate LSN647712 is a key synthetic intermediate for the drug substance lasmiditan manufacturing process. A three-step connected continuous flow process 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) was developed to deliver the ketone intermediate in a high chemical yield (>85%). This highly productive (>100 g/h lab system) and intensified process (τ ∼ 3 min) yields 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).
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