ChemicalBook CAS DataBase List LasMiditan

LasMiditan synthesis

5synthesis methods

Product Name:LasMiditan
CAS Number:439239-90-4
Molecular formula:C19H18F3N3O2
Molecular Weight:377.36

Lasmiditan, also known as COL-144 and LY573144, is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist (K1=2.21 μM) without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. Lasmiditan showed efficacy in its primary endpoint, with a 2-hour placebo-subtracted headache response of 28.8%, though with frequent reports of dizziness, paresthesias, and vertigo. Synthetic Description Reference: Carniaux, Jean-Francois; Cummins, Jonathan. Compositions and methods of synthesis of pyridinoylpiperidine derivatives as 5-HT1F agonists for treating and preventing migraine. Assignee Colucid Pharmaceuticals, Inc., USA. WO 2011123654. (2011). Synthetic Description Reference: Cohen, Michael Philip; Kohlman, Daniel Timothy; Liang, Sidney Xi; Mancuso, Vincent; Victor, Frantz; Xu, Yao-Chang; Ying, Bai-Ping; Zacherl, Deanna Piatt; Zhang, Deyi. Preparation of pyridinoylpiperidines as 5-HT1F agonists. Assignee Eli Lilly and Company, USA. WO 2003084949. (2003).

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

Sheng, Xiaohong; Sheng, Xiaoxia; Jiang, Xiawei. Preparation of crystalline form of lasmiditan and its pharmaceutical composition. Assignee SoliPharma LLC, Peop. Rep. China. WO 2018010345. (2018).

613678-03-8 Synthesis

(6-aMinopyridin-2-yl)(1-Methylpiperidin-4-yl)Methanone

613678-03-8
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79538-29-7 Synthesis

79538-29-7
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439239-90-4
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$49.00/10mg

Yield:439239-90-4 100%

Reaction Conditions:

in 1,4-dioxane for 3 h;Product distribution / selectivity;Heating / reflux;

Steps:

8
Combine 2-amino-6-(l-methylpiperidin-4-ylcarbonyl) pyridine (0.20 g, 0.92 mmol), 2,4, 6-Trifluorobenzoyl chloride (0.357 g, 1.84 mmol), and 1, 4-Dioxane (10 mL), and stir while heating at reflux. After 3 hr. , cool the reaction mixture to ambient temperature and concentrate. Load the concentrated mixture onto an SCX column (lOg), wash with methanol, and elute with 2M ammonia in methanol. Concentrate the eluent to obtain the free base of the title compound as an oil (0.365 g (>100%)). Dissolve the oil in methanol (5 mL) and treat with ammonium chloride (0.05 g, 0.92 mmol). Concentrate the mixture and dry under vacuum to obtain the title compound. HRMS Obs. m/z 378.1435, Calc. m/z 378.1429 ; m. p. 255°C (dec).

References:

ELI LILLY AND COMPANY WO2003/84949, 2003, A1 Location in patent:Page/Page column 35

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68947-43-3 Synthesis