The synthesis of Tepotinib is as follows:
Acetonitrile (700 ml) was added to the reaction vessel, and the compound represented by formula 7a (37.63 g, 0.1 mol), the compound represented by formula 8 (23.66 g, 0.12 mol), and potassium carbonate (34.55 g, 0.25 mol) were added under stirring.and tetrabutylammonium bromide (1.93g, 0.006mol), the reaction system was stirred and heated to reflux, and the reaction was stirred at reflux for 12h. After the reaction was completed, the temperature was cooled to room temperature, the reaction solution was concentrated under reduced pressure to dryness, and ethanol (360ml) was added. ), stir to dissolve, slowly add 1.5 mol/l hydrochloric acid aqueous solution dropwise, adjust the pH value to 1-2, cool down to 5-7 °C, stir and crystallize for 6 h, filter, and vacuum dry the solid at 45 °C for 6 h to obtain formula 1. The compound (44.42 g) was shown in a yield of 81.2% and a purity of 99.7% by HPLC.