3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine

372-48-5

383-63-1

956010-87-0

3-(Trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine (1a) was synthesized as follows: n-butyllithium (2.6 M hexane solution, 87.2 mL) was added slowly and dropwise to a solution of tetrahydrofuran (THF, 300 mL) containing N,N-diisopropylamine (25.0 g) under the protection of nitrogen and the temperature was kept at -5 to 0 °C. Subsequently, a solution of 2-fluoropyridine (25 g) in THF (50 mL) was added dropwise to the reaction system at -78 °C and stirred continuously for 1 hour at this temperature. Next, a THF (50 mL) solution of ethyl trifluoroacetate (47.6 g) was slowly added to the reaction solution at -78 °C and stirring was continued at the same temperature for 1 hour. Upon completion of the reaction, hydrazine monohydrate (41.3 g) was added to the system and the reaction mixture was heated to 60 °C and stirred for 6 hours. Subsequently, water (500 mL) was added and stirring was continued at 100 °C for 30 minutes. At the end of the reaction, the precipitate was collected by filtration and dried under reduced pressure to afford the target compound 3-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine (1a) (32.8 g, 85% yield) as a white solid. The product was confirmed by 1H-NMR (DMSO-d6) and LRMS (ESI) characterization.