Triethylamine → N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Participants

Reaction Steps

A mixture of 1-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (37 mg, 0.16 mmol), EDCI (91 mg, 0.48 mmol), and HOBt (64 mg, 0.48 mmol) in DMF (2 mL) was stirred at room temperature for 1 hour. 3-Fluoro-4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)aniline (30 mg, 0.079 mmol; prepared as in Example 5, Step D) was added, followed by Et3N (0.066 mL, 0.48 mmol). After stirring for 15 hours, the reaction mixture was diluted with EtOAc and washed with saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (2% MeOH in CH2Cl2) to afford 45 mg (96%) of the desired product. LRMS (ESI pos) m/e 594.2 (M+1). 1H-NMR (400 MHz, CD3OD/CDCl3) δ 8.72 (dd, 1H), 8.28 (d, 1H), 7.99 (dd, 1H), 7.92 (dd, 1H), 7.51 (m, 2H), 7.41 (m, 1H), 7.32 (m, 3H), 7.24 (d, 2H), 6.84 (d, 2H), 6.75 (t, 1H), 6.28 (d, 1H), 5.54 (s, 2H), 3.76 (s, 3H), 2.71 (s, 3H); 19F NMR (376 MHz, CD3OD/CDCl3) δ −113.2, −128.7.

Provenance & Evidence