Dimethylformamide → 4-(2,5-Difluoro-4-(1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)picolinamide

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Reaction Steps

To a homogeneous mixture of 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (Compound B of Example 101, 50 mg, 0.21 mmol) and 4-(4-amino-2,5-difluorophenoxy)picolinamide (Compound C of Example 112, 69 mg, 0.26 mmol) in DMF (3 mL) was added DIPEA (0.05 mL, 0.26 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)-uranium hexafluorophosphate (TBTU) (83 mg, 0.26 mmol). The resulting solution was stirred for 18 hours before being quenched with 10% LiCl (aq). The mixture was partitioned between EtOAc and 10% LiCl (aq), the layers separated, and the aqueous layer extracted with EtOAc. The combined organic layers were washed twice with 10% LiCl (aq), then concentrated in vacuo. The residue was purified by silica gel chromatography (eluting with 1:3 hexane/EtOAc) and the appropriate fractions were concentrated in vacuo to afford the title compound (22 mg, 22%). MS(ESI+) m/z 481 (M+H)+.

Provenance & Evidence