2-Aminopyridine → 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Participants

Reaction Conditions

Reaction Steps

A tautomeric mixture of 3-[(2-chloro-4-pyrimidinyl)acetyl]-N-(2,6-fluorophenyl)benzamide and 3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]-N-(2,6-difluorophenyl)benzamide (5.73 g, 14.8 mmol) was dissolved in 150 mL of DCM with stirring. NBS (2.63 g, 14.8 mmol) was added in a single portion, and the reaction was stirred for 15 minutes. The reaction was concentrated in vacuo. Dioxane (100 mL) was added to dissolve the residue with stirring. 2-Aminopyridine (4.18 g, 44.4 mmol) was added, and the reaction was heated to 60° C. for 16 hours. The reaction was cooled to rt and poured into half-saturated NaHCO3 solution and EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The mixture was purified by flash chromatography to afford 5.26 g (77%) of the desired product. 1H NMR (400 MHz, DMSO-d6): δ 10.20 (s, 1H), 9.40 (d, J=7.0 Hz, 1H), 8.56 (d, J=5.3 Hz, 1H), 8.33 (s, 1H), 8.08 (d, J=7.9 Hz, 1H), 7.85 (d, J=7.9 Hz, 1H), 7.81 (d, J=9.0 Hz, 1H), 7.66-7.54 (m, 2H), 7.89 (m, 1H), 7.27-7.15 (m, 4H).

Provenance & Evidence