Phosphorus oxychloride → HCID 86655258, compound

Participants

Reaction Conditions

Reaction Steps

2-Hydroxy-3-(2-(trifluoromethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl methanesulfonate (0.50 g, 1.3 mmol) taken up in phosphoryl trichloride (3.0 mL) was heated in a sealed tube to 80° C. for 48 h. The mixture was concentrated under reduced pressure and NaHCO3 was added to the residue until it turned basic. The solution was further diluted with water and extracted with EtOAc (3×). The combined organic extracts were dried over MgSO4 and concentrated under reduced pressure. The residue was purified column chromatography to give 2-chloro-3-(2-(trifluoromethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl methanesulfonate, which was dissolved in a 1:4:1 solution of 1 M LiOH/THF/MeOH (10 mL) and stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure and the remaining was acidified with 1 N HCl. The resulting precipitate was collected by vacuum filtration and purified via preparative HPLC to give the title compound (0.11 g, 0.32 mmol, 25%). LCMS m/z=330.2 [M+H]+, 1H NMR (400 MHz, methanol-d4) δ ppm 6.70 (d, J=8.7 Hz, 1H), 7.58-7.68 (m, 3H), 7.73 (m, 1H), 7.90 (d, J=8.7 Hz, 1H).

Provenance & Evidence