Water → 1-[2-Amino-3-(2,2-dimethyl-propyl)-3H-imidazo[4,5-b]pyridin-5-yl]-2-(4-fluoro-phenyl)-ethane-1,2-dione

Participants

Reaction Conditions

Reaction Steps

Add MgSO4 (82.7 g, 687.05 mmol) and NaHCO3 (14.4 g, 171.41 mmol) in deionized water (1524 mL) over 5 minutes to a stirring solution of 3-(2,2-dimethyl-propyl)-5-(4-fluoro-phenylethynyl)-3H-imidazo[4,5-b]pyridin-2-ylamine (110.76 g, 343.57 mmol) in acetone (3665 mL). Add Hyflo Super Cel® (171.1 g) followed by KMnO4 (108.6 g, 687.21 mmol). Heat at 40-45° C. for 3 hours and then cool to room temperature. Add saturated aqueous Na2SO3 (1,800 mL) followed by EtOAc (3,500 mL) and water (3,500 mL). Filter through bed of Hyflo Super Cel® washing with a mixture of 9% MeOH/EtOAc (2,860 mL). Separate layers of filtrate, back-extract aqueous layer 2×2,750 mL EtOAc. Combine organic extracts, wash 2×2,380 mL saturated aqueous sodium chloride (4760 mL), and dry over Na2SO4. Filter, then concentrate under reduced pressure to provide a dark red-brown solid (185 g). Add acetone (650 mL), filter suspension, wash collected solid 3×167 mL MTBE (501 mL), and dry under reduced pressure at 45° C. to provide 106.79 g (88%) of the desired compound as a light yellow solid.

Provenance & Evidence