Acetic Acid → Fluazaindolizine

Participants

Reaction Conditions

Reaction Steps

A stirred slurry of 8-chloro-6-(trifluoromethyl)imidazo[1,2,a]pyridine-2-carboxylic acid ethyl ester (3.0 g, 10.3 mmol) and 2-chloro-5-methoxybenzenesulfonamide (2.39 g, 10.8 mmol, 1.05 equiv) in n-chlorobutane (45 mL) was heated to 50° C. under nitrogen. To this slurry was added neat diethylaluminum chloride (1.40 mL, 11.3 mmol). After complete addition of diethylaluminum chloride the temperature of the reaction mixture was adjusted to 65-70° C. and was held at this temperature for 4.5 h. An additional portion of n-chlorobutane (12 mL) was added and heating at 70° C. was continued for an additional 1.5 h. Iso-propanol (1.6 mL, 20.5 mmol, 2 equiv) was added at 70° C. and the resulting mixture stirred for 5 min. Aqueous 10% acetic acid (15 mL, 25.6 mmol, 2.5 equiv) was then added over a period of 10 min at 60-65° C. The reaction was allowed to cool to room temperature and then stirred overnight. The resulting solid was filtered, washed with water (12 mL) followed by n-chlorobutane (12 mL), and suction-dried. The solid product was further dried in a vacuum oven at 50-60° C. to give the title compound (4.09 g, 85.2%). Powder X-ray diffraction data conformed with Form A of Compound 1 as in Characterization Example 2.

Provenance & Evidence