Methanesulfonamide → 5-chloro-4-[(5-chloro-6-cyclopropylpyridin-3-yl)oxy]-2-fluoro-N-(methanesulfonyl)benzamide

Participants

Reaction Conditions

Reaction Steps

The compound of Example 21 was also prepared according to the following method. To a solution of 5-chloro-4-[(5-chloro-6-cyclopropylpyridin-3-yl)oxy]-2-fluorobenzoic acid (Preparation 265, 45.0 g, 131.52 mmol) in tetrahydrofuran (180 mL) at room temperature was added methansulphonamide (25.02 g, 263.04 mmol), N-ethyl-N-diisopropylpropan-2-amine (68.81 mL, 394.56 mmol) and 1-propanephosphonic acid cyclic anhydride (167.36 g, 263.04 mmol as a 50% solution in ethyl acetate) and the mixture stirred and heated at 70-75° C. for 16 hours. The reaction mixture was concentrated under reduced pressure at 45° C. and water added (450 mL), the resulting slurry was stirred for 30 minutes, filtered and dried. The crude product was dissolved in 2-propanol (1285 mL) at 85° C. and cooled slowly over 16 hours. The resulting slurry was filtered, washed with 2-propanol (2×40 mL) and dried to give the title compound as an off-white solid (46 g, 83%).

Provenance & Evidence