3-Methylpyridine → 2-(3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-6-chloro-8-methyl-4H-benzo[d][1,3]oxazin-4-one

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (see WO 03/015519 for preparation) (93.6% purity, 16.16 g, 50.0 mmol), 6-chloro-8-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (99.0% purity, 11.22 g, 52.5 mmol), and 3-picoline (16.5 mL, 15.8 g, 170 mmol) in acetonitrile (65 mL) at about −5° C. was added dropwise methanesulfonyl chloride (5.0 mL, 7.4 g, 65 mmol) in acetonitrile (15 mL). After 15 minutes at −5 to 0° C., the reaction mixture was heated to 50° C. for 4 hours. The reaction mixture was then cooled to room temperature, water (20 mL) was added dropwise, and the reaction mixture was stirred 15 minutes. The mixture was filtered, and the solids were washed sequentially with 4:1 acetonitrile-water (2×35 mL) and acetonitrile (3×35 mL), and dried under nitrogen to afford the title product as a light yellow powder, 20.55 g (94.4% purity by HPLC, 85.8% yield calculated based on the purity).

Provenance & Evidence