Hydrochloric Acid → Azd-8330

Participants

Reaction Conditions

Reaction Steps

To a rapidly stirred mixture of 2-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (2-vinyloxyethoxy)-amide (4.2 g, 8.52 mmol) (prepared according to Example 16A, Step 2) above in ethyl acetate (126.00 mL) was added hydrogen chloride (17.05 mL, 17.0493 g, 17.05 mmol). After 2 hours, less than 1% of the starting material remained (by HPLC analysis) and the phases were allowed to settle. The lower aqueous phase was separated and discarded and the organic phase was washed with sodium chloride (42 mL, 15% wt/vol, then 2×25 mL, 9% wt/vol). The volume was then reduced by distillation of solvent (44 mL) at atmospheric pressure (65° C. head temperature). The solution was then cooled to 70° C., and Form 1, 2-(2-fluoro-4-iodophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide (40.3265 mg), made according to Example 16A, Step 4, was added. The mixture was stirred for 20 hours at 70° C. The temperature was reduced to 24° C. over 4 hours 15 minutes, and then lowered to 1° C. for 1 hour. The slurry was then filtered, the cake was washed with cold ethyl acetate (17 mL) and the solid was dried in a vacuum oven at 45° C., to provide 2-(2-fluoro-4-iodophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide Form 1 (3.15 g, 76%).

Provenance & Evidence