Water → Selumetinib sulfate

Participants

Reaction Conditions

Reaction Steps

Sulfuric acid (1.52 ml, 27.86 mmol) was added to a stirred suspension of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide (10 g, 0.0214 mol) (obtainable as described in Example 10 of WO 03/077914, which is incorporated herein by reference and as described below) in tetrahydrofuran (THF) (62 ml) and water (8 ml) whilst maintaining a temperature of 10° C. or lower. The stirred mixture was heated to 65° C. and held for 30 minutes before filtering to remove any extraneous matter. THF (150 ml) was then added to the mixture maintaining the temperature above 60° C. The mixture was then cooled to 0-5° C. over approximately 2 hour. The resulting slurry was filtered, washed with THF (30 ml) and dried under reduced pressure at 50° C. until a constant weight was achieved, to give 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide hydrogen sulfate (9.81 g, 0.17 mol, 82% yield) as an off white crystalline solid. The material was the same as that produced in Example 1 above.

Provenance & Evidence