Step C: Synthesis of N-(3-(2-(tert-butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide. To the reactor was added N-{3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (30 g, 1 eq.) and dichloromethane (300 mL). The reaction mixture was cooled to 10 °C and N-bromosuccinimide (NBS) (12.09 g, 1 eq.) was added in 3 portions, stirring for 10-15 min after each addition. After the addition was completed, the reaction mixture was warmed to 20 °C and stirred for 45 min. Water (150 mL) was added, stirred and layered. Water (150 mL) was again added to the dichloromethane layer, stirred and layered. The dichloromethane layer was concentrated to about 120 mL. ethyl acetate (210 mL) was added and concentrated to about 120 mL. dimethylacetamide (270 mL) was added and cooled to 10°C. The dichloromethane layer was then mixed with water (150 mL) and stirred. 2,2-Dimethylpropane sulfamide (1.3 g, 0.5 eq.) was added in 2 additions, stirring for 5 minutes after each addition. The reaction mixture was warmed to 20-25 °C and held for 45 minutes. It was then heated to 75°C and reacted for 1.75 hours. Cooled to 5°C and slowly added water (270 mL), controlling the temperature below 30°C. Ethyl acetate (120 mL) was added, stirred and layered. Add ethyl acetate (210mL) to the aqueous layer, stir and stratify. Ethyl acetate (210mL) was added to the aqueous layer again, stirred and layered. Combined the organic layers, washed 4 times with water (120mL) and stirred at 20-25°C overnight. Concentrate the organic layer to 120 mL. heat to 50 °C and slowly add heptane (120 mL). Heat to reflux, cool to 0°C and hold for 2 hrs. Filtered the solid and washed with heptane (2 x 60 mL). dried under vacuum at 30 °C to give the target product (28.8 g, 80% yield).
![N-{3-[5-(2-chloro-4-pyriMidinyl)-2-(1,1-diethylethyl)-1,3-thiazol-4-yl]-2-fluoraphenyl}-2,6-difluorobenzenesulfonaMide](/CAS/20150408/GIF/1195768-23-0.gif)