To an oven-dried vial was added 2-chloro-4-methylthiopyrimidine (0.885 g, 4.13 mmol), intermediate XX (1.25 g, 4.13 mmol), tris-(dibenzylideneacetone)dipalladium(0) (0.379 g, 0.413 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.985 g, 2.067 mmol), and potassium carbonate (1.143 g, 8.27 mmol). The vial was evacuated and backfilled with Ar (g) 3×. Degassed t-amyl alcohol (13.78 mL) was added, and the mixture was sealed and heated to 90° C. overnight. After cooling to room temperature, diluted with methanol, added 10 g silica, and concentrated in vacuo. Purified by CombiFlash (100:0 to 0:20 dichloromethane:methanol) to afford 4-[5-(3-methyl-5-{[4-(methylsulfanyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (0.990 g, 2.321 mmol, 56% yield) as a yellow solid. MS APCI: [M+H]+ m/z 427.1. rhSYK activity=+++.
