Dichloromethane → N-({1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]cyclobutyl}sulfonyl)acetamide

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The product of Step 1 (109 mg, 0.322 mmol), N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (INTERMEDIATE 3, 122 mg, 0.322 mmol), and PdCl2(dppf).CH2Cl2 (24 mg, 0.032 mmol) were combined in a vial, sealed, and purged with nitrogen (2×). Dioxane (2.0 mL) and 2 M Na2CO3 (0.48 mL, 0.97 mmol) were added, and the reaction was purged again with nitrogen (2×). The mixture was stirred in an oil bath at 100° C. overnight. The dark brown reaction was diluted with water and extracted with CH2Cl2 (2×). The combined organic layers were dried (Na2SO4), filtered and evaporated. Flash chromatography (dry load, 25-100% ethyl acetate in hexanes, then 0-10% methanol in ethyl acetate) provided an orange-brown residue. The residue was triturated with CH2Cl2, filtered, and dried to afford N-({1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutyl}sulfonyl)acetamide (85 mg, 52%) as a colorless solid. MS ESI: [M+H]+ m/z 512.0. 1H NMR (600 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.27 (s, 1H), 8.81 (d, J=4.9, 1H), 8.13 (s, 1H), 8.00 (s, 1H), 7.49 (s, 1H), 7.27 (d, J=4.9, 1H), 7.21 (s, 1H), 3.23-3.06 (m, 2H), 2.76-2.61 (m, 2H), 2.31 (s, 3H), 2.10-1.89 (m, 2H), 1.84 (s, 3H). rhSYK activity=+++

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