Acetyl chloride → N-(3-[2-(2-sulfamoylpropan-2-yl)-1,3-thiazol-5-yl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)acetamide

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Reaction Steps

2-[5-(3-Amino-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propane-2-sulfonamide (Example 71, 90 mg, 0.196 mmol) was suspended in CH2Cl2 (5 mL) with triethylamine (55 μL, 0.393 mmol), and acetyl chloride (28 μL, 0.393 mmol) was added. After stirring for 1 h at room temperature, additional acetyl chloride (28 μL, 0.393 mmol) and triethylamine (55 μL, 0.393 mmol) were added. After another 1 h at room temperature, the suspension was diluted with MeOH, silica was added, and the mixture was evaporated to dryness. Flash chromatography (dry load, 40-100% ethyl acetate in hexanes) afforded N-(3-[2-(2-sulfamoylpropan-2-yl)-1,3-thiazol-5-yl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)acetamide (34 mg, 35%) as a white solid. MS ESI: [M+H]+ m/z 501.0. 1H NMR (500 MHz, DMSO-d6) δ 10.35 (s, 1H), 10.07 (s, 1H), 8.82 (d, J=4.9, 1H), 7.94 (s, 1H), 7.91 (s, 1H), 7.83 (s, 1H), 7.61 (s, 1H), 7.29 (d, J=4.9, 1H), 7.05 (s, 2H), 2.05 (s, 3H), 1.79 (s, 6H). rhSYK activity=+++

Provenance & Evidence