反应详情

To a suspension of (1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylic acid (example 42(1), 50 mg, 0.099 mmol) in chloroform (800 μL) was added N-bromosuccinamide (21 mg, 0.12 mmol). The mixture was stirred at room temperature for 15 minutes, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (Biotage 10 G, eluting with 1:99 to 10:90 methanol:dichloromethane) to give (1S,4R)-4-[5-(2-bromo-3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid (22 mg, 0.038 mmol, 38% yield) as a pale yellow solid. ESI: [M+H]+ m/z 587.1. 1H NMR (500 MHz, CD3OD) δ 8.70 (d, J=4.9, 1H), 7.86 (d, J=2.6, 1H), 7.78-7.64 (m, 2H), 7.13 (d, J=4.9, 1H), 2.46 (s, 3H), 2.35 (dd, J=2.9, 12.8, 1H), 2.22 (ddd, J=6.1, 13.2, 24.2, 1H), 2.01 (dd, J=6.7, 14.5, 3H), 1.79 (d, J=14.4, 1H), 1.72 (dd, J=3.2, 13.5, 1H), 1.22 (s, 3H), 1.11 (s, 3H). rhSYK activity=+++

1. concentrationconcentrated under reduced pressure
2. customThe residue was purified by column chromatography on silica gel (Biotage 10 G, eluting with 1:99 to 10:90 methanol:dichloromethane)