反应详情

To a solution of N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (200 mg, 0.491 mmol) and Et3N (82 μL, 0.589 mmol) in dichloromethane (3.9 mL), methanesulfonyl chloride (57 μL, 0.736 mmol) was added. The reaction mixture was stirred at room temperature for 95 minutes. The mixture was then diluted with ethyl acetate, washed with saturated NaHCO3, followed by brine, dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography on silica (10-100% ethyl acetate in hexanes) and lyophilized to afford N-{3-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl}methanesulfonamide (113 mg, 0.233 mmol, 47.4% yield) as a white powder. MS ESI: [M+H]+ m/z 486.0. 1H NMR (500 MHz, DMSO-d6) δ 10.28 (s, 1H), 8.83 (m, 2H), 8.11 (s, 1H), 7.99 (s, 1H), 7.50 (s, 1H), 7.29 (m, 1H), 7.21 (s, 1H), 4.91 (dd, J=6.6, 16.1, 4H), 2.98 (s, 3H), 2.33 (s, 3H). rhSYK activity=+++

1. washwashed with saturated NaHCO3
2. dry with materialdried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated
5. customThe residue was purified by column chromatography on silica (10-100% ethyl acetate in hexanes)