反应详情

A mixture of 3-(3-tert-butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-benzoic acid (300.0 mg, 0.60 mmol), 1-(2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (93.8 mg, 0.71 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (136.6 mg, 0.71 mmol), 4-dimethylaminopyridine (87.3 mg, 0.71 mmol) and 1-hydroxybenzotriazole (96.6 mg, 0.71 mmol) in THF and DCM was stirred at room temperature overnight. Ethyl acetate and water were added, and the organic phase was washed with brine, dried over MgSO4. and evaporated at reduced pressure. HPLC purification (10-90% aqueous acetonitrile) afforded pure title compound (270 mg, 73%). 1H-NMR (DMSO-d6) δ 8.93 (s, 1H), 8.88 (s, 1H), 8.72 (t, J=6.07.66 (m, 2H), 8.30 (d, J=5.7 Hz), 8.13 (t, J=9.0 Hz, 1H), 7.98 (s, 1H), 7.89 (d, J=9.0 Hz, 1H), 7.69 (m, 2H), 7.19 (d, J=14.7 Hz, 1H), 6.96 (d, J=10.2 Hz, 1H), 6.76 (s, 1H), 6.72 (d, J=5.7 Hz, 1H), 6.41 (s, 1H), 3.95 (t, J=6.3 Hz, 1H), 3.68 (t, J=6.0 Hz, 1H) 3.28-3.45 (m, 2H), 1.314 (s, 3H), 1.27 (s, 9H), 1.22 (s, 3H); MS LC-MS [M+H]+=617.3, RT=2.54 min.

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3. customand evaporated at reduced pressure
4. customHPLC purification (10-90% aqueous acetonitrile)