[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:11]1[C:20]2[C:15](=[CH:16][C:17]([OH:21])=[CH:18][CH:19]=2)[CH:14]=[C:13]([NH:22][C:23]2[CH:27]=[C:26]([CH3:28])[NH:25][N:24]=2)[N:12]=1.Br[CH2:30][CH2:31][O:32][CH3:33]>CN(C)C=O.CO>[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:21][CH2:30][CH2:31][O:32][CH3:33])=[CH:18][CH:19]=2)[CH:14]=[C:13]([NH:22][C:23]2[CH:27]=[C:26]([CH3:28])[NH:25][N:24]=2)[N:12]=1Sodium hydride (17 mg, 60%) was added slowly to an ice-cooled solution of 1-(2,4-difluoro-phenyl)-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinolin-6-ol (150 mg) in 2 mL N,N-dimethylformamide (DMF). After stirred for 30 min, 1-Bromo-2-methoxy-ethane (59 mg) in 1 mL DMF was added cautiously by syringe. The mixture was warmed to room temperature and stirred overnight, then diluted with 1 mL methanol and directly sent to prep-HPLC. The product [1-(2,4-difluoro-phenyl)-6-(2-methoxy-ethoxy)-isoquinolin-3-yl]-(5-methyl-1H-pyrazol-3-yl)-amine (40 mg) was obtained as a yellow solid. LC-MS m/e 411(MH+). 1H NMR (400 MHz, DMSO) 9.12(s, 1H), 7.81(s, 1H), 7.61(m, 1H), 7.43(t, 1H), 7.34(d, 1H), 7.25(t, 1H), 7.10(d, 1H), 6.85(d, 1H), 5.81(s, 1H), 4.23(m, 2H), 3.71(m, 2H), 3.32(s, 3H), 2.20(s, 3H).
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