5-Aminoisoquinoline → 1-(1-cyclobutyl-1H-imidazol-4-yl)-3-isoquinolin-5-yl-urea
反応式
C1(O[C:8](=[O:19])[NH:9][C:10]2[N:11]=[CH:12][N:13]([CH:15]3[CH2:18][CH2:17][CH2:16]3)[CH:14]=2)C=CC=CC=1.[NH2:20][C:21]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:22]=1[CH:23]=[CH:24][N:25]=[CH:26]2>O1CCOCC1.CN(C=O)C>[CH:15]1([N:13]2[CH:14]=[C:10]([NH:9][C:8]([NH:20][C:21]3[CH:30]=[CH:29][CH:28]=[C:27]4[C:22]=3[CH:23]=[CH:24][N:25]=[CH:26]4)=[O:19])[N:11]=[CH:12]2)[CH2:16][CH2:17][CH2:18]1参加物
4
反応条件
- 温度
- 70 °C
実験手順
To a 1 dram vial with septa screw cap was added (1-cyclobutyl-1H-imidazol-4-yl)-carbamic acid phenyl ester (Example 4, 50 mg, 0.19 mmol), 5-aminoisoquinoline (30 mg, 0.21 mmol), and 1:1 dioxane-DMF (1 mL). The reaction mixture was heated at 70° C. for 2 h. The reaction mixture was adsorbed onto silica gel and was purified by silica gel chromatography (40:1 chloroform-methanol) to afford 30 mg (52% yield) of 1-(1-cyclobutyl-1H-imidazol-4-yl)-3-isoquinolin-5-yl-urea; 1H NMR (400 MHz, CD3OD) δ 9.21 (d, J=1.7 Hz, 1H), 8.45 (d, J=6.2 Hz, 1H), 8.24 (d, J=7.5 Hz, 1H), 7.98 (d, J=5.4 Hz, 1H), 7.84 (dd, J=2.3, 8.3 Hz, 1H), 7.66 (m, 1H), 7.54 (s, 1H), 7.12 (brs, 1H), 4.66 (m, 1H), 2.5–2.3 (m, 4H), 1.9 (m, 2H); MS (AP/CI): 308.0 (M+H)+.