反应详情

温度

95 °C

2-{5-[(Cyclopropylamino)carbonyl]-2-methylphenyl}-1-oxo-1,2-dihydroisoquinolin-7-yl trifluoromethanesulfonate (58 mg), palladium acetate (3 mg), BINAP (16 mg) and cesium carbonate (101 mg) were placed in a reaction tube under an atmosphere of argon. Toluene (0.5 ml) was added followed by N-methylpiperazine (0.041 ml) and the reaction mixture was stirred in a sealed tube at 95° C. for 16 hours. The reaction mixture was diluted with ethyl acetate and washed with water (2×), brine, dried (magnesium sulfate) and concentrated. Purification by RP-HPLC (5-95% MeCN: 1% NH4OH in H2O, 21 ml/min using a Waters Xterra Prep RP18 5 micron, 19×100 mm column) gave N-cyclopropyl-4-methyl-3-[7-(4-methylpiperazin-1-yl)-1-oxoisoquinolin-2(1H)-yl]benzamide (17 mg) as a pale yellow solid; NMR Spectrum: (DMSOd6) 0.55 (m, 2H), 0.69 (m, 2H), 2.09 (s, 3H), 2.29 (s, 3H), 2.56 (m, 4H), 2.85 (m, 1H), 3.29 (m, 4H), 6.65 (d, 1H), 7.11 (d, 1H), 7.48 (d, 1H), 7.52 (d, 1H), 7.61 (m, 2H), 7.74 (s, 1H), 7.87 (d, 1H), 8.43 (d, 1H); Mass Spectrum: M+H+ 417.

1. washwashed with water (2×), brine
2. dry with materialdried (magnesium sulfate)
3. concentrationconcentrated
4. customPurification by RP-HPLC (5-95% MeCN