反应详情

A solution of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (40 mg, 0.094 mmol), 2-(dimethylamino)acetic acid (19.43 mg, 0.188 mmol), N,N-diisopropylethylamine (0.033 mL, 0.188 mmol), and HATU (71.7 mg, 0.188 mmol) in DMF was stirred at rt for 1 h. The reaction mixture was diluted with CH2Cl2, washed with satd NaHCO3, separated, and concentrated. The residue was purified (ISCO, 5% NH4OH/MeOH/CH2Cl2, 40 g silica gel column) to obtain 20 mg of (R)-6-(3-(2-(dimethylamino) acetamido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide as a light yellow solid. LCMS: (M+H)+=510.40. 1H NMR (400 MHz, CDCl3) δ ppm 11.21 (1H, s), 7.69 (2H, d, J=8.56 Hz), 7.53 (1H, d, J=9.06 Hz), 7.37 (2H, d, J=8.56 Hz), 7.30 (1H, d, J=7.81 Hz), 6.12 (1H, d, J=8.81 Hz), 5.60 (1H, s), 3.96 (1H, dd, J=13.22, 3.15 Hz), 3.78-3.88 (1H, m), 3.60-3.78 (8H, m), 3.41-3.56 (2H, m), 2.92 (2H, s), 2.22 (6H, s), 1.65-2.03 (4H, m).

1. washwashed with satd NaHCO3
2. customseparated
3. concentrationconcentrated
4. customThe residue was purified (ISCO, 5% NH4OH/MeOH/CH2Cl2, 40 g silica gel column)