反应详情

温度

110 °C

2-[(2-bromo-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-benzamide (110 mg, 0.25 mmol) was suspended in dioxane (3 mL) and treated consecutively with DMF (1 mL), Pd2dba3 (5 mg, 0.005 mmol), Xantphos (9 mg, 0.015 mmol), cesium carbonate (98 mg, 0.3 mmol) and 4-methyl-piperazine-1-carboxylic acid amide (184 mg, 1.3 mmol). The reaction mixture was placed under a nitrogen atmosphere and heated for 3 hours at 110° C. (bath temperature). On cooling the volatiles were removed in vacuo and the residue was partitioned between CH2Cl2 and water. The organic phase was washed with brine, dried, filtered and concentrated. The residue was purified by chromatography using Isolute® Flash NH2 (Separtis) as stationary phase (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 95:5) to give 4-methyl-piperazine-1-carboxylic acid (4-{[2-(2-methyl-2H-indazol-6-ylcarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-amide (28 mg, 22%) as a foam; 1H-NMR (300 MHz, d6-DMSO) 10.14 (1H, s), 9.11 (1H, s), 8.25 (1H, S), 8.14 (1H, d), 8.10 (1H, s), 7.95 (1H, t), 7.80 (1H, s), 7.72 (1H, d), 7.63 (1H, d), 7.23-7.32 (2H, m), 6.94 (1H, d), 6.66 (1H, t), 6.53 (1H, d), 4.43 (2H, d), 4.13 (3H, s), 3.41-3.44 (4H, m), 2.25-2.28 (4H, m), 2.17 (3H, s); m/z (ES+) 499.

1. temperatureOn cooling the volatiles
2. customwere removed in vacuo
3. customthe residue was partitioned between CH2Cl2 and water
4. washThe organic phase was washed with brine
5. customdried
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by chromatography
9. washas stationary phase (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 95:5)