反应详情

温度

110 °C

2-[(2-bromo-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-benzamide (400 mg, 0.92 mmol) was suspended in dioxane (15 mL) and treated consecutively with DMF (5 mL), Pd2dba3 (19 mg, 0.02 mmol), Xantphos (32 mg, 0.06 mmol), cesium carbonate (358 mg, 1.1 mmol) and 3-hydroxy-pyrrolidine-1-carboxylic acid amide (358 mg, 2.75 mmol). The reaction mixture was placed under a nitrogen atmosphere and heated for 3 hours at 110° C. (bath temperature). On cooling the reaction was partitioned between EtOAc and water. The organic phase was washed with brine, dried, filtered and concentrated in vacuo. The residue was purified by chromatography on Isolute® Flash silica gel (Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 10:1) to give 3-hydroxy-pyrrolidine-1-carboxylic acid (4-{[2-(2-methyl-2H-indazol-6-ylcarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-amide (270 mg, 61%) as a solid; 1H-NMR (300 MHz, d6-DMSO) 10.14 (1H, s), 8.62 (1H, s), 8.25 (1H, s), 8.14 (1H, d), 8.10 (1H, s), 7.95 (1H, t), 7.90 (1H, s), 7.71-7.73 (1H, m), 7.64 (1H, d), 7.23-7.33 (2H, m), 6.93-6.95 (1H, m), 6.67 (1H, t), 6.53 (1H, d), 4.93 (1H, d), 4.43 (2H, d), 4.26 (1H, m), 4.13 (3H, s), 3.40-3.48 (4H, m), 1.79-1.94 (2H, m); m/z (ES+) 486 [M+H]+.

1. temperatureOn cooling the reaction
2. customwas partitioned between EtOAc and water
3. washThe organic phase was washed with brine
4. customdried
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by chromatography on Isolute® Flash silica gel (Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 10:1)