反应详情

To a solution of 1-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]indazole-3-carboxylic acid (100 mg, 0.25 mmol) in DMF (2 ml) was added HATU (189.46 mg, 0.5 mmol) followed by 2-oxa-6-azaspiro[3.3]heptane oxalate (94.26 mg, 0.5 mmol) and triethylamine (0.1 ml, 0.75 mmol). The reaction mixture was stirred at RT for 16 hr. Water (2 ml) was added to the reaction mixture and the product extracted into EtOAc (2×5 ml). The combined organics were washed with water (3 mL) and brine (3 mL) and concentrated in vacuo. The crude product was purified twice by flash chromatography (Biotage, 2-12% methanol in DCM) to give the title compound: 1H NMR (500 MHz, DMSO) delta 1.93 (3H, s), 4.31 (2H, s), 4.74 (4H, q, J=6.9 Hz), 4.87 (2H, s), 6.26 (1H, s), 7.02-7.32 (3H, m), 7.41 (1H, dd, J=8.4, 1.2 Hz), 7.51 (1H, t, J=4.9 Hz), 8.23 (1H, d, J=8.0 Hz), 8.39 (1H, d, J=5.5 Hz), 8.75-9.10 (3H, m); LC-MS: m/z=+483.10 (M+H)+.

1. extractionthe product extracted into EtOAc (2×5 ml)
2. washThe combined organics were washed with water (3 mL) and brine (3 mL)
3. concentrationconcentrated in vacuo
4. customThe crude product was purified twice by flash chromatography (Biotage, 2-12% methanol in DCM)