反应详情

温度

50 °C

To a solution of 1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (3.00 g, 7.87 mmol) in dry DCM (40 mL) was introduced thionyl chloride (6.85 mL, 94.46 mmol) and DMF (3 drops, cat.). The reaction mixture was warmed to 50° C. for 1 hr. After cooling to RT, the reaction mixture was concentrated in vacuo. The residue was re-dissolved in dry DCM (20 mL) and concentrated in vacuo (twice). After suspending the residue in dry DCM (30 mL), the solution was cooled to 0° C. under an atmosphere of nitrogen, and morpholine (1.37 mL, 15.74 mmol) added dropwise. The reaction mixture was warmed to RT for 16 hr. Following dilution with DCM (25 mL), 2M aqueous sodium carbonate (35 mL) was introduced. The resulting precipitate was collected by filtration and washed on the filter with DCM (5 mL) and dried. After suspension of the precipitate in 3:1 water/acetonitrile (10 mL), the slurry was collected by filtration and washed on the filter with further 3:1 water/acetonitrile (2×1 mL washes). The filter cake was dried under vacuum to furnish the title compound as an off-white solid: 1H NMR (500 MHz, DMSO) delta 3.41-3.76 (6H, m), 3.85-3.97 (2H, m), 7.05 (1H, d, J=5.5 Hz), 7.18 (2H, s), 7.74 (1H, dd, J=8.4, 1.1 Hz), 7.80 (1H, d, J=8.4 Hz), 8.34 (1H, d, J=5.5 Hz), 9.33 (1H, s); LC-MS: m/z=+450.90 (M+H)+.

1. temperatureAfter cooling to RT
2. concentrationthe reaction mixture was concentrated in vacuo
3. dissolutionThe residue was re-dissolved in dry DCM (20 mL)
4. concentrationconcentrated in vacuo (twice)
5. temperaturethe solution was cooled to 0° C. under an atmosphere of nitrogen
6. temperatureThe reaction mixture was warmed to RT for 16 hr
7. additionwas introduced
8. filtrationThe resulting precipitate was collected by filtration
9. washwashed on the
10. filtrationfilter with DCM (5 mL)
11. customdried
12. additionAfter suspension of the precipitate in 3:1 water/acetonitrile (10 mL)
13. filtrationthe slurry was collected by filtration
14. washwashed on the
15. filtrationfilter with further 3:1 water/acetonitrile (2×1 mL washes)
16. customThe filter cake was dried under vacuum