反应详情

温度

80 °C

The product of Step b above (258 mg, 1.09 mmol, 1 equiv) was combined with 5-aminoindazole (303 mg, 2.28 mmol, 1.2 equiv) and EDC (437 mg, 2.28 mmol, 1.2 equiv) in a round bottom flask. DMF (4.5 mL) was added, followed by DMAP (30 mg) and triethylamine (0.318 mL, 2.28 mmol, 1.2 equiv). The reaction mixture was heated to 80° C. for 2 hours. The reaction was cooled to room temperature and poured into a separatory funnel containing ethyl acetate and water. The layers were separated, and the organic layer was washed with 1M HCl (2×), satd. NaHCO3 (1×), and satd. NaCl (1×). The organic extracts were dried over Na2SO4, filtered and concentrated to a yellow solid. One-fourth of the residue was further purified by reverse-phase HPLC (0-80% CH3CN/H2O/0.1% TFA over 10 minutes, retention time 6.26 min) to provide 9 mg of the product as a colorless solid. NMR 1H NMR (400 MHz, DMSO-D6) 5 ppm 12.92 (br s, 1H), 9.56 (s, 1H), 9.12 (dd, J=1.6, 5.9 Hz, 1H), 8.04 (t, J=1.3 Hz, 1H), 7.97 (s, 1H), 7.43 (d, J=1.3 Hz, 2H), 7.40 (d, J=5.8 Hz, 1H), 7.34 (m, 2H), 7.17 (t, J=9.1 Hz, 2H), 5.45 (d, J=3.1 Hz, 1H) MS m/z 352 [M+H]+

1. temperatureThe reaction was cooled to room temperature
2. additionpoured into a separatory funnel
3. customThe layers were separated
4. washthe organic layer was washed with 1M HCl (2×)
5. dry with materialThe organic extracts were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated to a yellow solid
8. customOne-fourth of the residue was further purified by reverse-phase HPLC (0-80% CH3CN/H2O/0.1% TFA over 10 minutes, retention time 6.26 min)