反应详情

温度

90 °C

3-(4-Azidophenyl)propanoic acid (Bachem, 672 mg; 3.5 mmol; 1.0 eq.) and 3-ethynyl-1H-indazole (500 mg; 3.5 mmol; 1.0 eq.) were dissolved in 1,4-dioxane (7.5 mL). D-(−)-isoascorbic acid sodium salt (139 mg; 0.70 mmol; 0.2 eq.) followed by a solution of copper sulfate pentahydrate (35 mg; 0.14 mmol; 0.04 eq.) in water (0.75 mL) were added. The reaction mixture was stirred at 90° C. for 48 h. Dioxane was partially removed under reduced pressure, water was added and the mixture was extracted with EtOAc (three times). Combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude obtained was sonicated in DCM (5 mL) and heptane (10 mL). The resulting solid was filtered and dried under high vacuum to afford the title compound as a brown solid (875 mg, 75%). 1H NMR (300 Mz, DMSO-d6) δ: 13.37 (brs, 1H), 9.27 (s, 1H), 8.35 (d, J=8.1 Hz, 1H), 7.95 (d, J=8.4 Hz, 2H), 7.61 (d, J=8.4 Hz, 1H), 7.49 (d, J=8.4 Hz, 2H), 7.46-7.41 (m, 1H), 7.27-7.22 (m, 1H), 2.92 (t, J=7.5 Hz, 2H), 2.60 (t, J=7.5 Hz, 2H). HPLC (Condition A): Rt 3.14 min (purity 93.5%). MS (ESI+): 334.2, MS (ESI−): 332.2.

1. additionwere added
2. customDioxane was partially removed under reduced pressure, water
3. additionwas added
4. extractionthe mixture was extracted with EtOAc (three times)
5. washCombined organic layers were washed with brine
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude obtained
10. filtrationThe resulting solid was filtered
11. customdried under high vacuum