反应详情

温度

40 °C

To the product of Example 12 Step B (0.04 mmol), 1H-tetraazol-5-amine monohydrate (0.12 mmol, 12 mg), HOBt (0.08 mmol, 12 mg) and EDC (0.08 mmol, 15 mg) in 1 mL of DMF was added DIEA (0.08 mmol, 14 μL). The reaction was heated at 40° C. for 2.5 h, then concentrated under reduced pressure. The residue was taken up in ca. 2:1 dioxane/H2O and acidified with TFA, then purified by reverse-phase chromatography (Condition B). The product was lyophilized directly, affording the title compound as a white solid. 1H NMR (500 MHz, d6-DMSO): δ 12.35 (br s, 1H), 9.81 (br s, 1H), 8.01 (d, 2H), 7.52 (d, 2H), 7.28 (d, 2H), 6.91 (unres. d, 1H), 6.79 (dd, 1H), 4.75 (s, 2H), 3.69 (s, 3H), 2.01 (m, 2H), 1.83 (m, 2H), 1.69 (m, 2H), 1.16 (m, 2H), 1.04 (m, 11H), 0.85 (s, 9H). One proton obscured by H2O. MS (ESI): m/z 503 (M+H). HPLC A: 1.85 min.

1. concentrationconcentrated under reduced pressure
2. custompurified by reverse-phase chromatography (Condition B)