反应详情

温度

90 °C

3-iodo-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine (25.0 mg, 0.071 mmol), 5-bromobenzeno[B]thiophene-2-boronic acid (19.0 mg, 0.074 mmol), tetrakis(triphenylphosphine)palladium (0) (8.2 mg, 7.1 μmol), and sodium carbonate (15.0 mg, 0.141 mmol) were suspended in Dioxane (900 μl)/Water (100 μl). The mixture was sparged with argon for 10 minutes, heated to 90° C. and stirred overnight. The reaction mixture was diluted in ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (methanol/ethyl acetate gradient) to afford a tan solid that contained unidentified impurities. The residue was purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure to afford 3-(5-bromo-1-benzothien-2-yl)-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine. 1H NMR (500 MHz, DMSO-d6) δ 8.70 (s, 1H); 8.33 (s, 1H); 8.27 (s, 1H); 8.06 (s, 1H); 8.03 (d, 1H); 7.88 (d, 1H); 7.64 (s, 1H); 7.41 (dd, 1H); 7.03 (s, 1H); 4.05 (s, 3H); 3.88 (s, 3H). LRMS (ESI) calculated for C20H1679BrN4OS [M+H]+, 439.0; found 438.9.

1. customThe mixture was sparged with argon for 10 minutes
2. additionThe reaction mixture was diluted in ethyl acetate
3. washwashed with saturated aqueous sodium hydrogen carbonate and brine
4. dry with materialthen dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by column chromatography on silica gel (methanol/ethyl acetate gradient)
8. customto afford a tan solid
9. customThe residue was purified by preparative HPLC Reverse phase (C-18)
10. washeluting with Acetonitrile/Water+0.05% TFA
11. additionThe fractions containing product
12. additiondiluted in ethyl acetate
13. washwashed with aqueous sodium bicarbonate
14. dry with materialdried over sodium sulfate
15. filtrationThe solution was filtered
16. concentrationconcentrated under reduced pressure