反应详情

温度

150 °C

3-(3-Bromo-imidazo[1,2-a]pyridin-6-ylmethyl)-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Example 296, 77 mg, 0.189 mmol) was dissolved in DME (0.629 mL) with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (39.2 mg, 0.189 mmol), 2 M Na2CO3 solution (0.339 mL, 0.679 mmol) and tetrakis(triphenylphosphine)palladium (10.9 mg, 0.009 mmol). The RM was heated at 150° C. 5 min under microwave irradiations. It was taken up with EtOAc and washed with 10% Na2CO3 solution and brine. Then it was dried over Na2SO4, filtered and concentrated. The residue was dissolved in MeOH and passed through an SPE cartridge of PL-Thiol MP to remove the palladium. Then the filtrate was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and acetonitrile was removed. The aqueous solution was basified with 5% NaHCO3 solution and was extracted with EtOAc twice. Combined organic layers was washed with brine and dried over Na2SO4. It was filtered to afford after evaporation of the solvent the title compound as a white solid (tR 0.7 min (conditions 2), MH+=410).

1. custom5 min
2. washwashed with 10% Na2CO3 solution and brine
3. dry with materialThen it was dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in MeOH
7. customto remove the palladium
8. customThen the filtrate was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
9. customacetonitrile was removed
10. extractionwas extracted with EtOAc twice
11. washCombined organic layers was washed with brine
12. dry with materialdried over Na2SO4
13. filtrationIt was filtered
14. customto afford
15. customafter evaporation of the solvent the title compound as a white solid (tR 0.7 min (conditions 2), MH+=410)