反应详情

4-{4-[3-(5,7-Difluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (Example 244, 219 mg, 0.401 mmol) was dissolved in DCM (3 mL) with TFA (0.619 mL, 8.03 mmol). The RM was stirred at rt for 1 h 15 min and it was quenched with ice water. It was extracted with EtOAc twice. The combined organic layers was washed with brine and dried over Na2SO4. It was filtered and the solvent was removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and the 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 0.8 min (conditions 2), MH+=446).

1. customit was quenched with ice water
2. extractionIt was extracted with EtOAc twice
3. washThe combined organic layers was washed with brine
4. dry with materialdried over Na2SO4
5. filtrationIt was filtered
6. customthe solvent was removed
7. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
8. customthe acetonitrile was removed
9. extractionwas extracted with EtOAc twice
10. washCombined organic layers was washed with brine
11. dry with materialdried over Na2SO4
12. filtrationIt was filtered
13. customto afford
14. customafter evaporation of the solvent the title compound as a white solid (tR 0.8 min (conditions 2), MH+=446)