反应详情

5,7-Difluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline (Example 245, 40 mg, 0.090 mmol) was dissolved in MeOH (1.5 mL) with formaldehyde (0.034 mL, 0.449 mmol) and sodium cyanoborohydride (33.2 mg, 0.449 mmol). The RM was stirred at rt for 2 h. Water was added and it was extracted with EtOAc twice. Combined organic layers were washed with brine and dried over Na2SO4, 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 lyophilized. The residue was dissolved in MeOH and it was passed through an SPE cartridge of HCO3− to remove the TFA salt. The filtrate was evaporated to give the free salt of the title compound (tR 0.8 min (conditions 2), MH+=460).

1. extractionit was extracted with EtOAc twice
2. washCombined organic layers were washed with brine
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. customthe solvent was removed
6. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
7. dissolutionThe residue was dissolved in MeOH
8. customto remove the TFA salt
9. customThe filtrate was evaporated