反应详情

To abs. MeOH (6 mL) stirred at rt were added 7-fluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline (Example 180, 104 mg, 0.243 mmol), formaldehyde (0.034 mL, 1.216 mmol) and NaBH3CN (76 mg, 1.216 mmol). The RM was then brought to pH 5-6 with addition of acetic acid and stirred at rt for 2 h. It was then taken into DCM and washed with saturated NaHCO3 sol. The organic layer was then washed with brine, dried on Na2SO4, filtered and evaporated. A purification of the crude by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH with ammonia=100:0->90:10) gave the title compound (tR 3.07 min (conditions 3), MH+=442, 1H-NMR in DMSO-d6: 8.82 (d, 1H); 8.49 (s, 1H); 8.33 (d, 1H); 8.10-8.01 (m, 3H), 7.76 (d, 1H); 7.59 (s, 1H); 7.53 (d, 1H); 7.46 (dd, 1H), 4.53 (s, 2H); 4.20-4.10 (m, 1H); 2.85 (d, 2H); 2.18 (s, 3H); 2.06-1.92 (m, 6H).

1. washwashed with saturated NaHCO3 sol. The organic layer
2. washwas then washed with brine
3. customdried on Na2SO4
4. filtrationfiltered
5. customevaporated
6. customA purification of the crude by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH with ammonia=100:0->90:10)