反应详情

温度

0 °C

3-[(S)-1-(6-Fluoro-1H-indazol-5-yl)-ethyl]-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Example 165, 23 mg, 0.065 mmol) was dissolved in DMF (0.374 mL) and cooled down to 0° C. under nitrogen conditions. NaH (3.82 mg, 0.095 mmol) was added and the RM was stirred at 0° C. for 30 min. Then methyliodide (10.84 mg, 0.076 mmol) was introduced. The RM was allowed to warm up to rt and stirred for 2.5 h, then it was quenched with water. It was extracted twice with EtOAc. The organics were joined and washed with brine, dried over Na2SO4. The solvent was removed and the residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The acetonitrile was removed and the aqueous solution was basified with 5% NaHCO3. It was extracted twice with EtOAc and then the organics were joined and washed with brine. It was dried over Na2SO4 and the solvent was removed. The residue was triturated with pentane and the precipitate was filtered off to afford the title compound as a white solid (tR 1.0 min (conditions 2), MH+=376, 1H-NMR in DMSO-d6: 8.30 (s, 1H); 8.06 (d, 1H); 7.94 (s, 2H); 7.67 (s, 1H); 7.59 (d, 1H); 7.54 (d, 1H); 7.46 (d, 1H); 4.95 (q, 1H); 3.95 (s, 3H); 3.88 (s, 3H); 1.77 (d, 3H)).

1. temperatureto warm up to rt
2. stirringstirred for 2.5 h
3. customit was quenched with water
4. extractionIt was extracted twice with EtOAc
5. washwashed with brine
6. dry with materialdried over Na2SO4
7. customThe solvent was removed
8. customthe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
9. customThe acetonitrile was removed
10. extractionIt was extracted twice with EtOAc
11. washwashed with brine
12. dry with materialIt was dried over Na2SO4
13. customthe solvent was removed
14. customThe residue was triturated with pentane
15. filtrationthe precipitate was filtered off