反应详情

温度

80 °C

To a slurry of methyl 5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylate (2.11 g, 6.26 mmol) in ethanol (30 mL) in a pressure flask was added 1-[4-fluoro-2-(methylsulfonyl)phenyl]methanaminium chloride followed by N,N,N-diisopropylethylamine (2.17 mL, 12.52 mmol). The pressure flask was purged with nitrogen and closed. The reaction was heated to 80 degrees C. for 16 hours. The reaction containing residual solids was cooled and determined to be incomplete by LCMS analysis. Added degassed DMF (10 mL) to solubilize the remaining solids, resealed the pressure tube and reheated to 80 degrees C. overnight. The reaction was cooled, transferred to a round bottom flask and reduced to a small volume in vacuo. The residue was partitioned between methylene chloride and saturated aqueous sodium bicarbonate. The organic layer was washed with water, dried over Na2SO4, filtered and reduced to a small volume in vacuo. The residue was crystallized via the addition of 5 mL of methanol. The crystals were filtered and dried in vacuo to afford the title compound.

1. customThe pressure flask was purged with nitrogen
2. customclosed
3. additionThe reaction containing residual solids
4. temperaturewas cooled
5. additionAdded
6. customdegassed DMF (10 mL)
7. customreheated to 80 degrees C
8. customovernight
9. temperatureThe reaction was cooled
10. customtransferred to a round bottom flask
11. customThe residue was partitioned between methylene chloride and saturated aqueous sodium bicarbonate
12. washThe organic layer was washed with water
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. customThe residue was crystallized via the addition of 5 mL of methanol
16. filtrationThe crystals were filtered
17. customdried in vacuo