反应详情

温度

120 °C

A sealable vial was charged with (S)-2-(5-amino-3-(3-chloro-2-fluoro-6-morpholinopyridin-4-yl)-3,6-dihydro-2H-1,4-oxazin-3-yl)-4-bromophenol (234 mg, 0.482 mmol), cesium carbonate (471 mg, 1.445 mmol) and copper chloride (9.54 mg, 0.096 mmol The vial was evacuated and back-filled with nitrogen. NMP (1.5 mL) was added and the vial was evacuated and backfilled with nitrogen. 2,2,6,6-Tetramethyl-3,5-heptanedione (0.080 mL, 0.385 mmol) was added and the reaction mixture was heated to 120° C. for 1 h. The reaction mixture was cooled to room temperature, diluted with EtAOc and filtered through a pad of silica gel. The solvent was removed under reduced pressure and the residue was purified by preparative reversed-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 20 min to obtain 68 mg of (S)-7-bromo-1-fluoro-3-morpholino-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine.TFA.

1. customwas evacuated
2. additionback-filled with nitrogen
3. additionNMP (1.5 mL) was added
4. customthe vial was evacuated
5. temperatureThe reaction mixture was cooled to room temperature
6. additiondiluted with EtAOc
7. filtrationfiltered through a pad of silica gel
8. customThe solvent was removed under reduced pressure
9. customthe residue was purified by preparative reversed-phase preparative HPLC
10. customover 20 min