反应详情

To a solution of (S)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazine]-2′,7-diamine (0.095 g, 0.248 mmol) in DMF (1 mL) were added 5-chloro-2-pyridinecarboxylic acid (0.043 g, 0.273 mmol), 0-(−7-azabenzotriazol-1-yl)-n,′n,′n,′n′-tetramethyluronium pf6 (0.099 g, 0.261 mmol) and Hunig's base (0.086 ml, 0.497 mmol) and the resulting mixture was stirred at rt for 15 h. The mixture was quenched with 5 drops of 2 N HCl and stirred for 1 min followed by the addition of water and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-3% MeOH/DCM. The product was repurified by HPLC to afford (S)—N-(2′-amino-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-7-yl)-5-chloropicolinamide as a white solid (0.0334 g, 0.064 mmol, 25.8% yield). MS m/z=522.0 [M+H]+.

1. customThe mixture was quenched with 5 drops of 2 N HCl
2. stirringstirred for 1 min
3. additionfollowed by the addition of water
4. extractionextracted with EtOAc
5. dry with materialThe combined organics were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customchromatographed on silica gel using 0-3% MeOH/DCM
9. customThe product was repurified by HPLC