反应详情

A mixture of N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (618 mg, 1.499 mmol), 1,6-naphthyridin-5(6H)-one (PrincetonBio, Monmouth Junction, N.J., 146 mg, 0.999 mmol), copper (II) acetate (363 mg, 1.998 mmol), DBU (0.301 mL, 1.998 mmol) in DMSO (4 mL) in a microwave tube equipped with a magnetic stirring bar was irradiated at 100° C. for 15 min in a CEM microwave (J. Comb. Chem. 2008, 10, 358-360). The mixture was diluted with water (10 mL) and acidified with HCl (5 N) to pH ˜5. After agitating at rt overnight, the slurry was filtered and the solid was washed with water. The solid was washed with DCM (3×), acetone (3×), and MeOH (2×) to remove the less polar fraction. The resulting solid was dissolved in hot DMSO (6 mL) and filtered. The mother liquid was diluted with water (6 mL) and the resulting slurry was filtered and washed with water. The solid was dissolved in DMSO and purified by reverse-phase preparative HPLC (Phenomenex Luna column, 5 micron, C8(2), 100 Å, 150×21.2 mm, 0.1% TFA in CH3CN/H2O, gradient 5% to 90% over 10 min) The product fraction was concentrated, and neutralized with NaHCO3. The slurry was filtered and washed with water to provide N-(2-chloro-5-(5-oxo-1,6-naphthyridin-6(5H)-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (37 mg, 0.086 mmol, 8.60% yield) as an off-white powder.

1. customequipped with a magnetic stirring bar
2. customwas irradiated at 100° C. for 15 min in a CEM microwave (J. Comb. Chem. 2008, 10, 358-360)
3. filtrationthe slurry was filtered
4. washthe solid was washed with water
5. washThe solid was washed with DCM (3×), acetone (3×), and MeOH (2×)
6. customto remove the less polar fraction
7. dissolutionThe resulting solid was dissolved in hot DMSO (6 mL)
8. filtrationfiltered
9. additionThe mother liquid was diluted with water (6 mL)
10. filtrationthe resulting slurry was filtered
11. washwashed with water
12. dissolutionThe solid was dissolved in DMSO
13. custompurified by reverse-phase preparative HPLC (Phenomenex Luna column, 5 micron, C8(2), 100 Å, 150×21.2 mm, 0.1% TFA in CH3CN/H2O, gradient 5% to 90% over 10 min) The product fraction
14. concentrationwas concentrated
15. filtrationThe slurry was filtered
16. washwashed with water