Hydrochloric Acid → N-(2-chloro-5-(5-oxo-1,6-naphthyridin-6(5H)-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide

HRID 1963798Notes

Reaction equation

HRID 1963798 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.[N:28]1[C:37]2[CH:36]=[CH:35][NH:34][C:33](=[O:38])[C:32]=2[CH:31]=[CH:30][CH:29]=1.C1CCN2C(=NCCC2)CC1.Cl>CS(C)=O.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:1][C:2]1[C:7]([NH:8][S:9]([C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=2)(=[O:10])=[O:11])=[CH:6][C:5]([N:34]2[CH:35]=[CH:36][C:37]3[N:28]=[CH:29][CH:30]=[CH:31][C:32]=3[C:33]2=[O:38])=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 55203681,6-naphthyridin-5(6H)-oneHCID 53363355n-[2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-4-fluorobenzene-1-sulfonamide

Product 1

HCID 58229475N-(2-chloro-5-(5-oxo-1,6-naphthyridin-6(5H)-yl)pyridin-3-yl)-4-fluorobenzenesulfonamideYield 8.6%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-72c4d6ce38b048a797e83f8750c6b7d6
Source dataset
uspto-grants-2013_04
Patent number
US08415376B2

Reaction notes

Loading…