Cesium carbonate → N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)methanesulfonamide

HRID 222262Notes

Reaction equation

HRID 222262 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:16]=[CH:15][C:9]3=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=[C:8]3[C:7](=[O:17])[C:6]=2[CH:18]=1.[CH3:19][S:20]([NH2:23])(=[O:22])=[O:21].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:14][C:12]1[CH:13]=[C:8]2[C:7](=[O:17])[C:6]3[CH:18]=[C:2]([NH:23][S:20]([CH3:19])(=[O:22])=[O:21])[CH:3]=[CH:4][C:5]=3[CH:16]=[CH:15][C:9]2=[N:10][CH:11]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 72879MethanesulfonamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 159808187-Bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-B]pyridin-5-one

Product 1

HCID 15980822N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)methanesulfonamide

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
95 °C

Procedure

7-bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (5.00 g. 15.7 mmol), methyl sulfonamide (1.49 g, 15.7 mmol), Pd2(dba)3 (0.714 g, 0.78 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino) xanthene (XANTPHOS) (1.36 g, 2.35 mmol) and cesium carbonate (15.3 g, 47.0 mmol) were added to a dry flask through which argon was purged. The flask was charged with 100 mL of dry dioxane and argon was bubbled through the solution for 10 minutes. The reaction mixture was heated to 95° C. and stirred under argon. After 12 hours, the reaction mixture was concentrated and dissolved in 2000 mL ethyl acetate and 1000 mL water. The organic layer was separated and washed with 500 mL of brine, dried with magnesium sulfate, filtered, and concentrated. The resultant solids were dissolved in 150 mL of a 3:1 mixture of hot dichloromethane/methanol and allowed to cool to ambient temperature with stirring. After 3 h, 150 mL of hexanes were added and the resulting slurry was allowed to stir. After 12 hours, an additional 50 mL hexanes were added. After 4 hours, the solids were filtered and dried to afford the title compound.

Workup

  1. customwas purged
  2. additionThe flask was charged with 100 mL of dry dioxane and argon
  3. customwas bubbled through the solution for 10 minutes
  4. concentrationthe reaction mixture was concentrated
  5. dissolutiondissolved in 2000 mL ethyl acetate
  6. customThe organic layer was separated
  7. washwashed with 500 mL of brine
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. dissolutionThe resultant solids were dissolved in 150 mL of a 3:1 mixture of hot dichloromethane/methanol
  12. temperatureto cool to ambient temperature
  13. stirringwith stirring
  14. waitAfter 3 h
  15. addition150 mL of hexanes were added
  16. stirringto stir
  17. waitAfter 12 hours
  18. additionan additional 50 mL hexanes were added
  19. waitAfter 4 hours
  20. filtrationthe solids were filtered
  21. customdried

Sources & evidence

ORD record
ord-431626060b9346e5a7d12e1bf601d77a
Source dataset
uspto-grants-2012_06
Patent number
US08207186B2

Reaction notes

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