Methane → Gsk 894281

HRID 130465Notes

Reaction equation

HRID 130465 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:17]=[C:16]([N:18]3[CH2:23][C@H:22]([CH3:24])[NH:21][C@H:20]([CH3:25])[CH2:19]3)[CH:15]=[CH:14][C:13]=2[O:26][CH3:27])(=[O:10])=[O:9])=[CH:4][C:3]=1[F:28].C(=O)([O-])[O-].[Na+].[Na+].[CH3:35][C:36]1[O:40][C:39](B(O)O)=[CH:38][CH:37]=1.C>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>[CH3:25][C@H:20]1[NH:21][C@@H:22]([CH3:24])[CH2:23][N:18]([C:16]2[CH:15]=[CH:14][C:13]([O:26][CH3:27])=[C:12]([NH:11][S:8]([C:5]3[CH:6]=[CH:7][C:2]([C:39]4[O:40][C:36]([CH3:35])=[CH:37][CH:38]=4)=[C:3]([F:28])[CH:4]=3)(=[O:10])=[O:9])[CH:17]=2)[CH2:19]1

Participants

9

Reactant 4

HCID 297MethaneHCID 10340Sodium CarbonateHCID 27343725-Methyl-2-furanboronic Acid2×HCID 590070604-Bromo-N-[5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]-3-fluorobenzenesulfonamide

Product 1

HCID 24803511Gsk 894281

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent3×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred suspension of 4-bromo-N-[5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]-3-fluorobenzenesulfonamide (3.4 g, 7.2 mmol) in 1,2-dimethoxyethane (80 ml) was treated with a solution of sodium carbonate (3.8 g, 36 mmol) in water (20 ml). (5-Methyl-2-furanyl)boronic acid (1.4 g, 10.8 mmol) and bis(triphenylphosphine)palladium(II) chloride (10 mg, 0.2 mol %) were added with some water and the mixture was stirred at reflux for 3 hours. Additional (5-methyl-2-furanyl)boronic acid (420 mg, 3.3 mmol) was added and the mixture was heated at reflux for a further 30 minutes. After cooling to room temperature, ethyl acetate (50 ml), water (50 ml) and charcoal (3 g) were added and the mixture was stirred at room temperature for 30 minutes. The mixture was filtered through celite, the ethyl acetate layer separated and the aqueous layer was further extracted with ethyl acetate. The ethyl acetate extracts were combined washed with water and brine dried over anhydrous sodium sulfate and evaporated. The residue was purified by chromatography on a 100 g column eluting with 1:40 to 1:10 2M ammonia in methanol: dichloromethane. Residue was then triturated in ether, dissolved in ether/pentane and evaporated. Residue was then triturated in pentane, washed in pentane, air dried and then dried at 50° C. under argon and high vacuum to give the title compound (E248). MS (ES+) m/e 474 [M+H]+.

Workup

  1. temperatureat reflux for 3 hours
  2. temperaturethe mixture was heated
  3. temperatureat reflux for a further 30 minutes
  4. stirringthe mixture was stirred at room temperature for 30 minutes
  5. filtrationThe mixture was filtered through celite
  6. customthe ethyl acetate layer separated
  7. extractionthe aqueous layer was further extracted with ethyl acetate
  8. washThe ethyl acetate extracts were combined washed with water and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customevaporated
  11. customThe residue was purified by chromatography on a 100 g column
  12. washeluting with 1:40 to 1:10 2M ammonia in methanol
  13. customResidue was then triturated in ether
  14. dissolutiondissolved in ether/pentane
  15. customevaporated
  16. customResidue was then triturated in pentane
  17. washwashed in pentane
  18. customair dried
  19. customdried at 50° C. under argon

Sources & evidence

ORD record
ord-c77defd276ae44979335002271b04b6c
Source dataset
uspto-grants-2008_06
Patent number
US07381728B2

Reaction notes

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