Sodium Carbonate → GSK-894490A free base

HRID 130464Notes

Reaction equation

HRID 130464 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][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:34][C:35]1[O:39][C:38](B(O)O)=[CH:37][CH:36]=1>COCCOC.O.C(OCC)(=O)C.C.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>[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:38]4[O:39][C:35]([CH3:34])=[CH:36][CH:37]=4)=[CH:3][CH:4]=3)(=[O:10])=[O:9])[CH:17]=2)[CH2:19]1

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 27343725-Methyl-2-furanboronic AcidHCID 444527764-Bromo-N-[5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]benzenesulfonamide

Product 1

HCID 24755624GSK-894490A free base

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 297MethaneSolvent2×HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Bromo-N-[5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]benzenesulfonamide (32.96 g, 72.5 mmol) was suspended in 1,2-dimethoxyethane (300 ml) and treated with sodium carbonate (38.4 g, 363 mmol) dissolved in water (150 ml). (5-Methyl-2-furanyl)boronic acid (13.7 g, 109 mmol) and bis(triphenylphosphine)palladium(II) chloride (108 mg, 0.15 mmol) were added and the mixture was heated at reflux for 1.5 hours. The mixture was cooled and diluted with ethyl acetate, charcoal added and the mixture was stirred with charcoal for 45 minutes. The mixture was filtered through celite, the filtrate separated and washed with saturated sodium bicarbonate solution, water (×3), brine, dried over anhydrous sodium sulfate and concentrated to a crude solid, titrated with pentane and filtered. The combined residues were purified by flash chromatography (Biotage Flash 75+L, dichloromethane to 1:10 2M ammonia in methanol: dichloromethane) followed by trituration with pentane to give the title compound (E247). MS (ES+) m/e 456 [M+H]+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 1.5 hours
  3. temperatureThe mixture was cooled
  4. additionadded
  5. filtrationThe mixture was filtered through celite
  6. customthe filtrate separated
  7. washwashed with saturated sodium bicarbonate solution, water (×3), brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated to a crude solid
  10. filtrationtitrated with pentane and filtered
  11. customThe combined residues were purified by flash chromatography (Biotage Flash 75+L, dichloromethane to 1:10 2M ammonia in methanol: dichloromethane)

Sources & evidence

ORD record
ord-458d7ffa3ac94202a2e27e6c93d35dd5
Source dataset
uspto-grants-2008_06
Patent number
US07381728B2

Reaction notes

Loading…