Sodium Carbonate → N-[(2S)-5-(2,6-difluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide

HRID 1435728Notes

Reaction equation

HRID 1435728 reaction equation
[F:1][C:2]1[C:7](B(O)O)=[CH:6][CH:5]=[C:4]([F:11])[N:3]=1.Br[C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[CH2:18][C@H:17]([NH:22][S:23]([CH:26]([CH3:28])[CH3:27])(=[O:25])=[O:24])[CH2:16]2.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[C:7]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[CH2:18][C@H:17]([NH:22][S:23]([CH:26]([CH3:28])[CH3:27])(=[O:24])=[O:25])[CH2:16]3)=[CH:6][CH:5]=[C:4]([F:11])[N:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2762713(2,6-Difluoropyridin-3-yl)boronic acidHCID 46899974(S)-N-(5-bromo-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

Product 1

HCID 11523193N-[(2S)-5-(2,6-difluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (2,6-difluoro-3-pyridinyl)boronic acid (2 g, 12.56 mmol) in dry 1,4 dioxane (30 ml), polymer supported Pd(PPh3)4 (126 mg, 0.5 mmol/g, 0.063 mmol) was added along with N-[(2S)-5-bromo-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide (2 g, 6.28 mmol) and 7.3 ml of a 2M Na2CO3 solution in water and the resulting mixture was heated at 90° degrees for 3 hours. Then after cooling the resin was removed by filtration and then the solvent was removed under reduced pressure. The residue was taken up with AcOEt and water. The aqueous phase was separated and acidified with 3N HCl and extracted with AcOEt. Then pH was reverted to basic by addition of NaHCO3 and another extraction with AcOEt was performed. All the organic extracts were collected, dried on Na2SO4, filtered and evaporated. The crude was finally purified on a 40M+ silica cartridge eluting with a cyclohexane/AcOEt 80/20 mixture. 798 mg of title compound were recovered as whitish solid (36%) Due to the use of the chiral Intermediate 6, the title compound is believed to be N-[(2S)-5-(2,6-difluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide.

Workup

  1. temperaturethe resulting mixture was heated at 90° degrees for 3 hours
  2. temperatureThen after cooling the resin
  3. customwas removed by filtration
  4. customthe solvent was removed under reduced pressure
  5. customThe aqueous phase was separated
  6. extractionextracted with AcOEt
  7. additionbasic by addition of NaHCO3
  8. extractionanother extraction with AcOEt
  9. customAll the organic extracts were collected
  10. customdried on Na2SO4
  11. filtrationfiltered
  12. customevaporated
  13. customThe crude was finally purified on a 40M+ silica cartridge
  14. washeluting with a cyclohexane/AcOEt 80/20 mixture
  15. custom798 mg of title compound were recovered as whitish solid (36%) Due to the use of the chiral Intermediate 6

Sources & evidence

ORD record
ord-4224af1ef2264c3b8fa661a7b93e9b0f
Source dataset
uspto-grants-2009_11
Patent number
US07618969B2

Reaction notes

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