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

HRID 1435726Notes

Reaction equation

HRID 1435726 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[CH2:14][C@H:13]([NH:18][S:19]([CH:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[CH2:12]3)O1.Br[C:27]1[CH:28]=[N:29][CH:30]=[C:31](F)[CH:32]=1.[C:34]([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>[CH3:34][C:27]1[CH:32]=[C:31]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[CH2:14][C@H:13]([NH:18][S:19]([CH:22]([CH3:23])[CH3:24])(=[O:20])=[O:21])[CH2:12]3)[CH:30]=[N:29][CH:28]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 8202063-Bromo-5-fluoropyridineHCID 46899977(S)-N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

Product 1

HCID 11638501N-[(2S)-5-(5-methyl-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamideYield 79%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of N-[(2S)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide (700 mg, 1.92 mmol) in dry 1,4 dioxane (15 ml), polymer supported Pd(PPh3)4 (38 mg, 0.5 mmol/g, 0.019 mmol) was added along with 3-bromo-5-fluoropyridine (675 mg, 3.83 mmol) and 2.7 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. 270 mg of title compound were recovered as whitish solid along with 240 mg of slightly less pure fractions (overall yield 79%). Due to the use of chiral Intermediate 7, the final compound is believed to be N-[(2S)-5-(5-methyl-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. custom270 mg of title compound were recovered as whitish solid along with 240 mg of slightly less pure fractions (overall yield 79%)

Sources & evidence

ORD record
ord-2dcf9f101a7c4bd98138dcf2566dc3ba
Source dataset
uspto-grants-2009_11
Patent number
US07618969B2

Reaction notes

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