Potassium Iodide → N-((2S)-5-{[(6-methyl-3-pyridinyl)methyl]oxy}-2,3-dihydro-1H-inden-2-yl)-2-propanesulfonamide

HRID 1922306Notes

Reaction equation

HRID 1922306 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@H:6]([NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[CH2:5]2.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:25][C:26]1[CH:27]=[CH:28][C:29]([CH3:32])=[N:30][CH:31]=1.[I-].[K+]>CN(C)C=O.O.C(Cl)Cl.CCOCC>[CH3:32][C:29]1[N:30]=[CH:31][C:26]([CH2:25][O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[CH2:7][C@H:6]([NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[CH2:5]3)=[CH:27][CH:28]=1

Participants

9

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 122143385-(Chloromethyl)-2-methylpyridineHCID 66857149(S)-N-(5-hydroxy-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

Product 1

HCID 44124833N-((2S)-5-{[(6-methyl-3-pyridinyl)methyl]oxy}-2,3-dihydro-1H-inden-2-yl)-2-propanesulfonamideYield 45.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

In a 250 ml round-bottomed flask at room temperature under nitrogen, N-[(2S)-5-hydroxy-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide (5.31 g, 20.80 mmol, Description 3) was dissolved in N,N-dimethylformamide (25 ml) to give a colourless solution. Cesium carbonate (10.16 g, 31.2 mmol) was then added, followed by 5-(chloromethyl)-2-methylpyridine (4.26 g, 30.1 mmol, Description 6) dissolved in dry N,N-dimethylformamide (20 ml), and potassium iodide (0.863 g, 5.20 mmol). This resulting brown mixture was then allowed to stir at room temperature for the weekend. The mixture was brought to 0° C. and was diluted with water (100 ml) and DCM (150 ml) (exothermic reaction). Phases were separated and the aqueous phase was back extracted with DCM (2×100 ml). The combined organic phases were dried over Na2SO4, filtered and concentrated to give an oily residue, which was diluted in Et2O (250 ml) and washed with water (2×100 ml). The organic was dried again over Na2SO4, filtered and concentrated to give 8.8 g as a brown foam, which was purified by flash-chromatography (100 g SiO2 cartridge, eluting with cyclohexane/EtOAc=60/40, 1/1 and 40/60) to give N-((2S)-5-{[(6-methyl-3-pyridinyl)methyl]oxy}-2,3-dihydro-1H-inden-2-yl)-2-propanesulfonamide (free base) as a pale-yellow solid (3.43 g).

Workup

  1. customto give a colourless solution
  2. customwas brought to 0° C.
  3. customPhases were separated
  4. extractionthe aqueous phase was back extracted with DCM (2×100 ml)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give an oily residue, which
  9. washwashed with water (2×100 ml)
  10. dry with materialThe organic was dried again over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give 8.8 g as a brown foam, which
  14. customwas purified by flash-chromatography (100 g SiO2 cartridge, eluting with cyclohexane/EtOAc=60/40, 1/1 and 40/60)

Sources & evidence

ORD record
ord-b32dfb7ed00546e2b24d406672e45a46
Source dataset
uspto-grants-2012_05
Patent number
US08173820B2

Reaction notes

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