Methyl iodide → 5-methoxy-2-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

HRID 2180154Notes

Reaction equation

HRID 2180154 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[CH:11]=[CH:10][N:9]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:6]2=[N:7][CH:8]=1.[CH:21]([N-]C(C)C)(C)C.[Li+].C(NC(C)C)(C)C.CI>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[CH:11]=[C:10]([CH3:21])[N:9]([S:12]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)(=[O:14])=[O:13])[C:6]2=[N:7][CH:8]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 222736501H-Pyrrolo[2,3-B]pyridine, 5-methoxy-1-(phenylsulfonyl)-

Product 1

HCID 222736535-methoxy-2-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridineYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-25 °C

Procedure

A solution of 5-methoxy-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (900 mg, 3.12 mmol) in THF (22.5 ml) was added dropwise to a solution of lithium diisopropylamide (prepared from nBu-Li (2.5M in hexane); 2.5 ml) and diisopropylamine (874 μl) in THF (13.5 ml)) cooled at −25° C. and the mixture was stirred for 30 minutes. Methyl iodide (215 μl, 3.44 mmol) in THF (9 ml) was then added dropwise and the mixture was stirred for 10 minutes at −25° C., left to warm up to ambient temperature and stirred for 15 minutes. The mixture was then poured onto ice/water. The mixture was then extracted with ethyl acetate. The organic layer was separated, washed with water, brine, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography, eluting with ethyl acetate/petroleum ether (20/80 followed by 30/70). The fractions containing the expected product were combined and evaporated to give 5-methoxy-2-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (805 mg, 85%).

Workup

  1. stirringthe mixture was stirred for 10 minutes at −25° C.
  2. waitleft
  3. temperatureto warm up to ambient temperature
  4. stirringstirred for 15 minutes
  5. additionThe mixture was then poured onto ice/water
  6. extractionThe mixture was then extracted with ethyl acetate
  7. customThe organic layer was separated
  8. washwashed with water, brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by column chromatography
  13. washeluting with ethyl acetate/petroleum ether (20/80 followed by 30/70)
  14. additionThe fractions containing the expected product
  15. customevaporated

Sources & evidence

ORD record
ord-17eff27ad08845838c81908c84072bcf
Source dataset
uspto-grants-2005_05
Patent number
US06887874B2

Reaction notes

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