Water → 5-methoxy-1H-pyrrolo[2,3-b]pyridine

HRID 250582Notes

Reaction equation

HRID 250582 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[N:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[CH3:11][O-:12].[Na+].O.[Cl-].[NH4+].[OH-].[NH4+]>CN(C)C=O.CO.C(OCC)(=O)C.[Cu]I.[Cu]Br>[CH3:11][O:12][C:2]1[CH:3]=[C:4]2[CH:5]=[CH:6][NH:7][C:8]2=[N:9][CH:10]=1

Participants

10

Reactant 4

HCID 962WaterHCID 103079325-bromo-1H-pyrrolo[2,3-b]pyridine2×HCID 10942334Sodium Methoxide2×HCID 21863491Ammonium chloride ammonium hydroxide

Product 1

HCID 103078715-methoxy-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 24593copper(I) bromideCatalystHCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To 5-bromo-7-azaindole (67, 500.0 mg, 2.53 mmol) in N,N-dimethylformamide (8 mL) were added copper(I) iodide (966 mg, 5.08 mmol) and sodium methoxide in methanol (3 M, 5 mL). The reaction was stirred overnight at 120° C. under an atmosphere of Argon. The reaction was poured into water, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered. The filtrate was concentrated and purified with silica gel column chromatograph eluting with 20% ethyl acetate in hexane to give white solid (104, 140 mg, 28%). MS (ESI) [M+H+]+=149.1. In an alternative method, 2.3 g (11.7 mmol) 5-bromo-7-azaindole (67, 2.3 g, 11.7 mmol) was dissolved in 75 mL N,N-dimethylformamide and 50 mL methanol (50 mL), adding sodium methoxide (32 g, 0.6 mol) and copper-(I) bromide (3.2 g, 22.4 mmol) at room temperature. The reaction was stirred for three hours at 100° C. under an atmosphere of argon. The mixture was diluted with ethyl acetate and poured into a solution of ammonium chloride:ammonium hydroxide (4:1). The organic layer was extracted with ammonium chloride:ammonium hydroxide (4:1), washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The desired compound was isolated by silica gel column chromatography eluting with 30% to 70% ethyl acetate in hexanes to give a yellow solid (104, 0.27 g, 15.6%). MS (ESI) [M+H+]+=149.2.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. custompurified with silica gel column chromatograph
  6. washeluting with 20% ethyl acetate in hexane
  7. customto give white solid (104, 140 mg, 28%)
  8. stirringThe reaction was stirred for three hours at 100° C. under an atmosphere of argon
  9. extractionThe organic layer was extracted with ammonium chloride:ammonium hydroxide (4:1)
  10. washwashed with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-0315f9cc1833495abe9d43486708c22d
Source dataset
uspto-grants-2011_01
Patent number
US07863288B2

Reaction notes

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