1H-Pyrrolo(2,3-b)pyridine → 1H-Pyrrolo[2,3-b]pyridine-3-carbaldehyde

HRID 641792Notes

Reaction equation

HRID 641792 reaction equation
P(Cl)(Cl)(Cl)=O.[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[CH:8]=[CH:7]1.[C:15](=O)(O)[O-:16].[Na+]>CN(C=O)C>[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[C:8]([CH:15]=[O:16])=[CH:7]1

Participants

5

Reactant 3

HCID 92221H-Pyrrolo(2,3-b)pyridineHCID 24813Phosphorus oxychlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 53728121H-Pyrrolo[2,3-b]pyridine-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
5 °C

Procedure

Phosphorus oxychloride (36.5 mL) was added dropwise to cooled solution of DMF (40 mL) while maintaining the temperature below 10° C. The resulting solution was further cooled to 5° C. and a solution of 7-azaindole in DMF (40 mL) was added slowly over 30-40 min, maintaining the temperature below 25° C. The mixture was heated at 95° C. for 48 h then cooled to 35° C. and added cautiously with stirring over an hour to a cooled solution of saturated aqueous sodium bicarbonate solution (800 mL). The mixture was extracted with ethyl acetate (4×500 mL) and the combined extracts washed with water (500 mL) and brine (500 mL), then dried (MgSO4), filtered and concentrated in vacuo to afford a dark brown semi-solid. This crude product was purified using column chromatography eluting with a 50:50 mixture of ethyl acetate:hexane, gradually increasing to 90:10 mixture. 1H-NMR (400 MHz/D6-DMSO): δ=7.25 (m, 1H), 8.38 (m, 2H), 8.42 (s, 1H), 9.92 (s, 1H), 12.62 (br.s, 1H). MS (ES+): 147 [MH+].

Workup

  1. temperaturewhile maintaining the temperature below 10° C
  2. temperaturemaintaining the temperature below 25° C
  3. temperatureThe mixture was heated at 95° C. for 48 h
  4. temperaturethen cooled to 35° C.
  5. additionadded cautiously
  6. extractionThe mixture was extracted with ethyl acetate (4×500 mL)
  7. washthe combined extracts washed with water (500 mL) and brine (500 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto afford a dark brown semi-solid
  12. customThis crude product was purified
  13. washeluting with a 50:50 mixture of ethyl acetate
  14. temperaturehexane, gradually increasing to 90:10 mixture

Sources & evidence

ORD record
ord-440382d771264b45a68784546e4004fe
Source dataset
uspto-grants-2010_04
Patent number
US07696225B2

Reaction notes

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