Pyridine → HCID 46912083, compound

HRID 1678112Notes

Reaction equation

HRID 1678112 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)([Cl:8])=O.[C:11]1([N:17]2[C:21]3=[N:22][CH:23]=[CH:24][CH:25]=[C:20]3[CH2:19][C:18]2=O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.N1C=CC=CC=1>ClCCl>[Cl:8][C:18]1[N:17]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:21]2=[N:22][CH:23]=[CH:24][CH:25]=[C:20]2[C:19]=1[CH:3]=[O:4]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 149872061-Phenyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one

Product 1

HCID 46912083HCID 46912083, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

An ice-acetone cooled solution of anhydrous dimethylformamide (0.71 mL, 9.17 mmol) and anhydrous dichloromethane (1 mL) under a N2 atmosphere is treated drop-wise with phosphorus oxychloride (0.69 mL, 7.42 mmol). The resulting yellowish mixture is continued to stir for 30 mins to give an opaque gel. Crude 1-phenyl-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one is added portion wise as a solid over 10 minutes to form a red mixture. Further dichloromethane (1 mL) is added followed by pyridine (0.45 mL, 5.56 mmol) to give a dark red mixture. The reaction is allowed to warm slowly to room temperature over 1 hour, and stirred at room temperature for 38 hours. The red reaction mixture is concentrated, and the residue is treated with phosphorus oxychloride (8 mL) and the mixture heated in an oil bath at 110° C. for 3 hours. After concentration of the red mixture, the residue is treated with ice water, and treated with saturated aqueous sodium hydrogen carbonate solution until the effervescence ceases. The mixture is extracted with 5 portions of dichloromethane, the combined extracts are dried over magnesium sulfate, filtered and evaporated to leave an orange solid. The residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined and the solvent evaporated, and after trituration with heptane gives 220 mg of 2-chloro-1-phenyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde as a fluffy pink solid (53% yield from 3,3-dibromo-1-phenyl-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one). MS: m/e 257/259 (M+H). 1H NMR (300 MHz, CDCl3): 10.24 (1H, s), 8.62 (1H, dd), 8.39 (1H, dd), 7.68-7.56 (3H, m), 7.49 (2H, d), 7.31 (1H, dd).

Workup

  1. customto give an opaque gel
  2. customto form a red mixture
  3. customto give a dark red mixture
  4. stirringstirred at room temperature for 38 hours
  5. customThe red reaction mixture
  6. concentrationis concentrated
  7. additionthe residue is treated with phosphorus oxychloride (8 mL)
  8. temperaturethe mixture heated in an oil bath at 110° C. for 3 hours
  9. additionAfter concentration of the red mixture, the residue is treated with ice water
  10. additiontreated with saturated aqueous sodium hydrogen carbonate solution until the effervescence ceases
  11. extractionThe mixture is extracted with 5 portions of dichloromethane
  12. dry with materialthe combined extracts are dried over magnesium sulfate
  13. filtrationfiltered
  14. customevaporated
  15. customto leave an orange solid
  16. customThe residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane
  17. additionFractions containing the product
  18. customthe solvent evaporated

Sources & evidence

ORD record
ord-0ac35dd9ed174c27a7415ffb8dec8c73
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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