Pyridine → HCID 59754755, compound

HRID 1678115Notes

Reaction equation

HRID 1678115 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)([Cl:8])=O.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N:17]2[C:21]3=[N:22][CH:23]=[CH:24][CH:25]=[C:20]3[CH2:19][C:18]2=O)[CH:12]=1.N1C=CC=CC=1>ClCCl>[Cl:8][C:18]1[N:17]([C:13]2[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=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 67371976HCID 67371976, compound

Product 1

HCID 59754755HCID 59754755, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

An ice-acetone cooled solution of anhydrous dimethylformamide (0.71 mL, 9.2 mmol) and anhydrous dichloromethane (2 mL) under a N2 atmosphere is treated drop-wise with phosphorus oxychloride (0.93 mL, 10 mmol). The resulting yellowish mixture is continued to stir for 40 mins to give a cloudy mixture. A solution of 1-pyridin-3-yl-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one (370 mg, 1.75 mmol) and pyridine (0.30 mL, 3.7 mmol) in dichloromethane (1 mL) is added drop-wise over 20 minutes to form a red mixture. The reaction is allowed to warm slowly to room temperature over 1 hour, and stirred at room temperature for 24 hours. The red reaction mixture is concentrated, and the residue is treated with phosphorus oxychloride (10 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 a brown solid. The residue is purified by flash chromatography on a 10-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined and the solvent evaporated, and the residue is purified by flash chromatography on a 10-gram silica gel cartridge by elution with dichloromethane. After trituration with heptane 36 mg of 2-chloro-1-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde is obtained as a fluffy cream powder. A further 11 mg of product is obtained by purifying the heptane supernatant by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (99:1) increasing to ethyl acetate. Total yield, 47 mg, 10% yield. MS: m/e 258/260 (M+H).

Workup

  1. customto give a cloudy mixture
  2. customto form a red mixture
  3. stirringstirred at room temperature for 24 hours
  4. customThe red reaction mixture
  5. concentrationis concentrated
  6. additionthe residue is treated with phosphorus oxychloride (10 mL)
  7. temperaturethe mixture heated in an oil bath at 110° C. for 3 hours
  8. additionAfter concentration of the red mixture, the residue is treated with ice water
  9. additiontreated with saturated aqueous sodium hydrogen carbonate solution until the effervescence ceases
  10. extractionThe mixture is extracted with 5 portions of dichloromethane
  11. dry with materialthe combined extracts are dried over magnesium sulfate
  12. filtrationfiltered
  13. customevaporated
  14. customto leave a brown solid
  15. customThe residue is purified by flash chromatography on a 10-gram silica gel cartridge by elution with dichloromethane
  16. additionFractions containing the product
  17. customthe solvent evaporated
  18. customthe residue is purified by flash chromatography on a 10-gram silica gel cartridge by elution with dichloromethane

Sources & evidence

ORD record
ord-7a8fd1794ff64a3180ab55d4ffb524c8
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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