Hydrochloric Acid → 5-Chloro-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyrrolo[3,2-b]pyridine

HRID 1075569Notes

Reaction equation

HRID 1075569 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[Na].[CH3:12][N:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1.Cl>CO>[Cl:1][C:2]1[N:7]=[C:6]2[C:8]([C:16]3[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][CH:15]=3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 740491-Methyl-4-piperidoneHCID 5360545Sodium2×HCID 123842375-Chloro-1H-pyrrolo(3,2-b)pyridine

Product 1

HCID 154351335-Chloro-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyrrolo[3,2-b]pyridineYield 28.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 0.66 gm (4.3 mMol) 5-chloropyrrolo-[3,2-b]pyridine in 50 mL methanol were added 1.09 gm (47.6 mMol) sodium. The reaction mixture was stirred until all of the sodium had dissolved and then 1.6 mL (13 mMol) 1-methyl-4-piperidone were added. The reaction mixture was stirred at reflux for 7.5 hours and was then cooled to 0° C. To this mixture were then added hydrochloric acid until the pH of the solution was about 8. The reaction mixture was then concentrated under reduced pressure to an oil. This oil was dissolved in 3:1 chloroform:isopropanol and the resulting solution was washed sequentially with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The remaining organics were dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography, eluting with dichloromethane containing from 0-10% methanol. Fractions containing product were concentrated under reduced pressure to provide 0.30 gm (28%) of the title compound.

Workup

  1. dissolutionhad dissolved
  2. temperatureat reflux for 7.5 hours
  3. concentrationThe reaction mixture was then concentrated under reduced pressure to an oil
  4. dissolutionThis oil was dissolved in 3:1 chloroform
  5. washisopropanol and the resulting solution was washed sequentially with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  6. dry with materialThe remaining organics were dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washeluting with dichloromethane containing from 0-10% methanol
  9. additionFractions containing product
  10. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-b3107c262aaa435f944af84ca65ed1fe
Source dataset
uspto-grants-1999_05
Patent number
US05905084

Reaction notes

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