Hydrochloric Acid → 3-Methyl-2-(3-pyridyl)indole hydrochloride

HRID 593490Notes

Reaction equation

HRID 593490 reaction equation
[C:1]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)(=O)[CH2:2][CH3:3].[ClH:11].[C:12]1([NH:18]N)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl>C(O)C>[ClH:11].[CH3:3][C:2]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:18][C:1]=1[C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 60962Phenylhydrazine hydrochlorideHCID 740741-(3-Pyridyl)propan-1-one

Product 1

HCID 445539613-Methyl-2-(3-pyridyl)indole hydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

3-Methyl-2-pyridin-3-yl-1H-indole hydrochloride is synthesized based on the method described in U.S. Pat. No. 3,468,894. A flask is charged with 3-propionylpyridine (1.004 g, 7.279 mmol), phenylhydrazine hydrochloride (1.010 g, 6.915 mmol) and ethanol (15 mL). The mixture is heated to reflux for 1 h and cooled to room temperature. To a portion of the reaction mixture (2.5 mL) is added HCl (4M in dioxane, 1 mL, 4 mmol) and the mixture is heated to reflux. After 3 h, the mixture is concentrated in vacuo. The solid is dissolved in the minimum amount of boiling methanol (17 mL) and allowed to cool slowly to room temperature. A solid precipitates and after cooling to 0° C. for 30 min, the yellow solid is filtered off, washed with portions of cold methanol and dried under high vacuum to give 3-methyl-2-pyridin-3-yl-1H-indole hydrochloride as yellow needles. 1H NMR (400 MHz, MeOD) δ ppm (HCl salt) 2.56 (s, 3H), 7.09-7.13 (m, 1H), 7.23-7.26 (m, 1H), 7.43 (d, J=8.1 Hz, 1H), 7.63 (d, J=8.1 Hz, 1H), 8.14-8.18 (m, 1H), 8.74 (d, J=5.8 Hz, 1H), 8.83-8.85 (m, 1H), 9.08 (s, 1H).

Workup

  1. custom3-Methyl-2-pyridin-3-yl-1H-indole hydrochloride is synthesized
  2. temperatureThe mixture is heated
  3. temperatureto reflux for 1 h
  4. temperaturethe mixture is heated to reflux
  5. concentrationthe mixture is concentrated in vacuo
  6. dissolutionThe solid is dissolved in the minimum amount of boiling methanol (17 mL)
  7. temperatureto cool slowly to room temperature
  8. customA solid precipitates
  9. temperatureafter cooling to 0° C. for 30 min
  10. filtrationthe yellow solid is filtered off
  11. washwashed with portions of cold methanol
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-69c0bbc6aa444a758ce95f84575203b7
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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