Formaldehyde → 3-(Dimethylaminomethyl)-7-azaindole

HRID 2292575Notes

Reaction equation

HRID 2292575 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.Cl.[CH3:11][NH:12][CH3:13].[CH2:14]=O>C(O)CCC.C(=O)([O-])[O-].[K+].[K+]>[CH3:11][N:12]([CH2:14][C:3]1[C:4]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[NH:1][CH:2]=1)[CH3:13]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 92221H-Pyrrolo(2,3-b)pyridineHCID 10473Dimethylamine, hydrochloride

Product 1

HCID 53835493-(Dimethylaminomethyl)-7-azaindole

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 11430Potassium CarbonateSolvent

Procedure

A mixture of 1H-pyrrolo[2,3-b]pyridine (18.07 g, 153 mmol), dimethylamine hydrochloride (13.11 g, 161 mmol) and paraformaldehyde (4.92 g, 164 mmol) in n-butanol (500 ml) was heated at reflux for 35 minutes. The mixture was allowed to cool overnight and the precipitated solid collected by filtration. The filtrate was evaporated and the residue triturated with ethyl acetate to afford a second solid. The solids were combined, suspended in saturated aqueous potassium carbonate solution (500 ml) and extracted with dichloromethane (twice). The combined extracts were washed with saturated potassium carbonate (250 ml) then saturated sodium chloride solution (500 ml), dried (magnesium sulphate) then evaporated to a small volume, with the product crystallising out of solution during evaporation. Diethyl ether was added and the title compound collected as a solid (18.13 g, 67%). 1H NMR (360 MHz, DMSO) δ 2.19 (6H, s), 3.61 (2H, s), 7.03 (1H, dd, J1 =5, J2 =8 Hz), 7.36 (1H, d, J=2 Hz), 8.00 (1H, dd, J1 =2, J2 =8 Hz), 8.20 (1H, dd, J1 =2, J2 =5 HZ), 11.47 (1H, broad s).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 35 minutes
  3. temperatureto cool overnight
  4. filtrationthe precipitated solid collected by filtration
  5. customThe filtrate was evaporated
  6. customthe residue triturated with ethyl acetate
  7. customto afford a second solid
  8. extractionextracted with dichloromethane (twice)
  9. washThe combined extracts were washed with saturated potassium carbonate (250 ml)
  10. dry with materialsaturated sodium chloride solution (500 ml), dried (magnesium sulphate)
  11. customthen evaporated to a small volume, with the product
  12. customcrystallising out of solution during evaporation
  13. additionDiethyl ether was added
  14. customthe title compound collected as a solid (18.13 g, 67%)

Sources & evidence

ORD record
ord-29e51ae0f07c4c47af7b62273e5ae5b3
Source dataset
uspto-grants-1997_11
Patent number
US05684006

Reaction notes

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