Triethylamine → 5-Methoxy-3-methyl-1H-pyrrolo[3,2-b]pyridine

HRID 2382144Notes

Reaction equation

HRID 2382144 reaction equation
[CH2:1]([N:4]([C:11]1[C:12](Br)=[N:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=1)C(=O)C(F)(F)F)[CH:2]=[CH2:3].[Cl-].C([NH3+])CCC.C([NH3+])CCC.C([NH3+])CCC.C([NH3+])CCC.[Cl-].[Cl-].[Cl-].C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:18][O:17][C:14]1[N:13]=[C:12]2[C:2]([CH3:3])=[CH:1][NH:4][C:11]2=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 748912193-Bromo-3-(N-allyl-N-trifluoroacetyl)amino-6-methoxypyridineHCID 86639386Tetra(n-butylammonium) chloride

Product 1

HCID 151795865-Methoxy-3-methyl-1H-pyrrolo[3,2-b]pyridineYield 99.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of N-allyl-N-(2-bromo-6-methoxy-pyridin-3-yl)-2,2,2-trifluoro-acetamide (5.54 g, 16.3 mmol), palladium acetate (147 mg, 0.65 mmol), tetra(n-butylammonium) chloride (4.99 g, 17.9 mmol) and triethylamine (3.72 g, 26.8 mmol) in anhydrous DMF (35 mL) is stirred at 10° C. under N2 for an hour. DMF is evaporated off, and the residue is mixed with water (20 mL) and stirred at rt overnight. EtOAc (50 mL) is added. The organic layer is separated, dried (Na2SO4), filtered, and concentrated in vacuo. The residue is purified by silica gel column chromatography eluting with 30-70% EtOAc in heptane to afford 5-methoxy-3-methyl-1H-pyrrolo[3,2-b]pyridine (2.62 g) as a solid. 1H NMR (300 MHz, CDCl3): δ 2.38 (s, 3H), 4.05 (s, 3H), 6.62 (s, H), 7.12 (s, H), 7.54 (d, H), 7.94 (br, N—H).

Workup

  1. customDMF is evaporated off
  2. additionthe residue is mixed with water (20 mL)
  3. additionEtOAc (50 mL) is added
  4. customThe organic layer is separated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by silica gel column chromatography
  9. washeluting with 30-70% EtOAc in heptane

Sources & evidence

ORD record
ord-64db3a3841334936b8e0cdd681a7944e
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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