Water → 3-Bromo-1-methyl-6-(2-pyridylmethoxy)pyrrolo[2,3-b]pyridine

HRID 1622877Notes

Reaction equation

HRID 1622877 reaction equation
CC(C)([O-])C.[K+].[N:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][OH:14].[Br:15][C:16]1[C:24]2[C:19](=[N:20][C:21](F)=[CH:22][CH:23]=2)[N:18]([CH3:26])[CH:17]=1.O>CN(C=O)C>[Br:15][C:16]1[C:24]2[C:19](=[N:20][C:21]([O:14][CH2:13][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][N:7]=3)=[CH:22][CH:23]=2)[N:18]([CH3:26])[CH:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11474PiconolHCID 23665647Potassium tert-butoxideHCID 678140183-bromo-6-fluoro-1-methyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 678161163-Bromo-1-methyl-6-(2-pyridylmethoxy)pyrrolo[2,3-b]pyridineYield 99.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Potassium tert-butoxide (137.4 g; 1.19 mol) and DMF (1.44 L) are charged into a flask, and a solution of 2-pyridylmethanol (145.8 g, 1.34 mol) in DMF (306 mL) is added over 15 min. The flask is cooled as necessary to maintain room temperature. The mixture is stirred at room temperature for 40 minutes. A solution of 3-bromo-6-fluoro-1-methyl-pyrrolo[2,3-b]pyridine (170 g, 742.2 mmol) in DMF (306 mL) is added over 15 min., maintaining the temperature between 20 and 25° C. The mixture is stirred for 2 h. Water (1.7 L) is added slowly to the mixture, cooling as necessary, followed by extraction with EtOAc (4×1.0 L). The combined extracts are washed with water (4×1.0 L), then brine, and dried over sodium sulphate, filtered and concentrated to leave the product as a yellow solid (235.1 g, 0.74 moles). MS (m/z): 318.0/320.0.

Workup

  1. temperatureThe flask is cooled as necessary
  2. temperaturemaintaining the temperature between 20 and 25° C
  3. stirringThe mixture is stirred for 2 h
  4. temperaturecooling as necessary,
  5. extractionfollowed by extraction with EtOAc (4×1.0 L)
  6. washThe combined extracts are washed with water (4×1.0 L)
  7. dry with materialbrine, and dried over sodium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-5bb68e3447f847ab8b722104a6c2d8a4
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

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