Methyl iodide → 6-chloro-5-fluoro-1-methyl-1H-pyrrolo[2,3-b]pyridine

HRID 1622892Notes

Reaction equation

HRID 1622892 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[NH:8][CH:9]=[CH:10][C:5]2=[CH:4][C:3]=1[F:11].[C:12](=O)([O-])[O-].[K+].[K+].CI>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH3:12])[CH:9]=[CH:10][C:5]2=[CH:4][C:3]=1[F:11]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 534130616-chloro-5-fluoro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 866945676-chloro-5-fluoro-1-methyl-1H-pyrrolo[2,3-b]pyridineYield 28.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 6-chloro-5-fluoro-1H-pyrrolo[2,3-b]pyridine (4.15 g, 24.33 mmol) in DMF (50 mL), under a nitrogen atmosphere, is added potassium carbonate (6.73 g, 48.66 mmol), followed by methyl iodide (2.27 mL, 36.49 mmol), and reaction heated to 70° C. for 2 h. The reaction is cooled, poured onto brine (ca. 50 mL) and the product extracted with CHCl3 (ca. 2×30 mL). The combined organic extracts are dried over magnesium sulphate, filtered, and concentrated in vacuo to give a brown solid. This is purified by column chromatography on silica, eluting with 0 to 50% DCM in hexane, to give the title compound as a white solid (1.274 g, 6.90 mmol). MS (m/z): 185/187 (M+1).

Workup

  1. temperatureThe reaction is cooled
  2. additionpoured onto brine (ca. 50 mL)
  3. extractionthe product extracted with CHCl3 (ca. 2×30 mL)
  4. dry with materialThe combined organic extracts are dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a brown solid
  8. customThis is purified by column chromatography on silica
  9. washeluting with 0 to 50% DCM in hexane

Sources & evidence

ORD record
ord-700d24cee10142d2b4eb6f1218a356fd
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

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