Sodium Hydroxide → 3-bromo-5-fluoro-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridine

HRID 1622894Notes

Reaction equation

HRID 1622894 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[CH:18]=[CH:17][N:16]([CH3:19])[C:5]2=[N:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[OH-].[Na+].[Br:22]N1C(=O)CCC1=O>CN(C=O)C>[Br:22][C:18]1[C:4]2[C:5](=[N:6][C:7]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=3)=[C:2]([F:1])[CH:3]=2)[N:16]([CH3:19])[CH:17]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 67184N-bromobutanimideHCID 678162405-fluoro-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 678144933-bromo-5-fluoro-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridineYield 91.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-fluoro-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridine (1.00 g, 3.89 mmol) in DMF (30 mL), cooled to 15° C. under a nitrogen atmosphere, is added sodium hydroxide (0.171 g, 4.28 mmol), followed by N-bromosuccinimide (0.761 g, 4.28 mmol) portionwise over 5 minutes. After 15 minutes, the reaction is 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 oil. This is purified by column chromatography on silica, eluting with 0 to 100% EtOAc in hexane, to give the title compound as a light yellow solid (1.195 g, 3.55 mmol). MS (m/z): 336/338 (M+1).

Workup

  1. additionthe reaction is poured onto brine (ca. 50 mL)
  2. extractionthe product extracted with CHCl3 (ca. 2×30 mL)
  3. dry with materialThe combined organic extracts are dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a brown oil
  7. customThis is purified by column chromatography on silica
  8. washeluting with 0 to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-fc200875ff784207abd43050f800b1f8
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

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