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

HRID 1622893Notes

Reaction equation

HRID 1622893 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH3:11])[CH:9]=[CH:10][C:5]2=[CH:4][C:3]=1[F:12].[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][OH:20].[H-].[Na+]>CS(C)=O>[F:12][C:3]1[CH:4]=[C:5]2[CH:10]=[CH:9][N:8]([CH3:11])[C:6]2=[N:7][C:2]=1[O:20][CH2:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][N:13]=1

Participants

5

Reactant 3

HCID 11474PiconolHCID 24758Sodium hydride2×HCID 866945676-chloro-5-fluoro-1-methyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 678162405-fluoro-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridineYield 81.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred solution of 6-chloro-5-fluoro-1-methyl-1H-pyrrolo[2,3-b]pyridine (1.276 g, 6.91 mmol) and 2-pyridine methanol (0.800 mL, 8.29 mmol) in dimethyl sulphoxide (10 mL), under a nitrogen atmosphere, is added 60% sodium hydride (0.332 g, 8.29 mmol) portionwise, and reaction stirred at room temperature overnight. The reaction is then heated to 80° C. for 1 h, cooled to room temperature and further 60% sodium hydride (0.090 g, 2.32 mmol) added. After 30 minutes of stirring at room temperature, the reaction is further heated at 80° C. for 30 minutes. 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 oil. This is purified by column chromatography on silica, eluting with 0 to 80% EtOAc in hexane, to give the title compound as a light green oil (1.445 g, 5.62 mmol). MS (m/z): 258 (M+1).

Workup

  1. customreaction
  2. temperatureThe reaction is then heated to 80° C. for 1 h
  3. temperaturecooled to room temperature
  4. stirringAfter 30 minutes of stirring at room temperature
  5. temperaturethe reaction is further heated at 80° C. for 30 minutes
  6. temperatureThe reaction is cooled
  7. additionpoured onto brine (ca. 50 mL)
  8. extractionthe product extracted with CHCl3 (ca. 2×30 mL)
  9. dry with materialThe combined organic extracts are dried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give a brown oil
  13. customThis is purified by column chromatography on silica
  14. washeluting with 0 to 80% EtOAc in hexane

Sources & evidence

ORD record
ord-578d9061803b4d1e841042b8b792c425
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

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