Piconol → 3-bromo-1-cyclopropyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridine

HRID 1622882Notes

Reaction equation

HRID 1622882 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7](F)=[CH:8][CH:9]=2)[N:4]([CH:12]2[CH2:14][CH2:13]2)[CH:3]=1.[N:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:21][OH:22].[H-].[Na+]>CS(C)=O.CO>[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([O:22][CH2:21][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][N:15]=3)=[CH:8][CH:9]=2)[N:4]([CH:12]2[CH2:14][CH2:13]2)[CH:3]=1

Participants

6

Reactant 3

HCID 11474PiconolHCID 24758Sodium hydrideHCID 678163113-bromo-1-cyclopropyl-6-fluoro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 678142033-bromo-1-cyclopropyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridineYield 77.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

To a solution of 3-bromo-1-cyclopropyl-6-fluoro-1H-pyrrolo[2,3-b]pyridine (0.249 g, 0.98 mmol) in dimethyl sulfoxide (5 mL) is added 2-pyridinemethanol (188 μL, 1.95 mmol), followed by portionwise addition of sodium hydride (97.6 mg, 2.44 mmol). The mixture is stirred at room temperature for 5 min., then poured onto brine and extracted with EtOAc. The organic layers are combined, dried (magnesium sulphate) and concentrated in vacuo to give a brown oil. This is taken up in methanol and poured onto a SCX-2 ion-exchange column. This is washed with 3 column volumes of MeOH, and then the product collected in the subsequent one column volume flush with 7 M methanolic ammonia. The solution is then concentrated in vacuo to give the title compound as a yellow oil (0.263 g, 0.76 mmol). MS (m/z): 344/346 (M+1).

Workup

  1. additionpoured onto brine
  2. extractionextracted with EtOAc
  3. dry with materialdried (magnesium sulphate)
  4. concentrationconcentrated in vacuo
  5. customto give a brown oil
  6. additionpoured onto a SCX-2 ion-exchange column
  7. washThis is washed with 3 column volumes of MeOH
  8. customthe product collected in the subsequent one column volume
  9. customflush with 7 M methanolic ammonia
  10. concentrationThe solution is then concentrated in vacuo

Sources & evidence

ORD record
ord-22cf5935014d473f80bfe028f0b4623e
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

Loading…