Ethanol → 4-Azaindole

HRID 1916093Notes

Reaction equation

HRID 1916093 reaction equation
Br[C:2]1[N:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=N[CH:7]=1.F[C:12]1C(B(O)O)=CC=CN=1.C(=O)([O-])[O-].[Na+].[Na+].CCO>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:8]1[C:5]2[CH:12]=[CH:7][CH:2]=[N:3][C:4]=2[CH:10]=[CH:9]1

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 250673082-bromo-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 92264-AzaindoleYield 137.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a 25 mL microwave vial was added 2-bromo-5H-pyrrolo[2,3-b]pyrazine (0.5 g, 2.52 mmol), 2-fluoropyridin-3-ylboronic acid (600 mg, 4.26 mmol) and sodium carbonate (803 mg, 7.57 mmol) in dioxane (10.0 ml), water (5.00 ml), and EtOH (2.5 ml). The reaction mixture was bubbled through with argon for 10 mins. Pd(PPh3)4 (292 mg, 0.252 mmol). The reaction was bubbled through with argon for 5 mins. The vial was capped and heated in the microwave at 140° C. for 15 min. The reaction mixture was diluted with EtOAc and water. The combined organics were separated, dried (MgSO4), filtered and concentrated. The crude residue dissolved in DCM and treated with silica. The solvent was evaporated and the crude absorbed in silica was purified by SiO2 chromatography eluting with EtOAc/hexane gradient (0% to 60%) to afford 410 mg (76%) of pyrrolopyridine as a light yellow solid. MS m/z (ES): 215 (M+H)+.

Workup

  1. customThe reaction mixture was bubbled through with argon for 10 mins
  2. customThe reaction was bubbled through with argon for 5 mins
  3. customThe vial was capped
  4. additionThe reaction mixture was diluted with EtOAc and water
  5. customThe combined organics were separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe crude residue dissolved in DCM
  10. additiontreated with silica
  11. customThe solvent was evaporated
  12. customthe crude absorbed in silica
  13. customwas purified by SiO2 chromatography
  14. washeluting with EtOAc/hexane gradient (0% to 60%)

Sources & evidence

ORD record
ord-32c7b55d15574a3d8f7a37125d630d97
Source dataset
uspto-grants-2013_12
Patent number
US08618103B2

Reaction notes

Loading…