Potassium Carbonate → 5-pyridin-3-yl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

HRID 712591Notes

Reaction equation

HRID 712591 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH2:10][CH2:9][NH:8][C:5]2=[N:6][CH:7]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13](B(O)O)[CH:12]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:2]2[CH:3]=[C:4]3[CH2:10][CH2:9][NH:8][C:5]3=[N:6][CH:7]=2)[CH:12]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 219640795-Bromo-2,3-dihydro-7-azaindole

Product 1

HCID 675706995-pyridin-3-yl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridineYield 60.8%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5-Bromo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (500 mg, 2.5 mmol), 3-pyridinyl-boronic acid (370 mg, 3.0 mmol) and K2CO3 (694 mg, 5.0 mmol) are mixed in 6.5 mL of 1,4-dioxane and 0.65 mL of water. Argon gas is bubbled through the mixture for 10 min and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (178 mg, 0.25 mmol) is added. The mixture is heated at 100° C. for 16 hrs. Then the solvents are removed and EtOAc (50 mL) is added along with 30 mL of water. The mixture is filtered to remove any solid and the organic layer is separated. The aqueous layer is extracted with EtOAc (2×25 mL) and the organic layers are combined and concentrated to give the crude product. Purification by flash column chromatography affords 300 mg of 5-pyridin-3-yl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine.

Workup

  1. customArgon gas is bubbled through the mixture for 10 min
  2. customThen the solvents are removed
  3. additionEtOAc (50 mL) is added along with 30 mL of water
  4. filtrationThe mixture is filtered
  5. customto remove any solid
  6. customthe organic layer is separated
  7. extractionThe aqueous layer is extracted with EtOAc (2×25 mL)
  8. concentrationconcentrated
  9. customto give the crude product
  10. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-3281b763d231458fa7fc0c5c66cb8c03
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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