1,4-Dioxane → 5-cyclopropyl-1H-pyrrolo[2,3-b]pyridine

HRID 509932Notes

Reaction equation

HRID 509932 reaction equation
I[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[Br-].[CH:12]1([Zn+])[CH2:14][CH2:13]1.O1CCOCC1>Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1.CO>[CH:12]1([C:2]2[CH:3]=[C:4]3[CH:10]=[CH:9][NH:8][C:5]3=[N:6][CH:7]=2)[CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 242292145-Iodo-1H-pyrrolo[2,3-b]pyridineHCID 178419765HCID 178419765, compound

Product 1

HCID 582589265-cyclopropyl-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 2

HCID 178418745HCID 178418745, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

5-Iodo-1H-pyrrolo[2,3-b]pyridine (21, 0.343 g, 1.40 mmol), cyclopropylzinc bromide (22, 12.6 mL, 0.500 M in tetrahydrofuran, 6.32 mmol) and [1,3-bis(diphenylphosphino)propane]-nickel(II) chloride (76.2 mg, 0.14 mmol) and 5.37 mL of 1,4-dioxane were combined in a reaction vessel. The reaction was heated at 100° C. overnight, then methanol was added and the reaction was concentrated under vacuum. Ethyl acetate and water were added to the residue, then filtered through a bed of celite and the celite bed washed with ethyl acetate. The filtrate was separated and the aqueous layer extracted with ethyl acetate. The organic layers were combined and washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with ethyl acetate and hexane. Appropriate fraction were combined and concentrated under vacuum to provide the desired compound. MS (ESI) [M+H+]+=159.0.

Workup

  1. concentrationthe reaction was concentrated under vacuum
  2. additionEthyl acetate and water were added to the residue
  3. filtrationfiltered through a bed of celite
  4. washthe celite bed washed with ethyl acetate
  5. customThe filtrate was separated
  6. extractionthe aqueous layer extracted with ethyl acetate
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate concentrated under vacuum
  11. customThe resulting material was purified by silica gel column chromatography
  12. washeluting with ethyl acetate and hexane
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-763005697d17419b9823e16e3de7306a
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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