1,4-Dioxane → 4-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine

HRID 1403265Notes

Reaction equation

HRID 1403265 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Br-].[CH:12]1([Zn+])[CH2:16][CH2:15][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[C:3]3[CH:10]=[CH:9][NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 178419768HCID 178419768, compound

Product 1

HCID 116369524-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidineYield 16.4%

Reagents, catalysts & solvents 2

HCID 178418745HCID 178418745, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

4-chloro-7H-pyrrolo[2,3-d]pyrimidine (1, 0.503 g, 3.28 mmol), cyclopentylzinc bromide (47, 29.5 mL, 0.500 M in tetrahydrofuran, 14.7 mmol), [1,3-bis(diphenylphosphino)propane]nickel(II) chloride (0.178 g, 0.328 mmol) and 9.3 mL of 1,4-dioxane were combined. The reaction mixture was heated at 110° C. overnight. Methanol was added and the reaction was concentrated under vacuum. Ethyl acetate and water were added to the residue, filtered through a bed of celite, and the celite washed with ethyl acetate. The filtrate layers were separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, 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 fractions were combined and the solvents removed under vacuum to provide the desired compound (48, 0.101 g). MS (ESI) [M+H+]+=188.0.

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 washed with ethyl acetate
  5. customThe filtrate layers were separated
  6. extractionthe aqueous layer was 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. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-cd83e2910c594fcdb9fefda7cc872eac
Source dataset
uspto-grants-2014_12
Patent number
US08912204B2

Reaction notes

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