Acetonitrile → 4-Chloro-5-fluoro-7H-pyrrolo(2,3-d)pyrimidine

HRID 419721Notes

Reaction equation

HRID 419721 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][NH:5][C:4]2=[N:8][CH:9]=[CH:10][C:3]=12.[B-](F)(F)(F)[F:12].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1.C(#N)C>C(O)(=O)C>[Cl:1][C:2]1[C:3]2[C:10]([F:12])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 2724933SelectfluorHCID 178418725HCID 178418725, compound

Product 1

HCID 113212244-Chloro-5-fluoro-7H-pyrrolo(2,3-d)pyrimidineYield 58%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Combine 4-Chloropyrrolo[2,3-d]pyrimidine (2.985 g, 19.40 mmol), [1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate)] (Selectfluoro) (10.523 g, 29.704 mmol)], acetonitrile (200 mL), and acetic acid (40 mL) and heat to 70° C. for 24 hours. Monitor loss of starting material by HPLC then concentrate. Add two portions of toluene (50 mL) and evaporate. Filter crude material thru a pad of celite, washing with 1:1 EtOAc/CH2Cl2. Finally, concentrate the filtrate and chromatograph on a silica column eluting with CH2Cl2/MeOH [0-10% MeOH gradient]. Check fractions by MS and combine product fractions to provide 1.931 g (58%) of 4-Chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine.

Workup

  1. concentrationMonitor loss of starting material by HPLC then concentrate
  2. additionAdd two portions of toluene (50 mL)
  3. customevaporate
  4. filtrationFilter crude material
  5. washwashing with 1:1 EtOAc/CH2Cl2
  6. concentrationFinally, concentrate the filtrate and chromatograph on a silica column
  7. washeluting with CH2Cl2/MeOH [0-10% MeOH gradient]

Sources & evidence

ORD record
ord-643a43cae4ab40eeb81c094e2be65346
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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