Cesium carbonate → 5-Fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridine

HRID 1615939Notes

Reaction equation

HRID 1615939 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[N:9][NH:8][C:5]2=[N:6][CH:7]=1.[F:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH2:15]Br.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[N:9][N:8]([CH2:15][C:14]3[CH:17]=[CH:18][CH:19]=[CH:20][C:13]=3[F:12])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 67968alpha-Bromo-o-fluorotolueneHCID 178505979HCID 178505979, compound

Product 1

HCID 580656025-Fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

12.1 g (39.65 mmol) of the compound from Example 6A were initially charged in DMF (217 ml), and 8.25 g (43.62 mmol) of 2-fluorobenzyl bromide and 14.21 g (43.62 mmol) of cesium carbonate were then added. The mixture was stirred at RT for two hours. The reaction mixture was then poured onto water (1.17 l) and extracted twice with ethyl acetate (502 ml). The collected organic phases were washed with saturated aqueous sodium chloride solution (335 ml), dried, filtered and concentrated. The residue was chromatographed on silica gel (eluent: 97:3 petroleum ether/ethyl acetate) and the product fractions were concentrated. This gave 9.0 g (61% of theory) of the desired compound in solid form. The solid was taken up in ethyl acetate and washed with 10% aqueous sodium thiosulfate solution and then with saturated aqueous sodium chloride solution, dried and concentrated.

Workup

  1. additionThe reaction mixture was then poured onto water (1.17 l)
  2. extractionextracted twice with ethyl acetate (502 ml)
  3. washThe collected organic phases were washed with saturated aqueous sodium chloride solution (335 ml)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel (eluent: 97:3 petroleum ether/ethyl acetate)
  8. concentrationthe product fractions were concentrated
  9. washwashed with 10% aqueous sodium thiosulfate solution
  10. dry with materialwith saturated aqueous sodium chloride solution, dried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-65534c6af58f4a6e9df8d29c01e1bc34
Source dataset
uspto-grants-2014_07
Patent number
US08765769B2

Reaction notes

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