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

HRID 1777801Notes

Reaction equation

HRID 1777801 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+].[Cl-].[Na+]>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

6

Reactant 4

HCID 5234Sodium ChlorideHCID 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

141 g (462.11 mmol) of the compound from Example 5A were introduced into DMF (2538 ml), and 96.09 g (508.32 mmol) of 2-fluorobenzyl bromide and 165.62 g (508.32 mmol) of caesium carbonate were then added. The mixture was stirred at RT for two hours. The reaction mixture was then poured into saturated aqueous sodium chloride solution (13 670 ml) and extracted twice with ethyl acetate (5858 ml). The collected organic phases were washed with saturated aqueous sodium chloride solution (3905 ml), dried, filtered and concentrated. The residue was chromatographed on silica gel (mobile phase: petroleum ether/ethyl acetate 97:3) and the product fractions were concentrated. The resulting solid was dissolved in dichloromethane and washed once with saturated aqueous sodium thiosulphate solution (500 ml) and then with saturated aqueous sodium chloride solution (500 ml). The product was concentrated to dryness and the residue was suspended in diethyl ether, isolated by filtration with suction and dried under high vacuum. This gave 106.6 g (62% of theory) of the desired compound.

Workup

  1. additionwere then added
  2. extractionextracted twice with ethyl acetate (5858 ml)
  3. washThe collected organic phases were washed with saturated aqueous sodium chloride solution (3905 ml)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel (mobile phase: petroleum ether/ethyl acetate 97:3)
  8. concentrationthe product fractions were concentrated
  9. dissolutionThe resulting solid was dissolved in dichloromethane
  10. washwashed once with saturated aqueous sodium thiosulphate solution (500 ml)
  11. concentrationThe product was concentrated to dryness
  12. customisolated by filtration with suction
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-74a7149d3d1d4feea07b6ac607f6d46a
Source dataset
uspto-grants-2016_02
Patent number
US09266885B2

Reaction notes

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