Trityl chloride → 4-iodo-1-trityl-1H-pyrazolo[3,4-b]pyridine

HRID 384057Notes

Reaction equation

HRID 384057 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12.[H-].[Na+].[C:13](Cl)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN(C)C=O>[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:9]=[CH:10][C:3]=12

Participants

5

Reactant 3

HCID 6456Trityl chlorideHCID 24758Sodium hydrideHCID 576428014-Iodo-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 579696964-iodo-1-trityl-1H-pyrazolo[3,4-b]pyridineYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
5 °C

Procedure

4-iodo-1H-pyrazolo[3,4-b]pyridine (15 g, 61.22 mmol) was dissolved in dimethylformamide (300 mL) and the solution was cooled down in an ice bath to 5° C. Sodium hydride (60%, 2.938 g, 73.46 mmol) was added portionwise and left to stir at this temperature for 2 hours. After this time a solution of trityl chloride (18.77 g, 67.34 mmol) in dimethylformamide (150 mL) was added dropwise over 30 minutes. After an additional 2 hours of stirring, the solvent was removed by evaporation, and the residue was partitioned between ethyl acetate and saturated bicarbonate (2×100 ml). The organic layer was further washed with brine (100 ml), dried over magnesium sulfate and concentrated in vacuo to give a brown oil. This residue was purified on silica gel by flash column chromatography to afford the title compound as a white solid (less polar fraction: 2-regioisomer, 13.71 g, 46% yield; more polar fraction: 3-regioisomer, pale yellow solid, 8.06 g, 27% yield).

Workup

  1. waitleft
  2. stirringAfter an additional 2 hours of stirring
  3. customthe solvent was removed by evaporation
  4. customthe residue was partitioned between ethyl acetate and saturated bicarbonate (2×100 ml)
  5. washThe organic layer was further washed with brine (100 ml)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customto give a brown oil
  9. customThis residue was purified on silica gel by flash column chromatography

Sources & evidence

ORD record
ord-16626cab34424d09b47e60a73fdd1069
Source dataset
uspto-grants-2013_02
Patent number
US08367697B2

Reaction notes

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