Sodium hydride → 2,2-Dimethyl-propionic acid 5-bromo-3-iodo-pyrazolo[3,4-b]pyridin-1-ylmethyl ester

HRID 2388975Notes

Reaction equation

HRID 2388975 reaction equation
[Br: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.[H-].[Na+].[C:14]([O:20][CH2:21]Cl)(=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16]>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[N:9][N:8]([CH2:21][O:20][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 87885Chloromethyl pivalateHCID 178419453HCID 178419453, compound

Product 1

HCID 579757462,2-Dimethyl-propionic acid 5-bromo-3-iodo-pyrazolo[3,4-b]pyridin-1-ylmethyl esterYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Bromo-3-iodo-1H-pyrazolo[3,4-b]pyridine (3.00 g, 9.26 mmol) was dissolved in N,N-dimethylformamide (150 ml) at 4° C. To the solution was added sodium hydride (60%, 519 mg, 12.98 mmol) in small portions. The flask was warmed to room temperature and stirred for 1 hour. To the mixture was added chloromethyl pivalate (2.29 ml, 15.78 mmol). The reaction mixture was stirred for 2 hours at room temperature, and quenched with methanol. Saturated ammonium chloride solution was added, and the mixture was concentrated in vacuo. The residue was dissolved in dichloromethane, and the organic layer was washed four times with. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in acetone. The solution was filtered and the solid material collected was discarded. The filtrate was concentrated in vacuo. The crude material was re-crystallized in ether to give 2.80 g (69%) of 2,2-dimethyl-propionic acid 5-bromo-3-iodo-pyrazolo[3,4-b]pyridin-1-ylmethyl ester. 1H-NMR (250 MHz, DMSO-d6) δ 8.63 (s, 1H), 8.20 (s, 1H), 6.43 (s, 2H), 1.14 (s, 9H); MS m/z 437.8, 439.8 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred for 2 hours at room temperature
  2. customquenched with methanol
  3. additionSaturated ammonium chloride solution was added
  4. concentrationthe mixture was concentrated in vacuo
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washthe organic layer was washed four times with
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in acetone
  11. filtrationThe solution was filtered
  12. customthe solid material collected
  13. concentrationThe filtrate was concentrated in vacuo
  14. customThe crude material was re-crystallized in ether

Sources & evidence

ORD record
ord-e7b75e6b584b4a6bb6d924061a46fce1
Source dataset
uspto-grants-2012_09
Patent number
US08268994B2

Reaction notes

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