3,4-dihydro-2H-pyran → 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine

HRID 241058Notes

Reaction equation

HRID 241058 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[CH:10]=[N:9][NH:8][C:5]2=[N:6][CH:7]=1.[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>O1CCCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[CH:10]=[N:9][N:8]([CH:12]3[CH2:13][CH2:14][CH2:15][CH2:16][O:11]3)[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 404274545-Bromopyrazolo[3,4-b]pyridine

Product 1

HCID 583780645-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridineYield 90%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 5-bromo-1H-pyrazolo[3,4-b]pyridine (1.4 g, 7.2 mmol) and dihydropyran (3.3 mL, 36.0 mmol) in tetrahydrofuran (20 mL) was added (±)-camphorsulfonic acid (250 mg) and the reaction mixture was stirred at 65° C. for 16 hours. After cooling to room temperature it was diluted with ethyl acetate (250 mL), washed with saturated aqueous sodium bicarbonate (2×100 mL) and brine (100 mL), dried over sodium sulfate, filtered and concentrated. Gradient column chromatography (10% to 30% ethyl acetate in hexane) provided 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine (1.8 g, 90%). MS (EI) for C11H12BrN3O: 283 (MH+).

Workup

  1. temperatureAfter cooling to room temperature it
  2. washwashed with saturated aqueous sodium bicarbonate (2×100 mL) and brine (100 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ac6e226d760e4c878489c26270a85303
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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