3,4-dihydro-2H-pyran → 4-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 475254Notes

Reaction equation

HRID 475254 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.CC1C=CC(S(O)(=O)=O)=CC=1.O.[O:23]1[CH:28]=[CH:27][CH2:26][CH2:25][CH2:24]1>C1COCC1>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH:24]1[CH2:25][CH2:26][CH2:27][CH2:28][O:23]1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 223525484-bromo-1H-indazole

Product 1

HCID 574747294-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-bromo-1H-indazole (0.5 g, 2.53 mmol), p-TsOH.H2O (50 mg, 0.25 mmol), and 3,4-dihydro-2H-pyran (0.64 g, 7.61 mmol) in THF (20 mL) was degassed then heated to reflux overnight. After the solvent was removed, the residue was partitioned between DCM (300 mL) and water (50 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude residue was purified by SiO2 chromatography eluting with a DCM/MeOH gradient (0.5 to 1% MeOH) to afford 570 mg (81%) of 4-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (196) as yellow solid: MS (ESI) m/z=282.2 [M+1]+.

Workup

  1. customwas degassed
  2. temperaturethen heated
  3. temperatureto reflux overnight
  4. customAfter the solvent was removed
  5. customthe residue was partitioned between DCM (300 mL) and water (50 mL)
  6. customThe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was purified by SiO2 chromatography
  11. washeluting with a DCM/MeOH gradient (0.5 to 1% MeOH)

Sources & evidence

ORD record
ord-da37ed37e863430fa98fc1d0a9a82541
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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