3,4-dihydro-2H-pyran → 4-bromo-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 475130Notes

Reaction equation

HRID 475130 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[CH2:12]1[CH2:17][O:16][CH:15]=[CH:14][CH2:13]1.CC1C=CC(S(O)(=O)=O)=CC=1.O>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH:15]1[CH2:14][CH2:13][CH2:12][CH2:17][O:16]1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 247288014-Bromo-6-methyl-1H-indazole

Product 1

HCID 712727704-bromo-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-bromo-6-methyl-1H-indazole (1.05 g, 5 mmol), DHP (2.1 g, 25 mmol), and TsOH.H2O (96 mg, 0.5 mmol) in THF (50 ml) under nitrogen was heated at reflux overnight. The reaction mixture was concentrated in vacuo and to the residue was added DCM (300 mL) and water (50 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography by using petroleum ether:EtOAc (100:1) as eluting solvents to afford 4-bromo-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole as light yellow oil (1.1 g, 90%) MS (ESI): m/z=295.1 [M+1]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. concentrationThe reaction mixture was concentrated in vacuo and to the residue
  4. additionwas added DCM (300 mL) and water (50 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography
  9. washas eluting solvents

Sources & evidence

ORD record
ord-db63ac98724044c9ba9a957f45647367
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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