p-Toluenesulfonic acid → 5-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1057119Notes

Reaction equation

HRID 1057119 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1.CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>ClCCl>[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][O:11]1)[N:6]=[CH:5]2

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 218947395-Iodo-1H-indazole

Product 1

HCID 667934695-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 82.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-iodo-1H-indazole (0.90 g, 3.69 mmol) and 3,4-dihydro-2H-pyran (1.57 g, 18.7 mmol) in dry dichloromethane (20 mL), was added p-TsOH (0.08 g, 0.41 mmol) at room temperature. The resulting mixture was stirred overnight. Upon completion, saturated aqueous NaHCO3 (30 mL) was added slowly into the reaction mixture. The organic layer was separated, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0˜5% EtOAc in petroleum ether) affording the title compound (1.0 g). 1H NMR (400 MHz, DMSO-d6): δ 8.21 (s, 1H), 8.08 (s, 1H), 7.67 (dd, 1H), 7.61 (d, 1H), 5.85 (dd, 1H), 3.88-3.85 (m, 1H), 3.78-3.72 (m, 1H), 2.41-2.29 (m, 1H), 2.05-1.95 (m, 2H), 1.77-1.72 (m, 1H), 1.61-1.56 (m, 2H).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on silica gel (0˜5% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-34b637b9d61d4012964f625fe6e5c500
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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