p-Toluenesulfonic acid → 5-Bromo-4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1057130Notes

Reaction equation

HRID 1057130 reaction equation
[Br:1][C:2]1[C:3]([Cl:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>ClCCl>[Br:1][C:2]1[C:3]([Cl:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:13]1[CH2:14][CH2:15][CH2:16][CH2:17][O:12]1)[N:6]=[CH:5]2

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 457900305-bromo-4-chloro-1H-indazole

Product 1

HCID 667936115-Bromo-4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 81.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-bromo-4-chloro-1H-indazole (8.0 g, 34.6 mmol) and 3,4-dihydro-2H-pyran (8.72 g, 0.104 mol) in dry dichloromethane (200 mL) was added p-TsOH (0.657 g, 3.46 mmol) at room temperature. The resulting mixture was stirred at room temperature overnight. Upon completion, saturated aqueous NaHCO3 (100 mL) was added slowly to 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˜3% EtOAc in petroleum ether) affording the title compound (8.9 g). 1H NMR (300 MHz, DMSO-d6): δ 8.19 (s, 1H), 7.71 (m, 2H), 5.88 (dd, 1H), 3.89-3.84 (m, 1H), 3.79-3.73 (m, 1H), 2.42-2.32 (m, 1H), 2.05-1.95 (m, 2H), 1.75-1.70 (m, 1H), 1.60-1.54 (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˜3% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-5b096b64edf042a2adc4e6d41e57e1dc
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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