p-Toluenesulfonic acid → 5-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1057134Notes

Reaction equation

HRID 1057134 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[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[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[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 667931105-Bromo-7-fluoro-1H-indazole

Product 1

HCID 667932045-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-bromo-7-fluoro-1H-indazole (9.3 g, 43.26 mmol) and 3,4-dihydro-2H-pyran (4.36 g, 51.9 mmol) in dry dichloromethane (100 mL), was added p-TsOH (424 mg, 2.16 mmol) at room temperature. The resulting mixture was stirred overnight. Work-up: saturated aqueous NaHCO3 (30 mL) was slowly added 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˜10% EtOAc in petroleum ether) to give 5-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole as a light yellow solid. (7.8 g). 1H NMR (300 MHz, CDCl3): δ 7.98 (s, 1H), 7.64 (s, 1H), 7.22 (dd, 1H), 5.84 (dd, 1H), 4.07-4.02 (m, 1H), 3.78-3.71 (m, 1H), 2.62-2.53 (m, 1H), 2.16-2.07 (m, 2H), 1.79-1.71 (m, 2H), 1.63-1.33 (m, 1H).

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˜10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-09e58fc6c51a414f8df3df7020722f7c
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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