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

HRID 2069574Notes

Reaction equation

HRID 2069574 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.[CH2:12]1[CH2:17][O:16][CH:15]=[CH: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:15]1[CH2:14][CH2:13][CH2:12][CH2:17][O:16]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 DHP (4.36 g, 51.9 mmol) in dry dichloromethane (100 mL), was added PTSA (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-0c50119d03314d0581db58bd66b49030
Source dataset
uspto-grants-2012_10
Patent number
US08299112B2

Reaction notes

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