p-Toluenesulfonic acid → 5-Bromo-3-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1057138Notes

Reaction equation

HRID 1057138 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[F:11].CC1C=CC(S(O)(=O)=O)=CC=1.[O:23]1[CH:28]=[CH:27][CH2:26][CH2:25][CH2:24]1>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:24]1[CH2:25][CH2:26][CH2:27][CH2:28][O:23]1)[N:6]=[C:5]2[F:11]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 178506021HCID 178506021, compound

Product 1

HCID 667932975-Bromo-3-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 74.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 5-bromo-3-fluoro-1H-indazole (6.0 g, 27.9 mmol), p-TsOH (530.7 mg, 2.79 mmol) and 3,4-dihydro-2H-pyran (3.05 g, 36.3 mmol) in dichloromethane (80 mL) was stirred at room temperature for 18 h. The reaction mixture was diluted with dichloromethane (370 mL) and washed with water (230 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified on a silica gel column using EtOAc in petroleum ether (1:100 to 1:15) to afford the title compound as a yellow solid (6.2 g, yield 74.3%). 1H NMR (DMSO-d6, 400 MHz): δ 7.96 (s, 1H), 7.70 (d, 1H), 7.60 (d, 1H), 5.76 (dd, 1H), 3.84-3.80 (m, 1H), 3.71-3.64 (m, 1H), 2.20-2.15 (m, 1H), 1.97-1.87 (m, 2H), 1.69-1.64 (m, 1H), 1.53-1.47 (m, 2H).

Workup

  1. washwashed with water (230 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-38bc5a44078544db8957962147336c1c
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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