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

HRID 1254449Notes

Reaction equation

HRID 1254449 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.[CH2:23]1[CH2:28][O:27][CH:26]=[CH: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:26]1[CH2:25][CH2:24][CH2:23][CH2:28][O:27]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), PTSA (530.7 mg, 2.79 mmol) and DHP (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-6aec451684244628b55cf5887d3c8a64
Source dataset
uspto-grants-2013_06
Patent number
US08455534B2

Reaction notes

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