Cesium carbonate → 6-Fluoro-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-indazole

HRID 1402104Notes

Reaction equation

HRID 1402104 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.Br[CH2:12][CH2:13][O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:12][CH2:13][O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 178423506-Fluoro-1H-indazole

Product 1

HCID 866869686-Fluoro-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-indazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-fluoro-1H-indazole (2.0 g, 14.7 mmol), and 2-(2-bromo-ethoxy)-tetrahydro-pyran (3.38 g, 16.2 mmol) in DMF (25 mL) was treated with caesium carbonate (6.1 g, 18.7 mmol) and stirred at RT for 18 h. The solvent volume was reduced in vacuo, and the residue partitioned between EtOAc (100 mL) and water (100 mL). The aqueous layer was extracted into EtOAc (3×). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried (MgSO4) and evaporated in vacuo. The residue was purified by FCC, using 0-50% cyclohexane in EtOAc, to afford the title product and a yellow oil. LCMS (Method 1): Rt 3.42 min, m/z 181 [MH+] (M-THP). 1H NMR (300 MHz; CDCl3) 1.52-1.56 (6H, m), 3.39-3.49 (1H, m), 3.57-3.68 (1H, m), 3.89-3.91 (1H, m), 4.19-4.21 (1H, m), 4.56-4.57 (3H, m), 6.88 (1H, td, J 9.15 and 2.26), 7.30 (1H, m), 7.62 (1H, m), 8.04 (1H, s).

Workup

  1. customthe residue partitioned between EtOAc (100 mL) and water (100 mL)
  2. extractionThe aqueous layer was extracted into EtOAc (3×)
  3. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-7e4912be99384c87a413d081892271fb
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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