Ethyl Acetate → 4-(4',5'-difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole

HRID 551493Notes

Reaction equation

HRID 551493 reaction equation
Br[CH2:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][N:7]2[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.[F:18][C:19]1[C:24]([F:25])=[CH:23][C:22]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)=[C:21]([O:33][CH3:34])[CH:20]=1.C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>C1COCC1.O>[F:18][C:19]1[C:24]([F:25])=[CH:23][C:22]([C:26]2[CH:27]=[CH:28][C:29]([O:32][CH2:2][C:3]3[CH:11]=[CH:10][CH:9]=[C:8]4[C:4]=3[CH:5]=[N:6][N:7]4[CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)=[CH:30][CH:31]=2)=[C:21]([O:33][CH3:34])[CH:20]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 226612154-Bromomethyl-1-(tetrahydro-pyran-2-yl)-1H-indazoleHCID 582599934',5'-Difluoro-2'-methoxy-biphenyl-4-ol

Product 1

HCID 671519344-(4',5'-difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-1-(tetrahydro-pyran-2-yl)-1H-indazoleYield 52.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Bromomethyl-1-(tetrahydro-pyran-2-yl)-1H-indazole (0.5 g, 1.69 mmol), 3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-ol (0.4 g, 1.69 mmol) and potassium carbonate (0.23 g, 1.69 mmol) in 15 mL THF/3 mL DMF was heated to 70° C. overnight. The reaction was cooled and distributed between EtOAc and H2O. The organic layer was separated and concentrated in vacuo. The crude product was purified by flash chromatography with a gradient from 0-25% ethyl acetate in hexanes to yield 4-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole as a white solid (400 mg, 52.5%). HR-MS (ES) calculated for C26H24F2N2O3, 473.1646; found m/z 473.1647 [M+Na]+.

Workup

  1. temperatureThe reaction was cooled
  2. customThe organic layer was separated
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography with a gradient from 0-25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e6a3e5888284475b8b47c946844e1988
Source dataset
uspto-grants-2011_05
Patent number
US07947728B1

Reaction notes

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