Potassium Phosphate, Tribasic → 6-[5-Fluoro-4-methoxy-2-(2,2,2-trifluoro-ethyl)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carbonitrile

HRID 2038736Notes

Reaction equation

HRID 2038736 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:17]#[N:18])=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][CH:3]=1.[F:19][C:20]1[C:21]([O:40][CH3:41])=[CH:22][C:23]([CH2:35][C:36]([F:39])([F:38])[F:37])=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:19][C:20]1[C:21]([O:40][CH3:41])=[CH:22][C:23]([CH2:35][C:36]([F:39])([F:38])[F:37])=[C:24]([C:2]2[CH:10]=[C:9]3[C:5]([C:6]([C:17]#[N:18])=[N:7][N:8]3[CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)=[CH:4][CH:3]=2)[CH:25]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 712377736-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbonitrileHCID 712382822-[5-Fluoro-4-methoxy-2-(2,2,2-trifluoro-ethyl)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Product 1

HCID 712380616-[5-Fluoro-4-methoxy-2-(2,2,2-trifluoro-ethyl)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carbonitrileYield 31%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 6-bromo-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carbonitrile (Preparation 2, 3.99 g, 13.03 mmol) and 2-[5-fluoro-4-methoxy-2-(2,2,2-trifluoro-ethyl)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Preparation 36, 7.46 g, 15.63 mmol) in dioxane (60 mL) was added a solution of potassium phosphate (18.8 g, 39.09 mmol) in water (12 mL). The mixture was degassed with nitrogen, treated with tetrakis(triphenylphosphine) palladium(0) (3.01 g, 2.6 mmol) and heated at 110° C. for 18 hours. The reaction mixture was concentrated in vacuo and the residue was redissolved in EtOAc (500 mL) and filtered through Arbocel®, washing with EtOAc (2×500 mL). The combined organic phases were washed with water (300 mL), dried over MgSO4 and concentrated in vacuo to give a brown oil. The residue was purified by column chromatography on silica gel, eluting with 25% EtOAc in heptanes, to give the title compound (1.737 g) in a 31% yield.

Workup

  1. customThe mixture was degassed with nitrogen
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue was redissolved in EtOAc (500 mL)
  4. filtrationfiltered through Arbocel®
  5. washwashing with EtOAc (2×500 mL)
  6. washThe combined organic phases were washed with water (300 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customto give a brown oil
  10. customThe residue was purified by column chromatography on silica gel
  11. washeluting with 25% EtOAc in heptanes

Sources & evidence

ORD record
ord-8e5d33ea240e460b9c4325d1aa3e719a
Source dataset
uspto-grants-2013_11
Patent number
US08575336B2

Reaction notes

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