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Potassium Phosphate, Tribasic → 6-(2-Ethyl-5-fluoro-4-methoxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole

HRID 340068
Notes
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Reaction equation

HRID 340068 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][CH:3]=1.[CH2:17]([C:19]1[CH:24]=[C:23]([O:25][CH3:26])[C:22]([F:27])=[CH:21][C:20]=1B1OC(C)(C)C(C)(C)O1)[CH3:18].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>[CH2:17]([C:19]1[CH:24]=[C:23]([O:25][CH3:26])[C:22]([F:27])=[CH:21][C:20]=1[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][CH:3]=1)[CH3:18]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 672932406-bromo-1-(oxan-2-yl)-1H-indazoleHCID 712380622-(2-Ethyl-5-fluoro-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 712379806-(2-Ethyl-5-fluoro-4-methoxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazoleYield 71.4%

Reagents, catalysts & solvents 3

HCID 11979704
Tetrakis(triphenylphosphine)palladium
Catalyst
HCID 962WaterSolvent
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 6-bromo-1-(tetrahydro-pyran-2-yl)-1H-indazole (WO 2010/027500, 2.25 g, 8.0 mmol) and 2-(2-ethyl-5-fluoro-4-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Preparation 13, 2.24 g, 8.0 mmol) in dioxane (32 mL) was added potassium phosphate (5.1 g, 24 mmol) as a solution in water (8 mL). The reaction mixture was degassed with nitrogen and treated with tetrakis (triphenylphosphine) palladium(0) (1.85 g, 1.6 mmol). The reaction mixture was heated at 110° C. for 18 hours, cooled to room temperature and filtered through a pad of Arbocel®, washing with EtOAc (2×100 mL). The filtrate was washed with water (100 mL), dried over MgSO4 and concentrated in vacuo. The crude material was purified by column chromatography on silica gel eluting with 10% EtOAc in heptane to give the title compound as a white solid (2.024 g) in a 71% yield.

Workup

  1. customThe reaction mixture was degassed with nitrogen
  2. temperaturecooled to room temperature
  3. filtrationfiltered through a pad of Arbocel®
  4. washwashing with EtOAc (2×100 mL)
  5. washThe filtrate was washed with water (100 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by column chromatography on silica gel eluting with 10% EtOAc in heptane

Sources & evidence

ORD record
ord-6ddaf6549133401f8b714fc35d9dc855
Source dataset
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08895544B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes