Potassium Hydroxide → HCID 136085248, compound

HRID 2423071Notes

Reaction equation

HRID 2423071 reaction equation
Br[C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:14]([F:26])[CH:13]=1.[OH-:27].[K+].CC(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)C>O1CCOCC1.O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:11][C:9]1[CH:10]=[C:2]([OH:27])[C:3]2[CH:4]=[N:5][N:6]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[C:14]([F:26])[CH:13]=3)[C:7]=2[CH:8]=1

Participants

8

Reactant 3

HCID 14797Potassium HydroxideHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 59272970HCID 59272970, compound

Product 1

HCID 136085248HCID 136085248, compoundYield 17.1%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-bromo-6-chloro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazole (D10) (410 mg, 0.95 mmol) and KOH (212 mg, 3.8 mmol) in dioxane (10 mL) and water (10 mL) was sonicated under a flow of argon for 5 minutes after which the bis(1,1-dimethylethyl)[2′,4′,6′-tris(1-methylethyl)-2-biphenylyl]phosphane (24 mg, 0.057 mmol) and Pd2 dba3 (17 mg, 0.019 mmol) were added and it was heated to reflux for 2 hours. The mixture was then cooled to room temperature, diluted with EtOAc and water and the pH was adjusted to circa 7. The phases were separated, the aqueous re-extracted with EtOAc and the combined organics were finally dried over MgSO4. The crude material (450 mg) was purified by flash chromatography (Biotage SP4, 25+M silica column) with a gradient of EtOAc 0 to 50% in hexane to afford 60 mg of desired compound (D11).

Workup

  1. additionwere added
  2. temperatureit was heated
  3. temperatureto reflux for 2 hours
  4. customThe phases were separated
  5. extractionthe aqueous re-extracted with EtOAc
  6. dry with materialthe combined organics were finally dried over MgSO4
  7. customThe crude material (450 mg) was purified by flash chromatography (Biotage SP4, 25+M silica column) with a gradient of EtOAc 0 to 50% in hexane

Sources & evidence

ORD record
ord-b8719481f2954d40b58038e9b69c32c0
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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