Hydrochloric Acid → HCID 136085241, compound

HRID 2423080Notes

Reaction equation

HRID 2423080 reaction equation
Br[C:2]1[C:10]([Cl:11])=[CH:9][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.[OH2:27].[OH-].[K+].Cl>O1CCOCC1.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].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.O.C(OCC)(=O)C>[Cl:11][C:10]1[CH:9]=[CH:8][C:7]2[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)[N:5]=[CH:4][C:3]=2[C:2]=1[OH:27]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14797Potassium HydroxideHCID 59272962HCID 59272962, compound

Product 1

HCID 136085241HCID 136085241, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneCatalystHCID 312751,4-DioxaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 4-bromo-5-chloro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazole (D23) (0.32 g, 0.74 mmol) in 1,4-dioxane (5 mL)/water (5 mL) was stirred and treated with potassium hydroxide (0.17 g, 3.03 mmol), Pd2 dba3 (0.014 g, 0.015 mmol) and 2-di-tertbutylphosphino-2′,4′,6′-triisopropylbiphenyl (0.019 g, 0.045 mmol) and the mixture was heated to 90° C. under argon. After 3 hrs, the mixture was cooled and water/ethyl acetate were added followed by 2N HCl (1.3 mL) and the product was extracted into ethyl acetate. The combined extracts were washed with brine, dried, concentrated and chromatographed (silica, ethyl acetate/hexane) to give the title compound (D24) (0.195 g)

Workup

  1. temperaturethe mixture was cooled
  2. extractionthe product was extracted into ethyl acetate
  3. washThe combined extracts were washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customchromatographed (silica, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b1e98a773c304869a072cb618d1ce65a
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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