1,2-Dimethoxyethane → 1-{5-(1-Acetyl-1H-pyrazol-4-yl)-6-fluoro-3-[(E)-2-(4-fluorophenyl)vinyl]-1H-indazol-1-yl}ethanone

HRID 34132Notes

Reaction equation

HRID 34132 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[N:7](C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[N:6]=[C:5]2/[CH:31]=[CH:32]/[C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=1.[C:40]([N:59]1[CH:63]=[C:62](B(O)O)[CH:61]=[N:60]1)(C1C=CC=CC=1)(C1C=CC=CC=1)[C:41]1C=CC=CC=1.[OH2:67].O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].[CH2:78]([CH2:81][O:82]C)OC>C(OCC)(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:40]([N:59]1[CH:63]=[C:62]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][C:10]=2[F:11])[N:7]([C:81](=[O:82])[CH3:78])[N:6]=[C:5]3/[CH:31]=[CH:32]/[C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH:61]=[N:60]1)(=[O:67])[CH3:41]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 17749109Barium hydroxide, octahydrateHCID 22031737(1-Trityl-1H-pyrazol-4-yl)boronic acidHCID 689300565-Bromo-6-fluoro-3-[(E)-2-(4-fluorophenyl)vinyl]-1-trityl-1H-indazole

Product 1

HCID 600347731-{5-(1-Acetyl-1H-pyrazol-4-yl)-6-fluoro-3-[(E)-2-(4-fluorophenyl)vinyl]-1H-indazol-1-yl}ethanone

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 40 mg of 5-bromo-6-fluoro-3-[(E)-2-(4-fluorophenyl)vinyl]-1-trityl-1H-indazole, 29.4 mg of 1-tritylpyrazole-4-boronic acid, 4 mg of tetrakis(triphenylphosphine)palladium(0) and 32.8 mg of barium hydroxide octahydrate in a mixture of dimethoxyethane:water=0.6 mL:0.1 mL was stirred at 80° C. for a day. The solution was diluted with ethyl acetate and water, and the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. Then the solvent was evaporated. A solution of the crude product in 1 mL of dichloromethane was added with 0.2 mL of trifluoroacetic acid at room temperature, and stirred at this temperature for 1 hour. The reaction solution was poured to aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the then the solvent was evaporated. A solution of the crude product in 1 mL of tetrahydrofuran and 0.5 mL of diisopropylethylamine was added with 0.1 mL of acetic anhydride at room temperature and stirred at this temperature for a day. The reaction solution was evaporated, and the residue was purified and separated by silica gel column chromatography (ethyl acetate:n-hexane=1:3-1:1), to afford 13 mg of the title compound as colorless crystals.

Workup

  1. washthe organic layer was washed with saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThen the solvent was evaporated
  4. additionA solution of the crude product in 1 mL of dichloromethane was added with 0.2 mL of trifluoroacetic acid at room temperature
  5. additionThe reaction solution was poured to aqueous sodium hydrogen carbonate
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe then the solvent was evaporated
  10. additionA solution of the crude product in 1 mL of tetrahydrofuran and 0.5 mL of diisopropylethylamine was added with 0.1 mL of acetic anhydride at room temperature
  11. stirringstirred at this temperature for a day
  12. customThe reaction solution was evaporated
  13. customthe residue was purified
  14. customseparated by silica gel column chromatography (ethyl acetate:n-hexane=1:3-1:1)

Sources & evidence

ORD record
ord-115bb6c108254660b60ab40244abcf9c
Source dataset
uspto-grants-2008_09
Patent number
US07429609B2

Reaction notes

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