Water → 2-[4-[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]-5-pyridin-4-ylpyrazol-1-yl]ethanol

HRID 1726391Notes

Reaction equation

HRID 1726391 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([CH2:13][CH2:14][OH:15])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1.O.[CH2:17]([O:24]/[N:25]=[C:26]1\[CH2:27][CH2:28][C:29]2[C:34]\1=[CH:33][CH:32]=[C:31](B(O)O)[CH:30]=2)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:17]([O:24]/[N:25]=[C:26]1\[CH2:27][CH2:28][C:29]2[C:34]\1=[CH:33][CH:32]=[C:31]([C:2]1[CH:3]=[N:4][N:5]([CH2:13][CH2:14][OH:15])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1)[CH:30]=2)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 689224722-(4-bromo-5-(pyridin-4-yl)-1H-pyrazol-1-yl)ethanolHCID 87623866[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]boronic acid

Product 1

HCID 876252942-[4-[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]-5-pyridin-4-ylpyrazol-1-yl]ethanolYield 23.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

To 2-(4-bromo-5-(pyridin-4-yl)-1H-pyrazol-1-yl)ethanol (0.050 g; Example 2, Step 2) dissolved in 5 mL acetonitrile was added 2 mL water, (E)-1-(benzyloxyimino)-2,3-dihydro-1H-inden-5-ylboronic acid (0.058 g; Example 2, Step 4), and 0.155 g potassium carbonate. The mixture was purged with nitrogen and about 20 mg tetrakis(triphenyphosphine)palladium(0) catalyst was added. The mixture was heated at 75° C. After 1 hour, the reaction mixture was filtered through celite, the filter cake washed with ethyl acetate, and the filtrate evaporated under vacuum. The residue was partitioned between ethyl acetate and water. The ethyl acetate was washed with saturated aqueous sodium carbonate, brine, dried over magnesium sulfate, filtered, and evaporated under vacuum to yield 0.05 g crude product as a colorless glass. The crude material was purified by chromatography, eluting with a mixture of 8:1 dichloromethane-methanol to afford 18.6 mg (23% yield) product as a colorless glass. 1H NMR (CDCl3) was consistent with the desired structure. LC/MS showed one peak with a M+1 molecular ion of m/z 425.2 by positive ESI.

Workup

  1. customThe mixture was purged with nitrogen and about 20 mg tetrakis(triphenyphosphine)palladium(0) catalyst
  2. additionwas added
  3. filtrationthe reaction mixture was filtered through celite
  4. washthe filter cake washed with ethyl acetate
  5. customthe filtrate evaporated under vacuum
  6. customThe residue was partitioned between ethyl acetate and water
  7. washThe ethyl acetate was washed with saturated aqueous sodium carbonate, brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated under vacuum
  11. customto yield 0.05 g crude product as a colorless glass
  12. customThe crude material was purified by chromatography
  13. washeluting with a mixture of 8:1 dichloromethane-methanol

Sources & evidence

ORD record
ord-f2cdf4a13cd946da8745921483d871cc
Source dataset
uspto-grants-2009_02
Patent number
US07491829B2

Reaction notes

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