Hydrochloric Acid → (E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime

HRID 1726398Notes

Reaction equation

HRID 1726398 reaction equation
C([O:8]/[N:9]=[C:10]1\[CH2:11][CH2:12][C:13]2[C:18]\1=[CH:17][CH:16]=[C:15]([C:19]1[C:20]([C:27]3[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=3)=[N:21][N:22]([CH2:24][CH2:25][OH:26])[CH:23]=1)[CH:14]=2)C1C=CC=CC=1.Cl.[H][H]>CO.[OH-].[Pd+2].[OH-]>[OH:26][CH2:25][CH2:24][N:22]1[CH:23]=[C:19]([C:15]2[CH:14]=[C:13]3[C:18](=[CH:17][CH:16]=2)[C:10](=[N:9][OH:8])[CH2:11][CH2:12]3)[C:20]([C:27]2[CH:28]=[CH:29][N:30]=[CH:31][CH:32]=2)=[N:21]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 876234382-[4-[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]ethanolHCID 178418361HCID 178418361, compound

Product 1

HCID 57519545(E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oximeYield 53%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To (E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydroinden-1-one O-benzyl oxime (31.9 mg; Example 4, Step 4) in 5 mL methanol was added 38 μL 6M hydrochloric acid and about 5 mg palladium hydroxide (20% by weight on carbon). A hydrogen-filled balloon was attached to the reaction vessel and the mixture was stirred at ambient temperature for 1 hour. The mixture was filtered through celite, the celite was washed with methanol, and the filtrate treated with a small amount of saturated aqueous sodium bicarbonate. The filtrate was concentrated under vacuum and the residue was purified by chromatography, eluting with a 10:1 mixture of dichloromethane-methanol to yield 13.2 mg (53% yield) of a white solid. 1H NMR (CDCl3) was consistent with the desired structure 110. LC/MS showed one peak with a M+1 molecular ion of m/z 335.4 by positive ESI.

Workup

  1. filtrationThe mixture was filtered through celite
  2. washthe celite was washed with methanol
  3. additionthe filtrate treated with a small amount of saturated aqueous sodium bicarbonate
  4. concentrationThe filtrate was concentrated under vacuum
  5. customthe residue was purified by chromatography
  6. washeluting with a 10:1 mixture of dichloromethane-methanol

Sources & evidence

ORD record
ord-4dcfd1c4e25a48839992e029f27c41fb
Source dataset
uspto-grants-2009_02
Patent number
US07491829B2

Reaction notes

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