Hydroxylamine → HCID 136403314, compound

HRID 242218Notes

Reaction equation

HRID 242218 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:10]([C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=2)=[N:11][N:12]([CH3:17])[C:13]=1[CH:14]=[N:15][OH:16].O.[NH2:26]O.CCOC(C)=O>C(OC(=O)C)(=O)C>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[C:10]([C:18]2[CH:19]=[CH:20][C:21]([OH:24])=[CH:22][CH:23]=2)=[N:11][N:12]([CH3:17])[C:13]=1/[C:14](=[N:15]/[OH:16])/[NH2:26]

Participants

6

Reactant 4

HCID 787HydroxylamineHCID 962Water2×HCID 8857Ethyl AcetateHCID 136350246HCID 136350246, compound

Product 1

HCID 136403314HCID 136403314, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Procedure

To 4-(2,6-difluorophenyl)-3-(4-hydroxyphenyl)-1-methyl-1H-pyrazole-5-carbaldehyde oxime (30.0 mg, 0.09 mmol) in acetic anhydride (1 mL) was irradiated in the microwave for 20 min 1.5 ml water was added and the mixture was stirred at rt for 3 h, extracted with DCM, filtered through a phase separator and concentrated. The raw product was dissolved in DMSO (1 mL) and neutral hydroxylamine solution (50 wt % in water, 0.12 mL, 1.96 mmol) was added. The mixture was stirred in the microwave at 130° C. for 10 min. EtOAc and water were added and the phases were separated. The mixture was purified on preparative HPLC to give (Z)-4-(2,6-difluorophenyl)-N′-hydroxy-3-(4-hydroxyphenyl)-1-methyl-1H-pyrazole-5-carboximidamide (5.2 mg, 0.016 mmol, 18%). Identification of the title compound by 1H-NMR showed that the oxime product was a single isomer, but did not confirm whether the (E) or (Z) oxime isomer had been obtained. ES/MS m/z: 345.11 (M+H), 343.26 (M−H); 1H NMR (MeOD, 500 MHz): 7.37 (m, 1H), 7.15 (m, 2H), 6.96 (m, 2H), 6.65 (m, 2H) and 3.99 (s, 3H).

Workup

  1. additionwas added
  2. extractionextracted with DCM
  3. filtrationfiltered through a phase separator
  4. concentrationconcentrated
  5. dissolutionThe raw product was dissolved in DMSO (1 mL)
  6. stirringThe mixture was stirred in the microwave at 130° C. for 10 min
  7. customthe phases were separated
  8. customThe mixture was purified on preparative HPLC

Sources & evidence

ORD record
ord-6ad6172912ab4e66919258e23ebbdb1f
Source dataset
uspto-grants-2014_02
Patent number
US08653112B2

Reaction notes

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