Hydrochloric Acid → HCID 136350243, compound

HRID 242212Notes

Reaction equation

HRID 242212 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:8]([C:15]3[CH:20]=[CH:19][C:18]([O:21]C)=[CH:17][CH:16]=3)=[N:9][N:10]([CH3:14])[C:11]=2[CH:12]=O)=[C:5]([CH3:23])[O:4][N:3]=1.Cl.[NH2:25][OH:26].N1C=CC=CC=1.Cl.B(F)(F)F.S(C)C>CCO.C(Cl)Cl.CO>[CH3:1][C:2]1[C:6]([C:7]2[C:8]([C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)=[N:9][N:10]([CH3:14])[C:11]=2[CH:12]=[N:25][OH:26])=[C:5]([CH3:23])[O:4][N:3]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 1068Dimethyl SulfideHCID 6356Boron trifluorideHCID 443297Hydroxyamine hydrochlorideHCID 86668982HCID 86668982, compound

Product 1

HCID 136350243HCID 136350243, compoundYield 34.5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(3,5-dimethylisoxazol-4-yl)-3-(4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carbaldehyde (9.1 mg, 0.029 mmol), hydroxylamine hydrochloride (54.9 mg, 0.79 mmol) and pyridine (69 μL, 0.85 mmol) in dry EtOH (1 mL) was heated at 100° C. for 3 minutes in the microwave. 1 mL 2 M HCl and 5 mL DCM were added and the phases were separated. The organic phase was filtered through a phase separator and concentrated to give a raw product, that was dissolved in DCM (0.5 mL). BF3.Me2S (1 M solution in DCM, 0.5 mL, 0.5 mmol) was added and the mixture was stirred at room temperature over night. Methanol was added to quenched the reaction and the mixture was purified on preparative HPLC to give E12 4-(3,5-dimethylisoxazol-4-yl)-3-(4-hydroxyphenyl)-1-methyl-1H-pyrazole-5-carbaldehyde oxime (3.0 mg, 0.01 mmol, 32%). 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: 313.22 (M+H), 311.21 (M−H); 1H NMR (acetone-d6, 500 MHz): 7.92 (s, 1H), 7.31 (m, 2H), 6.79 (m, 2H), 4.08 (s, 3H), 2.15 (s, 3H) and 1.86 (s, 3H).

Workup

  1. customthe phases were separated
  2. filtrationThe organic phase was filtered through a phase separator
  3. concentrationconcentrated
  4. customto give a raw product, that
  5. customto quenched
  6. customthe reaction
  7. customthe mixture was purified on preparative HPLC

Sources & evidence

ORD record
ord-cd90bed817414b509a7a2c8cef64c0d1
Source dataset
uspto-grants-2014_02
Patent number
US08653112B2

Reaction notes

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