1,2-Dichloroethane → 2-{[(4-Fluorophenyl)methyl]oxy}-N-4-isoxazolyl-5-(1-methyl-1H-pyrazol-4-yl)benzamide

HRID 1623871Notes

Reaction equation

HRID 1623871 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:10]2[CH:18]=[CH:17][C:16]([C:19]3[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=3)=[CH:15][C:11]=2[C:12](O)=[O:13])=[CH:4][CH:3]=1.[O:25]1[CH:29]=[C:28]([NH2:30])[CH:27]=[N:26]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C)C=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:10]2[CH:18]=[CH:17][C:16]([C:19]3[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=3)=[CH:15][C:11]=2[C:12]([NH:30][C:28]2[CH:27]=[N:26][O:25][CH:29]=2)=[O:13])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 138042781,2-Oxazol-4-amineHCID 67108246HCID 67108246, compound

Product 1

HCID 699368062-{[(4-Fluorophenyl)methyl]oxy}-N-4-isoxazolyl-5-(1-methyl-1H-pyrazol-4-yl)benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-{[(4-fluorophenyl)methyl]oxy}-5-(1-methyl-1H-pyrazol-4-yl)benzoic acid (may be prepared as described in Description 121; 100 mg, 0.31 mmol), isoxazol-4-amine (38.6 mg, 0.46 mmol), HOBT (70.4 mg, 0.46 mmol) and EDC (88 mg, 0.46 mmol) in N,N-dimethylformamide (5 ml) was stirred at room temperature for 16 hours. Water (50 ml) was added. The mixture was extracted with ethyl acetate (50 ml×3). The combined organic layers were washed with brine (50 ml), dried over Na2SO4, and concentrated to give the crude product. The crude product was purified by a prep-HPLC (instrument: Gilson GX-281; Column: Shimadzu PRC-ODS, 15.0 um, 19 mm*250 mm; Mobile Phase: A: 0.05% NH3H2O/H2O; B: CH3CN; Gradient 0-8 min 42-54% B; 8-12 min 95%; Flow Rate (ml/min) 30.00; Detective Wavelength (nm) 214; Retention Time (min) 7.5) to yield the title compound as a white solid. 17 mg.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (50 ml×3)
  2. washThe combined organic layers were washed with brine (50 ml)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customto give the crude product
  6. customThe crude product was purified by a prep-HPLC (instrument
  7. customGradient 0-8 min 42-54% B
  8. custom8-12 min 95%

Sources & evidence

ORD record
ord-823bf75363a14ab2968c6026e3c7f727
Source dataset
uspto-grants-2014_07
Patent number
US08778939B2

Reaction notes

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