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

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.

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%

ORD-Eintrag

ord-823bf75363a14ab2968c6026e3c7f727

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08778939B2