Pyridine → 2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-4-fluoro-5-(3-fluoropyridin-2-yl)benzamide

온도

90 °C

To a solution of 2-chloro-4-fluoro-5-(3-fluoropyridin-2-yl)benzoic acid (Preparation 21, 160 mg, 0.59 mmol) in 2-Methyl-THF (3 mL) was added 5-amino-1-phenyl-1H-pyrazole-3-carbonitrile (Preparation 53, 120 mg, 0.65 mmol) and pyridine (0.14 mL, 1.77 mmol). The reaction was heated to 90° C. before the addition of propylphosphonic anhydride (752 mg, 1.18 mmol) and the reaction was continued heating at 90° C. for 16 hours. Further propylphosphonic anhydride (752 mg, 1.18 mmol) was added and the reaction continued to heat at 90° C. for 3 hours. The reaction was cooled to room temperature, diluted with EtOAc (20 mL) and washed with 2M NaOH(aq) (2×20 mL), saturated aqueous NH4Cl solution (20 mL), water (20 mL) and brine (20 mL). The organic layer was dried over magnesium sulphate and concentrated in vacuo. The residue was purified using reverse phase column chromatography eluting from 5-60% MeCN (with 0.1% HCO2H) in water (with 0.1% HCO2H) to afford the title compound (89 mg, 34%).

1. temperatureto heat at 90° C. for 3 hours
2. temperatureThe reaction was cooled to room temperature
3. washwashed with 2M NaOH(aq) (2×20 mL), saturated aqueous NH4Cl solution (20 mL), water (20 mL) and brine (20 mL)
4. dry with materialThe organic layer was dried over magnesium sulphate
5. concentrationconcentrated in vacuo
6. customThe residue was purified
7. washeluting from 5-60% MeCN (with 0.1% HCO2H) in water (with 0.1% HCO2H)

ORD 기록

ord-44e54a2c25f2483eb4ff565a07a8f27e

출처 데이터셋

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09328096B2