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

A mixture of 2-chloro-4-methyl-5-(pyridin-2-yl)benzoic acid (Preparation 25, 234 mg, 0.94 mmol), 5-amino-1-phenyl-1H-pyrazole-3-carbonitrile (Preparation 53, 191 mg, 1.04 mmol) and pyridine (0.23 mL, 2.83 mmol) in 2-methyl tetrahydrofuran (20 mL) was heated at reflux for 10 minutes. To this refluxing mixture was added propylphosphonic anhydride solution (2.8 mL, 50% w/w in EtOAc) and the reaction heated at reflux under an atmosphere of argon for 18 hours. The reaction mixture was cooled to room temperature and partitioned between EtOAc (100 mL) and 2M aqueous sodium hydroxide solution (50 mL). The organic layer was washed with 2M aqueous sodium hydroxide solution (50 mL), saturated aqueous ammonium chloride solution (50 mL), water (50 mL), dried over magnesium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 0-20% EtOAc in DCM followed by trituration with diethylether to afford the title compound as a white solid (119 mg, 31%).

1. temperaturewas heated
2. temperatureat reflux for 10 minutes
3. temperaturethe reaction heated
4. temperatureat reflux under an atmosphere of argon for 18 hours
5. custompartitioned between EtOAc (100 mL) and 2M aqueous sodium hydroxide solution (50 mL)
6. washThe organic layer was washed with 2M aqueous sodium hydroxide solution (50 mL), saturated aqueous ammonium chloride solution (50 mL), water (50 mL)
7. dry with materialdried over magnesium sulphate
8. concentrationconcentrated in vacuo
9. customThe residue was purified
10. washeluting with 0-20% EtOAc in DCM

ORD record

ord-a4cf6a8385ad45b6bac385093efd1809

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328096B2