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

Temperature

85 °C

To a solution of 5-amino-1-phenyl-1H-pyrazole-3-carbonitrile (Preparation 53, 400 mg, 2.17 mmol) in 2-methyltetrahydrofuran (12 mL) was added pyridine (524 uL, 6.51 mmol) and 5-bromo-2-chlorobenzoic acid (768 mg, 3.26 mmol). The mixture was heated to 85° C. and propylphosphonic anhydride (50% w/w in EtOAc, 3.10 mL, 4.34 mmol), was added dropwise. The reaction was heated at 85° C. for 16 hours, then stirred for 48 hours at room temperature. The reaction was quenched by the addition of 10% aqueous potassium carbonate solution (24 mL, 17.4 mmol) with stirring at room temperature for 1 hour. The reaction was diluted to 150 mL with EtOAc and washed with 10% aqueous solution of potassium carbonate (100 mL) followed by 2M aqueous HCl (100 mL). The organic layer was dried over magnesium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 0-1% methanol in dichloromethane to afford the title compound (640 mg, 74%).

1. temperatureThe reaction was heated at 85° C. for 16 hours
2. stirringwith stirring at room temperature for 1 hour
3. washwashed with 10% aqueous solution of potassium carbonate (100 mL)
4. dry with materialThe organic layer was dried over magnesium sulphate
5. concentrationconcentrated in vacuo
6. customThe residue was purified
7. washeluting with 0-1% methanol in dichloromethane

ORD record

ord-6ead1e7b070846c4bb4704a5bc65f1ab

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328096B2