Triethylamine → 3-bromo-6-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-2-fluorobenzamide

To a solution of 3-bromo-6-chloro-2-fluorobenzoic acid (1 g, 3.95 mmol) in DCM (20 mL) was added DMF (1 drop) followed by oxalyl chloride (0.7 mL, 7.89 mmol) dropwise. The reaction was stirred at room temperature for 30 minutes before concentrating in vacuo and azeotroping with DCM. The residue was dissolved in MeCN (5 mL) and 5-amino-1-phenyl-1H-pyrazole-3-carbonitrile (655 mg, 3.56 mmol) and triethylamine (0.55 mL, 3.95 mmol) in MeCN (7 mL) were added. The reaction was heated at 120° C. for 1 hour under microwave irradiation. 2M NaOH (aq) (20 mL) was added with vigorous stirring at room temperature for 1.5 hours. The organic layer was separated, washed with 2M HCl (aq) (2×20 mL), dried over magnesium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 10-30% EtOAc in heptanes to afford the title compound (200 mg, 13%).

1. concentrationbefore concentrating in vacuo
2. customazeotroping with DCM
3. dissolutionThe residue was dissolved in MeCN (5 mL)
4. temperatureThe reaction was heated at 120° C. for 1 hour under microwave irradiation
5. stirringwith vigorous stirring at room temperature for 1.5 hours
6. customThe organic layer was separated
7. washwashed with 2M HCl (aq) (2×20 mL)
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated in vacuo
10. customThe residue was purified
11. washeluting with 10-30% EtOAc in heptanes

ORD-Eintrag

ord-93a2a903959b4e6ea342aed2b7e5220e

Quelldatensatz

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09328096B2