4-Chlorobenzoyl chloride → 4-Chloro-N-((3-Chloro-5-Fluorophenyl)Carbamothioyl)Benzamide

4-Chlorobenzoyl chloride (10.2 g, 58.5 mmol) was dissolved in acetonitrile (230 mL) and the reaction vessel containing this mixture was cooled in an ice/water bath. To this mixture was added potassium thiocyanate (6.25 g, 64.4 mol, 1.10 equiv). The cooling bath was removed from the reaction vessel after 15 minutes and the resulting reaction slurry was stirred at room temperature for approximately 1 hour. 3-Chloro-5-fluoroaniline (7.05 mL, 70.2 mol, 1.2 equiv) was added as a solution in acetonitrile (7 mL) over 5 minutes to the reaction mixture. Next, the reaction mixture was stirred at room temperature overnight and then quenched with water (230 mL), and the resulting mixture was stirred at room temperature for 1 hour. The mixture was filtered to collect the solids, the isolated solids were rinsed with acetonitrile/water (1/1 mixture by volume, 50 mL), and the resulting solid was dried at 60° C. in vacuo to provide 20.5 g the title compound as a solid. 1H NMR (DMSO-d6) of the title compound: δ 12.5 (s, 1H), 11.8 (s, 1H), 8.01 (t, 1H, J=1.8), 7.96 (d, 2H, J=8.6), 7.67 (m, 2H), 7.59 (d, 2H, J=8.6), 7.33 (d, 1H, J=8.4). HPLC: >99% purity at 23.52 min.

1. additionthe reaction vessel containing this mixture
2. temperaturewas cooled in an ice/water bath
3. customThe cooling bath was removed from the reaction vessel after 15 minutes
4. customthe resulting reaction slurry
5. stirringNext, the reaction mixture was stirred at room temperature overnight
6. customquenched with water (230 mL)
7. stirringthe resulting mixture was stirred at room temperature for 1 hour
8. filtrationThe mixture was filtered
9. customto collect the solids
10. washthe isolated solids were rinsed with acetonitrile/water (1/1 mixture by volume, 50 mL)
11. customthe resulting solid was dried at 60° C. in vacuo

ORD record

ord-e959de5f35704cceb27348c0c4c4b37d

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266839B2