Methanesulfonamide → 4-[(5-Chloro-6-fluoropyridin-3-yl)oxy]-2,5-difluoro-N-(methylsulfonyl)benzamide

Temperatur

45 °C

Methanesulfonamide (52.0 mg, 0.547 mmol) was suspended in MeCN (3 mL) in a sealed vial. 2,3,4,6,7,8,9,10-Octahydropyrimidol[1,2-a]azepine (0.085 mL, 0.57 mmol) was added followed by 4-methylphenyl 4-[(5-chloro-6-fluoropyridin-3-yl)oxy]-2,5-difluorobenzoate (Preparation 67, 215.0 mg, 0.546 mmol). The mixture was heated at 45° C. for 2 hours. The reaction mixture was diluted in EtOAc (15 mL), then washed with 10% aqueous citric acid solution (2×15 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting solid was partitioned between DCM (10 mL) and water (10 mL). The organic layer was further washed water (2×10 mL) and concentrated in vacuo to yield the title compound as a white solid (75 mg). EtOAc (15 mL) was added to the combined aqueous. The organic layer was then washed with water (3×10 mL), dried over sodium sulfate, filtered and concentrated in vacuo to yield a second batch of the title compound as a white solid (75.0 mg, 35%):

1. washwashed with 10% aqueous citric acid solution (2×15 mL)
2. dry with materialThe organic layer was dried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe resulting solid was partitioned between DCM (10 mL) and water (10 mL)
6. washThe organic layer was further washed water (2×10 mL)
7. concentrationconcentrated in vacuo

ORD-Eintrag

ord-8998601744e04895b9f43ef675d76ee3

Quelldatensatz

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08592629B2