Dimethylformamide → 5-bromo-6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)nicotinamide

Temperatur

80 °C

5-Bromo-6-chloro-nicotinic acid (8 g, 33.8 mmol) was suspended in toluene (70 mL). DMF (0.77 mL, 10.15 mmol) was added followed by slow addition of SOCl2 (7.4 mL, 102 mmol) and the RM was stirred for 1 h at 80° C. After cooling at RT, the toluene was evaporated off under reduce pressure. The residue was dissolved in THF (70 mL) and cooled to −10-15° C. and treated with DIPEA (11.8 mL, 67.7 mmol) followed by the slow addition of a solution of 4-(chlorodifluoromethoxy)aniline (6.88 g, 35.5 mmol) in THF (70 mL) over 10 min. The RM was allowed to warm at RT and stirred for 1 h, the solvent was evaporated off under reduced pressure. The residue was dissolved in TBME, the solution was washed with 1 M HCl, 10% aq. NaHCO3 and brine, dried over Na2SO4 and concentrated under reduced pressure until crystallization started. n-Heptane was then added and the product was filtered and dried to afford the title compound as a beige crystalline powder. HPLC (Condition 4) tR=6.46 min, UPLC-MS (Condition 3) tR=1.29 min, m/z=411 [M+H]+.

1. temperatureAfter cooling at RT
2. customthe toluene was evaporated off
3. dissolutionThe residue was dissolved in THF (70 mL)
4. temperaturecooled to −10-15° C.
5. temperatureto warm at RT
6. stirringstirred for 1 h
7. customthe solvent was evaporated off under reduced pressure
8. dissolutionThe residue was dissolved in TBME
9. washthe solution was washed with 1 M HCl, 10% aq. NaHCO3 and brine
10. dry with materialdried over Na2SO4
11. concentrationconcentrated under reduced pressure until crystallization
12. additionn-Heptane was then added
13. filtrationthe product was filtered
14. customdried

ORD-Eintrag

ord-aeddcc9445624a41a680b5460c647eb5

Quelldatensatz

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09340537B2