Dimethylformamide → 4-(4-Chloro-2-fluorophenyl)-2-methylnicotinamide

Temperature

0 °C

4-(4-Chloro-2-fluorophenyl)-2-methylnicotinic acid (9 g, 33.9 mmol) (previous described in Example 16, Part E) was taken in DCM (50 mL) and cooled to 0° C. The solution was treated with oxalyl chloride (14.83 mL, 169 mmol) followed by slow addition of DMF (1 mL). The mixture was heated at 40° C. for 3 h. After cooling, the volatiles were removed under reduced pressure. The residue taken up in DCM (25 mL) was cooled to 0° C., and TEA (22.08 mL, 158 mmol) and ammonium chloride (16.94 g, 317 mmol) were added slowly. After stirring at room temperature for 1 h, the reaction mixture was washed with saturated aqueous NaHCO3 (10 mL), water (10 mL), and brine (10 mL). The organic layer was separated and dried with Na2SO4 to afford the 4-(4-chloro-2-fluorophenyl)-2-methylnicotinamide (3.5 g, 13.2 mmol, 42% crude yield) as a brown solid. The material was carried forward without further purification. LC/MS (ESI) m/e 264.4 [(M)+, calcd for C13H10ClFN2O 264.0] LC/MS retention time (method C): tR=1.58 min.

1. temperatureThe mixture was heated at 40° C. for 3 h
2. temperatureAfter cooling
3. customthe volatiles were removed under reduced pressure
4. temperaturewas cooled to 0° C.
5. washthe reaction mixture was washed with saturated aqueous NaHCO3 (10 mL), water (10 mL), and brine (10 mL)
6. customThe organic layer was separated
7. dry with materialdried with Na2SO4

ORD record

ord-75d713ea33ae4bd7b32147edc81d8f40

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901305B2