Triethylamine → 4-(4-chloro-2-fluorophenyl)-N,6-dimethylnicotinamide

To a solution of 4-(4-chloro-2-fluorophenyl)-6-methylnicotinic acid (500 mg, 1.88 mmol) in dichloromethane (10 mL) at 0° C. was added oxalyl chloride (0.988 mL, 11.29 mmol) drop wise followed by DMF (0.2 mL). The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was evaporated to dryness. The residue was taken in up dichloromethane (50 mL) and cooled to 0° C. Methylamine hydrochloride (1.27 g, 18.82 mmol) was added to followed by triethylamine (2.62 mL, 18.82 mmol) and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (100 mL). The organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure to afford 4-(4-chloro-2-fluorophenyl)-N,6-dimethylnicotinamide (520 mg, 1.43 mmol, 76% crude yield) as yellow solid. The material was carried forward without further purification. LC/MS (ESI) m/e 279.0 [(M+H)+, calcd for C14H13ClFN2O 279.1]; LC/MS retention time ((Method I) tR=1.82 min.

1. customThe reaction mixture was evaporated to dryness
2. temperaturecooled to 0° C
3. stirringthe reaction mixture was stirred at room temperature for 2 h
4. extractionextracted with dichloromethane (100 mL)
5. customThe organic layer was separated
6. dry with materialdried over Na2SO4
7. concentrationconcentrated under reduced pressure

ORD record

ord-ec04a21ae75d4058aecd897ba16270e0

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901305B2