Thionyl Chloride → HCID 86710329, compound

Temperature

65 °C

4-(4-chloro-2,5-difluorophenyl)nicotinic acid (170 mg, 0.630 mmol) was taken in thionyl chloride (0.14 mL, 1.89 mmol) and heated at 65° C. for 1 h. The solvent was evaporated under reduced pressure to afford a crude oil which was dissolved in dichloromethane and added to a mixture of methanamine hydrochloride (63.9 mg, 0.946 mmol) and DIEA (0.11 mL, 0.63 mmol) in DCM (8 mL) dropwise at 0° C. The reaction mixture was then allowed to warm to room temperature and stirred for 7 h. The reaction mixture was diluted with DCM (5 mL) and washed with water (3×5 mL) followed by brine (1×10 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure to provide the crude product which was purified by preparative thin layer chromatography (3:2 Ethyl acetate:hexane) to afford 4-(4-chloro-2,5-difluorophenyl)-N-methylnicotinamide (90 mg, 0.264 mmol, 42% yield) as a white solid. LC/MS (ESI) m/e 283.0 [(M+H)+, calcd for C13H10ClF2N2O 283.0]; LC/MS retention time (method A): tR=1.46 min.

1. customThe solvent was evaporated under reduced pressure
2. customto afford a crude oil which
3. temperatureto warm to room temperature
4. washwashed with water (3×5 mL)
5. dry with materialThe combined organic extracts were dried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customto provide the crude product which
8. customwas purified by preparative thin layer chromatography (3:2 Ethyl acetate:hexane)

ORD record

ord-2252826b92034c8cab3b83724b1db97c

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901305B2