Thionyl Chloride → HCID 10702456, compound

2,6 difluoronicotinic acid, (0.479 g, 3.012 mmol) was suspended in 30 mL dry methylene chloride and treated with thionyl chloride (2.5 mL, 34.27 mmol), under reflux for 90 minutes. The reaction mixture was cooled to room temperature and the solvents removed under reduced pressure on a rotary evaporator, the residue obtained was further dried under high vacuum to give 2,6 difluoronicotinoyl chloride. 2,6 difluoronicotinoyl chloride was suspended in 30 mL acetonitrile, to this was added 2-fluoro-5-chlorobenzamidine (0.52 g, 3.012 mmol) and di-isopropylehylamine (1.04 mL, 6/024 mmol). The reaction mixture was allowed to stir at room temperature for one hour, at this time the formation of the acyl amidine intermediate was confirmed by LCMS as set forth below. The reaction mixture was then heated to reflux for three hours and cooled to room temperature. The reaction mixture was concentrated to dryness on a rotary evaporator and the residue was taken up in water. The suspension obtained was placed in an ice bath and acidified with 10% aq. hydrochloric acid to pH 4. The solid precipitate that formed was filtered and washed with water and anhydrous ether and dried to give 0.611 g of 2-(2-fluoro, 5-chloro) phenyl-7-fluoro-pyrido-8-pyrimidone. ESIMS M+obsd. 294.3 M+cald. 293.66. 1H NMR d6 DMSO. δ13.15, bs, 1H; δ8.7, t, 1H; δ7.9, m, 1H; δ7.75, m, 1H; δ7.5, t, 1H; δ7.4, dd, 1H;

1. temperatureunder reflux for 90 minutes
2. customthe solvents removed under reduced pressure on a rotary evaporator
3. customthe residue obtained
4. customwas further dried under high vacuum

ORD record

ord-704eab8b58d1450ba6b57aafacb9b470

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07119199B2