Water → 7-Chloro-5-[[(2,3-difluorophenyl)methyl]thio]thiazolo[4,5-d]pyrimidin-2(3H)-one

To a stirred suspension of 7-amino-5-[[(2,3-difluorophenyl)methyl]thio][1,3]oxathiolo[5,4-d]pyrimidin-2-one (5.03 g) and benzyltrimethylammonium chloride (2.58 g) in acetonitrile (25 ml) at 50° C., was first added N,N-diethylaniline (2.46 g) followed by acetonitrile (5 ml), and then phosphorus oxychloride (7.41 g) followed by acetonitrile (5 ml). The reaction mixture was heated to reflux and maintained at this temperature for 36 hours, before cooling to ambient temperature and adding to water (25 ml) at 50° C. with stirring over 30 minutes. An additional acetonitrile (5 ml) rinse of the reaction vessel was added to the drown-out mixture, before heating to 75° C. and slowly cooling to 25° C. at <0.5° C./min. The resulting mixture was held at 25° C. for 30 minutes and then collected by filtration, washing four times with water (25 ml), to afford the title compound as an off-white solid (3.5 g).

1. temperatureThe reaction mixture was heated
2. temperatureto reflux
3. temperaturemaintained at this temperature for 36 hours
4. washAn additional acetonitrile (5 ml) rinse of the reaction vessel
5. additionwas added to the drown-out mixture
6. temperaturebefore heating to 75° C.
7. temperatureslowly cooling to 25° C. at <0.5° C./min
8. waitThe resulting mixture was held at 25° C. for 30 minutes
9. filtrationcollected by filtration
10. washwashing four times with water (25 ml)

ORD record

ord-b1f0669b29e54711a01784a187a16c3f

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07790883B2