Ethyl Acetate → 2-chloro-5-(2,2-difluoropropyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

Temperature

60 °C

2-Chloro-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (384 mg, 1.508 mmol), 2,2-difluoropropyl 4-nitrobenzenesulfonate (767 mg, 2.73 mmol), cesium carbonate (1240 mg, 3.81 mmol) were combined in DMA (2 mL) at ambient temperature for about 1 hour and then heated in an oil bath at 60° C. After about 22 hours, the reaction mixture was allowed to cool to ambient temperature, diluted reaction mixture with 25 mL EtOAc, transferred to a separatory funnel, and the reaction vessel rinsed twice with 10 mL 1:1 EtOAc/water. An additional 10 mL of water was then added, the layers were mixed and then separated. The organic layer was extracted with water (10 mL) and the combined aqueous layers were extracted with 10 mL of EtOAc, which was then extracted with 5 mL brine. The combined organic layers were dried over sodium sulfate, filtered, and concentrated on a rotovap to give a residue. The residue was combined with isopropanol (5 mL) and heated in an oil bath at 50° C. oil bath. An addition 1.5 mL was added and the solution was allowed to cool to ambient temperature with stirring to give a solid. Collected the solid by filtration, rinse the filter cake with 1 mL isopropanol and air dry for 2 hours, then dry under vacuum to give the title compound.

1. temperatureto cool to ambient temperature
2. additiondiluted
3. customtransferred to a separatory funnel
4. washthe reaction vessel rinsed twice with 10 mL 1:1 EtOAc/water
5. additionAn additional 10 mL of water was then added
6. additionthe layers were mixed
7. customseparated
8. extractionThe organic layer was extracted with water (10 mL)
9. extractionthe combined aqueous layers were extracted with 10 mL of EtOAc, which
10. extractionwas then extracted with 5 mL brine
11. dry with materialThe combined organic layers were dried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated on a rotovap
14. customto give a residue
15. temperatureheated in an oil bath at 50° C. oil bath
16. additionAn addition 1.5 mL
17. additionwas added
18. temperatureto cool to ambient temperature
19. customto give a solid
20. customCollected the solid
21. filtrationby filtration
22. washrinse the filter cake with 1 mL isopropanol and air
23. customdry for 2 hours
24. customdry under vacuum

ORD record

ord-0ef7b781b97345db96eae774b33b278d

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08163755B2