Sodium Bicarbonate → HCID 22258023, compound

Temperature

-78 °C

A tetrahydrofuran solution of lithium diisopropylamide (5.0 ml, 0.72 mmol) was added to a solution of 6-(3-fluorophenyl)methyl-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (Example 52, 0.24 g) in anhydrous tetrahydrofuran (5 ml), at −78° C. under nitrogen. After 15 minutes, further lithium diisopropylamide solution (2.5 ml, 0.36 mmol) was added. The reaction mixture was maintained at −78° C. for a further 3 hours. 3-{[Dimethyl-(1,1-dimethylethyl)silyl]oxy}propyl 4-methylphenylthiosulfonate (J. Med. Chem. 1995, 38, 2557., 0.286 g) was added and the mixture was heated at 50° C. for 30 minutes. The reaction mixture was added to saturated sodium hydrogen carbonate solution (50 ml) and extracted with ether (50 ml). The organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was dissolved in acetonitrile (10 ml) and then treated with 40% hydrofluoric acid (1 ml). After 1 hour, the mixture was added to saturated sodium hydrogen carbonate solution (100 ml) and extracted with ether (2×50 ml). The organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography over silica, eluting with ethyl acetate:isohexane (1:1) followed by recrystallisation from ethyl acetate/isohexane to give the title compound (0.058 g).

1. temperaturethe mixture was heated at 50° C. for 30 minutes
2. extractionextracted with ether (50 ml)
3. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
4. filtrationfiltered
5. customevaporated
6. dissolutionThe residue was dissolved in acetonitrile (10 ml)
7. additiontreated with 40% hydrofluoric acid (1 ml)
8. waitAfter 1 hour
9. additionthe mixture was added to saturated sodium hydrogen carbonate solution (100 ml)
10. extractionextracted with ether (2×50 ml)
11. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
12. filtrationfiltered
13. customevaporated
14. customThe residue was purified by column chromatography over silica
15. washeluting with ethyl acetate:isohexane (1:1)
16. customfollowed by recrystallisation from ethyl acetate/isohexane

ORD record

ord-eaab6107142e4b29a47453bf5d04297f

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06180635B2