Reaktion #10420

Reaktionsgleichung

sodium tert-butoxide

chlorosulfonyl isocyanate

sodium acetate

ethyl 2-cyclopropylamino-5-fluoro-6-methylsulfanylnicotinate

→

title compound

Ausbeute 18.5%

1-Cyclopropyl-6-fluoro-7-methylsulfanyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione

Ausbeute 18.5%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITto come to room temperature overnight
2. 2
   Sonstigeis recooled to −20° C.
3. 3
   workup.STIRRINGAfter stirring for 1 hour
4. 4
   Temperaturwithout cooling
5. 5
   Sonstigethe solvent is removed in vacuo
6. 6
   Temperaturwithout heating
7. 7
   SonstigeThe residue is triturated with a saturated solution of sodium acetate in brine
8. 8
   Extraktionextracted with ethyl acetate (3×75 mL)
9. 9
   TrocknenThe combined organic layers are dried (MgSO4)
10. 10
    Filtrationfiltered
11. 11
    Sonstigeevaporated in vacuo
12. 12
    workup.STIRRINGstirred at room temperature for 36 hours
13. 13
    SonstigeThe solvent is removed in vacuo
14. 14
    Sonstigethe residue triturated with 100 mL of 0.1 M formic acid
15. 15
    Extraktionextracted with ethyl acetate (3×100 mL)
16. 16
    WaschenThe combined organic layers are washed with water
17. 17
    Trocknendried (MgSO4)
18. 18
    Filtrationfiltered
19. 19
    Sonstigeevaporated in vacuo
20. 20
    Sonstigeto give a residue which
21. 21
    Sonstigeis chromatographed over flash grade silica gel (230–400 mesh)
22. 22
    Wascheneluting with dichloromethane

Vorschrift

A solution of 4.1 g (15.2 mmol) of ethyl 2-cyclopropylamino-5-fluoro-6-methylsulfanylnicotinate (Example 34) in 125 mL of dichloromethane is cooled to −20° C. and treated dropwise with 5.24 g (37 mmol) of chlorosulfonyl isocyanate. The reaction is stirred at −20° C. for 3 hours and allowed to come to room temperature overnight. The mixture is recooled to −20° C. and treated with 6.8 g (80 mmol) of solid sodium acetate. After stirring for 1 hour without cooling, the solvent is removed in vacuo without heating. The residue is triturated with a saturated solution of sodium acetate in brine and extracted with ethyl acetate (3×75 mL). The combined organic layers are dried (MgSO4), filtered and evaporated in vacuo. The residue is suspended in 100 mL of tetrahydrofuran and treated with 3.6 g (32 mmol) of solid sodium tert-butoxide and stirred at room temperature for 36 hours. The solvent is removed in vacuo, the residue triturated with 100 mL of 0.1 M formic acid and extracted with ethyl acetate (3×100 mL). The combined organic layers are washed with water, dried (MgSO4), filtered and evaporated in vacuo to give a residue which is chromatographed over flash grade silica gel (230–400 mesh) eluting with dichloromethane to give 0.75 g of the title compound, mp 220–222° C.

Quelle